Adolescent and Young Adult Patients with Vaginal Graft-vs-Host Disease and Hematocolpos Managed with Vaginal Stents: A Case Series.

STUDY OBJECTIVE: Vaginal stenosis can be acquired as a result of vaginal graft-vs-host disease (GVHD) in patients who have undergone hematopoietic stem cell transplant (HSCT). Little data exist to guide the management of vaginal GVHD, particularly in adolescent and young adult patients. The objective of this study was to detail the management of vaginal stenosis with lysis of adhesions and vaginal stent placement in 3 young patients with vaginal GVHD. METHODS: A retrospective chart review was done for 3 patients with vaginal GVHD causing vaginal stenosis with hematometrocolpos. All 3 were treated using vaginal stent placement. Additionally, a literature review was conducted through PubMed and Google Scholar to identify 21 case reports (with a total of 35 patients) of menstrual obstruction due to GVHD. RESULTS: Obstructive vaginal stenosis secondary to vaginal GVHD occurred in our patients at ages 15, 16, and 24 years. Resolution of hematocolpos was obtained with lysis of vaginal adhesions with vaginal stent placement in all patients, with varying regimens of systemic and topical hormones, topical corticosteroids, and dilator therapy. DISCUSSION: Vaginal stenosis secondary to vaginal GVHD should be considered in patients with a history of allogeneic HSCT presenting with amenorrhea, especially those with a diagnosis of primary ovarian insufficiency. The use of vaginal stents, along with postoperative medical and dilator management as appropriate, may prevent re-stenosis, although more information is needed regarding the efficacy of treatments.

Current Recommended Estrogen Dosing for Pubertal Induction in Turner Syndrome Results in Normal Uterine Growth.

CONTEXT: Most individuals with Turner syndrome (TS) require estrogen for pubertal induction. Current estrogen dosing guidelines are based on expert consensus opinion. OBJECTIVE: Evaluate whether current international guidelines for estrogen dosing during pubertal induction of individuals with TS result in normal uterine growth. We hypothesized that uterine size in individuals with TS who reached adult estrogen dosing is smaller than in mature females without TS. METHODS: Cross-sectional study of patients with TS at the Cincinnati Center for Pediatric and Adult Turner Syndrome Care. Twenty-nine individuals (age 15-26 years) with primary ovarian insufficiency who reached adult estrogen dosing (100 µg of transdermal or 2 mg of oral 17ß-estradiol) were included. Comparison of uterine measurements with a published sample of 292 age-appropriate (age 15-20 years) controls without TS. Uterine length, volume, and fundal-cervical ratio (FCR) were measured. Clinical information (karyotype, Tanner staging for breast development, laboratory data) was extracted from an existing institutional patient registry. RESULTS: There was no evidence of compromise of the uterine size/configuration in the TS cohort compared with the controls; in fact, uterine length, mean 7.7 cm (±1.3) vs 7.2 cm (±1.0) (P = .03), and volume, mean 60.6 cm3 (±26.6) vs 50.5 cm3 (±20.5) (P = .02), were both larger in individuals with TS. CONCLUSION: Current international guidelines for hormone replacement using 17ß-estradiol in individuals with TS appear adequate to allow for normal uterine growth by the end of pubertal induction.

Defining Success in the Delivery of Fertility-Related Care for Patients with Differences of Sex Development.

INTRODUCTION: Individuals with differences of sex development (DSD) experience complex, often competing, medical and psychosocial challenges surrounding fertility. The study aimed to characterize how "success" in fertility-related care is conceptualized and attained among individuals with a DSD, their parents or caregivers, healthcare providers, and other stakeholders. METHODS: As part of a larger study, DSD stakeholders (n = 110) participated in semi-structured interviews covering the clinical care of patients with DSD. Primary questions included "What is a successful outcome in DSD care?" and "How do you achieve it?" with fertility as either a spontaneous or suggested topic of discussion. Transcripts were analyzed utilizing a phenomenological approach. This analysis focuses on the extracted themes related to fertility. RESULTS: Fertility was discussed by 19/24 individuals with DSD, 12/19 parents or caregivers, 35/37 healthcare providers, and 19/30 other stakeholders. Components of successful fertility-related care included (1) specific discussions surrounding the relationship between DSD and fertility potential, options for fertility preservation, and options for non-biologic parenthood; (2) early and repeated introduction of these topics; and (3) consideration of age, developmental maturity, and cultural context on decisions around fertility. Challenges included the lack of fertility outcome data in this population and the irreversibility of gonadectomy. Trade-offs identified included anatomic typicality versus function, fertility preservation versus cancer risk reduction, and balancing the different priorities of stakeholders. DISCUSSION/CONCLUSIONS: A wide range of DSD stakeholders highlighted the importance of addressing fertility concerns in achieving favorable outcomes for individuals with DSD. These stakeholder perspectives should inform fertility-related education, shared decision-making processes, and clinical care.

