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Some transmasculine individuals may be interested in pausing gender-affirming testosterone therapy and carrying a pregnancy. The ovarian impact of taking and pausing testosterone is not completely understood. The objective of this study was to utilize a mouse model mimicking transmasculine testosterone therapy to characterize the ovarian dynamics following testosterone cessation. We injected postpubertal 9–10-week-old female C57BL/6N mice once weekly with 0.9 mg of testosterone enanthate or a vehicle control for 6 weeks. All testosterone-treated mice stopped cycling and demonstrated persistent diestrus within 1 week of starting testosterone, while control mice cycled regularly. After 6 weeks of testosterone therapy, one group of testosterone-treated mice and age-matched vehicle-treated diestrus controls were sacrificed. Another group of testosterone-treated mice were maintained after stopping testosterone therapy and were sacrificed in diestrus four cycles after the resumption of cyclicity along with age-matched vehicle-treated controls. Ovarian histological analysis revealed stromal changes with clusters of large round cells in the post testosterone group as compared to both age-matched controls and mice at 6 weeks on testosterone. These clusters exhibited periodic acid–Schiff staining, which has been previously reported in multinucleated macrophages in aging mouse ovaries. Notably, many of these cells also demonstrated positive staining for macrophage markers CD68 and CD11b. Ovarian ribonucleic acid-sequencing found upregulation of immune pathways post testosterone as compared to age-matched controls and ovaries at 6 weeks on testosterone. Although functional significance remains unknown, further attention to the ovarian stroma may be relevant for transmasculine people interested in pausing testosterone to carry a pregnancy.

Approximately 50% of transmasculine people use testosterone for gender affirmation, yet very little is known about the effects of testosterone on future reproductive capacity. Moreover, there are no data to guide fertility specialists on how to manage testosterone leading up to or during ovarian stimulation. Most clinics require cessation of testosterone prior to ovarian stimulation in this setting of no data; however, the current literature does suggest a potential increase in dysphoria with cessation of testosterone and during stimulation. This divergence begs the question of whether clinicians may be doing more harm than good by enacting this requirement. Here, we present two cases of transmasculine individuals who were on testosterone prior to stimulation and maintained their testosterone dosage throughout stimulation as proof of concept, followed by a discussion of current clinical practice and providing some rationale to support continuation of testosterone throughout stimulation.

To evaluate the impact of a single session of psychosocial counseling on patients with vulvodynia.Patients diagnosed with vulvodynia at a vulvovaginal specialty clinic were randomly assigned to receive either a one-on-one 30- to 45-min psychosocial counseling session with a psychosexual counselor plus written educational materials (intervention group) or written materials alone (control group). They completed a survey before and 6 weeks after randomization that included demographic information and validated measures of sexual function and illness perception.Thirty-one of 38 (81.6%) women approached chose to participate; 26 of the 31 (83.9%) completed the 6-week follow-up survey. Only the intervention group showed improvement in knowledge about vulvovaginal and sexual health, as well as in most measures of improvement in illness perception, as measured by the Brief Illness Perception Questionnaire (P 0.05). When compared directly with those in the control group, patients in the intervention group reported increased understanding of their vulvar symptoms (P 0.005) and lessened emotional impact of these symptoms (P = 0.035).Patients receiving one session of the one-on-one psychosocial counseling intervention reported improved understanding and lessened emotional impact of their vulvar symptoms, compared with the control group. This study suggests that improvement may occur following minimal intervention and supports the need for further study.

To determine the implications of an incidentally noted subchorionic hematoma on pregnancy outcomes in the infertile population.Retrospective cohort study at a tertiary care, university-based facility. All patients with intrauterine pregnancy on initial obstetric ultrasound presenting to an infertility clinic between January 2015 and March 2018 (n = 1210), regardless of treatment cycle, were included. Nonviable pregnancies were excluded. The main outcome measured was association between subchorionic hematoma and first trimester miscarriage.The prevalence of subchorionic hematoma was 12.5% (n = 151) and did not differ by type of fertility treatment. There was no association between subchorionic hematoma and first trimester miscarriage; however, among patients with subchorionic hematoma, those who reported both bleeding and cramping had an increased probability of miscarriage compared to those without symptoms (0.62 vs. 0.12, P 0.001). The live birth rate in this sample was 81.3% and there were no statistically significant differences in pregnancy outcomes between those with and without subchorionic hematoma.Among an infertile population, there was no increased risk of miscarriage when subchorionic hematoma was seen on early ultrasound; however, when patients noted both vaginal bleeding and cramping, their probability of miscarriage was significantly increased.

