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Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions.The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered.A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx.A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.

Supplementary Figure from Validation of BD Onclarity HPV Assay on Vaginal Self-Samples versus Cervical Samples Using the VALHUDES Protocol

Background:In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples.Methods:Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31–49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation.Results:The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90–1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02–1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94–1.06) and 1.15 (95% CI, 1.05–1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79–1.04) and 1.03 (95% CI, 0.95–1.13), respectively for Qvintip.Conclusions:Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples.Impact:VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening.

High-grade serous ovarian cancer (HGSOC) is responsible for the largest number of ovarian cancer deaths. The frequent therapy-resistant relapses necessitate a better understanding of mechanisms driving therapy resistance. Therefore, we mapped more than a hundred thousand cells of HGSOC patients in different phases of the disease, using single-cell RNA sequencing. Within patients, we compared chemonaive with chemotreated samples. As such, we were able to create a single-cell atlas of different HGSOC lesions and their treatment. This revealed a high intrapatient concordance between spatially distinct metastases. In addition, we found remarkable baseline differences in transcriptomics of ascitic and solid cancer cells, resulting in a different response to chemotherapy. Moreover, we discovered different robust subtypes of cancer-associated fibroblasts (CAF) in all patients. Besides inflammatory CAFs, vascular CAFs, and matrix CAFs, we identified a new CAF subtype that was characterized by high expression of STAR, TSPAN8, and ALDH1A1 and clearly enriched after chemotherapy. Together, tumor heterogeneity in both cancer and stromal cells contributes to therapy resistance in HGSOC and could form the basis of novel therapeutic strategies that differentiate between ascitic and solid disease.Implications:The newly characterized differences between ascitic and solid cancer cells before and after chemotherapy could inform novel treatment strategies for metastatic HGSOC.

Supplementary Figure from Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer

Supplementary Table from Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer

IntroductionMeta-analyses comparing hysteroscopic electromechanical morcellation with electrosurgical resection showed a shorter operating time for electromechanical morcellation, mainly for polypectomy. The Resectr (TM) 9Fr is a new hysteroscopic manual morcellator, designed to simplify this procedure. We aimed to compare manual with electromechanical morcellation for hysteroscopic polypectomy. Material and methodsThis two-center randomized controlled non-inferiority trial was performed from 2018 to 2021 in the Catharina Hospital and the Ghent University Hospital. The study was registered at the Dutch Trial Register (NL6922; ICTRP ID: NTR7118). One hundred and forty women with polyps (between 8 and 20 mm) scheduled for hysteroscopic removal were randomized between manual (Resectr (TM) 9Fr) or electromechanical (TruClear (TM)) morcellation. The primary outcome was time (instrumentation set-up, resection, and total procedure time). ResultsThe non-inferiority margin for the primary outcome time was 1.3. Mean instrumentation set-up time was 10% shorter with the manual compared with the electromechanical morcellator (estimated mean ratio manual/electromechanical = 0.9; 97.5% confidence interval [CI] 0.8-1.1). Mean resection time was 30% longer with the manual compared with the motor-driven system (estimated mean ratio manual/electromechanical = 1.3; 97.5% CI 0.9-1.9). Mean total procedure time was 10% longer with the manual compared with the electromechanical morcellator (estimated mean ratio manual/electromechanical = 1.1; 95% CI 0.91-1.298). The estimated odds (electromechanical/manual) of better surgeon's safety, effective and comfort scores were, respectively, 4.5 (95% CI 0.9-22.1), 7.0 (95% CI 1.5-31.9), and 5.9 (95% CI 1.1-30.3) times higher with the motor-driven compared with the manual morcellator. Conversion rates and incomplete resection rates were comparable in both groups (manual versus electromechanical) (7.6% [4/66] vs. 2.9% [2/68] and 6.1% [4/66] vs. 3.0% [2/66], respectively). No intraoperative and postoperative complications were registered. ConclusionsThe manual morcellator was non-inferior to the electromechanical morcellator for hysteroscopic polypectomy in terms of mean instrumentation set-up time and total procedure time. Results on resection time were inconclusive. Conversion and incomplete resection rates were within the range reported in the literature. Surgeon's reported rating for both devices was high, however, in favor of the motor-driven tissue removal system.

ObjectiveTo evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen.Study designWe pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m2. Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes.ResultsWe included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m2 reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event.ConclusionE4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns.Implications statementMost estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive.

