Evidence of Spermatogenesis in the Presence of Hypothalamic Suppression and Low Testosterone in an Adolescent Transgender Female: A Case Report.

Objective: To report a novel case of semen cryopreservation after testicular sperm extraction in an adolescent transgender female without cessation of gonadotropin-releasing hormone (GnRH) agonist therapy and feminizing hormone therapy. Methods: This is a case report of a 16-year-old transgender female using leuprolide acetate for 4 years and estradiol for 3 years requesting semen cryopreservation at the time of gender-affirming orchiectomy. She desired to proceed without cessation of gender affirming hormone therapy. The patient's consent was obtained for written publication. Results: The patient underwent testicular sperm extraction followed by orchiectomy. The sample was processed and cryopreserved in a 1:1 Test Yolk Buffer. Multiple early and late spermatids were identified as well as spermatagonium in the TESE specimen. Conclusions: Advanced spermatogenesis may occur in the presence of a GnRH agonist. Cessation of GnRH agonist therapy may not be essential for semen cryopreservation in adolescent transgender females.

Exploratory cohort study into underlying mechanism of differences in estrogen metabolism between Asian and Caucasian women during assisted reproductive technology treatment.

Objective: Explore whether racial differences in prevalence of CYP1A2∗1F polymorphism underlies estrogen metabolism differences among Asians and Caucasians. Design: Prospective cohort study. Setting: University-based fertility practice. Patients: Asian or Caucasian patients who underwent ovarian stimulation (OS) or programmed cycle frozen embryo transfer (FET) between October 2019 and April 2021. Interventions: None. Main Outcome Measures: Trigger-day serum E2 per oocyte retrieved in OS cycles, and E2 on day of lining check in FET cycles. Results: Seventy-one participants were enrolled, 55 in OS group (29 Caucasian and 26 Asian) and 16 in FET group (10 Caucasian and 6 Asian). Peak E2 per oocyte retrieved in the OS group (n = 48) differed by race, with significantly lower levels in Caucasians compared with Asians (177.5 ± 64.2 vs. 261.1 ± 139.5 pg/mL). Prevalence of CYP1A2∗1F polymorphism did not significantly differ by race. Compared using Kruskal-Wallis test, peak E2 per oocyte retrieved did not differ by CYP1A2∗1F genotype. In multivariate linear regression model, adjusting for body mass index, caffeine intake, and self-reported race, there remained no significant correlation. In FET group, serum E2 on day of lining check was also not significantly different by CYP1A2∗1F genotype. Conclusions: Although a consistent difference in serum E2 between Asians and Caucasians undergoing OS was noted, the CYP1A2∗1F polymorphism is unlikely the primary driver of this difference.

Hidden trauma: shedding light on the relationship between gun violence and infertility.

Objective: To study the existing data on the relationship between penetrating abdominopelvic injuries and fertility guidance on managing fertility concerns of these patients using a case report and scoping review. Design: Case report and scoping review. Setting: Not applicable. Patients: People who have experienced abdominopelvic trauma from gun violence or in the course of combat. Interventions: None. Main Outcome Measures: We extracted case report data from electronic health records. We performed a scoping review using PubMed and Scopus. Search terms were related to penetrating abdominopelvic trauma, gunshot wounds (GSW), war, and fertility/infertility. We evaluated the study year, age and race, mechanism of injury, fertility outcomes, and how fertility concerns were addressed with patients who experienced penetrating abdominopelvic trauma. Results: In the case report, the couple had 10 years of infertility. The male partner experienced an abdominopelvic GSW before attempting to conceive. After evaluation, he was diagnosed with retrograde ejaculation. He recalled being advised that his GSW might affect his future fertility. The couple has discontinued care.For the scoping review, 879 sources were identified and 25 studies were included in the review. Among the studies conducted in the United States, most patients included were African American.Eighty-eight percent (n = 22) of the sources acknowledged the importance of fertility or used fertility-related outcome measures. One study commented on how to address fertility concerns with victims of abdominopelvic penetrating trauma. Conclusions: There is a paucity of data on the intersection of penetrating abdominopelvic injuries and fertility or guidance on how to discuss fertility issues with patients.

Learning from Online Video Education (LOVE) improves confidence in fertility treatments: a randomized controlled trial.

