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Background: Colpectomy entails the surgical removal of the vaginal epithelium. It may be performed in trans-masculine individuals as gender-affirming surgery. Vaginal colpectomy is a complex procedure with potentially severe complications. As alternative, robotic-assisted laparoscopic colpectomy combined with robotic-assisted laparoscopic hysterectomy and possible bilateral salpingo-oophorectomy (RAC+) can be performed. Aim: To compare surgical outcomes of robotic-assisted colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy with a vaginal colpectomy after previous hysterectomy in trans masculine patients. Methods: A single-center retrospective cohort study included 310 transgender men who underwent either robotic-assisted colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy (RAC+) (n = 140) or vaginal colpectomy (n = 170) between January 2006 and December 2019. Surgical details and clinical outcomes were collected from all patients. Results: The median intra-operative blood loss was 100 mL (50–200) in RAC + and 300 mL (200–450) in vaginal colpectomy (p < 0.01). The median duration of hospital stay was 2 days (1–2) in the RAC + group and 3 days (2–4) in the vaginal group (p < 0.01). In the RAC + group 63 (45%) peri-operative complications were reported, compared to 93 (54.7%) in the vaginal group [OR 0.7 (0.4–1.1)]. The main difference was found in intra-operative complications (RAC+ 0.7% vs. vaginal 10.6%). Furthermore, the total number of complications graded 3a and higher was significantly lower in the RAC + group [OR 0.3 (0.2–0.7)]. Conclusion: Although RAC + entailed a more extensive procedure, compared to vaginal colpectomy, RAC + had a lower risk of severe peri-operative complications, requiring re-intervention; intra-operative blood loss was lower and hospital stay shorter. Both routes of colpectomy are complex procedures with potentially severe complications. Future studies are needed to study whether robot–colpectomy could be a safe alternative to vaginal colpectomy in patients with a previous hysterectomy. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate how adults, who started gender-affirming hormone treatment during adolescence, reflect on their reproductive decisions. Methods: We recruited transgender and gender-diverse (TGD) people who visited our gender identity clinic and commenced medical treatment in adolescence at least 9 years ago. We collected data through an online survey. Results: The cohort consisted of 89 participants (66 TGD people assigned female at birth (AFAB) and 23 TGD people assigned male at birth (AMAB) with a mean age of 32.4 years (range 25.5–51.2) at the time of study, and 15.6 years (range 11.5–20.6) at the start of medical treatment. All participants initiated medical treatment before 2014, when laws requiring sterilization for legal gender recognition were still in place, and only 30% of participants reported to have received information about fertility preservation, which none of them pursued. In addition, 96% of participants underwent gonadectomy and thus became permanently infertile, which was troublesome for 27%. With today's knowledge, 44% of TGD people AFAB and 35% of TGD people born AMAB would pursue fertility preservation. The percentage of participants with a (future) desire for children increased from 34% at the start of medical treatment (at adolescent age) to 56% at the time of this study (at adult age), of whom 23% had currently started a family. Conclusion: It is important to inform transgender adolescents about the effect of medical treatment on fertility and the options for fertility preservation since many may develop a desire for (biological) children when they reach adulthood. [ABSTRACT FROM AUTHOR]

Background: We present a case of non-puerperal induced lactation in transgender woman. Medical literature on lactation induction for transgender women is scarce, and the majority of literature and protocols on lactation induction is based on research in cisgender women. Healthcare professionals may lack the precise knowledge about lactation induction and may therefore feel insecure when advice is requested. Subsequently, there is a rising demand for guidelines and support. Methods: Patient medical record was consulted and a semi-structured interview was conducted to explore the motive for lactation induction, the experience of lactation induction, and to gather additional information about the timeline and course of events. Case presentation: In this case a 37-year-old transgender woman, who was under the care of the centre of expertise on gender dysphoria in Amsterdam, and in 2020 started lactation induction because she had the wish to breastfeed her future infant. She was in a relationship with a cisgender woman and had been using gender affirming hormone therapy for 13 years. Prior to initiating gender affirming hormone therapy she had cryopreserved her semen. Her partner conceived through Intracytoplasmic Sperm Injection, using our patient's cryopreserved sperm. To induce lactation, we implemented a hormone-regimen to mimic pregnancy, using estradiol and progesterone, and a galactogogue; domperidone. Our patient started pumping during treatment. Dosage of progesterone and estradiol were significantly decreased approximately one month before childbirth to mimic delivery and pumping was increased. Our patient started lactating and although the production of milk was low, it was sufficient for supplementary feeding and a positive experience for our patient. Two weeks after birth, lactation induction was discontinued due to suckling problems of the infant and low milk production. Conclusions: This case report underlined that lactation induction protocols commonly used for cisgender women are also effective in transgender women. However, the amount of milk produced may not be sufficient for exclusive nursing. Nevertheless, success of induced lactation may be attributed to its importance for parent-infant bonding, rather than the possibility of exclusive chestfeeding. [ABSTRACT FROM AUTHOR]

