Cervicovaginal and Anal Self-Sampling for Human Papillomavirus Testing in a Transgender and Gender Diverse Population Assigned Female at Birth: Comfort, Difficulty, and Willingness to Use.

Purpose: Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face numerous barriers to preventive care, including for cervical cancer screening. At-home human papillomavirus (HPV) testing may expand access to cervical cancer screening for TGD people AFAB. This study assessed the perceptions of TGD individuals AFAB who self-collected cervicovaginal and anal samples. Methods: We recruited TGD individuals AFAB to collect cervicovaginal and anal specimens at home using self-sampling for HPV testing, and individuals reported their perceptions of self-sampling. Associations between demographic and health characteristics and each of comfort of use, ease of use, and willingness to use self-sampling were estimated using robust Poisson regression. Results: Of 137 consenting participants, 101 completed the sample collection and the surveys. The majority of participants reported that the cervicovaginal self-swab was not uncomfortable (68.3%) and not difficult to use (86.1%), and nearly all (96.0%) were willing to use the swab in the future. Fewer participants found the anal swab to not be uncomfortable (47.5%), but most participants still found the anal swab to not be difficult to use (70.2%) and were willing to use the swab in the future (89.1%). Participants were more willing to use either swab if they had not seen a medical professional in the past year. Conclusions: TGD individuals AFAB were willing to use and preferred self-sampling methods for cervicovaginal and anal HPV testing. Developing clinically approved self-sampling options for HPV testing could expand access to cancer screening for TGD populations.

Prevalence and Determinants of Cervicovaginal, Oral, and Anal Human Papillomavirus Infection in a Population of Transgender and Gender Diverse People Assigned Female at Birth.

Purpose: The human papillomavirus (HPV) causes cervicovaginal, oral, and anogenital cancer, and cervical cancer screening options include HPV testing of a clinician-collected sample. Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face many barriers to preventive care, including cancer screening. Self-sampling options may increase access and participation in HPV testing and cancer screening. This study estimated the prevalence of HPV in self-collected cervicovaginal, oral, and anal samples from Midwestern TGD individuals AFAB. Methods: We recruited TGD individuals AFAB for an observational study, mailing them materials to self-collect cervicovaginal, oral, and anal samples at home. We tested samples for high-risk (HR; 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and other HPV genotypes (6, 11, 66, 68, 73, 90) using a polymerase chain reaction mass array test. Prevalence ratios for HPV infection at each site as a function of participant characteristics were estimated in log-binomial models. Results: Out of 137 consenting participants, 102 completed sample collection. Among those with valid tests, 8.8% (HR = 6.6%; HPV 16/18 = 3.3%) were positive for oral HPV, 30.5% (HR = 26.8%; HPV 16/18 = 9.7%) for cervicovaginal HPV, and 39.6% (HR = 33.3%; HPV 16/18 = 8.3%) for anal HPV. A larger fraction of oral (71.4%) than anal infections (50.0%) were concordant with a cervicovaginal infection of the same type. Conclusions: We detected HR cervicovaginal, oral, and anal HPV in TGD people AFAB. It is essential that we reduce barriers to cancer screening for TGD populations, such as through the development of a clinically approved self-screening HPV test.

A Review of Animal Models Investigating the Reproductive Effects of Gender-Affirming Hormone Therapy.

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.

Differentiating gender-based reproductive concerns among adolescent and young adult cancer patients: A mixed methods study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Body image disturbances in adolescent and young adult cancer patients confronting infertility risk and fertility preservation decisions.

PURPOSE: Body image is a major psychosocial concern for all cancer patients but can affect the adolescent and young adult (AYA) population in distinct ways. Similarly, the prospect of infertility and the fertility preservation process can create additional stress during cancer treatment. Discussions regarding infertility inherently implicate the body and its reproductive function, but downstream effects on self-perception have not been previously described. The aim of this study was to explore the experiences of AYAs as they considered their risk of infertility and options for fertility preservation (FP), specifically the ways in which this impacted body image and FP decision-making. METHODS: AYA cancer patients (n = 27) aged 12-25 years whose cancer and treatment conferred risk of infertility were recruited through electronic health record query at an NCI-Designated Comprehensive Cancer Center. 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 body image were identified. RESULTS: Body image concerns, related to both physical appearance and body functioning emerged. Common concerns included anticipating change as it pertains to the body and its functions, physical discomfort, fear of judgment, and meeting expectations of the body. While these themes are broad in nature, they have been previously explored in relation to body image in general and their emergence in the oncofertility space provides guidance for further optimization of infertility and fertility preservation discussions. CONCLUSIONS: AYA cancer patients experience a multitude of body image related disturbances when faced with the possibility of infertility and fertility preservation. In identifying and exploring these themes, future opportunities for improving oncofertility practice and discussions among AYAs with a focus on body image positivity are called upon.