The clinical application of prediction models is increasing within the field of gynaecology and obstetrics. This is mostly due to the fact that clinicians and patients prefer individualized counselling and person specific, more objective outcome assessment. To prevent using inadequate models, it is important to construct and perform prediction model studies correctly. Therefore, the TRIPOD statement (the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) was developed. The aim of this review is to obtain an overview of the existing published prediction models for benign gynaecology and to investigate to what extent these studies meet the TRIPOD criteria. We performed a literature search in the databases PubMed, Embase and Cochrane Library from inception to August 2020. Searching the cross-references of the relevant studies within our search identified additional articles. Publications were included if the aim of the study was to develop a multivariable prediction model within the field of benign gynaecology. Two independent reviewers extracted the data. Analysis of the studies was performed by using a checklist derived from the TRIPOD criteria. Based on our search, 2487 studies were selected, including potential duplications. Eventually, a total of twenty-two studies were selected. 91% of these studies handled their predictors by univariable analysis before developing a multivariable prediction model. Fifteen studies described having missing data, but not all of them (9%) handled these missing data. Four different internal validation methods were used in twenty studies. Fifteen studies (68%) had prediction models with a C-index ≥ 0.7, which indicates a good model. Half of the studies (50%) did not measure the calibration, overall performance was described in two studies (9%). External validation was performed in 9% of the studies. The correct development of a prediction model within benign gynaecology and subsequent transparent reporting of the model development is important to facilitate clinical use. Without transparent reporting, wrong assumptions can be made leading to incorrect application of a specific prediction model. This overview shows that excepting carrying out an external validation, only one article met all the criteria. Therefore, we strongly recommend use of the TRIPOD criteria for developing and validating a prediction model (study). In addition, prior to publication, content experts should critically and statistically review the prediction model. If too many criteria are not met, refusing publication should be considered.

Objective Urine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. Methods VALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples ( NCT03064087 ). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator. Results As no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN ≤ 32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI: 0.88–1.01) and specific (relative specificity 1.03; 95% CI: 0.95–1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI: 0.89–1.05) and specificity (1.02; 95% CI: 0.93–1.12) was found. Additionally, an exploratory cut-off (CN ≤ 33.86) was defined which further improved sensitivity and analytical test performance. Conclusion HrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

High-grade serous ovarian cancer (HGSOC) is responsible for the largest number of ovarian cancer deaths. The frequent therapy-resistant relapses necessitate a better understanding of mechanisms driving therapy resistance. Therefore, we mapped more than a hundred thousand cells of HGSOC patients in different phases of the disease, using single-cell RNA sequencing. Within patients, we compared chemonaive with chemotreated samples. As such, we were able to create a single-cell atlas of different HGSOC lesions and their treatment. This revealed a high intrapatient concordance between spatially distinct metastases. In addition, we found remarkable baseline differences in transcriptomics of ascitic and solid cancer cells, resulting in a different response to chemotherapy. Moreover, we discovered different robust subtypes of cancer-associated fibroblasts (CAF) in all patients. Besides inflammatory CAFs, vascular CAFs, and matrix CAFs, we identified a new CAF subtype that was characterized by high expression of STAR, TSPAN8, and ALDH1A1 and clearly enriched after chemotherapy. Together, tumor heterogeneity in both cancer and stromal cells contributes to therapy resistance in HGSOC and could form the basis of novel therapeutic strategies that differentiate between ascitic and solid disease. Implications: The newly characterized differences between ascitic and solid cancer cells before and after chemotherapy could inform novel treatment strategies for metastatic HGSOC.