Hormonal treatments and surgical interventions practiced with the aim to affirm gender identity in transgender and gender diverse patients may impact their future reproductive ability, family building, and family planning options. Whereas it is recommended by international guidelines to discuss the potential risks of infertility and to present fertility preservation (FP) options to transgender individuals and their families prior to initiating any of these treatments, many barriers still remain. Further, transgender and gender diverse individuals often experience barriers to accessing contraception, abortion, pre-conception care, and comprehensive perinatal care. In this review we summarize the current literature on reproductive healthcare issues reported in transgender people including fertility issues, fertility preservation (FP), contraception, pregnancy and lactation and perinatal health. A narrative literature search of major databases (Pubmed, Medline, PsycInfo, Google Scholar, Web of Science) was conducted. Given the paucity and heterogeneity of studies, summative review tactics were not available. The literature was critically reviewed by international experts in the field with focus on the impact of gender-affirming medical interventions on future fertility, current FP options and reproductive health issues in transgender people. The current literature supports that transgender and gender diverse individuals may wish to have genetically related children in the future, rendering the issue of FP relevant to this patient group. The cryopreservation of mature gametes is an efficacious option for FP for post-pubertal adolescents and adults. It is recommended to discuss these options at time of planning for gender-affirming hormonal therapy (GAHT) or engaging with other gender-affirming procedures that can limit future fertility. Discontinuation of GAHT may allow individuals to undergo FP later, but data are limited and there is the concern of symptoms and consequences of stopping GAHT. For pre-pubertal and early pubertal children, FP options are limited to the cryopreservation of gonadal tissue. At present the tissue can become functional only after re-transplantation, which might be undesirable by transgender individuals in the future. Preconception counseling, prenatal surveillance, perinatal support, contraceptive, and pregnancy termination related healthcare need to be meaningfully adapted for this patient population, and many knowledge gaps remain. Specialized FP reproductive healthcare for transgender and gender diverse individuals is in early evolution. Research should be conducted to examine effects of medical interventions on fertility, timing of FP, gamete preservation and outcome of the fertility treatments. Strategies to inform and educate transgender and gender diverse patients can lead to optimization of reproductive care and counseling and decision making of FP for this population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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 The Netherlands. 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. Trial registration Current Controlled Trials ISRCTN 48210491

Abstract Background 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. Methods/Design 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. 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. Discussion 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. Trial registration Current Controlled Trials ISRCTN37002267

Study Question: Can secondary follicles be obtained from cultured cryopreserved-thawed human ovarian cortical tissue?, Summary Answer: We obtained high-quality secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue from cis female donors (cOVA), but not from trans masculine donors (tOVA) in the same culture conditions., What Is Known Already: The in vitro growth of oocytes present in unilaminar follicles into metaphase II stage (MII) oocytes has been previously achieved starting from freshly obtained ovarian cortical tissue from adult cis female donors. This involved a multi-step culture protocol and the first step included the transition from unilaminar follicles to multilayered secondary follicles. Given that the ovarian cortex (from both cis female and trans masculine donors) used for fertility preservation is cryopreserved, it is crucial to investigate the potential of unilaminar follicles from cryopreserved-thawed ovarian cortex to grow in culture., Study Design, Size, Duration: Cryopreserved-thawed ovarian cortical tissue from adult trans masculine donors (n = 3) and adult cis female donors (n = 3) was used for in vitro culture following the first culture step described in two published culture protocols (7-8 days and 21 days) and compared to freshly isolated ovarian cortex from trans masculine donors (n = 3) and to ovarian cortex prior to culture., Participants/materials, Setting, Methods: Ovarian cortical tissue was obtained from adult trans masculine donors undergoing gender-affirming surgery while using testosterone, and from adult cis female donors undergoing oophorectomy for fertility preservation purposes before chemotherapy. The ovarian cortex was fixed either prior (day 0) or after the culture period. Follicular survival, growth, and morphology were assessed through histology and immunofluorescence., Main Results and the Role of Chance: We quantified the different stages of follicular development (primordial, primary, secondary, and atretic) after culture and observed an increase in the percentage of secondary follicles as well as an increase in COLIV deposition in the stromal compartment regardless of the culture media used. The quality of the secondary follicles obtained from cOVA was comparable to those prior to culture. However, in the same culture conditions, the secondary follicles from tOVA (fresh and cryo) showed low-quality secondary follicles, containing oocytes with small diameter, granulosa cells that expressed abnormal levels of KRT19 and steroidogenic-marker STAR and lacked ACTA2+ theca cells, when compared to tOVA secondary follicles prior to culture., Limitations, Reasons for Caution: The number of different donors used was limited., Wider Implications of the Findings: Our study revealed that cryopreserved-thawed cOVA can be used to generate high-quality secondary follicles after culture and those can now be further tested to evaluate their potential to generate functional MII oocytes that could be used in the clinic. However, using the same culture protocol on tOVA (fresh and cryo) did not yield high-quality secondary follicles, suggesting that either the testosterone treatment affects follicular quality or adapted culture protocols are necessary to obtain high-quality secondary follicles from tOVA. Importantly, caution must be taken when using tOVA to optimize folliculogenesis in vitro., Study Funding/competing Interest(s): This research was funded by the European Research Council Consolidator Grant OVOGROWTH (ERC-CoG-2016-725722 to J.S.D.V. and S.M.C.D.S.L.), the Novo Nordisk Foundation (reNEW NNF21CC0073729 to H.C., F.W., J.S.D.V., S.M.C.D.S.L.), and China Scholarship Council (CSC 202008320362 and CSC 202008450034 to H.C. and F.W.), respectively. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