Objective To establish if the cessation of testosterone (T) therapy reverses T-induced acyclicity in a transgender mouse model that allows for well-defined T cessation timing. Design Experimental laboratory study using a mouse model. Setting University-based basic science research laboratory. Animals A total of 10 C57BL/6NHsd female mice were used in this study. Intervention(s) Postpubertal C57BL/6NHsd female mice were subcutaneously implanted with T enanthate (n = 5 mice) or placebo (n = 5 mice) pellets. Pellets were surgically removed after 6 weeks to ensure T cessation, after which the mice were followed for four estrous cycles after the resumption of cyclicity. Main Outcome Measure(s) Primary outcomes included daily vaginal cytology and weekly T levels before, during, and after T enanthate or placebo pellet implantation and removal. Secondary outcomes included ovarian follicle distribution and corpora lutea numbers, body metrics, and terminal diestrus hormone levels. Result(s) T-treated mice (100%) resumed cycling within one week of T pellet removal after six weeks of T therapy. T levels were significantly elevated during T therapy and decreased to control levels after surgical pellet removal. No detectable differences were observed in the follicle count, corpora lutea formation, diestrus hormone levels, or body metrics after four estrous cycles, with the exception of persistent increased clitoral area between T-treated mice and controls. One T-treated mouse was sacrificed early due to vaginal prolapse and not included in subsequent analyses. Conclusion(s) Our results demonstrated a close temporal relationship between estrous cycle return and T levels dropping to control levels following T pellet removal. The return of regular cyclic ovulatory function is also supported by the formation of corpora lutea and the lack of detectable differences in key reproductive parameters as compared to controls four cycles after T cessation. These results may be relevant to understanding the reversibility of T-induced amenorrhea and possible anovulation in transgender men interested in pausing T to pursue pregnancy or oocyte donation. Results may be limited by the duration of T treatment, lack of functional testing, and physiological differences between mice and humans.

Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (E2) levels and potential delays in treatment with ovarian stimulation for fertility preservation (FP). The aim of this study was to compare recurrence and survival in breast cancer patients who pursued FP without concurrent letrozole to those who did not (non-FP). We reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005–01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan–Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows. 332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p

STUDY QUESTION Can mice serve as a translational model to examine the reproductive consequences of pubertal suppression with GnRH agonist (GnRHa) followed by testosterone (T) administration, a typical therapy in peripubertal transmasculine youth? SUMMARY ANSWER An implanted depot with 3.6 mg of GnRHa followed by T enanthate at 0.45 mg weekly can be used in peripubertal female mice for investigating the impact of gender-affirming hormone therapy in transmasculine youth. WHAT IS KNOWN ALREADY There is limited knowledge available in transgender medicine to provide evidence-based fertility care, with the current guidelines being based on the assumption of fertility loss. We recently successfully developed a mouse model to investigate the reproductive consequences of T therapy given to transgender men. On the other hand, to our knowledge, there is no mouse model to assess the reproductive outcomes in peripubertal transmasculine youth. STUDY DESIGN, SIZE, DURATION A total of 80 C57BL/6N female mice were used in this study, with n = 7 mice in each experimental group. PARTICIPANTS/MATERIALS, SETTING, METHODS We first assessed the effectiveness of GnRHa in arresting pubertal development in the female mice. In this experiment, 26-day-old female mice were subcutaneously implanted with a GnRHa (3.6 mg) depot. Controls underwent a sham surgery. Animals were euthanized at 3, 9, 21 and 28 days after the day of surgery. In the second experiment, we induced a transmasculine youth mouse model. C57BL/6N female mice were subcutaneously implanted with a 3.6 mg GnRHa depot on postnatal day 26 for 21 days and this was followed by weekly injections of 0.45 mg T enanthate for 6 weeks. The control for the GnRH treatment was sham surgery and the control for T treatment was sesame oil vehicle injections. Animals were sacrificed 0.5 weeks after the last injection. The data collected included the day of the vaginal opening and first estrus, daily vaginal cytology, weekly and terminal reproductive hormones levels, body/organ weights, ovarian follicular distribution and corpora lutea (CL) counts. MAIN RESULTS AND THE ROLE OF CHANCE GnRHa implanted animals remained in persistent diestrus and had reduced levels of FSH (P = 0.0013), LH (P = 0.0082) and estradiol (P = 0.0155), decreased uterine (P LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Although it is an appropriate tool to provide relevant findings, precaution is needed to extrapolate mouse model results to mirror human reproductive physiology. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this study describes the first mouse model mimicking gender-affirming hormone therapy in peripubertal transmasculine youth. This model provides a tool for researchers studying the effects of GnRHa-T therapy on other aspects of reproduction, other organ systems and transgenerational effects. The model is supported by GnRHa suppressing puberty and maintaining acyclicity during T treatment, lower LH levels and absence of CL. The results also suggest GnRHa+T therapy in peripubertal female mice does not affect ovarian reserve, since the number of primordial follicles was not affected by treatment. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Michigan Institute for Clinical and Health Research grants KL2 TR 002241 and UL1 TR 002240 (C.D.C.); National Institutes of Health grants F30-HD100163 and T32-HD079342 (H.M.K.); University of Michigan Office of Research funding U058227 (A.S.); American Society for Reproductive Medicine/Society for Reproductive Endocrinology and Infertility grant (M.B.M.); and National Institutes of Health R01-HD098233 (M.B.M.). The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core Facility was supported by the Eunice Kennedy Shriver NICHD/NIH grants P50-HD028934 and R24-HD102061. The authors declare that they have no competing interests.

