Reassignment Surgery Research Articles

Virtual reality versus webinar trans healthcare training for emergency medicine residents: a feasibility study

Introduction Transgender and gender non-binary (TGNB) patient care is not routinely taught in medical training. As a result, clinicians frequently lack knowledge regarding gender-affirming practices, surgeries and medications. TGNB-specific health knowledge and care delivery are further negatively impacted by pervasive societal transphobia. Virtual reality (VR)-based instruction may provide learners with opportunities for perspective taking, empathy building and attitudinal shifting to improve care delivery to TGNB patients. Methods This was a feasibility trial that compared passive VR and webinar in changing learner attitudes, knowledge and medical decision-making (MDM). Residents were recruited from five US emergency medicine (EM) residencies and were randomized to either VR or webinar educational intervention arm. Pre- and post-intervention assessments were matched using a unique identifier. Participants provided feedback about platform usability. Results From August 2020 to October 2021, 206 resident participants were randomized into a case-based VR experience or webinar intervention on TGNB-specific EM medicine; 52 residents completed all three steps of the study. Webinar participants demonstrated more changes in attitudinal statements than VR participants. No improvements in knowledge or MDM were appreciated in either intervention arm. Participants in both arms shared positive and critical feedback about the intervention they accessed, with convenience and ease of use being valued for asynchronous webinar learning. Discussion The webinar arm demonstrated a higher increase in empathy or change in attitude compared to VR learners. As VR becomes more technologically agile, accessible and reliable, more work is needed to see if this novel format is an educational tool that closely approximates the standardized patient encounter.

Study of the Position of the Court Decision as a requirement to fulfil the condition of "Important Event" as in the Recording of the Application for Gender Reassignment

Study of the Position of the Court Decision as a requirement to fulfil the condition of "Important Event" as in the Recording of the Application for Gender Reassignment

Patient-reported outcome measures for assessing urinary dysfunction following gender-affirming genital surgery: A narrative review of the literature.

Gender-affirming genital surgery is one of several surgical procedures available to transgender and nonbinary (TGNB) individuals to improve congruence between their gender identity and sex assigned at birth. Despite increasing utilization of these procedures, patient-reported outcome measures (PROMs) to assess subjective outcomes following gender-affirming genital surgery remain limited. Our aim was to provide a synopsis of PROMs currently being used to evaluate urinary outcomes among TGNB patients following gender-affirming genital surgery and to assess each PROM for content that is relevant to TGNB patients. A multidatabase search was performed (Embase and PubMed) using search terms that included transgender, patient-reported outcome measures, questionnaire, and gender-affirming surgery. Studies that assessed subjective outcomes related to urinary outcomes and pelvic floor dysfunction following gender-affirming genital surgery were reviewed. Gender-affirming genital surgery included vaginal reconstruction (vaginoplasty) and penile reconstruction (phalloplasty and metoidioplasty). Included studies were evaluated for relevant content items and summarized in table. Our literature search identified 820 unique articles. Twenty-seven full articles were included in the final review. Until recently, measurement tools have been limited to unvalidated ad hoc questionnaires or PROMs developed for other conditions, such as urinary incontinence or vaginal prolapse, that are validated among the predominantly cisgender general population. Of the selected studies, PROMs used to evaluate urinary and pelvic floor dysfunction following gender-affirming genital surgery included self-construced ad hoc questionnaires (10 studies), Amsterdam Overactive Pelvic Floor Scale (four studies), King's Health Questionnaire (two studies), Pelvic Floor Distress Inventory (PFDI)-20 (two studies), Sheffield Pelvic Organ Prolapse (one study), International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI) (one study), and ICIQ-Female Lower Urinary Tract Symptoms (one study). The PFDI-20 asked about the most relevant symptoms to TGNB patients following genital surgery; however, not all cisgender validated questionnaires included important questions about voiding position, splayed or misdirected stream. The Affirming Surgery Form and Function Individual Reporting Measure (AFFIRM) questionnaire is the first PROM for assessing subjective urinary outcomes that are validated for TGNB individuals, and the GENDER-Q is a promising new PROM with the aim of evaluating outcomes following surgical and other gender-affirming treatments. Despite recent advancements, a need remains for standardized assessment tools to evaluate pelvic floor dysfunction and urinary symptoms following gender-affirming genital surgery. Questionnaires developed for the general population to assess symptoms of pelvic organ prolapse and other urinary dysfunction do not fully capture the experiences unique to TGNB individuals undergoing this type of surgery. Nonetheless, PROMs validated specifically for TGNB individuals are necessary to more accurately evaluate outcomes of gender-affirming genital surgery, allow for informed patient counseling, and create evidence-based changes to improve these interventions.

