Novel Gonadotrophin Releasing Hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix, and linzagolix have assessed treatment efficacy for fibroid related heavy menstrual blood loss in comparison to placebo. Marketing authorization has already been granted by several agencies including those in Europe, the United Kingdom, and the United States. Prior to marketing authorization, the European Medicines Agency recommends that Phase III registration trails should assess treatment efficacy in a representative study population, assess relevant outcomes with a comparison to gold-standard alternative treatment options and that long-term safety data will adequately be collected. In this review, we demonstrate limitations in the trial data generated to date, namely a lack of generalizability due to the restricted population studied, the absence of any comparison to alternative treatment methods, and findings limited to specific subgroups of patients because of the type of outcomes assessed. Symptoms related to uterine fibroids adversely affect many women’s quality of life and effective medical treatments are lacking. However, despite the urgent need for effective treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness, and cost-effectiveness in a representative population compared with alternative treatment methods before introduction into mainstream clinical practice.

BACKGROUND: About 8,800-34,200 Gender Dysphoria (GD)- and 39,000-650,800 Mayer-Rokitansky-Küster-Hauser (MRKH)-patients undergo vaginoplasty annually. Various procedures are available, but comparisons are lacking. OBJECTIVES: To highlight information gaps, weaknesses and strengths of vaginoplasty techniques, to aid well-informed decision making by patients and healthcare professionals. SEARCH STRATEGY: A systematic search in Medline, EMBASE, Web of Science and Scopus until October 6, 2022, by PICO method and PROSPERO registration. SELECTION CRITERIA: Original retrospective studies on complete neovaginal creation in adult GD- and MRKH-patients and discussing anatomy, Quality of Life (QoL), satisfaction, sexual function, complications or complaints. DATA COLLECTION AND ANALYSIS: The 95% confidence intervals were calculated with DerSimonian and Laird random-effects. Methodological quality and potential bias were assessed. MAIN RESULTS: In total, 35 GD- and 16 MRKH-studies were eligible. Vagina length was 11.6 and 9.5 cm, respectively. In GD-patients, Hemorrhage (6%), prolapse (1%), gastrointestinal complications (1%), revisions (26%), pain (6%), regret (1%), fecal- (11%) and urinary issues (17%) were reported. Necrosis, stenosis, dyspareunia and revisions decreased, while duration increased with higher graft quantity. Intestinal-vaginoplasty reported 100% sensation. MRKH-patients reported more necrosis (17%) [McIndoe] and average satisfaction with sexual function (91%) and vaginal discharge (32%). They were more sexually active (86%) and had 100% anatomical satisfaction. Only Intestinal-vaginoplasty reported overall dissatisfaction. CONCLUSIONS: For GD- and MRKH-patients, multiple safe vaginoplasty techniques demonstrated acceptable outcomes, with significantly improved QoL and self-image. However, standardized validation tools are needed for well-informed decision-making. Direct technique comparisons per patient-cohort and exploration of tissue-engineering methods are critical for future surgical advancements.

BACKGROUND: About 430,000-1,000,000 Gender Dysphoria- and Mayer-Rokitanksy-Küster-Hauser-patients undergo vaginoplasty each year. Various surgical procedures are available, but direct comparisons are lacking. This inhibits well-informed decision making by patients and healthcare professionals. OBJECTIVES: Highlight information gaps, weaknesses and strengths of todays vaginoplasty techniques. SEARCH STRATEGY: A systematic search in Medline, EMBASE, Web of Science and Scopus until March 8, 2022 was conducted, by PICO method and PROSPERO registration. SELECTION CRITERIA: Original retrospective studies on complete neovaginal creation in adult Gender Dysphoria- and Mayer-Rokitanksy-Küster-Hauser-patients and discussing anatomical outcome, Quality of Life, satisfaction, sexual function, complications and/or complaints. DATA COLLECTION AND ANALYSIS: Data was extracted and methodological quality and potential bias were assessed. The 95% confidence intervals were calculated with DerSimonian and Laird random-effects. MAIN RESULTS: A total of 47 articles were eligible. Surgery took 198 minutes with 10.2 cm vaginal length. Major complications included 5% hemorrhage, 1% gastrointestinal complications, 1% prolapse, 3% tissue necrosis and 6% stenosis, with 31% revisions. Patients reported 25% excessive discharge, 6% pain, 11% fecal- and 17% urinary issues and one case of hair growth. Patients also reported 95% aesthetic- and 93% anatomical satisfaction, 10% overall dissatisfaction and 1% regret. Reports showed 75% sexual activity, 13% dyspareunia, 87% sensation and 84% overall functional satisfaction. CONCLUSIONS: Multiple vaginoplasty techniques demonstrated safe and acceptable outcomes, with significant improvement of Quality of Life and self-image. However, standardized validation tools are needed for well-informed decision-making. Direct technique comparisons with similar cohorts and exploration of tissue-engineering methods are critical for future surgical advancements.