This study aimed to discuss fertility concerns unique to the lesbian, gay, bisexual, transgender, queer, plus and single-parent-to-be populations and review special considerations regarding the evaluation and treatment of these patients relevant to the practicing reproductive medicine provider. The use of assisted reproductive technology has rapidly increased over the past 50 years. Given these trends, providers can expect a greater diversity of patients making use of these technologies. Both the lesbian, gay, bisexual, transgender, queer, plus community and single parents-to-be represent understudied and important populations who often require the use of assisted reproductive technology to build their families. The American Society for Reproductive Medicine advocates for equitable treatment of patients regardless of sexual orientation and partner status, and health care providers working in the fertility field should be comfortable and confident in assessing the needs of and providing care to these populations.

Objective To examine whether F2-isoprostanes, a marker of systematic oxidative stress, are associated with antimullerian hormone (AMH), an indicator of ovarian reserve, in a population-based cohort of women of black and white ethnicities. Design Cross-sectional analysis. Setting Not applicable. Patients The CARDIA Women’s Study, a population-based cohort. Black (n = 398) and white (n = 432) late reproductive−aged women (mean age 40 ± 3.6 years) without histories of gynecologic surgery. Main Outcome Measures Log-transformed serum AMH concentrations. Results Linear regression models evaluated whether plasma F2-isoprostanes were associated with log-transformed AMH after adjustment for age, race, smoking, body mass index, and oral contraceptive pill use. Higher levels of F2-isoprostanes were associated with lower AMH levels (β −0.048 per standard deviation, 95% confidence interval −0.087, −0.01). The observed associations were stronger at younger ages (P=.04 for interaction between levels of age and F2-isoprostanes). Indicators of other steps in the oxidative stress pathway (superoxide dismutase, paraoxonase activity, oxidized low-density lipoprotein cholesterol, and carotenoids) were not associated with AMH, although lower phospholipase A2 activity (β 0.036 per standard deviation, 95% confidence interval 0.001, 0.071) was associated with lower AMH across all ages. Conclusion In a population-based cohort, higher levels of F2-isoprostanes were associated with lower ovarian reserve, particularly at younger ages.

Impairment of fertility and sexual/reproductive health are common after oncologic therapy, and are known to have negative impacts on romantic relationships and psychosocial well-being among childhood cancer survivors. The Pediatric Initiative Network (PIN) is an international, multidisciplinary group of providers within the Oncofertility Consortium dedicated to preserving and protecting the fertility of children and adolescents at risk for infertility due to medical conditions or treatments. The PIN and its Best Practices and Research committees meet virtually throughout the year, with one annual in-person meeting. The purpose of this “proceedings” is to highlight key discussion points from the annual PIN meeting which took place on November 11, 2019, to 1) provide a context for pediatric groups across the country on what oncofertility programs are currently doing and why, and 2) inform stakeholders of past, present and future initiatives that may be of value to them and the patient populations they serve.

PURPOSE OF REVIEW: The purpose of this review is to provide an up-to-date overview of gender-affirming hormone therapy, including the various hormone regimens available, the efficacy and potential risks of these treatments, and considerations for surveillance and long-term care. RECENT FINDINGS: Recent studies reaffirm that hormone therapy has positive physical and psychological effects for many transgender individuals. The overall risks of treatment are low. Transgender women may have an increased risk of venous thromboembolism and breast cancer based on recent cohort studies, but these findings have yet to be confirmed with randomized controlled trials. Important long-term considerations include metabolic, cardiovascular, and skeletal health. SUMMARY: High-quality, long-term studies on the effectiveness and safety of various gender-affirming hormone treatment regimens are lacking, but the currently available evidence suggests that it is overall safe and effective with appropriate oversight.

