Pubertal Suppression in Early Puberty Followed by Testosterone Mildly Increases Final Height in Transmasculine Youth.

Context: Treatment for transmasculine youth (TMY) can involve testosterone treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHas can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY. Objective: Our objective was to determine how GnRHa treatment before testosterone impacts FAH. Methods: Retrospective cohort study at 5 US transgender health clinics. Participants were 32 TMY treated with GnRHas in early to midpuberty before testosterone (GnRHa + T group) and 62 late/postpubertal TMY treated with testosterone only (T-only group). Results: The difference between FAH minus midparental target height (MPTH) was +2.3 ± 5.7 cm and -2.2 ± 5.6 cm in the GnRHa + T and T-only groups, respectively (P < .01). In the GnRHa + T group, FAH was 1.8 ± 3.4 cm greater than predicted adult height (PAH) (P < .05) and FAH vs initial height (IH) z-score was 0.5 ± 1.2 vs 0.16 ± 1.0 (P < .05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59 cm (95% CI 0.31, 0.9 cm), stage 3 breast development at start of GnRHa was associated with 6.5 cm lower FAH compared with stage 2 (95% CI -10.43, -2.55), and FAH was 7.95 cm greater in the GnRHa + T group than in T-only group (95% CI -10.85, -5.06). Conclusion: Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/postpuberty. TMY considering GnRHas should be counseled that GnRHas may mildly increase their FAH if started early.

Assessing Attitudes and Understanding After Ovarian Tissue Cryopreservation: A Follow-Up Telephone Interview Survey.

Purpose: Assessing patient and guardian experiences regarding their history of ovarian tissue cryopreservation (OTC) years after initial procedure. Methods: Cross-sectional follow-up telephone survey. A questionnaire developed by The Pediatric Initiative Network of the Oncofertility Consortium, modified to assess intent and attitudes regarding OTC, tissue access knowledge, financial burden of tissue storage, and intent to use tissue, was utilized. Interviews were conducted for those who underwent OTC at a metropolitan children's hospital between 2013 and 2022. Results: Of 60 eligible patients, 39 interviews were completed. Contacted patients were 3-28 years old, with minors accompanied by guardians. Average age at OTC was 8.5 years old, and 5.1% (2/39) were deceased at the time of contact. All interviewees underwent OTC for fertility preservation before gonadotoxic treatment. Seventy percent of patients (7/10) and 48.1% (13/27) of guardians stated they would use frozen tissue for pregnancy, with 50% (5/10) of patients and 59.3% (16/27) of guardians not understanding tissue access. Regret occurred in 10% (1/10) of patients and 3.4% (1/29) of guardians. It was associated with 10.8% (4/37) of tissue discard due to failed storage payments. Financial concerns occurred in 29.7% (11/37) of interviewees. Overall, 92.3% (36/39) would recommend OTC, and 94.9% (37/39) would repeat their choice to undergo OTC. Conclusion: Follow-up after OTC is essential to patient understanding of tissue status, access, and payments. Most do not regret OTC, except in cases of financial burden leading to tissue discard. Follow-up should be sequentially scheduled and include counseling on financial assistance programs.

Future Fertility Among Pediatric Cancer Patients: Experiences and Perspectives of Health Workers in a Low-Resource Setting.

Purpose:Although fertility preservation for patients with childhood and adolescent cancer is considered standard of care in the high-resource settings, it is rarely offered in low-resource settings. This study explores the experiences and perspectives of oncology health care professionals in Uganda to identify contextual barriers and facilitators to addressing oncofertility in low-resource settings. Methods: Using ground theory, we conducted in-depth face-to-face interviews of health care professionals managing pediatric patients at the Uganda Cancer Institute (UCI). Using a systematic, semi-structured interview guide, participants were asked open-ended questions about their understanding of fertility preservation and their perspectives on implementing this care at their institution. Although all the eligible health care providers were interviewed, interview transcripts were uploaded into NVivo version 12 and openly coded as per theoretical requirements. Codes were refined into categories and later into structured themes. Results: Twelve health care professionals were interviewed. Most participants identified as female (n = 9). Their role in the medical team varied from nurses (n = 6), medical officers (n = 3), pediatric oncologists (n = 2), and pediatric oncology fellow (n = 1). Six themes were noted as follows: (1) importance of information, (2) importance of future fertility, (3) inadequate consideration to future fertility, (4) communication barriers, (5) inadequate knowledge, and (6) resource barriers. Conclusion: Although health care providers at the UCI face contextual barriers to addressing future fertility among patients with pediatric cancer, they value preserving fertility in this population. Future initiatives that aim to introduce oncofertility care in low-resource settings should prioritize educating providers and building capacity to meet the oncofertility needs in this setting.