Fertility treatments like in vitro fertilization (IVF) or oocyte cryopreservation (OC) require the daily use of injectable gonadotropins and has been associated with treatment burden and attrition from fertility treatment. We conducted a randomized clinical trial to determine (1) whether educational videos about fertility medications improved infertility self-efficacy scale (ISES), fertility quality of life treatment (FertiQoL-T), and Perceived stress scale (PSS) scores and (2) if such videos improved confidence and reduced medication errors during a first ovarian stimulation cycle. Participants were given access to an online portal with randomized access to either placebo control videos focused on an orientation to IVF or experimental videos that reviewed the preparation and administration of medications used during ovarian stimulation in addition to the placebo videos. Participants completed pre and post-treatment questionnaires. 368 patients enrolled and 257 participants completed the study. There were no differences in ISES, FertiQoL-T or PSS scores between the two groups in an intention-to-treat (p = 0.18, 0.72, and 0.92, respectively) or per-protocol analysis (p = 0.11, 0.38, and 0.37, respectively). In the per protocol analysis, participants who watched experimental videos were four-fold more likely to report confidence administering medications OR 4.70 (95% CI: 2.10, 11.1; p < 0.01) and were 63% less likely to make medication errors OR 0.37 (95% CI: 0.14, 0.90; p = 0.03). Participants had similar likelihoods of rating videos as helpful and recommending videos to others (p = 0.06 and 0.3, respectively). Educational videos about fertility medications may not influence psychological well-being but might improve confidence in medication administration and reduce medication errors. Trial registration number: NCT02979990.

Primary ovarian insufficiency secondary to chemotherapy with inotuzumab ozogamicin and other agents.

Recent advances in targeted therapy with monoclonal antibodies have significantly improved outcomes for people with cancer, sometimes allowing patients to avoid ovotoxic agents altogether. The current understanding is that monoclonal antibody cancer therapies that are not targeted to ovarian antigens should not impact ovarian reserve or increase the risk of primary ovarian insufficiency (POI). We present a case of rapid onset POI in a 23-year-old patient following chemotherapy for relapse/refractory B-cell acute lymphoblastic leukemia with a monoclonal antibody drug-conjugate, inotuzumab ozogamicin, that targets CD22. She was also treated with intrathecal methotrexate, cytarabine, and vincristine which are typically considered low risk for ovotoxicity. She was ovulatory with an AMH of 1.0 ng/mL prior to treatment and 2 months later was found to have an undetectable AMH. The patient experienced a canceled fertility preservation cycle due to an absent response to gonadotropins during ovarian stimulation. Consideration should be given to potential gonadal effects of monoclonal antibody therapies that may not have previously been explored.

Minding the gender gap in fertility: The rationale, obstacles, and strategies to improve utilization of fertility preservation.

The aim of this commentary is to describe the sex differences in reproductive capacity and specifically the decline in oocyte quality and quantity with advancing age. Furthermore, the use of oocyte vitrification as a strategy to circumvent ovarian aging is discussed, as are disparities in access to fertility preservation.

Considering race in the administration of fertility preservation. A commentary on: "Equal opportunity for all? An analysis of race and ethnicity in fertility preservation in a major American city".

Studies that focus on disparities in care should aim to discern differences both within their communities and also among larger populations to improve the applicability of important findings. Such work should attempt to discern what factors may be influential in creating or contributing to racial inequities.

Differences in perceived stress during ovarian stimulation between women with infertility and those pursing oocyte cryopreservation.

OBJECTIVE: To determine whether the purpose of ovarian stimulation (oocyte cryopreservation [OC] versus in vitro fertilization (IVF) is associated with perceived stress before or after ovarian stimulation; and whether perceived stress is associated with ovarian stimulation outcomes. DESIGN: Prospective cohort study. SETTING: Academic practice. PATIENTS: Women undergoing their first ovarian stimulation cycle as part of a randomized clinical trial, the Learning from Online Video Education (LOVE) study (NCT02979990). INTERVENTIONS: Questionnaire before and after ovarian stimulation. MAIN OUTCOME MEASURES(S): Perceived stress scale (PSS) scores before and after stimulation. The number of oocytes collected was a secondary measure. RESULTS: After adjustment for age, income, race, education, financial assistance, and fertility diagnosis, the indication for treatment (IVF vs. OC) was a significant predictor of pretreatment PSS scores. IVF participants had higher pretreatment scores (18.01 ± 6.43) than did OC participants (15.62 ± 5.61). Posttreatment PSS scores did not differ between the two groups. IVF participants experienced a decrease of 0.85 ± 2.34 points in PSS scores after treatment, whereas OC participant scores were stable over time. The trajectory of PSS scores differed between the two groups and neared significance. Financial support was a significant predictor of pretreatment and posttreatment PSS scores for the entire cohort. Neither pretreatment nor posttreatment PSS was predictive of the number oocytes collected. CONCLUSION: Compared with OC patients, IVF patients have higher stress levels, which decrease after ovarian stimulation. Perceived stress does not affect oocyte yield.

