Classification of Atretic Small Antral Follicles in the Human Ovary

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.</p

The ESEP study: Salpingostomy versus salpingectomy for tubal ectopic pregnancy; The impact on future fertility: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>For most tubal ectopic pregnancies (EP) surgery is the treatment of first choice. Whether surgical treatment should be performed conservatively (salpingostomy) or radically (salpingectomy) in women wishing to preserve their reproductive capacity, is subject to debate. Salpingostomy preserves the tube, but bears the risks of both persistent trophoblast and repeat ipsilateral tubal EP. Salpingectomy, avoids these risks, but leaves only one tube for reproductive capacity. This study aims to reveal the trade-off between both surgical options: whether the potential advantage of salpingostomy, i.e. a better fertility prognosis as compared to salpingectomy, outweighs the potential disadvantages, i.e. persistent trophoblast and an increased risk for a repeat EP.</p> <p>Methods/Design</p> <p>International multi centre randomised controlled trial comparing salpingostomy versus salpingectomy in women with a tubal EP without contra lateral tubal pathology. Hemodynamically stable women with a presumptive diagnosis of tubal EP, scheduled for surgery, are eligible for inclusion. Patients pregnant after in vitro fertilisation (IVF) and/or known documented tubal pathology are excluded. At surgery, a tubal EP must be confirmed. Only women with a tubal EP amenable to both interventions and a healthy contra lateral tube are included. Salpingostomy and salpingectomy are performed according to standard procedures of participating hospitals. Up to 36 months after surgery, women will be contacted to assess their fertility status at six months intervals starting form the day of the operation.</p> <p>The primary outcome measure is the occurrence of spontaneous viable intra uterine pregnancy. Secondary outcome measures are persistent trophoblast, repeat EP, all pregnancies including those resulting from IVF and financial costs. The analysis will be performed according to the intention to treat principle. A cost-effectiveness analysis will be performed within a decision analysis framework, based on costs per live birth, including IVF treatment whenever a spontaneous pregnancy does not occur. Patients' preferences will be assessed using a discrete choice experiment.</p> <p>Discussion</p> <p>This trial will provide evidence on the trade off between salpingostomy and salpingectomy for tubal EP in view of the pros and cons of both interventions and will offer guidance to clinicians in making the right treatment choice.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN37002267</p

The METEX study: Methotrexate versus expectant management in women with ectopic pregnancy: A randomised controlled trial

Background: Patients with ectopic pregnancy (EP) and low serum hCG concentrations and women with a pregnancy of unknown location (PUL) and plateauing serum hCG levels are commonly treated with systemic methotrexate (MTX). However, there is no evidence that treatment in these particular subgroups of women is necessary as many of these early EPs may resolve spontaneously. The aim of this study is whether expectant management in women with EP or PUL and with low but plateauing serum hCG concentrations is an alternative to MTX treatment in terms of treatment success, future pregnancy, health related quality of life and costs. Methods/Design: A multicentre randomised controlled trial in TheNetherlands. Hemodynamically stable patients with an EP visible on transvaginal ultrasound and a plateauing serum hCG concentration < 1,500 IU/L or with a persisting PUL with plateauing serum hCG concentrations < 2,000 IU/L are eligible for the trial. Patients with a viable EP, signs of tubal rupture/abdominal bleeding, or a contra-indication for MTX will not be included. Expectant management is compared with systemic MTX in a single dose intramuscular regimen (1 mg/ kg) in an outpatient setting. Serum hCG levels are monitored weekly; in case of inadequately declining, systemic MTX is installed or continued. In case of hemodynamic instability and/or signs of tubal rupture, surgery is performed. The primary outcome measure is an uneventful decline of serum hCG to an undetectable level by the initial intervention. Secondary outcomes are (re)interventions (additional systemic MTX injections and/or surgery), treatment complications, health related quality of life, financial costs, and future fertility. Analysis is performed according to the intention to treat principle. Quality of life is assessed by questionnaires before and at three time points after randomisation. Costs are expressed as direct costs with data on costs and used resources in the participating centres. Fertility is assessed by questionnaires after 6, 12, 18 and 24 months. Patients' preferences will be assessed using a discrete choice experiment. Discussion: This trial will provide guidance on the present management dilemmas in women with EPs and PULs with low and plateauing serum hCG concentrations

Randomized comparison of health-related quality of life in women with ectopic pregnancy or pregnancy of unknown location treated with systemic methotrexate or expectant management

