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Transgender and nonbinary people with female birth sex may utilize testosterone therapy for masculinization. Individuals interested in reproduction using their own gametes should be offered fertility preservation prior to starting testosterone. However, logistical and practical barriers prevent many from accessing fertility preservation options prior to starting testosterone. Some of these transmasculine and nonbinary individuals may later become interested in carrying a pregnancy or using their oocytes for reproduction after being on testosterone. Many questions remain about the reproductive impact of long-term masculinizing testosterone therapy. Emerging literature has documented pregnancies and successful assisted reproduction for some people after taking testosterone, but it is not known whether individuals can expect these successful outcomes. Testosterone appears to impact the reproductive tract, including the ovaries, uterus, and fallopian tubes, but the reversibility and functional impact of these changes also remain unclear. A greater understanding of the impact of masculinizing testosterone on reproductive capacity remains a priority area for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a single session of psychosocial counseling on patients with vulvodynia. Methods: 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. Results: 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). Conclusion: 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. Synopsis: A single one‐on‐one psychosocial counseling session for patients with vulvodynia improves their understanding of their vulvar symptoms and lessens the emotional impact of their illness. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to describe the multidisciplinary approach and controlled ovarian hyperstimulation (COH) outcomes in adolescent and young adult (AYA) patients (ages 13–21) who underwent oocyte cryopreservation for fertility preservation (FP). Methods: Multi-site retrospective cohort was performed from 2007 to 2018 at Northwestern University and Michigan University. Data were analyzed by chi-square test, t-test, and logistic regression. Results: Forty-one patients began COH of which 38 patients successfully underwent oocyte retrieval, with mature oocytes obtained and cryopreserved without any adverse outcomes. To treat this group of patients, we use a multidisciplinary approach with a patient navigator. When dividing patients by ages 13–17 vs. 18–21, the median doses of FSH used were 2325 and 2038 IU, the median number of mature oocytes retrieved were 10 and 10, and median number frozen oocytes were 11 and 13, respectively. Median days of stimulation were 10 for both groups. There was no statistical difference in BMI, AMH, peak E2, FSH dosage, days stimulated, total oocytes retrieved, mature oocytes retrieved, and oocytes frozen between the two groups. Three patients were canceled for poor response. Conclusion: COH with oocyte cryopreservation is a feasible FP option for AYAs who may not have other alternatives when appropriate precautions are taken, such as proper counseling and having a support team. These promising outcomes correspond to similar findings of recent small case series, providing hope for these patients to have genetically related offspring in the future. [ABSTRACT FROM AUTHOR]

Gender-affirming hormone therapy (GAHT) is an important component in the process of transitioning for many transgender and gender-diverse (TGD) individuals. Multiple medical organizations recommend fertility preservation counseling prior to initiation of GAHT; however, there remains little high-quality data regarding the impact of GAHT on fertility and reproductive function. A PubMed literature review was performed using Boolean search operators linking keywords or phrases such as "mouse", "rat", "primate", "animal model", "transgender", "gender", "estrogen", "testosterone", "fertility", and "fertility preservation". Recent research has produced a number of animal models of GAHT that utilize similar hormonal regimens and produce similar phenotypic results to those used and observed in human patients. Specific to testosterone(T)-containing GAHT, animals demonstrate loss of menstrual cyclicity with therapy, resumption of menses on cessation of therapy, suppression of gonadotropin levels, and physical changes such as clitoromegaly. Models mimicking GAHT for transmasculine individuals in the peripubertal period demonstrate that pretreatment with GnRHa therapy does not modify the effects of subsequent T administration, which were similar to those described in adult models. Both models suggest promising potential for future fertility with cessation of T. With estradiol (E)-containing GAHT, animals exhibit decreased size of testicles, epididymis, and seminal vesicles, as well as ongoing production of spermatocytes, and seminiferous tubule vacuolization. Given the ethical challenges of conducting human studies in this area, high-fidelity animal models represent a promising opportunity for investigation and could eventually transform clinical counseling about the necessity of fertility preservation. Future studies should better delineate the interactions (if any exist) between treatment attributes such as dosing and duration with the extent of reversibility of reproductive perturbations. The development of models of peripubertal feminizing GAHT is an additional area for future work. [ABSTRACT FROM AUTHOR]