Background: : Urine collection is a non-invasive self-sampling method offering the prospect of reaching women un (der)-screened for cervical cancer. The VALHUDES research framework was designed to address the lack of clinical accuracy data for high-risk (hr)HPV testing using urine samples. Objectives: : Here, we report on the analytical and clinical accuracy of hrHPV testing on first-void urine, collected at home, using an extended HPV genotyping assay. Study design: : Paired first-void urine (Colli-Pee with UCM, Novosanis; index test) and clinician-collected cervical samples (Cervex-Brush, Rovers in PreservCyt Solution, Hologic; comparator test) were collected from 492 women aged 19 to 72 years attending colposcopy (reference test, with histology if indicated) (VALHUDES; NCT03064087). Extended HPV genotyping was performed on paired samples with the BD Onclarity HPV Assay. Cut-offs defined for cervical samples were also applied for first-void urine. Results: : HrHPV testing in first-void urine was similarly sensitive for both CIN2+ (ratio 1.00; 95% CI: 0.93-1.07) and CIN3 (ratio 0.98; 95% CI: 0.88-1.08), and marginally less specific for 2 (ratio 0.92; 95% CI: 0.84-0.996) compared to cervical samples. HPV test agreement between sample pairs expressed as Cohen's Kappa (kappa) was moderate to excellent for overall hrHPV and individual genotypes (or groups) (kappa=0.56-0.85). Conclusions: : BD Onclarity HPV Assay on first-void urine has similar clinical sensitivity and somewhat lower specificity to detect cervical precancer to testing on clinician-collected cervical samples.

Background: In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples. Methods: Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31–49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation. Results: The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90–1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02–1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94–1.06) and 1.15 (95% CI, 1.05–1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79–1.04) and 1.03 (95% CI, 0.95–1.13), respectively for Qvintip. Conclusions: Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples. Impact: VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening.

Since the inclusion of Premenstrual Dysphoric Disorder (PMDD) as a mood disorder in the DSM-5, Premenstrual Syndrome (PMS) symptoms have received more attention from researchers and clinicians. In this large-scale study, we investigated core psychological concepts relevant to mood disorder vulnerability between people with 1) no to mild, 2) moderate to severe, and 3) PMDD levels of PMS symptoms. Several trait measures related to mood disorders including depressive symptoms, feelings of stress and anxiety, and ruminative thinking were measured (single measurement, N = 380) along with state (momentary) reports of stress and stress-related perseverative thinking (measured twice, once in the follicular and once in the premenstrual/luteal phase, N = 237). We consistently observed that participants with higher severity of PMS symptoms also scored higher on depression, anxiety, stress, and rumination (trait measures). We also found consistent increases in momentary stress and stress-related perseverative ruminative thinking with increased PMS symptoms at each of our two test moments (in the middle of the follicular and premenstrual/luteal phase respectively). Interestingly, we did not find significant differences between our two test moments for any group, despite PMS being characterized by specific systems in the premenstrual/luteal phase. However, this could be due to noise surrounding the testing moments due to the temporal resolution of the questionnaires and the menstrual cycle estimation method. Nevertheless, these results suggest that stress and rumination are important psychological mechanisms to consider in PMS. Future PMS research studying stress and rumination on a day-to-day basis in combination with hormonal measures is warranted.

There is increased awareness of transgender physical and mental health widely and in academic research. A significant proportion of transgender men will retain their cervix with an increased risk of cervical cancer. In this review of cervical cancer screening among transgender men, we try to estimate how many transgender men still have a cervix, understand to identify challenges and barriers to cervical screening and propose possible solutions. Organised cervical screening programmes need to consider the needs of this population, in particular the provision of HPV self-sampling. TWEETABLE ABSTRACT: Transgender men need access to cervical screening.

Study Objective: External validation of our previously presented and locally established prediction models to help counsel patients for failure of endometrial ablation (EA) or surgical re-intervention within 2 years after EA, called ‘Failure model’ and ‘Re-intervention model’ respectively. Design: Retrospective external validation study, minimal follow-up time of 2 years.Setting: Two non-academic teaching hospitals in the Netherlands.Patients: Pre-menopausal women (18+) who had undergone EA for abnormal uterine bleeding problems between January 2010 and November 2012. A total of 329 patients were eligible for analysis.Interventions: Interventions used for EA were Novasure (Hologic, Marlborough, Massachusetts, US) and ThermaChoice III (Ethicon, Sommerville, US). Measurements and Main Results: The Area Under the Receiver Operating characteristics Curve (AUROC) for the outcome parameter of failure within 2 years after EA was 0.59 (95% CI 0.53 – 0.65). Variables in this model were dysmenorrhea, age, parity ≥5 and preoperative menorrhagia. The Hosmer-Lemeshow test showed no significant difference between the observed and predicted outcome. (Chi-square: 4.62, P-value: .80) The AUROC for the outcome parameter surgical re-intervention within 2 years was 0.62 (95% CI 0.53 – 0.70) Variables in this model were dysmenorrhea, age, menstrual duration> 7 days, parity ≥5 and a previous caesarean section. The Hosmer-Lemeshow test showed no significant difference between the observed and predicted outcome (Chi-square 11.34, P-value .18).Conclusion: Both the failure model and the re-intervention model can be used to predict unsuccessful endometrial ablation in the general population within two years after the procedure. It can be used prior to surgery to facilitate tailor-made shared decision-making, and help counsel patients with regards to the potential outcome of their treatment with the use of a personally calculated percentage.