Quantifying upper lip height difference between two young male and female populations by direct surface measurement: Implications for gender-affirming upper lip shortening surgery

The female upper lip is shorter than its male counterpart. We have recently described a precise direct surface measurement technique of the philtral height. In this study we aim to quantify the difference in philtral height using this same measuring technique between two groups of young male and female Lebanese subjects. The mean philtral height obtained in the young male group was 15.7 ± 1.7 mm. By comparing this result to the previously described mean philtral height of 14.3 ± 1.9 mm in the young female group, we obtained a mean difference of 1.3 ± 1.8 mm between the two groups. This result confirms and quantifies by direct surface measurement the gender difference in upper lip height and should be considered when planning a gender-affirming upper lip shortening surgery.

La première chirurgie de reassignation sexuelle réussie : Magnus, Dora et l’institut de sexologie de Berlin en 1931

Magnus Hirschfeld was a brilliant German doctor campaigning for the decriminalization and destigmatization of homosexuality. During the very liberal Weimar Republic (1918-1933) he published his avant-garde articles, he created his Institute of Sexual Sciences (Institut für Sexualwissenschaft), where the first published transgender surgery took place, performed on Dora Richter in 1931 (we will be interested in this first report of successful intervention) and multiplied the interventions to abolish paragraph 175, penalizing "sodomy". Ultimately the rise of Nazism forced him to flee his country and end his life in France. Hirschfeld's work remained unfinished. His political activism and his over-media coverage earned him numerous criticisms even within the gay and lesbian movement of the time. Who was this strange doctor (the Einstein of sex, as an American promoter presented him during his conferences in 1930) who combined the faults, for the time, of being at the same time Jewish, homosexual and leftist?

Population transmasculine : hormonothérapie, prévention et soins en santé sexuelle et reproductive, revue de la littérature et propositions de suivi

Transmasculine individuals have a poor access to health care, mostly regarding the sexual and reproductive health. Despite a lack of official guidelines, they need a gynecological follow-up, the aim of this review was to describe it. The present study involved an exhaustive search of MEDLINE, 68 articles were included to analyze the impact of hormonal therapy, prevention, and care regarding sexual and reproductive health of transmasculine individuals. Despite a lack of solid data, the global literature agrees that transmasculine individuals require sexual and reproductive health care. Care must be adapted to each pathway and may be impacted by gender-affirming care. The cancer risk does not seem to be increased in this population, particularly in relation to hormonal therapy. Prevention programs do not differ from those offered to cis women in the absence of gender-affirming surgeries. Transmasculine individuals require follow-up and care adapted to their needs and their pathways. Healthcare professionals must be trained to provide such care.

25. Barriers and Facilitators of Proper Gender Identification at Outpatient Surgical Centers Providing Gender-affirming Surgery

25. Barriers and Facilitators of Proper Gender Identification at Outpatient Surgical Centers Providing Gender-affirming Surgery

Receipt of Gender-Affirming Surgeries Among Transgender and Gender Diverse Veterans.