Purpose: To characterize how employer coverage of planned oocyte cryopreservation (POC) might impact medical career decision-making. Methods: A cross-sectional survey was distributed to all medical students at two large academic programs in December 2022 to better understand attitudes towards childbearing, POC, and how employer coverage of POC might influence future career decisions. Results: Of the 630/1933 (32.6%) medical students who participated, 71.8% identified as women and 28.1% as men. More women (89.2%) than men (75.1%, P < 0.001) felt pressure to delay childbearing. Regarding childbearing, women more than men were concerned about the physical demand of residency (76.5% vs. 50.8%, P < 0.001), stigma in residency hiring practices (41.2% vs. 9.0%, P < 0.001), and parental leave interfering with team dynamics (49.6% vs. 20.9%, P < 0.001). Respondents were more likely to pursue POC if it were covered by residency employer health insurance (60.0% vs. 11.6%, P < 0.001). Women were more likely than men to state that employer-sponsored POC would influence their residency ranking (46.0% vs. 23.7%, P < 0.001), pursuit of additional degrees (50.9% vs. 30.5%, P < 0.001), and pursuit of fellowship training (50.9% vs. 30.5%, P < 0.001). Additionally, 25.4% of women and 19.8% of men felt their choice in medical specialty would be impacted by employer-sponsored POC. Conclusions: Medical students, particularly women, feel pressure to delay childbearing during medical training and are concerned about future fertility. Both male and female students were interested in employer-sponsored POC and more likely to pursue it with financial coverage. Further research is needed to determine the full impact of employer-sponsored POC on medical career decision-making. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To compare long-term outcomes of cancer patients who pursued fertility preservation (FP) with those who did not and compare random-start (RS) and menstrual cycle-specific (CS) protocols for FP.Design: Retrospective cohort.Setting: Single urban academic institution.Patient(s): Oncology patients who contacted the FP patient navigator, 2005-2015.Intervention(s): None.Main Outcome Measure(s): Time to cancer treatment, disease-free survival, and reproductive outcomes in FP versus no-FP patients and cycle outcomes for RS versus CS protocols. Data were analyzed by χ2 and logistic regression.Result(s): Of 497 patients who met the inclusion criteria, 41% elected FP. The median number of days to cancer treatment was 33 and 19 days in the FP and no-FP groups, respectively. There was no difference in cancer recurrence or mortality. There were no differences in stimulation parameters, outcomes, or days to next cancer treatment in RS versus CS protocols. Twenty-one patients returned to use cryopreserved specimens, resulting in 16 live births. Eight of 21 returning patients used a gestational carrier. Thirteen FP (6.4%) and 16 no-FP (5.5%) patients experienced a spontaneous pregnancy.Conclusion(s): FP is both safe and efficacious for eligible cancer patients. Only 10% of patients returned to use cryopreserved specimens, and almost half used a gestational carrier, suggesting the need for further research into reproductive decision-making in cancer survivors. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas (fibroids) represent the most common class of benign tumors in women. Multiple leiomyomas usually arise from the uterus of a symptomatic woman. These tumors cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are responsible for more than 200,000 hysterectomies in the United States annually. Each leiomyoma seems to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a mutation. Tumor expansion is sustained by cell proliferation together with the production of large amounts of extracellular matrix. Estrogen and progesterone stimulate the growth of leiomyomas. Estrogen, together with its receptor ERa, enables progesterone action via induction of progesterone receptor (PR) expression. Progesterone induces the growth of leiomyoma by regulation of a set of key genes that control proliferation and apoptosis. A distinct cell population with stem-progenitor properties is indispensable for progesterone-dependent growth of leiomyomas. This stem-progenitor cell population is deficient in ERa and PR and dependent on the much higher levels of these steroid receptors in surroundingmature leiomyoma ormyometrial cells. Progesterone sends paracrine signals from these mature cells to stem cells. The WNT/β-catenin pathway comprises a key component of this paracrine signaling system. The majority of medical treatments currently available for leiomyoma works by inhibiting estrogen or progesterone production or action, but tumors tend to regrow once treatment is stopped. Targeting stem cells and their paracrine interactions with more differentiated cell populations within leiomyoma may lead to the development of more effective therapeutics. [ABSTRACT FROM AUTHOR]