To study the impact on health-related quality of life (HRQoL) of treatment with systemic methotrexate (MTX) or expectant management in women with ectopic pregnancy or pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations. HRQoL was assessed alongside a randomized clinical trial (RCT) with the use of standard self-administered psychometric measure questionnaires. All women who participated in the multicenter RCT comparing treatment with systemic MTX to expectant management in women with ectopic pregnancy or persisting PUL were eligible for the HRQoL measurements. HRQoL measures of three standardized questionnaires (SF-36, RSCL, HADS). Data were available for 64 of 73 women (78%) randomized in the RCT. We found no difference in HRQoL between the two treatment groups. The need for additional treatment, i.e. additional MTX injections or surgical intervention, had no impact on HRQoL. Women treated with MTX or expectant management for an ectopic pregnancy or persisting PUL have comparable quality of lif

Outcomes of oocyte vitrification in trans masculine individuals

Research question: What are the outcomes and experiences of oocyte vitrification treatment in trans masculine individuals (TMI) before and after testosterone use? Design: This retrospective cohort study was conducted at the Amsterdam UMC in the Netherlands between January 2017 and June 2021. The TMI who had completed an oocyte vitrification treatment were consecutively approached for participation. Informed consent was provided by 24 individuals. Participants (n = 7) who initiated testosterone therapy were advised to stop 3 months before stimulation. Demographic characteristics and oocyte vitrification treatment data were retrieved from medical records. Evaluation of the treatment was collected via an online questionnaire. Results: The median age of participants was 22.3 years (interquartile range 21.1–26.0) and mean body mass index was 23.0 kg/m2 (SD 3.2). After ovarian hyperstimulation, a mean of 20 oocytes (SD 7) were retrieved and a mean of 17 oocytes (SD 6) could be vitrified. Aside from a lower cumulative FSH dose, there were no significant differences between the prior testosterone users and testosterone naïve TMI. The overall satisfaction of oocyte vitrification treatment in participants was high. Hormone injections were considered the most strenuous part of treatment by 29% of participants, closely followed by oocyte retrieval (25%). Conclusions: No difference in response to ovarian stimulation was found for oocyte vitrification treatment between the prior testosterone users and testosterone naïve TMI. The questionnaire identified hormone injections as the most burdensome aspect of oocyte vitrification treatment. This information can be used to improve gender sensitive fertility counselling and fertility treatment strategies

Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview

INTRODUCTION: Genital gender affirming surgery (gGAS) is usually the final stage in the medical transition for transgender men and consists of creating a neophallus and neo-scrotum, with or without urethral lengthening(UL). To reduce the complication risks of UL, a mandatory colpectomy is performed prior to UL. Colpectomy is considered a complex surgery, which may lead to various perioperative complications. There are few long-term complications reported. AIM: To describe the clinical presentation and management of 3 consecutive transgender men presenting with a perineal cyst following gGAS. METHODS: After obtaining informed consent all clinical data was collected, including medical history, current symptoms, imaging, as well as surgery and histological outcomes. Furthermore, a literature search was performed. MAIN OUTCOME MEASURE: To hypothesize the aetiology of the perineal cyst based on current published literature. RESULTS: Three otherwise healthy transgender men, ages 26-46 with a similar medical history, presented with a perineal cyst several months or years following colpectomy and gGAS with UL. All patients underwent surgery to remove the cyst. Several theories regarding aetiology of this perineal cyst are discussed in this report. CONCLUSION: There remain several gaps in our knowledge regarding the aetiology and management of this perineal cyst. Therefore, further research is necessary. Asseler JD, Ronkes BL, Groenman FA, et al. Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview. J Sex Med 2021;XX:XXX-XXX

Advances in vector-mediated gene transfer

Clinical applications of gene transfer technology initially targeted the treatment of inherited monogenetic disorders and cancers refractory to conventional therapies. Today, gene transfer approaches are being developed for most tissues and for multiple disorders including those affecting quality of life. The focus herein is eventual application of gene transfer technology for the management of organ-directed autoimmunity. A specific example is presented: Sjögren's syndrome and localized salivary gland gene transfer. The status of relevant pre-clinical gene transfer studies is reviewed, with an emphasis on use of adenoviral and adeno-associated viral vectors. Current limitations of effective organ-directed gene transfer are also discussed

Successful restoration of spermatogenesis following gender-affirming hormone therapy in transgender women