Ovarian stimulation for fertility preservation or family building in a cohort of transgender men.

PURPOSE: The purpose of this study was to compare ovarian stimulation and pregnancy outcomes between transgender men (1) with and without a history of testosterone use (HRT) and (2) to cisgender women. METHODS: Retrospective chart review between January 1st 2015 and March 1st, 2019 of transgender men and cisgender women seeking ovarian stimulation (OS) matched by BMI and age. Outcomes were compared using Fisher's exact or Wilcoxon's rank sum tests. RESULTS: Thirteen transgender men presented for OS, 7 who used HRT. When comparing transgender men with and without a history of HRT, there were no differences in the baseline follicle count, cycle length, or FSH and hmG used (p = 0.193, 0.306, 0.200, and 0.197, respectively). Transgender men who used HRT had lower peak estradiol and oocytes retrieved compared to transgender men with no HRT use; peak estradiol levels of 1175 pg/mL IQR [559.5-2684]) vs 2713.5 pg/mL IQR [2335-3105]; oocytes retrieved 12 IQR [4-26]) vs. 25.5 [18-28] (p = 0.046. and 0.038, respectively). There were no differences in the estradiol level per oocyte, meiosis II oocyte yield, or maturity rate (MII/oocytes) between the two groups (p = 1.000, 0.148, and 0.147, respectively). Peak estradiol levels were lower among transgender men compared to cisgender women (p = 0.016), but the remaining cycle characteristics were similar between the two groups. Three successful pregnancies were conceived using the oocytes of transgender men who used HRT. CONCLUSION: HRT use may not negatively impact ovarian stimulation outcomes. Clinical pregnancies are possible from the oocytes of transgender men with a history of HRT.

Semen Parameters Among Transgender Women With a History of Hormonal Treatment.

OBJECTIVE: To report on the semen quality parameters in transgender women who pursued semen cryopreservation either in the presence or absence of gender-affirming hormonal medication. MATERIALS AND METHODS: This retrospective cohort study was conducted as a chart review of consecutive transgender women presenting for semen cryopreservation between January 1, 2012 and March 31, 2018. Demographic data and semen parameters were assessed. Primary outcomes were the semen parameters in subjects with either no exposure, previous exposure or current exposure to gender-affirming hormonal medication. RESULTS: Twenty-eight patients presented for semen cryopreservation and produced 69 specimens. Using a Kruskal-Wallis test, semen analyses were compared between patients who had never used gender-affirming hormonal medication, those who had previously used hormonal medication but discontinued prior to specimen collection, and those who used medication at the time of specimen collection. Median semen parameters for each group were as follows: volume-2.7 mL, 2.1 mL, 0.9 mL, respectively (P = .12); concentration-63.6 M/mL, 39.0 M/mL, 2.4 M/mL, respectively (P < .01); percent motility-51.5%, 34.3%, 15.6%, respectively (P < .01); and the total motile count was 63.2 M,39.1 M, 0.2 M, respectively (P < .01). Fifteen specimens were collected after discontinuing hormonal medication with a mean discontinuation period of 4.4 months. CONCLUSION: Specimens collected in the presence of hormonal medication were associated with abnormal semen parameters. Specimens collected after discontinuation of gender-affirming treatments were comparable to transgender women who had never used hormonal medication. Transgender women should be counseled about the potential impact of gender-affirming hormones and to consider fertility preservation prior to gender-affirming treatments.

Impact of the levonorgestrel-releasing intrauterine device on controlled ovarian stimulation outcomes.