Gender-affirming surgery (GAS) can be an important part of comprehensive care for transgender and gender diverse (TGD) individuals, but this care is not provided by the Department of Veterans Affairs (VA) because of an exclusion in the medical benefits package. To describe the receipt of GAS by veterans and assess the associations between key sociodemographic characteristics and receipt of chest ("top") and genital ("bottom") surgeries. Cross-sectional national survey (the GendeR Affirming Care Evaluation (GRACE)), among TGD Veterans conducted between September 2022 and July 2023. A total of 6653 Veterans (54% response rate) completed the survey. Self-reported "top" and "bottom" GAS were key outcomes. Covariates included gender identity, sex assigned at birth, age, race, ethnicity, income, employment status, education, relationship status, sexual orientation, and geographic region. Among all respondents, 39% had ≥ 1 GAS. Among the 4430 veterans interested in top surgery, 38% received it; 23% of 3911 veterans interested in bottom surgery had received it. In multivariable models, older age (50 + vs. 18-39) was associated with higher receipt of top and bottom surgery while nonbinary gender identity (vs. binary gender identity), lower household income (< $50,000 vs. > $75,000), less education (less than a college graduate vs. Master's degree or more), sexual orientations other than heterosexual, and residing in a region other than the Pacific were associated with lower receipt of top and bottom surgery. Individuals assigned male (vs. assigned female) at birth had lower receipt of top surgery and higher receipt of bottom surgery. GAS receipt was low and there were important disparities by gender, sex, income, education, sexual orientation, and region. By removing the exclusion to providing GAS, VA could reduce barriers to accessing GAS and decrease disparities among TGD veterans.

Techniques chirurgicales avancées dans la féminisation du front et la redéfinition de la ligne des cheveux chez les patientes transgenres

Facial Gender-Affirming Surgery (FGAS) has emerged as a transformative option for individuals who wish to align their external appearance with their asserted gender identity. This article delves into the surgical techniques employed in forehead feminization and hairline redefinition, highlighting the nuanced approaches used to modify specific facial characteristics to achieve the desired feminizing outcomes. Our extensive experience, encompassing over 2300 forehead feminization surgeries conducted over the past 16 years, provides a robust foundation for understanding the complexities and intricacies of these procedures. This knowledge is crucial for maxillofacial and plastic surgeons, as well as other healthcare professionals involved in comprehensive gender-affirming care, ensuring they are well-equipped to deliver optimal results for their patients.

Self-described religious and spiritual identities of patients receiving gender-affirming surgeries: Implications for chaplaincy practice

Studies of the U.S. population in general and transgender and gender diverse (TGD) communities specifically suggest that religion and spirituality (R/S) can function in both positive and negative ways, including on health outcomes. Patients recovering from gender-affirming surgeries were asked by chaplains, during the course of spiritual care visits, to describe their R/S identities in their own words. Seventy-five responses were included in the study and were coded. Six themes and 10 sub-themes were identified. The themes were (1) centeredness in self; (2) transcendent belief system; (3) non-religious belief systems; (4) importance of prayer; (5) R/S identity and practice as fixed and consistent; and (6) R/S identity and practice as flexible, contextual, and transforming. The findings broadly reflected national data about R/S belonging, including trends related to the growing share of the population that identifies as atheist, agnostic, or spiritual but not religious; ambivalent relationships with R/S communities due to transphobia; and R/S beliefs and practices as supportive. Implications for chaplaincy practice are discussed, including the need for chaplains to understand both demographic trends and the intersections of R/S and transphobia.

Trends in Top Surgery Patient Characteristics, Wound Complications, and CPT Code Use by Plastic Surgeons: A Decade-Long Analysis.

Gender-affirming top surgery is becoming increasingly common, with greater diversity in the patients receiving top surgery. The purpose of this study was to examine national trends in patient demographics, characteristics, wound complication rates, and concurrent procedures in patients receiving gender-affirming top surgeries. Patients with gender dysphoria who underwent breast procedures, including mastectomy, mastopexy, breast augmentation, or breast reduction by a plastic surgeon between 2013 and 2022, were identified from the American College of Surgeons National Surgical Quality Improvement Program database. These procedures were considered to be gender-affirming "top surgery." Univariate analyses were performed to examine trend changes in the patient population and types of additional procedures performed over the last decade. There was a 38-fold increase in the number of patients who received top surgery during the most recent years compared to the first 2 years of the decade. Significantly more individuals receiving top surgery in recent years were nonbinary ( P < 0.01). There was a significant decrease in percentage of active smokers ( P < 0.01) while there was an increase in percentage of patients with diabetes ( P = 0.03). While there was a significant increase in the number of obese patients receiving top surgery ( P < 0.01), there were no differences in postoperative wound complications between the years. Significantly more patients received additional procedures ( P < 0.01) and had about a 9-fold increase in distinct number of additional CPT codes from 2013-2014 to 2021-2022. Our study found that there has been (1) a significant increase in the number of top surgery patients from 2013 to 2022 overall and (2) a particular increase in patients with preoperative comorbidities, such as a higher body mass index and diabetes. Understanding current and evolving trends in patients undergoing surgical treatment for gender dysphoria can inform individualized care plans that best serve the needs of patients and optimize overall outcomes.