Understanding PCOS-Related Content across Social Media Platforms-A Cross-Sectional Analysis.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is commonly diagnosed in adolescence, and information about the condition is often shared online. We aimed to assess the extent, content, and engagement of PCOS-related information across social media platforms. METHODS: We performed a cross-sectional content analysis of PCOS-related posts on TikTok, Instagram, and Reddit. Top PCOS posts were collected from TikTok and Instagram (N = 100). Two researchers independently coded all posts using a codebook including symptoms, interventions, and qualities. Logistic regression assessed the relationship between user engagement and creator conflicts of interest. On Reddit, posts from 2020 to 2022 (N = 34,208) were collected. Topic modeling using latent Dirichlet allocation and non-negative matrix factorization (NMF) was applied to discover topics in the textual data. RESULTS: PCOS content received high engagement across all platforms, with an average of 1.8 million views on TikTok. "Weight" and "Diet" were the most frequently mentioned topics on TikTok and Instagram, and interactions with medical providers were discussed in 30% of posts. A financial conflict of interest was present in 45% of TikTok posts and 89% of Instagram posts. NMF identified 15 coherent topics, including symptoms, interventions, interactions with the medical system, and information-seeking. Reddit posts under "Symptom Management" received the most comments. DISCUSSION: PCOS content is present and pervasive across social media platforms, suggesting the ability of information from non-clinician sources to reach and engage with a large population using novel modes of health information sharing. Further studies of this content will allow for a deeper understanding of patient perceptions, misconceptions, and knowledge of PCOS, with the potential to inform patient-centered counseling.

Vaginal Foreign Bodies in the Pediatric and Adolescent Age Group: A Review of Current Literature and Discussion of Best Practices in Diagnosis and Management.

The self-insertion of a vaginal foreign body (VFB) is common in the female pediatric and adolescent age group. Prompt disclosure to parents usually results in a call to the primary care provider and a visit to the pediatrician's office, local emergency department, or urgent care center. However, some foreign bodies may go unnoticed for extended periods, causing distressing symptoms and complications. Large case series providing comprehensive epidemiological data on this topic are scarce. This review summarizes the current literature on VFBs and compiles best practices for the diagnosis and management of VFBs in the pediatric and adolescent population.

Should Ovarian Tissue Cryopreservation in Pediatric Patients with Turner Syndrome Be Limited to the Research Setting?

Now that ovarian tissue cryopreservation (OTC) has become standard of care for patients receiving gonadotoxic therapies, discussion has turned toward offering OTC to pediatric patients with Turner syndrome outside of research. Although patients with Turner syndrome have unmet fertility needs and the authors support efforts for fertility preservation in these individuals, safety and efficacy data about OTC in this population are limited. Building on longstanding debates around offering experimental therapies as research or outside of research (as "innovative therapy"), we considered the suitability of offering OTC for patients with Turner syndrome as innovative therapy. On the basis of pathophysiology and preliminary research data, we argue that there is significant uncertainty about whether the risk-benefit profile of OTC for patients with Turner syndrome is favorable. This reduces the weight of arguments in favor of offering it as innovative therapy. Furthermore, as Turner syndrome is rare, widespread availability of OTC could make it difficult to develop generalizable knowledge. The benefits of innovative therapy for acquiring experience from use in humans and avoiding research-related procedures are of limited importance too, as OTC is already an established procedure, and current studies involve limited procedures that restrict access. OTC should therefore only be offered to patients with Turner syndrome in research settings until additional data suggest that the risk-benefit profile is likely favorable.

Botulinum Toxin Injections as a Treatment of Refractory Vulvodynia in Adolescents: A Case Series.