Objective: To compare postoperative reproductive outcomes between salpingectomy and neosalpingostomy for bilateral severe hydrosalpinges. Design: Single center, prospective cohort study. Setting: A hospital affiliated to a medical college in China. Population: Women aged 20 to 45 years old, diagnosed with bilateral hydrosalpinges and scheduled for surgery were initial eligibility criteria. Women with previous tubal surgery or tubal pregnancy, no fertility intention, or no confirmation of severe bilateral hydrosalpinges during surgery were excluded. Methods: Bilateral salpingectomy or neosalpingostomy was performed based on a shared decision approach. Main outcome measures: The primary outcome was the cumulative livebirth rate. Secondary outcomes included time to first live birth, biochemical pregnancy, clinical miscarriage, ectopic pregnancy, mode of conception, and gestational age at delivery. Results: A total of 113 women were involved in the analysis. When the result of In Vitro Fertilization (IVF) in the neosalpingostomy group was incorporated, salpingectomy resulted in a higher cumulative livebirth rate (85.3% vs 76.0%, hazard ratio of the whole survival curve = 2.18, 95% CI 1.37 - 3.45), a lower risk of ectopic pregnancy (1.8% vs 20.7%, risk ratio = 0.07, 95% CI 0.01 - 0.57), and a shorter time to live birth than neosalpingostomy. 16/58 (27.6%) women in the neosalpingostomy group had a live birth via natural conception, compared to 0/55 (0.0%) in the salpingectomy group. Conclusions：Salpingectomy for bilateral severe hydrosalpinges resulted in a higher cumulative livebirth rate and a lower risk of ectopic pregnancy. However, neosalpingostomy can offer certain option for women to conceive naturally without IVF treatment.

Objective: To compare the effect of a hysteroscopic niche resection with a Levenorgestrel-releasing intrauterine device (LNG-IUD) on postmenstrual spotting in women with a symptomatic niche in the uterine cesarean scar. Design: Single center, prospective cohort study. Setting: A hospital affiliated to a medical college in China. Population: Women diagnosed with a niche by MRI scan and postmenstrual spotting of at least two days. Method: Women were allocated to two groups based on the shared medical decision-making approach, and were followed up for 1 year after treatment. Main outcome measures: The primary outcome was effectiveness in reducing postmenstrual spotting. Secondary outcomes were menstrual characteristics, direct medical costs, complications and side effects. Results: Effectiveness of LNG-IUD was significantly higher than a hysteroscopic niche resection during the first year, based on linear mixed models (P=0.009), and the effectiveness increased overtime within 1 year. Postmenstrual spotting reduced statistically in both groups. More slight side effects, although not statistically significant, were reported in LNG-LUD group at obviously lower direct medical costs. Conclusion：LNG-IUD is more effective in the treatment of postmenstrual spotting from the 6th month onwards than a hysteroscopic niche resection in women with a symptomatic niche at lower direct costs. Key Words：Niche, uterine cesarean scar, hysteroscopy niche resection, LNG-IUD, postmenstrual spotting, amenorrhea Tweetable abstract: LNG-IUD is more effective in the treatment of postmenstrual spotting related to a niche than hysteroscopic niche resection.