Differences in Subjective Transition Outcomes Between Transgender and Gender-Diverse Individuals Who Completed Mandatory Psychiatric Assessment and Those Who Received Gender-Affirmative Medical Treatment in Croatia: A Cross-Sectional Online Survey.

The aim of this study was to evaluate different aspects of transition outcomes in groups of transgender and gender diverse (TGD) people based on their transition status. We divided the 70 TGD participants (19 individuals assigned male at birth and 51 assigned female at birth) into two groups: those who had completed their psychiatric and psychological evaluation (PPE), which is mandatory in Croatia, and those who had undergone gender-affirming medical treatment (GAMT) (both gender-affirming hormone treatment and gender-affirming surgery). The online survey included sociodemographic questions and a custom-designed nine-item scale. The items were specifically designed based on the DSM-5-TR criteria for gender dysphoria to assess subjectively perceived transition outcomes. We conducted a factor analysis of the scale followed by structural equation modeling for confirmation. Chi-squared and Mann-Whitney U tests were used to compare group differences. The following three-factor structure was confirmed: better functioning, reduced body dysphoria, and satisfaction with decision. A positive influence of better functioning on satisfaction with the decision was found. In addition, our results showed that TGD individuals who had undergone GAMT scored higher on better functioning than those who had just completed PPE. Both groups consistently scored high on satisfaction with the decision, with no statistically significant differences between them. Our findings suggest that TGD individuals view gender-affirming medical care as beneficial to their overall functioning.

Temporary Declines and Demand Resurgence: Gender-Affirming Surgery Volume and Complication Trends During and After the COVID-19 Pandemic.

The COVID-19 pandemic prompted surgical volume reductions due to lockdown measures. This study evaluates COVID-19's impact on gender-affirming surgery (GAS) volume and complications from the pandemic onset through the recovery period. The 2019-2021 National Surgical Quality Improvement Program databases were queried for transgender or gender-diverse patients using ICD-10 codes. Five time periods were analyzed: Pre-pandemic, Immediate pre-pandemic and COVID-19 outbreak, Initial COVID-19 peak, Pre-COVID-19 vaccine, and Post-vaccine release. Complications included reoperation, urinary tract infections, and wound complications. Multivariate logistic regressions assessed factors associated with undergoing surgery during the initial COVID-19 peak and experiencing surgical complications. Out of 2,963,230 patients, 4637 underwent GAS between 2019 and 2021. Chest feminizing and masculinizing procedures comprised 60.1% of all GAS. During the initial COVID-19 peak, all GAS surgeries nearly halved, with breast augmentations dropping to 15.3% of pre-pandemic volumes. White patients constituted a significantly higher proportion of GAS patients during the initial COVID-19 peak than in 2019 (74.7% vs. 61.0%, p = 0.014). Post-vaccine, GAS levels surged, exceeding pre-pandemic volumes by 45.5% and initial peak levels by 188.5%. The overall complication rate was 4.9%, and was significantly associated with older age, increased operative time, feminizing and masculinizing genital surgeries, and hysterectomies. The initial COVID-19 peak showed no significant correlations with surgical complications. GAS volume temporarily decreased during the initial COVID-19 outbreak and has since rebounded and surpassed pre-pandemic levels, corresponding with past-decade trends. Complication risks remained consistent despite the pandemic, though the results highlight potentially significant race-based disparities in GAS access during COVID-19. During the COVID-19 pandemic, public health measures led to severe volume reductions in gender-affirming surgical (GAS) procedures. Since the initial COVID-19 peak, GAS volumes have fully recovered and surpassed pre-pandemic volumes. Surgical complication rates for various GAS procedures were within expected ranges, emphasizing the overall safety of these surgeries. The study's results highlight racial disparities in undergoing GAS during the COVID-19 pandemic, with White patients disproportionately represented among those who had surgery during the COVID-19 lockdown. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .

Nonbinary and Transgender Male Patient Preferences for Gender-Affirming Top Surgery.