BACKGROUND: Vulvodynia involves vulvar discomfort that occurs in the absence of an identifiable cause. Because vulvodynia is often accompanied by myofascial pain and pelvic floor tension, transvaginal botulinum toxin (BT) injection into the pelvic floor has been proposed as a possible treatment. METHODS: Retrospective case series RESULTS: Three adolescents with vulvodynia had a suboptimal response to treatment with several interventions, including neuromodulators (oral and topical), tricyclic antidepressants (oral and topical), and pelvic floor physical therapy. Subsequently, these patients underwent BT injections to the pelvic floor as treatment with varying responses. CONCLUSION: In select adolescent patients with vulvodynia, transvaginal BT injection into the pelvic floor can be an effective treatment. Further studies are needed to assess the optimal dosing, frequency, and sites of BT injections in the treatment of vulvodynia in pediatric and adolescent patients.

Shared Decision-Making About Future Fertility in Childhood Cancer Survivorship: Perspectives of Parents in Uganda.

Background: Despite a plethora of literature on barriers to addressing future fertility in childhood cancer survivors, the data are not representative of limited middle-income settings. Unique and context-specific factors may influence addressing future fertility care among childhood cancer survivors in Uganda. This study aimed to explore the experiences, attitudes, and perceptions of parents on their interactions with health providers about future fertility, as part of their child's cancer survivorship. Methods: Using grounded theory, semistructured interviews were conducted with parents of children diagnosed with cancer, <18 years of age, and not in the induction or consolidation phases of treatment. Transcripts were thematically analyzed. Results: A total of 20 participants were interviewed, with the majority identifying as female (n = 18). The global theme that arose was the importance of shared decision-making, and the key themes encompassing this were as follows: (1) importance of accurate information, (2) respect of autonomy, and (3) engagement and psychosocial support. Conclusion: In Uganda, parents of children with cancer value a multifaceted approach to satisfactory decision-making within the context of oncofertility.

Shifts in Gender-Related Medical Requests by Transgender and Gender-Diverse Adolescents.

PURPOSE: Gender-affirming hormones and/or surgeries seeking to change the body can have potentially lasting effects. Changes in requests for these therapies among gender-diverse youth are not well-understood. The study aim is to characterize factors associated with shifts in gender-related medical requests. METHODS: This mixed-methods study used retrospective chart review and qualitative interviews with clinicians. Of 130 youth receiving clinical gender care at Children's National Hospital, 68 met inclusion criteria. Qualitative interview analysis was performed to identify patterns and themes around shifts in gender-related medical requests over time. Statistical analysis employed chi-square and t-tests to compare characteristics in the shift versus no-shift groups and kappa statistics to calculate qualitative coding agreement. RESULTS: Of the 68 youth followed over time (mean age 15.11 years, 47% autistic, 22% nonbinary), 20 (29%) reported a shift in request. No significant differences were found by age, autism status, or designated sex at birth. More youth with shifts were nonbinary (p = .012). Six shift profiles were identified from qualitative interviews with excellent reliability (κ = 0.865). Four of the profiles reflect shifts in request prior to starting treatment (85% sample); two involved shifts after commencing treatment (15%). The most common profile reflected a medical request that was made, withdrawn, and re-requested (45%). DISCUSSION: Shifts in gender-affirming medical requests by gender-diverse youth may not be uncommon during the adolescent's gender discernment process, and may more likely occur among nonbinary youth. Many individuals who experience shifts away from medical treatment may later resume the request.

The management of congenital adrenal hyperplasia during preconception, pregnancy, and postpartum.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency caused by mutations in the CYP21A2 gene. Although women with CAH have decreased fecundity, they are able to conceive; thus, if pregnancy is not desired, contraception options should be offered. If fertility is desired, women with classic CAH should first optimize glucocorticoid treatment, followed by ovulation induction medications and gonadotropins if needed. Due to the possible pregnancy complications and implications on the offspring, preconception genetic testing and counseling with a high-risk obstetrics specialist is recommended. For couples trying to avoid having a child with CAH, care with a reproductive endocrinology and infertility specialist to utilize in vitro fertilization can be offered, with or without preimplantation genetic testing for monogenic disorders. Prenatal screening and diagnosis options during pregnancy include maternal serum cell free-DNA for sex of the baby, and chorionic villus sampling and amniocentesis for diagnosis of CAH. Pregnant women with classic CAH need glucocorticoids to be adjusted during the pregnancy, at the time of delivery, and postpartum, and should be monitored for adrenal crisis. Maternal and fetal risks may include chorioamnionitis, maternal hypertension, gestational diabetes, cesarean section, and small for gestational age infants. This review on CAH due to 21-hydroxylase deficiency highlights reproductive health including genetic transmission, contraception options, glucocorticoid management, fertility treatments, as well as testing, antenatal monitoring, and management during pregnancy, delivery, and postpartum.