OBJECTIVE: To report differences in ovarian stimulation outcomes in women using a levonorgestrel-releasing intrauterine device (LNG-IUD). DESIGN: Retrospective cohort study. SETTING: University-based infertility practice. PATIENT(S): Female patients pursuing either social oocyte cryopreservation or oocyte donation. INTERVENTION(S): Chart review of all female patients presenting from January 1, 2012, to June 30, 2017, for social oocyte cryopreservation or oocyte donation. Demographic data, cycle performance data, and the presence or absence of an LNG-IUD at the time of ovarian stimulation were compared. MAIN OUTCOME MEASURE(S): Total oocyte yield and total mature oocyte yield. Secondary measures included clinical pregnancy rate and live birth rate in recipients of donor oocytes. RESULT(S): Univariate analysis of predicted oocyte yield and mature oocyte yield showed no significant difference between subjects with and without an LNG. When controlling for history of recent hormonal contraceptive use, initial antral follicle count (AFC), age, body mass index (BMI), gonadotropin dose, and stimulation day/protocol, no significant differences were seen in total oocyte yield or mature oocyte yield in the presence or absence of an LNG-IUD. Univariate analysis of the effect of LNG-IUDs on the predicted clinical pregnancy rate and live birth rate did not significantly differ for oocyte recipients. Controlling for history of recent hormonal contraceptive use, initial AFC, age, BMI, gonadotropin dose, and stimulation day/protocol also showed no significant differences in the predicted clinical pregnancy rate and live birth rate. CONCLUSION(S): LNG-IUDs do not affect cycle performance in women undergoing ovarian stimulation cycles.

Transitioning from Infertility-Based (ART 1.0) to Elective (ART 2.0) Use of Assisted Reproductive Technologies and the DOHaD Hypothesis: Do We Need to Change Consenting?

The use of assisted reproductive technologies (ARTs) has increased significantly in recent years. While this is partially due to improved access for infertile patients, another contribution to the growth of ART utilization is represented by individuals without infertility, who electively chose to freeze their gametes and embryos for future use, before ever attempting conception spontaneously. Overall, the safety of ART for parents and children is well described and the risks are modest. However, while long-term health consequences for offspring as postulated by the Developmental Origin of Health and Disease (DOHaD) hypothesis are unknown, numerous animal studies suggest a predisposition for chronic diseases like hypertension and glucose intolerance. In this article, we argue that a key difference exists between infertile patients, who need to use ART as the only means to achieve pregnancy, and (likely) fertile patients who elect to use ART techniques as a family planning option. We believe that these two sets of patients are different and their risks-benefit ratios are different. We propose that while all patients should be aware of the risks, patients planning to utilize ART techniques without a diagnosis of infertility should be encouraged to think critically about the additional risks, particularly the "potential" long-term risks that may be imposed from these elective procedures.

Spindle cell sarcoma of the vulva with myofibroblastic differentiation.

OBJECTIVE: Primary vulvar sarcomas are rare lesions of the lower genital tract. We report the case of a patient with a spindle cell sarcoma of the vulva. MATERIALS AND METHODS: A 44-year-old woman presented with a painless vulvar mass. Vulvar biopsy demonstrated a spindle cell sarcoma with myofibroblastic differentiation. RESULTS: Pretreatment evaluation revealed no evidence of metastatic disease, and magnetic resonance imaging found no local masses. The patient underwent right radical vulvectomy with negative margins and tolerated the procedure well. CONCLUSIONS: Women undergoing gynecologic care should have routine evaluation of the vulva to detect these rare neoplasms.

Evaluation of the canalicular entrance into the lacrimal sac: an anatomical study.

PURPOSE: The purpose of this study was to investigate the prevalence of a common canalicular entrance in the lacrimal sac and to investigate the anatomy of the canalicular/lacrimal sac junction with direct visualization using a novel cadaveric dissection technique. METHODS: Preserved cadavers were dissected to allow direct visualization of the canalicular entrance(s) to the lumen of the lacrimal sac. The prevalence of a common canaliculus and the anatomical variations of the canalicular/lacrimal sac mucosal fold of tissue were recorded. RESULTS: One hundred twenty-four lacrimal systems (95 cadavers; 43 female, 52 male) were included in the study analysis. Overall, 123 lacrimal systems demonstrated a common canaliculus entering the lacrimal sac. Only one demonstrated 2 separate orifices (right orbit; male) in the sac (0.08%; 95% confidence interval, 0.1%-4.4%). Seventy-four lacrimal systems had some variation of a canalicular/lacrimal sac mucosal fold (59.7%). The remaining 50 (40.3%) had no visible canalicular/lacrimal sac mucosal fold. CONCLUSIONS: This study provides direct anatomical evidence that the prevalence of separate canalicular orifices in the lacrimal sac is lower than previously reported (<1%). Additionally, the presence of a valve-like structure at the canalicular/lacrimal sac junction is common. These observations can potentially play a role in evaluating and treating lacrimal system pathology.