This study aimed to identify patient preferences and outcomes of chest masculinization surgery in patients identifying as nonbinary versus transgender (trans-) males. Patients who underwent chest masculinization (2003-2022) were included. Demographics, medical comorbidities, surgical approaches, complications, secondary procedures, and BODY-Q chest module survey responses were compared between cohorts. Three hundred two patients were included. Thirteen percent identified as nonbinary and 87% as trans-male. The most common surgical approach in both groups was double incision with free nipple-areola graft (63% vs 71%, P = 0.33). Nonbinary patients more frequently opted for double incision without free nipple areola graft compared to trans-male patients (18% vs 2.7%, P < 0.001). Other unique surgical requests of nonbinary patients included nipple areola preservation and small breast mound preservation (5.2%) and balance between losing bulk and achieving a more androgynous appearance (5.3%). The survey response rate was 31% (93/302). Both groups reported improved quality of life postoperatively (P = 0.16). Three nonbinary patients elected not to keep their nipple-areola complexes (P = 0.005). Trans-male patients were more likely to report having a male chest as very important for their gender identity (82% vs 95%, P = 0.043). Nonbinary patients were less likely to prefer small nipples (82% vs 95%, P = 0.033) and 18% stated that they preferred no nipples (vs 2.7% trans-male patients, P < 0.001). Nonbinary patients have distinct surgical preferences regarding nipple-areola complexes. Chest masculinization planning can differ for this group of patients compared to their trans-male counterparts.

Association between genital gender-affirming surgery and psychiatric comorbidities in individuals with gender incongruence.

Previous studies present mixed evidence on the relationship between psychiatric comorbidities and genital gender-affirming surgery (GGAS) in individuals with gender incongruence (GI). This research aims to investigate the psychiatric comorbidity rates post-GGAS in the GI population-namely, depressive disorders, anxiety disorders, posttraumatic stress disorders, substance abuse disorder, and suicidality. Based on the TriNetX health care database, an international database with >250 million patients, a cross-sectional study was executed comparing psychiatric comorbidity rates among cases of GI with and without GGAS. Individuals were matched for demographic and health-related variables, which included history of cardiovascular disease, diabetes, and obesity. The main focus was to establish the rates and changes in psychiatric comorbidities following GGAS. Among individuals with GI, the study identified 4061 with GGAS and 100 097 without. At 1 year post-GGAS, there was a significant decrease in depression (odds ratio [OR], 0.748; 95% CI, 0.672-0.833; P < .0001), anxiety (OR, 0.730; 95% CI, 0.658-0.810; P < .0001), substance use disorder (OR, 0.730; 95% CI, 0.658-0.810; P < .0001), and suicidality (OR, 0.530; 95% CI, 0.425-0.661; P < .0001), and these reductions were maintained or improved on at 5 years, including posttraumatic stress disorder (OR, 0.831; 95% CI, 0.704-0.981; P = .028). The findings indicate that GGAS may play a crucial role in diminishing psychiatric comorbidities among individuals with GI. This is the largest known study to evaluate the effect of GGAS on psychiatric comorbidities in the GI population, offering robust evidence. The reliance on the precision of CPT and ICD-10 codes for data extraction poses a limitation due to potential coding inaccuracies. The evidence suggests a significant association between GGAS and reduced psychiatric comorbidities in individuals with GI.

Technical Pearls and Pitfalls of Facial Feminization Surgery: A Review of Techniques From a Single Institutional Practice.

Facial feminization surgery (FFS) is an emerging practice that falls under the broader umbrella of gender-affirming surgery. Various approaches exist to feminize the face, yet few published articles describe in detail the techniques of each component procedure. Considering the diversity of interventions employed, the objective of this manuscript is to highlight FFS techniques utilized by the senior author and create a corresponding media gallery. All patients with the diagnosis of gender dysphoria that were referred to the senior author for FFS consultation between June 2017 and August 2022 were reviewed. Data were retrospectively collected from electronic medical records according to the institutional review board (IRB)-approved study protocol. Data collected and analyzed included demographics, operative documentation, and postoperative follow-up. Multimedia material was collected intraoperatively and postoperatively. A total of 231 patients underwent 262 operations with a total of 1224 FFS procedures. The average follow-up time was 7.7 ± 11 months. Out of the 262 operations, 24 (9.2%) patients experienced minor complications, including 3 (1.1%) with wound dehiscence, 13 (5.0%) with hematomas, and 14 (5.3%) with postoperative infection requiring antibiotics. Of those, 3 (1.1%) required a return to the operating room for washout or removal of malar implants. Although there is a consensus on the fundamental surgical principles to achieve adequate feminization of the facial architecture, the specific techniques to do so differ according to individual practices. As techniques diverge, so do their risk profiles and outcomes; techniques must, thus, align with patients' interventional goals. The material presented here is one of many that can support trainees and junior surgeons as they build a gender-affirming practice.