Time to therapy and safety of testicular tissue cryopreservation in children undergoing gonadotoxic treatment or hematopoietic stem cell transplant.

BACKGROUND: With the use of multimodal treatments and hematopoietic stem cell transplant, the majority of children diagnosed with malignancies and hematologic diseases are now surviving into adulthood. Due to the gonadotoxic effects and potential for future infertility associated with many of these treatments, fertility counseling with sperm cryopreservation prior to starting therapy is the standard of care for post-pubertal males. Unfortunately, the options are limited for pre-pubertal patients or those unable to provide a specimen. Testicular tissue cryopreservation (TTC) is an investigational method to surgically obtain germ cells from testicular tissue and potentially restore future spermatogenesis. While TTC has been shown to be safe, little is reported on the time to treatment following the procedure to ensure adequate wound healing and avoid delays in definitive therapy. OBJECTIVES: The primary outcome was the time to initiation of treatment following TTC. Secondary outcomes were complication rates, delays in treatment due to TTC, and presence of germ cells. METHODS: We conducted a single-institution retrospective cohort study of patients undergoing TTC between 2017 and 2023. Patients at significant risk for treatment related infertility based on established criteria were eligible for TTC. Patients were excluded if they received their oncology or hematology care elsewhere. All patients were enrolled in an IRB approved research protocol with 75% of the tissue submitted for cryopreservation and 25% for research purposes. Time to therapy was defined as the first receipt of gonadotoxic treatment following TTC. RESULTS: A total of 122 patients (53 = malignant, 69 = non-malignant) underwent TTC with a median age of 5.9 years (IQR 2.3-9.35). Germ cells were identified in 115 (94%) specimens. A total of 109 (89%) patients underwent concomitant procedures. The median time to initiation of therapy was 5 (IQR 1.0-7.0) and 7 days (IQR 6.0-13.0) for malignant and non-malignant disease, respectively. The 30-day surgical complication rate was 2.5% and was similar between malignant vs non-malignant diagnoses (p = 0.58). All surgical complications were managed non-operatively. No patients had a delay in definitive treatment due to concern for wound healing or complications. DISCUSSION: Our surgical complication rates are similar to previous studies and are not affected by the time to treatment following TTC. Limitations of the study are its retrospective design, single institution, and short-term follow up. CONCLUSION: TTC can be performed safely, efficiently, and in conjunction with other necessary procedures without resulting in delays of definitive treatment. TTC affords the opportunity for fertility preservation in children who have no other options.

Atypical Presentation of Granulosa Cell Tumor in an Adolescent: A Case Report.

BACKGROUND: Granulosa cell tumors (GCTs) frequently present with elevated levels of estrogen and inhibin. Most diagnoses in the pediatric and adolescent population are juvenile-type GCTs; adult-type GCTs in this population are rare. CASE: We describe a 14-year-old female who presented with a large adnexal mass and clinical hyperandrogenism. Laboratory evaluation revealed elevated levels of free and total testosterone, low-normal estradiol, and mildly elevated alpha-fetoprotein (AFP). Other tumor markers, including inhibin, were within normal limits. Intraoperative assessment with unilateral oophorectomy, pathology, and imaging resulted in a diagnosis of a stage IA adult-type GCT. SUMMARY AND CONCLUSION: GCTs often result in elevated estrogen and inhibin B levels; however, this case demonstrates that non-classic elevations in testosterone and normal inhibin levels should not eliminate concern for a GCT, particularly in the setting of a large ovarian mass.

Sexual and Reproductive Health Concerns in Adults With Cloacal Anomalies: A Qualitative Study.