Purpose: To compare long-term outcomes of gynecologic cancer patients who pursued controlled ovarian hyperstimulation (COH) for fertility preservation (FP) with those who did not. Methods: Retrospective cohort, COH, and health outcomes in gynecologic cancer patients; data were analyzed by chi-square test, t-tests, and logistic regression. Results: Ninety patients with a gynecologic malignancy contacted the FP patient navigator: 45.6% (n = 41) had ovarian cancer, 25.6% (n = 23) endometrial cancer, 18.9% (n = 17) cervical cancer, 5.6% (n = 5) uterine cancer, and 4.4% (n = 4) multiple gynecologic cancers. From this cohort, 32 underwent COH, 43 did not, and 18 pursued ovarian tissue cryopreservation (OTC; 3 patients had both COH and OTC). Median age and type of cancer were not significantly different between the groups. COH patients had a range of 1–35 oocytes retrieved. Days to next cancer treatment in the COH group was 36 days; for those who declined COH, it was 22 days (not significant [NS], p > 0.05). There were two recurrences reported in the stimulation group and four in the no stimulation group (NS). Five deaths were reported, two in the stimulation group, none in the no stimulation group, and three in the OTC group (NS); 34% (n = 11) COH patients returned to use cryopreserved specimens, of which 45% (n = 5) had a live birth. Conclusion: Although time to next treatment was longer in the group of patients who underwent COH, this did not reach statistical significance. It appears that in selected patients with GYN malignancies, COH for oocyte or embryo cryopreservation is safe, with reasonable stimulation outcomes and no difference in long-term outcomes.

STUDY QUESTION Are serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated brominated diphenyl ethers (OH-BDEs) associated with IVF endpoints? SUMMARY ANSWER Positive associations were observed for BDE153 and several OH-BDEs with IVF endpoints. WHAT IS KNOWN ALREADY PBDEs have been voluntarily phased out of production in the USA and EU due to their persistence and toxicity to humans and ecosystems. PBDEs have been associated with implantation failure among women undergoing IVF, yet some animal studies suggest greater toxicity from their metabolites, OH-BDEs. STUDY DESIGN, SIZE, DURATION We evaluated a subset of 215 women (contributing 330 IVF cycles) enrolled between 2005 and 2016 in a longitudinal cohort based at Massachusetts General Hospital Fertility Center. PARTICIPANTS/MATERIALS, SETTING, METHODS The following PBDEs were quantified: 47, 99, 100, 153 and 154 and the following OH-BDEs: 3-OH-BDE47, 5-OH-BDE47, 6-OH-BDE47 and 4-OH-BDE49. Clinical endpoints of IVF treatments were abstracted from electronic medical records. Associations of log-transformed PBDEs and OH-BDEs with IVF outcomes were assessed using multivariable generalized mixed models and cluster weighted generalized estimating equation models adjusted for lipids, age, BMI, race, year of sample collection, IVF protocol and FSH levels. Outcomes were adjusted to represent a percent change in outcome with an increase equal to the magnitude of the difference between the 75th and 25th percentiles for each specific compound (interquartile range (IQR) increase). MAIN RESULTS AND THE ROLE OF CHANCE Detection frequencies were highest for congeners 47 and 153 (82% ≥ method detection limit (MDL)) and metabolites 3 and 5-OH-BDE47 and 4-OH-BDE49 (92% > MDL). PBDE and OH-BDE geometric mean concentrations declined by up to 80% between participants recruited in 2005 and those recruited in 2016. An IQR increase of BDE153 was associated with an increase in the probability of implantation (relative risk (RR) = 1.26, 95% CI: 1.16, 1.36), clinical pregnancy (RR = 1.32, 95% CI: 1.19, 1.46) and live birth (RR = 1.34; 95% CI: 1.15, 1.54). An IQR increase in 3 and 5-OH-BDE47 was associated with increased probabilities of implantation (RR = 1.52; 95% CI: 1.11, 2.09), clinical pregnancy (RR = 1.66; 95% CI: 1.17, 2.36), and live birth (RR = 1.61; 95% CI: 1.07, 2.40). When models were stratified by race (White (86%)/Other race (14%)), associations remained positive for White women, yet inverse associations were observed for Other race women. An IQR increase in BDE47 was associated with a 46% decreased probability of clinical pregnancy (95% CI: 0.31, 0.95) for Other race women. LIMITATIONS, REASONS FOR CAUTION Despite the long half-lives of PBDEs and OH-BDEs, exposure misclassification is possible for women who underwent multiple treatment cycles over several months or years. It is also possible another medium, such as follicular fluid would be optimal to characterize exposure. We also tested associations for multiple congeners and metabolites with multiple outcomes. WIDER IMPLICATIONS OF THE FINDINGS Detections of serum concentrations of PBDEs and OH-BDEs were highest in the early years of the study and suggests that the phase-out of these compounds has contributed to a decrease in exposure. The negative associations found for PBDEs and IVF outcomes among other race women suggests the potential for racial disparity. Potential racial disparities in PBDE exposure and exploration of alternative flame retardants with reproductive health outcomes should be the focus of future investigations. STUDY FUNDING/COMPETING INTEREST(S) Funding for this research was supported by the National Institutes of Environmental Health Sciences (NIEHS) [R01 ES009718, ES022955, ES000002 and 009718T32ES007069]. The authors have no conflicts of interest.