Impact of employer-covered planned oocyte cryopreservation on decision-making for medical training.

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.

Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy.

During peri-puberty, bone growth and the attainment peak bone mass is driven predominantly by sex steroids. This is important when treating transgender and gender diverse youth, who have become increasingly present at pediatric clinics. Analogues of gonadotropin-releasing hormone (GnRH) are commonly prescribed to transgender and gender diverse youth prior to starting gender-affirming hormone therapy (GAHT). However, the impact of GnRH agonists on long bones with the addition of GAHT is relatively unknown. To explore this, we developed a trans-masculine model by introducing either GnRHa or vehicle treatment to female-born mice at a pre-pubertal age. This treatment was followed by male GAHT (testosterone, T) or control treatment three weeks later. Six weeks after T therapy, bone quality was compared between four treatment groups: Control (vehicle only), GnRHa-only, GnRHa + T, and T-only. Bone length/size, bone shape, mechanical properties, and trabecular morphology were modulated by GAHT. Independent of GnRHa administration, mice treated with T had shorter femurs, larger trabecular volume and increased trabecular number, higher trabecular bone mineral density, and wider superstructures on the surface of bone (e.g., third trochanters) when compared to control or GnRHa-only mice. In conclusion, prolonged treatment of GnRHa with subsequent GAHT treatment directly affect the composition, parameters, and morphology of the developing long bone. These findings provide insight to help guide clinical approaches to care for transgender and gender diverse youth.

"Doing it on my own terms": Transgender and nonbinary adults' experiences with HPV self-swabbing home testing kits.

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 current 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 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.

A Mouse Model to Investigate the Impact of Gender Affirming Hormone Therapy with Estradiol on Reproduction.

Gender-affirming hormone therapy (GAHT) can help transgender and/or gender diverse (TGD) individuals achieve emobidment goals that align with their transition needs. Clinical evidence from estradiol (E)-GAHT patients indicate widespread changes in tissues sensitive to E and testosterone (T), particularly in the reproductive system. Notably, E-GAHTs effects on hormones and reproduction vary greatly between patients. With the goal of informing clinical research and practice for TGD individuals taking E, this study examines intact male mice implanted with capsules containing one of three different E doses (low 1.25 mg; mid 2.5 mg; high 5 mg), or a blank control capsule. All E-GAHT doses suppress T and follicle stimulating hormone levels while elevating E levels. Only the high E-GAHT dose significantly supresses luteinizing hormone levels. All E-GAHT doses affect epididymis tubule size similarly while seminiferous tubule morphology and bladder weight changes are dose-dependent. E-GAHT does not alter the presence of mature sperm, though E-exposed sperm have altered motility. These data represent the first evidence that mouse models offer an effective tool to understand E-GAHTs impact on reproductive health and the dose-dependent effects of this model permit examinations of diverse patient outcomes.

Prevalence and determinants of cervicovaginal, oral, and anal HPV infection in a population of transgender and gender diverse people assigned female at birth.

Introduction: HPV causes oral, cervicovaginal, and anogenital cancer, and cervical cancer screening options include HPV testing of a physician-collected sample. Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face discrimination and stigma in many healthcare settings; are believed to be a lower risk for cervical cancer by many physicians; are less likely to be up to date on preventive health care services such as pelvic health exams; and are more likely to have inadequate results from screening tests. Self-sampling options may increase access and participation in HPV testing and cancer screening. Methods: We recruited 137 TGD individuals AFAB for an observational study, mailing them a kit to self-collect cervicovaginal, oral, and anal samples at home. We tested samples for HPV genotypes 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73 and 90 using a PCR mass array test. Results: 102 participants completed the study. Among those with valid tests, 8.8% were positive for oral HPV, 30.5% were positive for cervicovaginal HPV, and 39.6% were positive for anal HPV. A large fraction of anal (50.0%) and oral (71.4%) infections were concordant with a cervicovaginal infection of the same type. Conclusions: HPV infection in TGD people AFAB may be just as high, if not higher, than in cisgender women. It is essential that we reduce barriers to cancer screening for TGD populations, such as through the development of a clinically approved self-screening HPV test.

Cervicovaginal and anal self-sampling for HPV testing in a transgender and gender diverse population assigned female at birth: comfort, difficulty, and willingness to use.