We aimed to evaluate the feasibility of a heart-shaped intrauterine balloon as antiadhesion method immediately after hysteroscopic adhesiolysis in terms of surgeon's and patient's experience. This feasibility study was performed at the Ghent University Hospital (Belgium) from 2018 to 2020. A heart-shaped intrauterine balloon was inserted in 10 women immediately after hysteroscopic adhesiolysis and left in place for 7 days under antibiotic prophylaxis. Insertion and removal of the balloon was easy in 7 women out of 10 (5-point Likert scale), and successful in all cases. The median pain score during balloon wearing on a visual analogue scale (VAS) was 1.7 (IQR 1.0-4.2). Seven out of 10 women were satisfied (5-point Likert scale). Eight out of 10 women would probably or certainly recommend the procedure to a friend (5-point Likert scale) and would use the balloon again. The heart-shaped intrauterine balloon as antiadhesion method is feasible in terms of surgeon's and patient's experience. Designing a proper Randomised Controlled Trial (RCT) is worth the effort. What is already known on this subject? Intrauterine adhesion (IUA) reformation is high and different methods to prevent this subsequent to an operative hysteroscopy have been assessed. The use of antiadhesion gel, acting as a mechanical barrier, may decrease the occurrence of IUAs compared to no treatment or placebo. A heart-shaped intrauterine balloon is another example of a mechanical barrier. A small number of studies, of varying quality and with heterogeneous results, have been performed. A proper RCT, comparing the intrauterine balloon to no treatment or placebo, is needed.What the results of this study add? The heart-shaped intrauterine balloon as antiadhesion method is feasible in terms of surgeon's and patient's experience.What the implications are of these findings for clinical practice and/or further research? Designing a proper RCT is worth the effort.

Introduction: Safety and efficacy of prophylactic HPV vaccines against HPV infection and associated cervical cancers and precursors is well documented in the literature; however, their efficacy against vulval and vaginal endpoints has not been previously assessed.Areas covered: Published results of trials involving licensed HPV vaccines were included. Main efficacy outcomes were histologically confirmed high-grade vulval and vaginal precancer distinguishing those associated with vaccine HPV types and any vulval and vaginal precancerous lesions. Exposure groups included women aged 15-26 or 24-45 years being initially negative for high-risk HPV (hrHPV), negative for the HPV vaccine types, and women unselected by HPV status.Expert opinion: Our results show that the HPV vaccines are equally highly efficacious against vulval/vaginal disease as previously noted for cervical disease. The vaccines demonstrated excellent protection against high-grade vulval and vaginal lesions caused by vaccine-related HPV types among young women who were not initially infected with hrHPV types or types included in the vaccines (vaccine efficacies more than 90%). No protection against high-grade vulval and vaginal lesions associated with HPV16/18 was observed for mid-adult women. Trials were not powered to address protection against invasive cancers.

Purpose The importance of the surrounding ovarian stromal cells and extracellular matrix in the development and maturation of follicles has recently gained attention. An aberrant extracellular matrix has been described in ovaries of patients with polycystic ovary syndrome where a more rigid structural environment, possibly induced by endogenous testosterone, impairs normal folliculogenesis. In this context, we describe the textural parameters of the ovarian cortex of transgender men after prolonged testosterone administration compared to the textural parameters of the non-exposed ovarian cortex originating from female oncological patients. Methods Texture profile analysis (TPA) was performed on ovarian cortex (5 × 5 mm) of oncological and transgender patients in order to measure stiffness, hardness, cohesiveness, and springiness of the ovarian cortex (LRXplus universal testing system). Statistical analysis was performed using repeated measurements mixed models and the Spearman rank order correlation test (IBM SPSS Statistics 23). Results A total of 36 frozen-thawed cortical strips (5 × 5 mm) were subjected to TPA. The superficial part of cortex fragments originating from transgender persons (fragments < 1.4 mm; N = 10) appeared to be significantly stiffer compared to cortex derived from oncology patients (fragments < 1.4 mm; N = 7) (6.78 ± 1.38 N/mm versus 5.41 ± 0.9 N/mm respectively, p = 0.036). Conclusions This is the first application of TPA in ovarian cortex to study the physical properties. Comparing the physical properties, we objectively describe an increased cortical stiffness in the most outer part of the ovarian cortex following prolonged testosterone administration in transgender men compared to the ovarian cortex of oncological patients. This preliminary and novel approach could be the start of future research to understand the physical properties of ovarian tissue. Electronic supplementary material The online version of this article (10.1007/s10815-019-01513-x) contains supplementary material, which is available to authorized users.