P-355 Effect of biphasic CAPA-IVM on ovarian tissue oocytes of transgender men

Abstract Study question Can CAPA-IVM (Biphasic in-vitro maturation) with C-type natriuretic peptide (CNP), followed by in vitro maturation (IVM) improve ovarian tissue oocyte (OTO) maturation in transgender patients? Summary answer CAPA-IVM did not show any significant difference in maturation competence and frequency of chromosomal aberrations when compared with standard and in-house IVM. What is known already OTO-IVM is a method of fertility preservation in patients where prior ovarian stimulation is undesired. It has resulted in live births in cancer and polycystic ovarian syndrome (PCOS) patients. CAPA-IVM has further improved oocyte competency in these patients by synchronizing nuclear and cytoplasmic maturity. Similarly, OTO can be collected from transgender men without ovarian stimulation during gender reassignment surgery. While oocytes do survive and mature, OTO-IVM in transgender men is characterized by decreased fertilization rate and severely compromised developmental competency. We investigated whether CAPA-IVM can improve cytoplasmic immaturity for transgender OTO. Study design, size, duration Patients were recruited from July 2022 to July 2023. Both ovaries were collected from 9 transgender patients (age= 20-24 years, mean age=22 years) who underwent gender reassignment surgery after testosterone treatment (mean length= 34 months). All ovaries were collected in cold medium (4oC) and manipulation was performed within 30 minutes of the collection for the retrieval of cumulus oocyte complexes (COCs). Participants/materials, setting, methods Collected COCs were cultured either in in-house IVM and Standard (Medicult) IVM medium for 48 hours or in biphasic CAPA-IVM for 54 hours (24 hours pre-maturation culture and 30 hours IVM). Following maturation, oocytes were analyzed for calcium (Ca2+)-releasing potential and developmental competency after ICSI. In vitro matured MI (metaphase I) oocytes from stimulated IVF patients served as controls. Genetic analysis was performed on subsequent embryos to detect chromosomal abnormalities in all groups. Main results and the role of chance After culturing 330 COCs, the survival rate following maturation was similar in the in-house IVM (79%) compared to Medicult (72%, p = 0.221) and CAPA-IVM (73%, p = 0.251). A similar maturation rate (i.e. 55-57%) was observed in the different groups. Following ICSI, 15/25 (60%) CAPA-IVM, 13/19 (68.5%) Medicult IVM, and 17/28 (61%) in-house IVM oocytes were normally fertilized, which was lower than controls (24/29, 83%). Blastocyst rate was inferior in all OTO groups and significantly lower (p = 0.031) in Medicult-IVM (0/13) compared to controls (7/24). Ca2+-releasing potential of oocytes was determined as a product of amplitude and frequency, in arbitrary units (AU). The average values for CAPA-IVM (1.74AU), Medicult IVM (1.24AU), and in-house IVM (1.54AU) were significantly lower (p = 0.022, p = 0.008 and p = 0.017 respectively) compared to controls (4.76AU). Shallow whole genome sequencing of developed embryos (Day 2- Day 5) showed that 8/13 (61.5%) in CAPA-IVM, 4/8 (50%) in In-house IVM, 1/6 (17%) in Medicult, and 4/12 (33%) in the Control group were chromosomally normal. Limitations, reasons for caution The limited inclusion of patients warrants caution in the interpretation of the results. Moreover, the lack of a better control group might mask the properties of OTO-IVM. Wider implications of the findings Our preliminary results do not demonstrate an improvement in oocyte maturation and embryo development with the implementation of CAPA-IVM. However, future proteomics and transcriptomic studies would shed more light on the advantages of the current IVM systems and decipher the true potential of OTO-IVM from transgender men. Trial registration number not applicable