Background: Uterine leiomyoma is the most common benign tumor in women and is thought to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a cellular insult. Leiomyomas cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are the most common indication for hysterectomy in the USA. A slow rate of cell proliferation, combined with the production of copious amounts of extracellular matrix, accounts for tumor expansion. A common salient feature of leiomyomas is their responsiveness to steroid hormones, thus providing an opportunity for intervention.Methods: A comprehensive search of PUBMED was conducted to identify peer-reviewed literature published since 1980 pertinent to the roles of steroid hormones and somatic stem cells in leiomyoma, including literature on therapeutics that target steroid hormone action in leiomyoma. Reviewed articles were restricted to English language only. Studies in both animals and humans were reviewed for the manuscript.Results: Estrogen stimulates the growth of leiomyomas, which are exposed to this hormone not only through ovarian steroidogenesis, but also through local conversion of androgens by aromatase within the tumors themselves. The primary action of estrogen, together with its receptor estrogen receptor α (ERα), is likely mediated via induction of progesterone receptor (PR) expression, thereby allowing leiomyoma responsiveness to progesterone. Progesterone has been shown to stimulate the growth of leiomyoma through a set of key genes that regulate both apoptosis and proliferation. Given these findings, aromatase inhibitors and antiprogestins have been developed for the treatment of leiomyoma, but neither treatment results in complete regression of leiomyoma, and tumors recur after treatment is stopped. Recently, distinct cell populations were discovered in leiomyomas; a small population showed stem-progenitor cell properties, and was found to be essential for ovarian steroid-dependent growth of leiomyomas. Interestingly, these stem-progenitor cells were deficient in ERα and PR and instead relied on the strikingly higher levels of these receptors in surrounding differentiated cells to mediate estrogen and progesterone action via paracrine signaling.Conclusions: It has been well established that estrogen and progesterone are involved in the proliferation and maintenance of uterine leiomyoma, and the majority of medical treatments currently available for leiomyoma work by inhibiting steroid hormone production or action. A pitfall of these therapeutics is that they decrease leiomyoma size, but do not completely eradicate them, and tumors tend to regrow once treatment is stopped. The recent discovery of stem cells and their paracrine interactions with more differentiated cell populations within leiomyoma has the potential to provide the missing link between developing therapeutics that temper leiomyoma growth and those that eradicate them. [ABSTRACT FROM AUTHOR]

Objective. Many women with endometriosis experience significant delay between the onset of symptoms and definitive diagnosis. Much is published on physician awareness of endometriosis and on the experiences of women with the condition. There is a paucity of data, however, surrounding perceptions of endometriosis in the general population. This study aims to assess knowledge of endometriosis among individuals of both genders. Design. Survey study. Setting. Family waiting room of a large university hospital. Population. A total of 543 men and women. Methods. Surveys were distributed to men and women over the age of 18 in the family waiting room of a large university hospital. Main outcome measures. A series of questions regarding the etiology, symptoms, and treatments for endometriosis were combined into a composite knowledge score. Results. Knowledge of endometriosis was positively correlated with female gender, education level, regular health care, and exposure to individuals with the disease. Women diagnosed with endometriosis were more likely to have discussed symptoms of the condition with their physicians than women without the diagnosis. Conclusions. Individuals of both genders have limited knowledge of the signs and symptoms of endometriosis, which may contribute to the delay in diagnosis of the condition. [ABSTRACT FROM AUTHOR]

Background: Current medical therapies for endometriosis result in delayed conception and have not been shown to provide any fertile benefit subsequent to treatment. Thiazolidinediones (TZDs) do not impede conception and have been shown to reduce endometriotic lesions in animal models; however, no studies have been performed in humans. The aim of this study was to provide preliminary data about the effectiveness of a TZD in treating endometriosis-related pain.Methods: Case series of women with endometriosis recruited from the University of Michigan as part of an open-label prospective phase 2a clinical trial. Participants were given rosiglitazone, 4 mg daily, for 6 months. Subjective endometriosis symptoms were assessed using a modified Biberoglu and Behrman symptom severity scale and the McGill pain questionnaire.Results: Two of the 3 patients exhibited improvement in severity of symptoms and pain levels with a concurrent decrease in pain medication, while 1 experienced no change. Rosiglitazone was well tolerated by all patients.Conclusions: Combined with data gathered from studies in rats and nonhuman primates, the results from this study offer positive justification for using TZDs as a well-tolerated treatment for endometriosis that can address pain without impeding ovulation and without the need for add-back therapy. [ABSTRACT FROM AUTHOR]