Objective. The introduction of advanced endoscopic systems, such as the Storz Image1S and the Olympus Endoeye, heralds a new era of 3-dimensional (3D) visualization. The aim of this report is to provide a comprehensive overview of the neurophysiology of 3D view, its relevance in videoscopy, and to quantify the benefit of the new 3D technologies for both rigid and articulated instruments. Method. Sixteen medical students without any laparoscopic experience were trained each for a total of 27 hours. Proficiency scores were determined for rigid and articulated instruments under 2D and 3D visualization conditions. Results. A reduction in execution time of 14%, 28%, and 36% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. A reduction in errors of 84%, 92%, and 87% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. Conclusion. 3D visualization greatly augments endoscopic procedures. The advanced endoscopic systems employed in the recent study caused no visual fatigue or discomfort. The benefit of 3D was most distinct with articulated instruments.

OBJECTIVE: To compare hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) versus total laparoscopic hysterectomy (TLH) as a day-care procedure. DESIGN: Parallel group, 1:1 randomised single-centre single-blinded trial, designed as a non-inferiority study with a margin of 15%. SETTING: Belgian teaching hospital. POPULATION: Women aged 18-70 years scheduled to undergo hysterectomy for benign indications. METHODS: Randomisation to TLH (control group) or vNOTES (experimental group). Stratification according to uterine volume. Blinding of participants and outcome assessors. MAIN OUTCOME MEASURES: The primary outcome was hysterectomy by the allocated technique. We measured the proportion of women leaving within 12 hours after hysterectomy and the length of hospital stay as secondary outcomes. RESULTS: We randomly assigned 70 women to vNOTES (n = 35) or TLH (n = 35). The primary endpoint was always reached in both groups: there were no conversions. We performed a sensitivity analysis for the primary outcome, assuming one conversion in the vNOTES group and no conversions in the TLH group: the one-sided 95% upper limit for the differences in proportions of conversion was estimated as 7.5%, which is below the predefined non-inferiority margin. More women left the hospital within 12 hours after surgery after vNOTES: 77 versus 43%, difference 34% (95% CI 13-56%), P = 0.007. The hospital stay was shorter after vNOTES: 0.8 versus 1.3 days, mean difference -0.5 days, (95% CI -0.98 to -0.02), P = 0.004. CONCLUSIONS: vNOTES is non-inferior to TLH for successfully performing hysterectomy without conversion. Compared with TLH, vNOTES may allow more women to be treated in a day-care setting. TWEETABLE ABSTRACT: RCT: vNOTES is just as good as laparoscopy for successful hysterectomy without conversion but allows more day-care surgery. ispartof: BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY vol:126 issue:1 pages:105-113 ispartof: location:England status: published