Increasing numbers of transgender individuals are presenting for gender-affirming medical care. For trans women, gender-affirming hormone therapy (GAHT) promotes feminization but also inhibits spermatogenesis. There is a common untested assumption that this inhibition is permanent, resulting in infertility. In this longitudinal study, we report the recovery of viable spermatozoa in nine trans women who stopped GAHT for reproductive purposes. Our preliminary findings suggest that the negative impact of GAHT on spermatogenesis can be reversed, casting doubt on previous claims that GAHT in trans women inevitably leads to permanent infertility. Larger studies are needed to confirm our findings, which have implications not only for fertility counseling and the reproductive options of transgender individuals but also efforts to restrict access to GAHT based on fertility grounds

A cohort study on factors impairing semen quality in transgender women

Background: Transgender women (people assigned male genders at birth with female gender identities) can choose to cryopreserve semen before their medical transition, to retain the possibility to parent genetically related offspring later in life. Our previous retrospective study showed that semen quality in transgender women was decreased compared with the general population. The etiology of this impaired semen quality remains largely unknown. However, impaired semen quality might be related to habitual behavior more typically observed in transgender women, for example, the desire to hide their testicles because of genital dysphoria. Therefore, we decided to conduct a consecutive study with prospectively obtained data on behavior and lifestyle in transgender women. Objective: This study aimed to study the influence of a low ejaculation frequency, wearing tight undergarments, and bringing the testes in the inguinal position (tucking) on semen quality in transgender women at the time of fertility preservation. Study Design: In this cohort study, transgender women were included between May 2018 and September 2020, at the time of fertility counseling, before the start of hormonal treatment. Data were collected on demographics, lifestyle factors, medical history, endocrine laboratory results, and semen parameters. Semen parameters were categorized using reference values for human semen of the World Health Organization and compared with semen quality in the general population. The odds ratios with 95% confidence intervals were calculated using multivariable logistic regression analysis to assess the impact of tucking, wearing tight undergarments, and a low ejaculation frequency on semen quality, correcting for potential confounders. Results: Overall, 113 transgender women were included. Median semen parameters were significantly decreased than the general population. Crude logistic regression analyses showed an association between always wearing tight undergarments (odds ratio, 3.06; 95% confidence interval, 1.11–8.49) and extensive tucking (odds ratio, 6.09; 95% confidence interval, 1.54–24.01) on having a total motile sperm count of <5 million. Multivariable analyses showed that the association with tucking was independent of demographic factors, lifestyle factors, and medical history (odds ratio, 7.95; 95% confidence interval, 1.66–37.99). However, this was not the case for the association with always wearing tight undergarments (odds ratio, 2.89; 95% confidence interval, 0.95–8.82). Ejaculation frequency did not influence total motile sperm count. Conclusion: Behavioral factors, including wearing tight undergarments and extensive tucking, may contribute to the lower semen quality in transgender women. These results will enable optimization of fertility counseling on how to adjust lifestyle before pursuing semen cryopreservation

Incidence of testicular cancer in trans women using gender-affirming hormonal treatment: a nationwide cohort study

Objective: To assess the incidence of testicular cancer in trans women (male sex assigned at birth, female gender identity) using gender-affirming hormonal treatment. Patients and Methods: Data of trans women starting hormonal treatment at our gender identity clinic between 1972 and 2017 were linked to the national pathology database to obtain testicular cancer diagnoses. The standardised incidence ratio (SIR) was calculated using the number of observed testicular cancer cases in our cohort and the number of expected cases based on age-specific Dutch incidence rates. Subgroup analyses were performed in testicular tissues sent for histopathological analysis at the time of bilateral orchidectomy, and when follow-up exceeded 5 years. Results: The cohort consisted of 3026 trans women with a median follow-up time of 2.3 interquartile range (IQR) (1.6–3.7) years. Two testicular cancer cases were identified whilst 2.4 cases were expected (SIR 0.8, 95% confidence interval 0.1–2.8). In addition, one testicular cancer case was encountered in an orchidectomy specimen (0.1%). In the 523 trans women with a follow-up time of >5 years (median [IQR] 8.9 [6.4–13.9] years), no testicular cancer was observed. Conclusion: Testicular cancer risk in trans women is similar to the risk in cis men. The testicular cancer cases occurred within the first 5 years after commencing hormonal treatment, and the percentage of cases encountered at the time of bilateral orchidectomy was low. As no testicular cancer was observed in trans women with a long follow-up period, long-term hormonal treatment does not seem to increase testicular cancer risk