Few studies have examined the distinct reproductive concerns (RC) of men and women in the adolescent and young adult (AYA) cancer patient population. The purpose of this mixed-methods study was to explore and differentiate the RC of AYAs. Participants completed the Reproductive Concerns After Cancer (RCAC) scale and participated in a semistructured interview. Interviews were deductively coded based on an analytic schema derived from the RCAC. After identifying participants through the electronic health record, 27 younger AYAs, ages 12–25, enrolled in the study. Four inductive themes emerged and differed by gender. These include differential temporality, acceptance, and openness to alternatives, partner influence, and parental/guardian influence. AYA men reported fewer RC (M = 49.4, SD = 9.6) compared to AYA women (M = 56.8, SD = 8.4). Oncofertility care providers are advised to account for short- and long-ranging concerns based on AYAs' gender. Future evaluations of patient-reported outcome measures specific to AYA RC are recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Financial concern is a major issue for adolescent and young adult (AYA) cancer patients. Furthermore, unaddressed oncofertility challenges (e.g., infertility) are linked to psychological distress and decreased overall quality of life. Little is known about how financial concern in terms of oncofertility (i.e., concern regarding affording fertility preservation [FP] services) impacts AYAs' decision making and experiences. Methods: AYA cancer patients (n = 27) aged 12–25 years whose cancer treatment conferred risk of infertility were recruited through electronic health record query. Participants completed semi-structured interviews, which were recorded, transcribed, and deductively coded for themes related to information needs, knowledge of treatment effects on fertility, and reproductive concerns after cancer. Emergent, inductive themes related to financial concern were identified. The Institutional Review Board at the University of Michigan approved this study (HUM#00157267). Results: Financial concern was a dominant theme across the qualitative data. Emergent themes included (1) varied access to health insurance, (2) presence of parental/guardian support, (3) reliance upon financial aid, (4) negotiating infertility risk, and (5) lack of preparation for long-term costs. AYAs relied heavily upon parents for out-of-pocket and insurance coverage support. Some participants sought financial aid when guided by providers. Several participants indicated that no financial support existed for their circumstance. Conclusions: Financial consequences in terms of oncofertility are a major issue affecting AYA cancer patients. The incidence and gravity of financial concern surrounding affording oncofertility services merits attention in future research (measuring financial resources of AYAs' parental/support networks), clinical practice (strategically addressing short- and long-term costs; tailored psychosocial support), and health care policy (promoting legislation to mandate pre- and post-treatment FP coverage). [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) carries a significant health risk for people with a cervix. Among transgender and nonbinary people, however, testing and treatment for HPV can pose difficulties and even be traumatic at times. This study is part of a larger mixed-methods study conducted in Michigan in 2020, and it explores the experiences of transmasculine and nonbinary people with at-home self-swabbing HPV test kits and knowledge of HPV transmission/screenings. Phenomenological qualitative methods were used by conducting virtual qualitative interviews with ten transmasculine and nonbinary individuals with cervixes, ages 23–59. Interviews were independently coded by members of the research team and a tabletop theming method was used. Four themes were generated from the data: (1) multilevel barriers; (2) "get it done, so I know that I am safe"; (3) contrasting preferences for care; and (4) community calls for change. The discussion focuses on the implications of these findings for improving sexual health care for the transgender and nonbinary community, along with directions for further research. [ABSTRACT FROM AUTHOR]

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  < 0.0001) and ovarian weights (P  = 0.0002), and a lack of CL at 21 days after GnRHa implantation. T-only and GnRHa+T-treated animals were acyclic throughout the treatment period, had sustained elevated levels of T, suppressed LH levels (P  < 0.0001), and an absence of CL compared to controls (P  < 0.0001). Paired ovarian weights were reduced in the T-only and GnRHa+T groups compared with the control and GnRHa-only groups. 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. [ABSTRACT FROM AUTHOR]