Objectives To compare hysteroscopic morcellation with bipolar resection for the removal of submucous type 0 and 1 myomas, in terms of procedure time (primary outcome), adverse events, tissue availability, short term effectiveness and postoperative adhesion formation (secondary outcomes). Study design The study was performed from May 2011 to May 2018 in the Catharina hospital (Eindhoven, the Netherlands) and the Ghent University hospital (Ghent, Belgium). Women with type 0 and 1 submucous myomas up to 3 cm were randomized to hysteroscopic morcellation with the T r u C l e a r T M 8.0 Tissue Removal System or to bipolar resection with a rigid 8.5-mm resectoscope. Skewed time variables were log-transformed and analyzed with the Student t-test. Multiple linear regression analysis was performed to assess the effect of myoma diameter on operating time. Results Forty-five and 38 women were included in the hysteroscopic morcellation and resection group, respectively. The median operating time was significantly shorter for hysteroscopic morcellation compared with resection (9.2 min [interquartile range 5.6–14.4] versus 13.4 min [interquartile range 8.6–17.5], P = .04). In the morcellation group, operating time, corrected for the myoma diameter, was reduced by 26 % (95 % CI 5–43%; P = .02). The median setup time was significantly longer in the morcellation group (5.2 min [interquartile range 4.2–6.9] versus 3.8 min [interquartile range 3.3–5.3], P = .006). The median total procedure time was not significantly different between the two techniques (14.4 min [interquartile range 11.4–19.2] versus 17.3 [interquartile range 12.7–23.8], P = .18). Two procedures of the morcellation group were converted to bipolar resection because of the myoma hardness. Complete resection was found in 89 % of the morcellation group and 95 % of the resection group. Adverse events occurred in 3 patients of the morcellation group, namely a fluid deficit > 2500 mL with the need of potassium suppletion, an asystolic vasovagal response after conversion to resection and postoperative fever requiring antibiotics. Tissue was available for pathology analysis in all cases. Routine second-look hysteroscopy performed in one center showed no intrauterine adhesions. Conclusion Overall, there is no difference in total procedure time between hysteroscopic morcellation using the T r u C l e a r T M system compared to bipolar resection for the removal of smaller type 0 and 1 submucous myomas. Although hysteroscopic morcellation is faster, its setup time is longer. Calcified myomas can be challenging and fluid deficit remains a limiting factor.

Background Exposure to green space has beneficial effects on several cognitive and behavioral aspects. However, to our knowledge, no study addressed intelligence as outcome. We investigated whether the level of urbanicity can modify the association of residential green space with intelligence and behavior in children. Methods and findings This study includes 620 children and is part of the East Flanders Prospective Twin Survey (EFPTS), a registry of multiple births in the province of East Flanders, Belgium. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) in 620 children (310 twin pairs) between 7 and 15 years old. From a subset of 442 children, behavior was determined based on the Achenbach Child Behavior Checklist (CBCL). Prenatal and childhood residential addresses were geocoded and used to assign green space indicators. Mixed modeling was performed to investigate green space in association with intelligence and behavior while adjusting for potential confounding factors including sex, age, parental education, neighborhood household income, year of assessment, and zygosity and chorionicity. We found that residential green space in association with both intelligence and behavior in children was modified by the degree of urbanicity (p < 0.001). In children living in an urban environment, multivariable adjusted mixed modeling analysis revealed that an IQR increment of residential green space (3,000-m radius) was associated with a 2.6 points (95% CI 1.4–3.9; p < 0.001) higher total intelligence quotient (IQ) and 2.0 points (95% CI −3.5 to −0.4; p = 0.017) lower externalizing behavioral score. In children residing in a rural or suburban environment, no association was found. A limitation of this study is that no information was available on school location and the potential for unmeasured confounding (e.g., time spend outdoors). Conclusions Our results indicate that residential green space may be beneficial for the intellectual and the behavioral development of children living in urban areas. These findings are relevant for policy makers and urban planners to create an optimal environment for children to develop their full potential., Esmée M Bijnens and colleagues reveal beneficial effects of a green environment on a child's development and behaviour., Author summary Why was this study done? This study examines residential surrounding green space in association with intelligence and behavior in a study area that includes a spectrum of urban to rural environments. Previous studies mainly focused on urban areas, whereas only a few studies have explored differences in the effect of green space on cognition in nonurban settings. Understanding the health disparities that exist between urban and rural environments is essential for maintaining and improving human well-being in a rapidly urbanizing world. What did the researchers do and find? This longitudinal birth cohort study of twins assessed intelligence in 620 children between 7 and 15 years old. Our results indicate that residential green space is especially beneficial for intellectual and behavioral development of children living in an urban environment. What do these findings mean? We show that low residential green space in urban children is associated with a “shift” towards a higher incidence of low IQ demonstrating the public health impact of our findings.