PURPOSE: To characterize patient preferences regarding gender-affirming hormone therapy (HT) providers and telemedicine use. METHODS: Between May and October 2019, a survey was administered to adult patients attending a tertiary medical center's HT clinic. The survey included questions on demographics, barriers to care, and preferences for HT follow-up care. Interest in telemedicine was measured using a Likert scale. Multivariable logistic regression was used to identify patient factors associated with interest in telemedicine. RESULTS: Among 111 patients, 63.1% (n=70) preferred an in-person visit with a specialist and 21.6% (n=24) preferred a video visit with their specialist. While only 15.3% (n=17) preferred follow-up with a primary care provider (PCP), 71.0% (n=80) felt comfortable transitioning future care to a PCP. Notably, 52.3% (n=58) of patients were interested in a telemedicine visit. Factors associated with interest in telemedicine included identifying as a transgender man (aOR 3.94, 95% CI [1.24–12.53], p=0.02), minority race/ethnicity (aOR 6.71, 95% CI [1.79–25.17], p=0.005), no need to travel (aOR 3.34, 95% CI [1.14–9.85], p=0.03), no concerns about video visits (aOR 14.66, 95% CI [4.34–49.56], p

Transgender and nonbinary individuals have a long-standing history of prejudice and discrimination on the basis of gender identity which has led to disparities in health access and outcomes. Over the past decade advocacy efforts have increased legal protections and societal acceptance of gender diversity; however, the transgender and nonbinary community remains an underserved population in medicine. Reproductive medicine highlights this disparity as transgender individuals must overcome significant barriers to access effective counseling and interventions for fertility and pregnancy care. Transgender individuals have the same desire to parent as cisgender people, with motivations, including the intents to nurture and to build families, but face many unique challenges in this pathway to achieve parenthood. Although gender-affirming care has clear life-saving benefits for transgender and nonbinary individuals, such treatment also represents a threat to an individual’s future reproductive potential. As higher numbers of transgender and nonbinary individuals initiate gender-affirming care during their reproductive years, effective fertility preservation counseling and access to fertility preservation services is integral to patient-centered care. Limited literature on the experiences of transgender and nonbinary individuals with fertility and pregnancy services illustrates the diversity of such experiences and impact on gender identity while emphasizing the need for inclusivity and higher standards for gender-affirming care. In delivering fertility and pregnancy care, providers need to avoid making assumptions of sexual orientation based on gender identity, utilize gender-neutral terminology and consistently address patients by their preferred name and pronouns to minimize the potential for gender dysphoria. At the clinic level, inclusive intake forms and educations materials, providing gender neutral bathrooms and developing policies against gender-based discrimination can create an environment that is both welcoming and affirming to transgender and nonbinary patients. Fertility and pregnancy care for transgender individuals is an evolving field with further research into the impact of gender-affirming hormones on fertility, development of treatment guidelines and continued advocacy for increased access and insurance coverage necessary to break down barriers to transgender parenting.

Adolescents and young adults (AYAs) at risk of primary ovarian insufficiency (POI) often request fertility preservation consultation. We report consult/treatment outcomes for 21 cancer survivors and 3 mosaic Turner syndrome (TS) patients (mean age 21.6 at consult, 3 with POI). Ten AYAs (9 survivors, 1 mosaic TS) attempted ovarian stimulation; 4 cancelled for poor response. Of completed cycles, mean 3.8 mature oocytes were retrieved, with mean anti-Müllerian hormone 0.653 ng/mL. Ovarian stimulation for mosaic TS AYA and survivors is possible, even with diminished ovarian reserve. Further study is needed to establish guidelines for patient selection, treatment timing, and stimulation protocols.