P-105 Gender affirming hormone therapy affects the spermatogonial cell compartment in transwomen

Abstract Study question What are the specific changes under gender affirming hormone therapy (GAHT) in the spermatogonial cell compartment in testicular tissues of transwomen? Summary answer GAHT has a negative effect on the most undifferentiated PIWIL4+ spermatogonia potentially leading to reduced chances for fertility preservation in transwomen. What is known already Transwomen take GAHT to achieve transition between the gender assigned at birth and their gender identity. GAHT leads to a reduction of the most advanced germ cells and a reduction of MAGEA4 positive spermatogonia (pan spermatogonial marker). Single-cell RNA sequencing studies identified spermatogonial subpopulations based on the expression of the marker genes PIWIL4, FGFR3, NANOS3, GFRA1, KIT, UTF1. PIWIL4+ cells are considered the origin of germ cell differentiation (state 0). State 1 and 2 spermatogonia are characterized by expression of GFRA1 and KIT, respectively. Study design, size, duration On the day of gender affirming surgery (GAS) testicular tissues and blood samples were collected of 25 age matched trans women (mean 28.1 yr), who underwent comparable GAHT regimens (10 or 12.5 mg cyproterone acetate and estrogens) between 2013 and 2018. 8 adult cis men (mean 34.5 yr) with complete spermatogenesis served as controls. Age, start and type of GAHT were assessed using a questionnaire. This study was approved by the local ethics committee. Participants/materials, setting, methods We performed immunohistochemical stainings to evaluate the expression of spermatogonial markers (MAGEA4, UTF1, PIWIL4, FGFR3, NANOS3, GFRA1) in Bouin’s-fixed testicular tissue sections. For each marker the number of positive cells per round tubular cross-section was determined in 25 round tubules. The spermatogonial proliferation rate was evaluated using immunofluorescence co-stainings for GFRA1/MIKI67/MAGEA4 and KIT/MKI67/MAGEA4. We scored 400 MAGEA4+ cells per individual and determined the proportion of GFRA1+/KIT+. MKI67+ cells among the GFRA1+/KIT+ were evaluated. Main results and the role of chance The number of MAGEA4+ spermatogonia and the proportion of PIWIL4+ spermatogonia within the MAGEA4+ spermatogonia were reduced in transwomen compared to controls (p &amp;lt; 0.001). In contrast, the relative proportion of UTF1+, FGFR3+ and NANOS3+ spermatogonia was comparable. The number of spermatogonia per tubule correlated negatively with the age at start of GAHT (p &amp;lt; 0.01) and the age on the day of GAS (p &amp;lt; 0.001). The treatment duration correlated negatively with the proportion of PIWIL4+ (p &amp;lt; 0.01) and NANOS3+ spermatogonia (p &amp;lt; 0.05). The immunofluorescence stainings in transwomen revealed a similar ratio of proliferating KI67+ spermatogonia, both within the GFRA1+ and KIT+ cells, compared to controls. These results show the negative effects of the GAHT itself on the population of spermatogonia as well as the individual susceptibility depending on age-related factors. These results have the potential to better define the chances for fertility preservation under GAHT. Limitations, reasons for caution Transwomen are a very heterogeneous patient group varying in age, different GAHT, different treatment durations, intake of co-medications and possible pre-existing medical conditions. Hence, testicular size and histological appearance of transwomen’s testes are heterogeneous. Wider implications of the findings Transwomen, who wish to have own biological children, have to be counseled with regard to fertility preservation, best before initiation of GAHT, in order to avoid adverse effects on spermatogonia. Individual counselling has to take place with regard to fertility preservation. Trial registration number 2012-555-f-S

P-693 Three-dimensional modeling of follicular microenvironment dynamics in the human adult ovary