Background: Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face numerous barriers to preventive care, including for HPV and cervical cancer screening. Self-sampling options may expand access to HPV testing for TGD people AFAB. Methods: We recruited TGD individuals AFAB to collect cervicovaginal and anal specimens at-home using self-sampling for HPV testing, and individuals reported their perceptions of self-sampling. Associations between demographic and health characteristics and each of comfort of use, ease of use, and willingness to use self-sampling were estimated using robust Poisson regression. Results: The majority of the 101 participants who completed the study reported that the cervicovaginal self-swab was not uncomfortable (68.3%) and not difficult to use (86.1%), and nearly all (96.0%) were willing to use the swab in the future. Fewer participants found the anal swab to not be uncomfortable (47.5%), but most participants still found the anal swab to not be difficult to use (70.2%) and were willing to use the swab in the future (89.1%). Participants were more willing to use either swab if they had not seen a medical professional in the past year. About 70% of participants who reported negative experiences with either self-swab were still willing to use that swab in the future. Conclusions: TGD AFAB individuals were willing to use and preferred self-sampling methods for cervicovaginal and anal HPV testing. Developing clinically approved self-sampling options for cancer screening could expand access to HPV screening for TGD AFAB populations.

In vitro fertilization outcomes in a mouse model of gender-affirming hormone therapy in transmasculine youth.

OBJECTIVE: To investigate in vitro fertilization (IVF) outcomes in an adolescent transmasculine mouse model mimicking gender-affirming hormone therapy in prepubertal youth, both on testosterone (T) and after T washout. DESIGN: Experimental laboratory study using a validated mouse model. SETTING: University-based basic science research laboratory. ANIMAL(S): A total of 80 prepubertal 26-day-old C57BL/6N female mice were used in this study. INTERVENTION(S): Animals (n = 10/group) were implanted subcutaneously with gonadotropin-releasing hormone agonist at 3.6 mg or received sham surgery. After 21 days, they were implanted with silastic tubing containing either T 10 mg or placebo for 6 weeks. After 6 weeks, a group of animals were superovulated for immediate IVF, and another group had the implant removed and went through superovulation for IVF after 2 weeks (washout IVF). The total number of oocytes yielded, oocyte maturity rate, fertilization rate, and numbers of 2-cell embryos, 4-8-cell embryos, morula, blastocysts, and hatching blastocysts were recorded. RESULT(S): Testosterone treatment negatively impacted IVF outcomes in animals stimulated when receiving T, but not after T washout. Pretreatment with gonadotropin-releasing hormone agonist did not affect IVF outcomes. CONCLUSION(S): Although current T had a negative impact on IVF outcomes compared with controls, animals were still able to produce viable oocytes for fertilization and develop into blastocysts. Future efforts to study the impact of long-term T exposure on oocyte quality, especially aneuploidy rates, pregnancy outcomes, and live birth rates, are necessary.

Reproductive capacity after gender-affirming testosterone therapy.

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.

Reproductive endocrinologist and infertility specialists' knowledge, skills, behaviors, and attitudes regarding the care for transgender and gender-diverse individuals.

Objective: To investigate associations between reproductive endocrinology and infertility (REI) providers' prior training and current knowledge, skills, attitudes, and behaviors regarding fertility preservation and family building for transgender and gender-diverse (T/GD) patients. Design: The survey was distributed to members of the Society for Reproductive Endocrinology and Infertility, the REI-physician-focused professional body within the American Society for Reproductive Medicine, with additional participants recruited through snowball sampling. Results: Participants (n = 206) reported on training in T/GD care; 51% endorsed prior training. Most participants (93%) believed T/GD individuals were as fit for parenthood as cisgender individuals. Prior training was associated with an increased likelihood of offering T/GD health resources and more frequent consultations with specialist colleagues.Common barriers to providing care indicated by respondents included cost, delays in gender-affirming care, and lack of knowledge of the potential impact of hormonal interventions. Common facilitators included education and training, prior experience, and affordability of services. Conclusions: Most REI providers believed T/GD individuals are fit for parenthood and agreed that prior training facilitates care for T/GD patients. The lack of provider knowledge emerged as a barrier to care. Although training helped facilitate some components of care, systemic barriers such as the cost and variability of patient population characteristics/experiences are important considerations when serving T/GD individuals.

Reproductive late effects after hematopoietic stem cell transplant in pediatric, adolescent, and young adult cancer survivors.

Reproductive late effects after hematopoietic stem cell transplant can have a significant impact on cancer survivors' quality of life. Potential late effects include gonadal insufficiency, genital graft-versus-host disease, uterine injury, psychosexual dysfunction, and an increased risk of breast and cervical cancer in patients treated with total body irradiation. Despite guidelines, screening and treatment are not standardized among at-risk patients. Provider barriers include lack of knowledge of at-risk therapies and evidenced-based guidelines. Patient barriers include a reluctance to report symptoms and lack of awareness of treatment options. System barriers include inefficient implementation of screening tools and poor dissemination of guidelines to providers who serve as the medical home for survivors. This review guides the clinician in identifying and managing reproductive late effects after hematopoietic stem cell transplant to improve outcomes.

Impaired in vitro fertilization outcomes following testosterone treatment improve with washout in a mouse model of gender-affirming hormone treatment.