Introduction The impact of testosterone (T) on reproductive potential is poorly understood. Masculinizing hormones have demonstrated mixed effects on ovarian histology and data on assisted reproductive outcomes are limited to small case series. There is consensus among major medical societies to encourage fertility preservation counseling prior to initiation of gender-affirming hormone care, however, it is uncertain whether a break in T treatment prior to undergoing oocyte cryopreservation is beneficial. We hypothesized that T treatment would not have an impact on IVF outcomes. Methods C57BL/6N female mice were implanted with silastic tubing with either 10 mg testosterone enthanate in ethanol (n = 20) or ethanol alone (n = 18) at 10 weeks of age. Four groups of C57BL/6N female mice were used in this study: 1) current T implant 2) current sham implant 3) T cessation 4) control cessation. Biweekly blood samples and vaginal cytology were undertaken to monitor T levels and estrous cycles. For groups 1 and 2, mice were stimulated twelve weeks following implantation. For groups 3 and 4, implants were removed after twelve weeks and mice were stimulated two weeks after explantation. All mice were stimulated with 0.2 mL intraperitoneal CARD HyperOva followed 48 hours later by 7.5 IU intraperitoneal human chorionic gonadotropin (hCG). Oocytes were collected 14 hours after hCG injection and fertilized in vitro with sperm from 12-week-old B6D2F1/J male mice. 2-cell embryos were transferred into the oviducts of pseudopregnant recipient females. The study was powered to detect a 25% difference in 2-cell embryos. Data were analyzed using Chi-squared and unpaired t-tests with Prism 9.0. Results All T treated mice ceased cycling within one week of implantation and developed clitoromegaly. The current T implant group had fewer total oocytes retrieved (17.00 vs 36.00; p < 0.0001), mature oocytes (13.00 vs 28.10; p = 0.0002) and 2-cell embryos (12.78 vs 26.90; p = 0.0007) as compared to the current sham implant group. There was no significant difference in maturity (76.47% vs 78.06%; p = 0.6937) or fertilization rate (75.16% vs 74.72%; p = 0.9161). Pseudopregnant females who had 2-cell embryos transferred from current T implant mice were less likely to have a live birth than those with transfers from current sham implant mice (25.00% vs 80.00%; p = 0.0196). In contrast, comparison of IVF outcomes in the T cessation group with corresponding control cessation group revealed no significant differences between total oocytes (22.30 vs 30.75; p = 0.0708), mature oocytes (20.80 vs 27.75; p = 0.1288), or 2-cell embryos (20.40 vs 27.38; p = 0.104). Conclusion In a mouse model of gender-affirming testosterone, active T treatment negatively impacted IVF outcomes. Improved outcomes following cessation of T treatment support reversibility of T impact on reproductive potential. Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.

Transmasculine individuals are often prescribed testosterone (T) for masculinizing hormone therapy. Mouse models mimicking transmasculine T therapy require reliable long-term T administration. The objectives of this study were three-fold, namely, to compare: 1) the release dynamics of three different subcutaneous delivery systems of T enanthate administration (subcutaneous injections, commercially available pellets, and silastic implants) over a 6-week period in postpubertal C57BL/6N mice, 2) to compare the timing for T levels in plasma to return to baseline and cyclicity to resume after cessation of T between injections and pellets, 3) to utilize silastic implants to achieve sustainable increase in T levels utilizing T enanthate and crystalline T. All three modes of T administration resulted in an increase in T levels in plasma. Pharmacokinetic analyses showed a similar overall exposure to T enanthate over 6 weeks (integrated area) for, subcutaneous injection (0.45 mg two times per week and 0.90 mg one time per week), pellet (5 mg 60-day release), and silastic implant (5 mg 21 week) groups. Crystalline T had lower solubility and a decreased integrated area compared to T enanthate, even when implanted at a higher dosage, indicating different pharmacokinetic profiles based on type of T formulation when utilizing the same silastic delivery method. Surgical removal of pellets and silastic tubing led to a quick drop in T levels and resumption of estrous cyclicity, while cessation of injections required a long washout period for T levels to drop and estrous cycles to resume. Sustained elevation in T levels was achieved for at least 21 weeks with silastic implants. As all three delivery methods are able to elevate T levels in female mice for at least 6 weeks, choice of T administration method should be based on outcomes of interest and study design.