Abstract Study question How does the ovarian microenvironment, involving neural fibers, vascular networks, and immune cells, interplay with follicular dynamics in the human adult ovary? Summary answer Neural fibers growing into the ovarian cortex and vascular network expansion were associated with primordial follicle activation and growth. Macrophages associated with antral follicular atresia. What is known already The ovarian follicles, responsible for preserving and supplying oocytes, play a crucial role in fertility, with their fate influenced by the ovarian microenvironment. However, the three-dimensional (3D), irregular, and dynamic structural changes of the ovarian microenvironment are difficult to interpret using two-dimensional analysis. 3D-imaging technologies have been developed to reveal intricate structural and functional relationships particularly in rodents, but these approaches have not been widely adopted for human ovarian research. Study design, size, duration Our study aims to explore the follicular microenvironment dynamics in the human adult ovary. In this work, we optimized whole-mount immunofluorescence using TUBB3, PODXL, PECAM1, ACTA2 and CD68, and conducted 3D imaging on intact adult ovarian tissue, offering a visualization of the 3D structures and dynamic changes within ovarian follicles, neural fibers, vascular networks, and immune cells in human adult ovary at the single-cell level. Participants/materials, setting, methods The human ovarian samples were collected from donors (N = 5) who underwent oophorectomy after testosterone treatment. Part of the intact ovary, including cortex and medulla, was fixed and used for whole-mount immunofluorescence using markers for neural fibers (TUBB3), blood vessels (PODXL, PECAM1, ACTA2), and immune cells (CD68). Subsequently, an enhanced iDiSCO method was employed for tissue clearance. Finally, 3D images were acquired using a lightsheet microscope, followed by image analysis and 3D reconstruction using Imaris software. Main results and the role of chance Our results showed that TUBB3-labeled nerve fibers predominantly distributed in the ovarian cortex, with few presented in the medullary region. Notably, their presence surrounding secondary and antral follicles was limited. We observed a rich distribution of PODXL-labeled capillaries surrounding primordial and primary follicles in the cortical layer of the adult ovary. As follicles progressed to the secondary stage, PECAM1-labeled vasculature contributed to the construction of a vascular network enveloping the secondary follicles and connecting extensively to larger-caliber arteries containing (ACTA2+) smooth muscle cells. In antral follicles, large larger-caliber arteries were also detected, maintaining proximity to the theca cell layer. Interestingly, in cases of follicular atresia, vascular invasion within the follicular cavity was observed. Additionally, clusters of CD68+ macrophages exhibited a scattered distribution around the follicles at various stages, with a significant accumulation in atretic small-antral follicles. Limitations, reasons for caution Our study was conducted on ovaries from a limited number of donors after gender-affirming surgery. Although we aimed to provide insights into the ovarian microenvironment, we were so far unable to obtain ovaries with large antral follicles, ovulatory follicles and the formation of the corpus luteum. Wider implications of the findings The views provided by 3D-image analysis of the human ovary will augment the current knowledge of the complex interactions between the follicles and the ovarian microenvironment. 3D ovarian mapping will also provide a roadmap for generating oocytes in vitro for fertility preservation and ovarian disease modelling. Trial registration number N/A.

O-116 Fertility in transmasculine people

Abstract Transgender and gender diverse (TGD) people apply for gender-affirming care at any age to manage gender identities or expressions that differ from the gender socially attributed to their sex assigned at birth. Gender-affirming hormonal treatment (GAHT) and gender-affirming surgery (GAS) may alter reproductive function and/or anatomy, limiting future reproductive options to varying degrees, if persons have the wish to either give birth and, or to become a biological parent. The desire to have children in TGD people does not differ from that of the cis population. In those persons assigned female at birth but who identify as male or genderdivers medical transition often comprises testosterone to induce masculinisation. The effect of testosterone on the uterus and ovaries and further reproductive outcome has not been fully clarified so far. There are several histological studies showing ovarian cortical and stromal changes following testosterone exposure, it is uncertain what the consequences for future fertility may be. It seems there is persistent activity in folliculogenesis by the descriptions of follicle count, distribution and oocyte retrieval. However, there are studies showing a negative effect on fertilization rate in presence of testosterone. Reports on successful ovarian stimulation, fertilizations, pregnancies and live births have been published, with and without testosterone discontinuation. In this lecture an overview will be given of the recent literature and guidelines on fertility outcome in TGD people assigned female at birth, specifically the effect of medical transition. Recommendations on counseling and ways of fertility preservation will be discussed.