The ovarian surface epithelium (OSE), the outermost layer of the ovary, undergoes rupture during each ovulation and plays a crucial role in ovarian wound healing while restoring ovarian integrity. Additionally, the OSE may serve as the source of epithelial ovarian cancers. Although the OSE regenerative properties have been well studied in mice, understanding the precise mechanism of tissue repair in the human ovary remains hampered by limited access to human ovaries and suitable in vitro culture protocols. Tissue-specific organoids, miniaturized in vitro models replicating both structural and functional aspects of the original organ, offer new opportunities for studying organ physiology, disease modeling, and drug testing. Here, we describe a method to isolate primary human OSE (hOSE) from whole ovaries and establish hOSE organoids. We include a morphological and cellular characterization showing heterogeneity between donors. Additionally, we demonstrate the capacity of this culture method to evaluate hormonal effects on OSE-organoid growth over a 2-week period. This method may enable the discovery of factors contributing to OSE regeneration and facilitate patient-specific drug screenings for malignant OSE.

Background: Colpectomy entails the surgical removal of the vaginal epithelium. It may be performed in trans-masculine individuals as gender-affirming surgery. Vaginal colpectomy is a complex procedure with potentially severe complications. As alternative, robotic-assisted laparoscopic colpectomy combined with robotic-assisted laparoscopic hysterectomy and possible bilateral salpingo-oophorectomy (RAC+) can be performed. Aim: To compare surgical outcomes of robotic-assisted colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy with a vaginal colpectomy after previous hysterectomy in trans masculine patients. Methods: A single-center retrospective cohort study included 310 transgender men who underwent either robotic-assisted colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy (RAC+) ( n  = 140) or vaginal colpectomy ( n  = 170) between January 2006 and December 2019. Surgical details and clinical outcomes were collected from all patients. Results: The median intra-operative blood loss was 100 mL (50-200) in RAC + and 300 mL (200-450) in vaginal colpectomy ( p  < 0.01). The median duration of hospital stay was 2 days (1-2) in the RAC + group and 3 days (2-4) in the vaginal group ( p  < 0.01). In the RAC + group 63 (45%) peri-operative complications were reported, compared to 93 (54.7%) in the vaginal group [OR 0.7 (0.4-1.1)]. The main difference was found in intra-operative complications (RAC+ 0.7% vs. vaginal 10.6%). Furthermore, the total number of complications graded 3a and higher was significantly lower in the RAC + group [OR 0.3 (0.2-0.7)]. Conclusion: Although RAC + entailed a more extensive procedure, compared to vaginal colpectomy, RAC + had a lower risk of severe peri-operative complications, requiring re-intervention; intra-operative blood loss was lower and hospital stay shorter. Both routes of colpectomy are complex procedures with potentially severe complications. Future studies are needed to study whether robot-colpectomy could be a safe alternative to vaginal colpectomy in patients with a previous hysterectomy., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 Taylor & Francis Group, LLC.)

Background: There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined., Objective: This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management., Study Design: We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth., Results: Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P =.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P =.01) after a curettage, and 6 months (interquartile range, 4-15; P =.03) after a laparoscopic niche resection., Conclusion: Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies., (© 2022 The Authors.)

Objective: 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., Study Design: HRQoL was assessed alongside a randomized clinical trial (RCT) with the use of standard self-administered psychometric measure questionnaires., Patients and Setting: 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., Main Outcome Measure: HRQoL measures of three standardized questionnaires (SF-36, RSCL, HADS)., Results: 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., Conclusion: Women treated with MTX or expectant management for an ectopic pregnancy or persisting PUL have comparable quality of life., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)