PURPOSE: Oocytes and embryos can be vitrified with and without dimethyl sulfoxide (DMSO). Objectives were to compare no vitrification (No-Vitr), vitrification with DMSO (Vitr + DMSO), and vitrification without DMSO (Vitr - DMSO) on fresh/warmed oocyte survival, induced parthenogenetic activation, parthenogenetic embryo development, and embryonic maternal imprinted gene expression. METHODS: In this prospective controlled laboratory study, mature B6C3F1 female mouse metaphase II oocytes were treated as: i) No-Vitr, ii) Vitr + DMSO/warmed, and iii) Vitr - DMSO/warmed with subsequent parthenogenetic activation and culture to the blastocyst stage. Oocyte cryo-survival, parthenogenetic activation and embryo development, parthenogenetic embryo maternal imprinted gene expression were outcome measures. RESULTS: Oocyte cryo-survival was significantly improved in Vitr + DMSO versus Vitr - DMSO at initial warming and 2 h after warming. Induced parthenogenetic activation was similar between all three intervention groups. While early preimplantation parthenogenetic embryo development was similar between control, Vitr + DMSO, Vitr - DMSO oocytes, the development to blastocysts was significantly inferior in the Vitr - DMSO oocytes group compared to the control and Vitr + DMSO oocyte groups. Finally, maternal imprinted gene expression was similar between intervention groups at both the 2-cell and blastocyst parthenogenetic embryo stage. CONCLUSION(S): Inclusion of DMSO in oocyte vitrification solutions improved cryo-survival and developmental potential of parthenogenetic embryos to the blastocyst stage without significantly altering maternal imprinted gene expression.

Purpose of review To provide an overview of the current state of knowledge of fertility risks of gender-affirming therapy, review fertility preservation options for transgender individuals and ways to minimize gender dysphoria during fertility treatment, and identify gaps in knowledge. Recent findings Recent studies have corroborated older data that gender-affirming hormone therapy creates histopathological changes in the gonads; however, the newer data suggests that some function of the gametes may be preserved. One study in transgender men reported successful in-vitro maturation of testosterone-exposed oocytes with normal spindle structures, and recent studies in transgender women reveal early spermatogenesis in estradiol-exposed testes and some recovery of semen parameters following cessation of hormones. Particular attention has recently been given to fertility preservation in transgender adolescents, revealing unmet informational needs in this population and very few are actually pursuing fertility preservation, even with counseling. Summary There is currently a paucity of data on the fertility effects of gender-affirming hormones, necessitating fertility preservation counseling prior to initiation of therapy. Several modifications can be made to fertility preservation protocols and procedures to decrease gender dysphoria or distress in transgender individuals, but outcome data is still lacking. Achieving high-quality data collection will likely require cooperation across multiple institutions.

PURPOSE: To explore the attitudes of reproductive endocrinology and infertility (REI) and maternal–fetal medicine (MFM) subspecialists regarding the necessity and appropriateness of body mass index (BMI) cutoffs for women seeking fertility treatment. METHODS: Members of the Society for Reproductive Endocrinology and Infertility (SREI) and the Society for Maternal Fetal Medicine (SMFM) were invited to participate in a survey querying their knowledge of existing institutional or clinic BMI policies and personal opinions regarding upper and lower BMI cutoffs for a range of fertility treatments, including oral ovulation agents, gonadotropins, and in vitro fertilization. RESULTS: Respondents included 398 MFMs and 201 REIs. The majority of REI and MFM providers agreed with upper limit BMI cutoffs (72.5% vs 68.2%, p = 0.29), but REIs were twice as likely to support lower limit BMI restrictions compared to MFMs (56.2% vs 28.4%, p

Breast cancer is the most common malignancy diagnosed in women of childbearing age. A breast cancer diagnosis in this young patient population can be uniquely complex to navigate when considering the potential impact of fertility loss associated with specific gonadotoxic therapies. Another unique challenge for young breast cancer patients is pregnancy-associated breast cancer (PABC), which occurs in approximately 1 of every 3000 pregnancies. Pregnancy adds a layer of complexity to breast cancer treatment planning as many therapies can affect the developing fetus. These two clinical challenges require nuanced multidisciplinary approaches to facilitate optimal treatment outcomes. We sought to review and summarize the management strategy options for both fertility preservation and PABC. A guideline and literature review was performed for fertility preservation, young patients with breast cancer, and pregnancy-associated breast cancer. Fertility preservation options, both established and experimental, are detailed. Suggested clinical practice guidelines for PABC are also presented, which delineate breast cancer treatment recommendations based on pregnancy trimester. A multidisciplinary approach to patient care, including oncologists and early referral to reproductive specialists, can provide young breast cancer patients with options for fertility preservation. Under the guidance of a multidisciplinary treatment team, PABC can also be diagnosed and treated to permit the best possible outcomes for the mother and the developing fetus.