Understanding Fertility Attitudes and Outcomes Among Survivors of Adolescent and Young Adult Cancers in a Low-Resource Setting: A Registry-Based Computer-Assisted Telephone Interview Survey.

Purpose: To establish the extent of self-reported reproductive failure associated with cancer treatment, and attitudes toward fertility among adolescent and young adult (AYA) cancer survivors in Uganda. Methods: A registry-based computer-assisted telephone interview survey was conducted in Uganda. The survey population were survivors of childhood, adolescent and early adulthood cancers diagnosed between 2007 and 2018. The survey explored fertility outcomes, experiences of oncofertility and fertility attitudes of AYA cancer survivors. Results: Thirty-four (female = 14 and male = 20) interviews were completed. Survivors were 18-35 years of age. The median age at cancer diagnosis was 23.5 for females and 17.5 for males. Kaposi's sarcoma contributed to 44% of primary cancer diagnoses. All the survivors had received chemotherapy alone or in combination with other modalities and 79% of survivors had not received satisfactory information about future fertility before cancer treatment. Twenty one percent of males and 46% females met the criteria for infertility and 60% of these had met this criterion after their cancer diagnosis. Eighty two percent wanted to raise a biologically related child. Forty seven percent would be dissatisfied with their lives if they were unable to have a child or additional children. Conclusion: AYA cancer survivors in this low-resource setting reported reproductive failure, despite a strong fertility desire. Information and counseling provided on therapy-related problems before cancer treatment was insufficient and reinforces the need to build capacity for oncofertility resources within the region.

Effects of Ovarian Tissue Cryopreservation on Primary Ovarian Insufficiency in Girls Undergoing Bone Marrow Transplantation.

OBJECTIVE: To determine if removing an ovary for ovarian tissue cryopreservation (OTC) increased rates of primary ovarian insufficiency (POI) in girls undergoing bone marrow transplantation (BMT). Institutional review board approval was obtained from all 3 clinical sites. DESIGN: Multicenter retrospective cohort study SETTING: Academic children's hospitals PATIENTS: Females aged 2-21 who underwent BMT with or without OTC from 2010 to 2017. INTERVENTIONS: None MAIN OUTCOME MEASURES: Rates of POI in girls who underwent OTC vs those who underwent BMT alone as determined by serum markers, presence of menses, or clinical diagnosis. RESULTS: A total of 142 patients were identified, 43 who had OTC and 99 with BMT alone. The rate of POI in girls undergoing OTC was 65% vs 41.8% in those who underwent BMT alone (P = .26). CONCLUSIONS: Although this study was not powered to detect a lack of difference, it is reassuring that there does not seem to be a clinically significant increase in POI in patients undergoing OTC.

Anatomic nomenclature and 3-dimensional regional model of the human ovary: call for a new paradigm.

The ovaries are the female gonads that are crucial for reproduction, steroid production, and overall health. Historically, the ovary was broadly divided into regions defined as the cortex, medulla, and hilum. This current nomenclature lacks specificity and fails to consider the significant anatomic variations in the ovary. Recent technological advances in imaging modalities and high-resolution omic analyses have brought about the need for revision of the existing definitions, which will facilitate the integration of generated data and enable the characterization of organ subanatomy and function at the cellular level. The creation of these high-resolution multimodal maps of the ovary will enhance collaboration and communication among disciplines and between clinicians and researchers. Beginning in March 2021, the Pediatric and Adolescent Gynecology Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited subject-matter experts to participate in a series of workshops and meetings to standardize ovarian nomenclature and define the organ's features. The goal was to develop a spatially defined and semantically consistent terminology of the ovary to support collaborative, team science-based endeavors aimed at generating reference atlases of the human ovary. The group recommended a standardized, 3-dimensional description of the ovary and an ontological approach to the subanatomy of the ovary and definition of follicles. This new greater precision in nomenclature and mapping will better reflect the ovary's heterogeneous composition and function, support the standardization of tissue collection, facilitate functional analyses, and enable clinical and research collaborations. The conceptualization process and outcomes of the effort, which spanned the better part of 2021 and early 2022, are introduced in this article. The institute and the workshop participants encourage researchers and clinicians to adopt the new systems in their everyday work to advance the overarching goal of improving human reproductive health.