Objective: To determine the implications of an incidentally noted subchorionic hematoma on pregnancy outcomes in the infertile population. Methods: 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. Results: 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. Conclusion: 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. Subchorionic hematomas noted incidentally are not associated with an increased miscarriage risk in the infertile population unless patients present with both bleeding and cramping. [ABSTRACT FROM AUTHOR]

Objective: Gender-affirming hormones (GAH)—the use of sex hormones to induce desired secondary sex characteristics in transgender individuals—is vital healthcare for many transgender people. Among prescribers of GAH, there is debate regarding the value of a universal requirement for an evaluation by a mental health provider prior to GAH initiation. The purpose of this qualitative study was to describe the range of attitudes and approaches to mental health evaluation among GAH providers in the United States. We analyzed the providers' attitudes and base our recommendations on this analysis. Methods: We conducted semi-structured interviews with 18 healthcare providers who prescribe GAH across the United States. Participants were purposefully recruited using professional networks and snowball sampling to include those who require mental health evaluation and those who do not. We adapted domains from the Theoretical Domains Framework—a framework for understanding influences on health professional behavior—to inform the interviews and analysis. Guided by these domains, we iteratively coded text and identified theoretical relationships among the categories. Results: While some felt a universal requirement for mental health "clearance" was necessary for the identification of appropriate candidates for GAH, others described this requirement as a form of "gatekeeping" that limits access to care. Themes we identified included providers' ability to ascertain gender identity; concern about mental illness; GAH provider and mental health provider expertise; and provider roles. All providers appreciated the potential advantages of mental health support during GAH treatment. Conclusion: Providers in our study practice on a continuum of care rather than adhering to strict rules about the requirement for mental health evaluation prior to GAH treatment. Where they fall on this continuum is influenced primarily by their perceptions of transgender identity and transition, and their interpretation of risk for significant mental illness and its association with transness. Providers who required universal evaluation by a mental health professional tended to hold essentialist, medicalized, and binary ideas of gender and transness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine use of and attitudes toward complementary and alternative medicine (CAM) among infertility patients and subspecialty physicians. Methods: Infertility patients were asked to complete anonymous written surveys at an academic infertility practice; members of the Society for Reproductive Endocrinology and Infertility were electronically surveyed. Both groups were assessed regarding their use of and attitudes toward CAM. Results: The response rate was 32.1% (115/358) among patients and 22.6% (225/995) among physicians (P <0.05). In total, 105 (91.3%; 95% confidence interval [CI], 85.8–96.2) patients used CAM, and 84 (73.0%; 95% CI, 64.9–81.1) regarded it as beneficial to their fertility treatment. However, only 30 (26.1%; 95% CI, 18.0–34.0) patients reported CAM use to physicians, with the most common reason being that they were “never asked.” Overall, 202 (89.8%; 95% CI, 85.9–93.8) physicians reported inquiring about CAM. Conclusion: Significant discrepancies exist between subfertile patients and physicians in attitudes toward the use of CAM. The current prevalence of CAM use among infertility patients requires greater physician attention and justifies further study on the risks and benefits of integrating CAM into the biomedical treatment of infertility. [Copyright &y& Elsevier]

Abstract: Background: The use of complementary and alternative medicine (CAM) by patients and physicians has increased markedly in recent years. Many case reports, case series, and uncontrolled trials of varying quality have been completed; however, there is now a slowly increasing number of randomized controlled trials (RCTs) examining the use of CAM. Objectives: To identify, survey, and review RCTs investigating the use of CAM for infertility treatment. Search strategy: The MEDLINE and Cochrane databases were electronically searched. Selection criteria: RCTs examining modalities for treatment or improvement of health status were reviewed. Data collection and analysis: RCTs were included based on use of objective measures, articles written in English, availability through the University of Michigan database, and clear published clinical outcomes. Main results: Thirty-seven articles assessing a variety of CAM modalities met inclusion criteria. Acupuncture, selenium supplementation, weight loss, and psychotherapeutic intervention had 3 or more studies demonstrating beneficial effect. Other interventions had been studied less and evidence for them was limited. Conclusions: Although there is preliminary evidence of the effectiveness of some CAM interventions among infertile patients, many of these interventions require further investigation before they can be considered for routine clinical use. [Copyright &y& Elsevier]