There are an estimated 1.4 million transgender adults in the United States, and lack of providers knowledgeable in transgender care is a barrier to health care. Obstetricians and Gynecologists can help increase access in part by becoming competent in gender-affirming hormone therapy. For transgender men, testosterone protocols can be extrapolated from those used for hypogonadal cisgender men. Unfortunately, there are not any high-quality, long-term prospective studies on the effectiveness and safety of different testosterone regimens specifically in transgender men, but the available data suggest that gender-affirming testosterone therapy is safe and effective with proper screening and monitoring.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines – oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health – in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Purpose: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. Methods: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. Results: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. Conclusion: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (EWe reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005-01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan-Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows.332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p 0.05). Cancer recurrence was noted in 7 (4.7%) FP patients and 13 (7.9%) non-FP patients (NS), and mortality in 5 (3.2%) FP patients and 7 (4.2%) non-FP patients (NS). Within the FP group, no significant differences were found in recurrence or mortality based on ER status, age, BMI, peak EFP is safe and effective in breast cancer patients, regardless of receptor status; E

The impact and reversibility of long-term gender-affirming testosterone (T) therapy on the reproductive axis of transgender men has not been well-established. Little is known about outcomes for transgender men interested in pausing T therapy to harvest oocytes or get pregnant. We previously established a translational mouse model to investigate T-induced acyclicity and ovarian perturbations. We hypothesized that the duration of T-induced acyclicity would impact the reversibility of cyclic and ovarian changes. To test this hypothesis, T-treated mice were assigned to two groups: (SHORT) 6 weeks of T therapy with immediate reversibility (1.5 mg T propionate pellet implant/removal, n = 5) and (LONG) 6 weeks of T therapy with a prolonged T washout phase (subcutaneous oil injections of T enanthate at 0.9 mg once weekly, n = 5). Control groups (placebo pellets n = 5, sesame oil vehicle injections n = 5) were run in parallel. Estrous cycles were monitored using daily vaginal cytology. Following cessation of T therapy, mice were sacrificed in diestrus after resumption of cyclicity for 4 cycles and ovarian histology examined. Data were analyzed in GraphPad Prism using Welch’s t-test or Mann-Whitney where appropriate. T therapy led to persistent diestrus within a week after T administration for all T-treated mice and none of the controls. The total duration of acyclicity was 6±1 weeks for the SHORT group, which was significantly shorter than the 11±2 weeks for the LONG group (mean ± s.d., p = 0.0079). With resumption of cyclicity, both the SHORT and LONG groups had a significantly lower percentage of days in estrus and higher percentage of days in metestrus as compared to their parallel age-matched controls. Ovarian histology for the SHORT group all showed regular corpora lutea and minimal stromal changes, however, 3/5 mice in the LONG group lacked corpora lutea and 4/5 revealed marked stromal cell hypertrophy. Similar stromal cell changes were not seen in control mice. In conclusion, the length of time of T-induced acyclicity appears to impact the development of stromal cell hypertrophy and formation of corpora lutea even after resumption of cyclicity with similar alterations to the estrous cycles. These findings may have clinical relevance for transgender men interested in fertility, based on duration of gender-affirming T therapy. Future work will aim to separate out the respective contributions of T exposure and acyclicity to the stromal phenotype.

Studies show that a subset of transgender men desire children; however, there is a paucity of literature on the effect of gender-affirming testosterone therapy on reproductive function. In this manuscript, we will review the process of gender-affirming hormone therapy for transgender men and what is known about ovarian and uterine consequences of testosterone exposure in transgender men; draw parallels with existing animal models of androgen exposure; summarize the existing literature on parenting experiences and desires in transgender people; discuss considerations for assisted reproductive technologies and fertility preservation; and identify gaps in the literature and opportunities for further research.

Background and Objectives Breast cancer treatment can cause premature ovarian failure, yet the majority of young cancer patients do not receive adequate education about treatment effects before initiating chemotherapy. We studied the impact of an oncofertility program on access to fertility preservation. Methods An oncofertility program was initiated to foster collaboration between oncologists and reproductive endocrinologists, and to help increase access to fertility preservation. Documented conversations about fertility concerns, specialist referrals, appointments, and fertility preservation procedures were compared between breast cancer patients from 2004 to 2006, before oncofertility program initiation, and 2007–2012, after program initiation. The study included women