Objective To evaluate the mode of delivery and stillbirth rates over time among women with obstetric fistula. Design Retrospective record review. Setting Tanzania, Uganda, Kenya, Malawi, Rwanda, Somalia, South Sudan, Zambia and Ethiopia. Population A total of 4396 women presenting with obstetric fistulas for repair who delivered previously in facilities between 1990 and 2014. Methods Retrospective review of trends and associations between mode of delivery and stillbirth, focusing on caesarean section (CS), assisted vaginal deliveries and spontaneous vaginal deliveries. Main outcome measures Mode of delivery, stillbirth. Results Out of 4396 women with fistula, 3695 (84.1%) delivered a stillborn baby. Among mothers with fistula giving birth to a stillborn baby, the CS rate (overall 54.8%, 2027/3695) rose from 45% (162/361) in 1990–94 to 64% (331/514) in 2010–14. This increase occurred at the expense of assisted vaginal delivery (overall 18.3%, 676/3695), which declined from 32% (115/361) to 6% (31/514). Conclusions In Eastern and Central Africa, CS is increasingly performed on women with obstructed labour whose babies have already died in utero. Contrary to international recommendations, alternatives such as vacuum extraction, forceps and destructive delivery are decreasingly used. Unless uterine rupture is suspected, CS should be avoided in obstructed labour with intrauterine fetal death to avoid complications related to CS scars in subsequent pregnancies. Increasingly, women with obstetric fistula add a history of unnecessary CS to their already grim experiences of prolonged, obstructed labour and stillbirth. Tweetable abstract Caesarean section is increasingly performed in African women with stillbirth treated for obstetric fistula., Tweetable abstract Caesarean section is increasingly performed in African women with stillbirth treated for obstetric fistula.

Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1–3 months), subdermal implants (every 3–5 years) and intrauterine systems (every 3–5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications. Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties. Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30–34 h. Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.

Uterus transplantation is an experimental infertility treatment for women with uterine factor infertility. During donor uterus retrieval and subsequent storage, ischemia and other stressors are likely to occur, resulting in the delayed restoration of organ function and increased graft rejection. The uterus expresses connexin-based hemichannels, the opening of which can promote ischemic cell death, as well as gap junctions that may expand cell death by bystander signaling. We investigated if connexin channel inhibition with connexin channel inhibitor Gap27 could protect the uterus against cell death during the storage period. The study involved 9 female patients undergoing gender-change surgery. Before uterus removal, it was exposed to in situ warm ischemia with or without reperfusion. Uterus biopsies were taken before, during, and after ischemia, with or without reperfusion, and were subsequently stored under cold (4ᵒC) or warm (37ᵒC) conditions. TUNEL cell death assay was done at various time points along the combined in vivo/ex vivo experimental timeline. We found that Gap27 protected against storage-related cell death under cold but not warm conditions when the uterus had experienced in situ ischemia/reperfusion. For in situ brief ischemia without reperfusion, Gap27 reduction of cell death was delayed and significantly less, suggesting that protection critically depends on processes initiated when the organ was still in the donor. Thus, the inclusion of the connexin channel inhibitor Gap27 during cold storage protects the uterus against cell death, and the degree of protection depends on the history of exposure to warm ischemia. Gap27 protection may be indicated for uteri from deceased donors, in which ischemia is likely because life-saving organs have retrieval priority.

In recent years, next generation sequencing (NGS) technology has been widely used for the discovery of novel human papillomavirus (HPV) genotypes, variant characterization and genotyping. Here, we compared the analytical performance of NGS with a commercial PCR-based assay (Anyplex II HPV28) in cervical samples of 744 women. Overall, HPV positivity was 50.2% by the Anyplex and 45.5% by the NGS. With the NGS, we detected 25 genotypes covered by Anyplex and 41 additional genotypes. Agreement between the two methods for HPV positivity was 80.8% (kappa = 0.616) and 84.8% (kappa = 0.652) for 28 HPV genotypes and 14 high-risk genotypes, respectively. We recovered and characterized 243 complete HPV genomes from 153 samples spanning 40 different genotypes. According to phylogenetic analysis and pairwise distance, we identified novel lineages and sublineages of four high-risk and 16 low-risk genotypes. In total, 17 novel lineages and 14 novel sublineages were proposed, including novel lineages of HPV45, HPV52, HPV66 and a novel sublineage of HPV59. Our study provides important genomic insights on HPV types and lineages, where few complete genomes were publicly available.