STUDY OBJECTIVE: Long-term gynecologic data are lacking to inform the care of patients with cloacal malformations. We seek to examine perceived sexual and reproductive health challenges of patients born with cloacal anomalies and characterize the experiences of patients as adults. DESIGN AND SETTING: Virtual semi-structured focus groups and single-participant interviews were conducted using an online video platform. Retrospective chart review was performed to abstract available demographics and surgical history. PARTICIPANTS: Adult patients were contacted from a database of 143 patients born with cloaca who had been seen at or referred to a tertiary care pediatric colorectal center. Participants were recruited until data collection reached thematic saturation. Twenty patients aged 18-53 years participated in 5 focus groups and 3 single-participant interviews. The hospital IRB determined the research activities to be exempt from IRB review and oversight. INTERVENTIONS AND MAIN OUTCOME MEASURES: Interviews and focus groups were transcribed and analyzed using the constant comparative method to identify themes regarding sexual and reproductive health and compared with medical and surgical history abstracted from chart review. RESULTS: Participants reported many perceived barriers to intercourse and intimacy including bowel and bladder continence management. All participants reported discussion of pregnancy and fertility with healthcare providers as important. Other common themes included concerns about independence and transitioning from pediatric to adult providers. CONCLUSION: Anorectal malformations are associated with sexual and reproductive health concerns. Patients seek guidance on family building, intimacy, and transition to adult care. Future quantitative study of these topics is needed to develop best practices for counseling and clinical management of these patients. LEVEL OF EVIDENCE: Level VI. TYPE OF STUDY: Prognosis Study.

Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Individuals with Turner Syndrome.

STUDY OBJECTIVE: Incidence of abnormal uterine bleeding (AUB) during pubertal induction among individuals with Turner syndrome (TS) has not been described previously. We estimated the incidence and characterized factors associated with AUB among individuals with TS. A secondary objective was to evaluate the management of AUB among this patient population. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We conducted a retrospective chart review to evaluate individuals with TS undergoing hormone replacement therapy (HRT) for pubertal induction with transdermal estrogen. A total of 45 participants were identified between January 2007 and June 2019. RESULTS: Of the 45 individuals with TS included, 16 (35%) experienced AUB. Individuals with AUB most commonly experienced prolonged (44%), prolonged and heavy (25%), and intermenstrual (19%) bleeding. Individuals who experienced AUB were more likely to experience spontaneous bleeding (69% vs 28%) and a duration of unopposed estrogen greater than 18 months (63% vs 41%), undergo progestin cycling less often than monthly (69% vs 0%), use a micronized progestin dose of less than 200 mg (25% vs 14%), and be noncompliant with HRT (19% vs 0%) compared with those who did not experience AUB. CONCLUSION: There is a relatively high incidence of AUB among individuals with TS undergoing pubertal induction with transdermal estrogen. Care providers should consider the clinical factors examined to guide monitoring and management of individuals with TS on HRT.

Mental health impacts of reproductive coercion among women in Côte d'Ivoire.

OBJECTIVE: To assess the independent associations of partner-perpetrated reproductive coercion, intimate partner violence (IPV), in-law reproductive coercion, and in-law abuse with recent probable post-traumatic stress disorder (PTSD), and to test their relationship with PTSD symptoms when controlling for the other types of abuse among partnered women in rural Côte d'Ivoire. METHODS: Cross-sectional analyses were conducted using logistic generalized estimating equations, which accounted for village-level clustering. Data were drawn from baseline data from a randomized controlled trial among 24 villages in rural Côte d'Ivoire (n=953 partnered women). Three adjusted models were used to test associations of reproductive coercion and abuse with probable PTSD. RESULTS: Partner-perpetrated reproductive coercion was experienced by 176 (18.5%) women. In model 3, which accounted for the co-occurrence of abuses, partner-perpetrated reproductive coercion (odds ratio [OR] 2.3; 95% confidence interval [CI], 1.4-3.9) and partner-perpetrated IPV (OR 1.7; 95% CI, 1.1-2.7) were the most significant predictors of past-week probable PTSD (P<0.05). CONCLUSION: Reproductive coercion may be a significant contributor to poor mental health. The mental health impacts of reproductive coercion and IPV should be considered within psychosocial programming for rural Ivorian communities to address the full range of traumatic experiences that may have been experienced by women.