Purpose: The main objective of Repro-Can-OPEN Study Part 2 is to learn more about oncofertility practices in optimum resource settings to provide a roadmap to establish oncofertility best practice models. Methods: As an extrapolation for oncofertility best practice models in optimum resource settings, we surveyed 25 leading and well-resourced oncofertility centers and institutions from the USA, Europe, Australia, and Japan. The survey included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. Results: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed three major characteristics of oncofertility practice in optimum resource settings: (1) strong utilization of sperm freezing, egg freezing, embryo freezing, ovarian tissue freezing, gonadal shielding, and fractionation of chemo- and radiotherapy; (2) promising utilization of GnRH analogs, oophoropexy, testicular tissue freezing, and oocyte in vitro maturation (IVM); and (3) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, in vitro spermatogenesis, and stem cell reproductive technology as they are still in preclinical or early clinical research settings. Proper technical and ethical concerns should be considered when offering advanced and experimental oncofertility options to patients. Conclusions: Our Repro-Can-OPEN Study Part 2 proposed installing specific oncofertility programs for common cancers in optimum resource settings as an extrapolation for best practice models. This will provide efficient oncofertility edification and modeling to oncofertility teams and related healthcare providers around the globe and help them offer the best care possible to their patients. [ABSTRACT FROM AUTHOR]

Objective: To examine whether F2-isoprostanes, a marker of systematic oxidative stress, are associated with antimüllerian 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.0001). Those who supported upper BMI restrictions were more likely to be female and report existing institutional BMI cutoffs. The majority of respondents (99.3%) believed that an official statement to guide clinicians should be issued by a national professional organization. Conclusions: Although practice patterns widely vary, the majority of REIs and MFMs believe that there should be a BMI cutoff above which women should not be offered immediate fertility treatment. Furthermore, there is a reported need for a written statement by a national professional organization to guide clinical practice and to ensure that OB/GYN subspecialists are providing consistent, fair, and safe recommendations to infertile women at the extremes of BMI. [ABSTRACT FROM AUTHOR]

The article focuses on a retrospective chart review of lymphoma patients who underwent fertility preservation (FP). The review aims to evaluate differences in time to treatment (TTT) associated with FP. It examines the impact of FP on treatment delay and progression-free survival in women with lymphoma.

• Compared the release dynamics of three different delivery methods of subcutaneous testosterone administration. • The body's overall exposure to T seems similar across administration methods for T enanthate. • Pellets and silastic tubing allow for quick return to baseline T levels and regular estrous cyclicity. • Silastic implants can be used for long-term elevation in T levels. 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. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas are extremely common estrogen and progesterone-dependent tumors of the myometrium and cause irregular uterine bleeding, severe anemia, and recurrent pregnancy loss in 15-30% of reproductive-age women. Each leiomyoma is thought to arise from a single mutated myometrial smooth muscle stem cell. Leiomyoma side-population (LMSP) cells comprising 1% of all tumor cells and displaying tumor-initiating stem cell characteristics are essential for estrogen- and progesterone-dependent in vivo growth of tumors, although they have remarkably lower estrogen/progesterone receptor levels than mature myometrial or leiomyoma cells. However, how estrogen/progesterone regulates the growth of LMSP cells via mature neighboring cells is unknown. Here, we demonstrate a critical paracrine role of the wingless-type (WNT)/β-catenin pathway in estrogen/progesterone-dependent tumorigenesis, involving LMSP and differentiated myometrial or leiomyoma cells. Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues. In LMSP cells cocultured with mature myometrial cells, estrogen-progesterone selectively induced nuclear translocation of β-catenin and induced transcriptional activity of its heterodimeric partner T-cell factor and their target gene AXIN2, leading to the proliferation of LMSP cells. This effect could be blocked by a WNT antagonist. Ectopic expression of inhibitor of β-catenin and T-cell factor 4 in LMSP cells, but not in mature leiomyoma cells, blocked the estrogen/progesterone-dependent growth of human tumors in vivo. We uncovered a paracrine role of the WNT/β-catenin pathway that enables mature myometrial or leiomyoma cells to send mitogenic signals to neighboring tissue stem cells in response to estrogen and progesterone, leading to the growth of uterine leiomyomas. [ABSTRACT FROM AUTHOR]