The East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East Flanders, Belgium. Since its start in 1964, over 10,000 twin-pairs have been registered. EFPTS has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are recruited at birth; basic perinatal data are recorded; chorion type and zygosity are established; since 1969, placental biopsies have been taken and frozen at -20°C for future research. Since its origin, the EFPTS has included placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic-diamniotic pairs (early, with splitting before the fourth day after fertilization), the monochorionic-diamniotic pairs (intermediate, splitting between the fourth- and the seventh-day postfertilization) and the monochorionic-monoamniotic pairs (late, splitting after the eighth day postfertilization). Studies can be initiated taking into account primary biases, those originating 'in utero'. Such studies could throw new light on the consequences of early embryological events and the gene-environment interactions as far as periconceptional and intrauterine environment are concerned. ispartof: TWIN RESEARCH AND HUMAN GENETICS vol:22 issue:6 pages:454-459 ispartof: location:England status: published

Uterus transplantation has revolutionized the approach of uterine factor infertility. The restricted duration of exposure of immunosuppressive drugs to originally immunocompetent healthy women should control the increased infection risk. Considering the relative small number of uterus transplantations performed so far, the relative risk to contract especially severe and/or opportunistic infections remains uncertain. The surgical procedure and the presence of commensal vaginal flora shift the focus in the uterus transplant recipients toward targeted antimicrobial prophylaxis with particular attention to fungal infections. An analysis of the published data so far suggests that infections per se can contribute to graft loss, which is a rather unique feature for solid organ transplant recipients. Also of interest is the occurrence of CMV infection considering the risk of transfection during pregnancy, especially after relatively early embryo transfer. Adding up to prophylaxis by valganciclovir, the risk of CMV should possibly be contained by avoiding both allocation of CMV-positive cadaveric donors to CMV-negative recipients and the use of polyclonal induction. Recommendations and guidelines should be developed taking into account the current knowledge in the field of infectious diseases after transplantation while integrating outcome data from a joint registry set up by the International Society of Uterus Transplantation (ISUTx).

Background Treatment of retained products of conception (RPOC) can be expectant, medical or operative. Surgical removal of RPOC may lead to intrauterine adhesions (IUA) and Asherman’s syndrome. Objective To evaluate how treatment options for RPOC affect future fertility by means of a systematic review. Search strategy MEDLINE, EMBASE, The Cochrane Library, and clinical trial registers were searched, and reference lists were scanned. Selection criteria Randomised controlled trials (RCT) comparing different treatment options for RPOC (conservative, medical or surgical treatment, including curettage and/or hysteroscopic techniques, with or without application of anti-adhesion therapy), in women of reproductive age, were eligible for inclusion. Data collection and analysis Reviewers independently performed data extraction and quality of evidence assessment. For dichotomous variables, results were presented as risk ratio (RR) with 95% CI. Main results Two studies were included. Nonsignificant differences were observed between the use of an anti-adhesion barrier gel versus no treatment after operative hysteroscopy in IUAs (RR 0.32, 95% CI 0.04 to 2.80, P value = 0.30) and clinical pregnancy (RR 2.22, 95% CI 0.67 to 7.42, P value = 0.19), and between hysteroscopic morcellation versus loop resection in IUAs (RR 0.86, 95% CI 0.06 to 13.12, P value = 0.91). Conclusion There is insufficient evidence on how different treatment options for RPOC affect future reproductive outcomes. Results from ongoing RCTs are needed to guide clinicians towards choosing the best treatment.

Sexual functioning is an important concern for women in the postpartum period. The aim of this research was to investigate the prevalence and determinants of dyspareunia and sexual dysfunction before and after childbirth.Between November 2013 and April 2014, 109 women in their third trimester of pregnancy were enrolled in a prospective cohort study at Ghent University Hospital. Dyspareunia, sexual functioning and quality of life (QOL) were evaluated at enrolment and again 6 weeks and 6 months postpartum. Sexual functioning and QOL were assessed using validated self-report questionnaires: the Female Sexual Function Index and the Short Form-36 health survey. Dyspareunia was evaluated by a specific self-developed questionnaire.One hundred and nine women were enrolled; respectively, 71 (65.1%), 66 (60.6%) and 64 (58.7%) women returned the questionnaires prepartum, and 6 weeks and 6 months postpartum. Sexual functioning at 6 weeks was predictive of sexual functioning at 6 months postpartum (rThe impaired postpartum sexual functioning, the high prevalence of dyspareunia postpartum and their impact on QOL indicate the need for further investigation and extensive counselling of pregnant women, especially primiparous women, about sexuality after childbirth.