BACKGROUND: The impact of gender-affirming testosterone on fertility is poorly understood, with ovarian histopathologic studies showing variable results, some with a detrimental effect on reproductive capacity and uncertain reversibility. Assisted reproductive outcome data are restricted to small case series that lack the ability to inform clinical practice guidelines and limit fertility preservation counseling for transgender and nonbinary individuals. OBJECTIVE: This study aimed to determine the impact of current testosterone and testosterone washout on in vitro fertilization outcomes in a mouse model for gender-affirming hormone treatment. We hypothesized that current or previous testosterone treatment would not affect in vitro fertilization outcomes. STUDY DESIGN: C57BL/6N female mice (n=120) were assigned to 4 treatment groups: (1) current control, (2) current testosterone, (3) control washout, and (4) testosterone washout. Testosterone implants remained in situ for 6 or 12 weeks, representing the short- and long-term treatment arms, respectively. Current treatment groups underwent ovarian stimulation with implants in place, and washout treatment groups were explanted and had ovarian stimulation after 2 weeks. Oocytes were collected, fertilized, and cultured in vitro, with one arm continuing to the blastocyst stage and the other having transfer of cleavage-stage embryos. Statistical analysis was performed using GraphPad Prism, version 9.0 and R statistical software, version 4.1.2, with statistical significance defined by P<.05. RESULTS: Current long-term testosterone treatment impaired in vitro fertilization outcomes, with fewer mature oocytes retrieved (13.7±5.1 [standard deviation] vs 28.6±7.8 [standard deviation]; P<.0001) leading to fewer cleavage-stage embryos (12.1±5.1 vs 26.5±8.2; P<.0001) and blastocysts (10.0±3.2 vs 25.0±6.5; P<.0001). There was recovery of in vitro fertilization outcomes following washout in the short-term treatment cohort, with incomplete reversibility in the long-term cohort. Testosterone did not negatively affect maturity, fertilization, or blastulation rates. CONCLUSION: In a mouse model of gender-affirming hormone treatment, testosterone negatively affected oocyte yield without affecting oocyte quality. Our findings suggest that testosterone reversibility is duration-dependent. These results demonstrate the feasibility of in vitro fertilization without testosterone discontinuation while supporting a washout period for optimization of mature oocyte yield.

Fertility assessment and treatment in adolescent and young adult cancer survivors.

In the survivorship setting, adolescent and young adult (AYA) cancer survivors frequently demonstrate little knowledge of infertility risk, are unclear regarding their fertility status, and may under- or overestimate their treatment-related risk for infertility. In female AYA survivors, ovarian function usually parallels fertility, and can be assessed with serum hormone levels and ultrasonography. Posttreatment fertility preservation may be appropriate for survivors at risk for primary ovarian insufficiency. In male AYA survivors, fertility and gonadal function are not always equally affected, and can be assessed with a semen analysis and serum hormones, respectively. As reproductive health issues are commonly cited as an important concern by survivors of AYA cancer, multidisciplinary care teams including oncology, endocrinology, psychology, and reproductive medicine are advocated, with the aim of optimal provision of fertility advice and care for AYA cancer survivors.

Determining the Sex Assigned at Birth of Transgender and Nonbinary Populations in Administrative Claims Databases Utilizing Diagnostic and Procedure Codes.

Purpose: Widespread conflation of sex assigned at birth and gender has hindered the identification of transgender and nonbinary people in large datasets. The study objective was to develop a method of determining the sex assigned at birth of transgender and nonbinary patients utilizing sex-specific diagnostic and procedural codes, for future use in administrative claims databases, with a goal of expanding the available datasets for exploring sex-specific conditions among transgender and nonbinary people. Methods: Authors reviewed indexes of International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes, and medical record data from a single institution's gender-affirming clinics. Sex-specific ICD and CPT codes were identified through author review and consultation with subject experts. Patient's sex assigned at birth determined by chart review, as a gold standard, was compared with sex assigned at birth determined by querying their electronic health records for natal sex-specific codes. Results: Sex-specific codes correctly identified 53.5% (n=364) of transgender and nonbinary patients assigned female sex at birth, and 17.3% (n=108) of those assigned male sex at birth. Codes were 95.7% and 98.3% specific for assigned female and male sex at birth, respectively. Conclusions: ICD and CPT codes can be used to specifically determine the sex assigned at birth in databases where this information is not recorded. This methodology has novel potential for use in exploring sex-specific conditions among transgender and nonbinary patients in administrative claims data.

Presence of ovarian stromal aberrations after cessation of testosterone therapy in a transgender mouse model†.

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.

Banking on Fertility Preservation: Financial Concern for Adolescent and Young Adult Cancer Patients Considering Oncofertility Services.

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).