Reproductive health and knowledge among youth with sickle cell disease.

Knowledge related to reproductive health in adolescents with sickle cell disease (SCD) is not fully addressed. We evaluated reproductive health and knowledge among adolescent girls with SCD. Seventy-nine adolescents, 13-21 years of age completed a survey on reproductive health and knowledge with menarche age 13.2 (± 1.7) years. Fifty-four percent reported dysmenorrhea and 49% reported SCD pain a week before menstrual cycle. Sixty-two percent reported discussing contraception and pregnancy with medical providers. Adolescents reported late menarche, dysmenorrhea, and pain with menses. Knowledge of overall reproductive health was inadequate. There is an urgent need to improve reproductive education in this population.

Fetal and Newborn Management of Cloacal Malformations.

Cloaca is a rare, complex malformation encompassing the genitourinary and anorectal tract of the female in which these tracts fail to separate in utero, resulting in a single perineal orifice. Prenatal sonography detects a few cases with findings such as renal and urinary tract malformations, intraluminal calcifications, dilated bowel, ambiguous genitalia, a cystic pelvic mass, or identification of other associated anomalies prompting further imaging. Multi-disciplinary collaboration between neonatology, pediatric surgery, urology, and gynecology is paramount to achieving safe outcomes. Perinatal evaluation and management may include treatment of cardiopulmonary and renal anomalies, administration of prophylactic antibiotics, ensuring egress of urine and evaluation of hydronephrosis, drainage of a hydrocolpos, and creation of a colostomy for stool diversion. Additional imaging of the spinal cord and sacrum are obtained to plan possible neurosurgical intervention as well as prognostication of future bladder and bowel control. Endoscopic evaluation and cloacagram, followed by primary reconstruction, are performed by a multidisciplinary team outside of the neonatal period. Long-term multidisciplinary follow-up is essential given the increased rates of renal disease, neuropathic bladder, tethered cord syndrome, and stooling issues. Patients and families will also require support through the functional and psychosocial changes in puberty, adolescence, and young adulthood.

Primary Amenorrhea and Differences of Sex Development.

Primary amenorrhea may be a feature or a presenting sign of a difference of sex development, most often due to a congenital anatomic difference or hypergonadotropic hypogonadism. History and physical exam are very important, including whether any variation in external genitalia was present at birth as well as a careful review of pubertal development. Further evaluation includes hormone measurement, imaging, and genetic evaluation. Those with a disorder of sexual development diagnosis should receive care through a multidisciplinary team with psychosocial support.

Fertility and CAR T-cells: Current practice and future directions.

Chimeric antigen receptor (CAR) T-cells serve to overcome chemotherapeutic resistance and have been proven to be highly effective in B-cell hematologic malignancies. Although initial use has been in patients with multiply relapsed/refractory disease, as CAR T-cells are used earlier in the treatment paradigm, it will be important to explore implications of this novel therapy on cancer late-effects. We sought to assess the current framework for considerations of fertility surrounding CAR T-cell use and identify opportunities for education and future research. To assess current practice patterns regarding post-CAR T-cell fertility, peri-CAR T-cell fertility guidance, utilization of fertility preservation surrounding CAR T-cell administration and identify future areas of research, a cross-sectional survey assessing practice patterns regarding fertility counseling and outcomes surrounding CAR T-cell therapy was distributed electronically to approximately 300 Center for International Blood and Marrow Transplant Research medical centers treating patients with CAR T-cell therapy in the United States and internationally between October 12 and November 2, 2021. One medical provider was asked to complete the study survey on behalf of their institution. We received 96 survey responses, of which 66 centers utilized CAR T-cells and provided at least partial responses that were used for the primary analysis. Centers were varied in demographics, experience in administering CAR T-cells, and aspects of patients receiving CAR T-cells. Eighteen centers exclusively treated pediatric patients, and patients at these centers were more likely to be treated for B-cell acute lymphoblastic leukemia. Seven pregnancies and 5 live births after CAR T-cells were reported from 6 centers (1 pediatric-only). Most centers had no established guidelines in place regarding fertility preservation in the peri-CAR T-cell period or regarding recommendations for avoiding pregnancy/fathering a child after receiving CAR T-cells. Areas for future research were elicited from responding centers and categorized into 3 broad themes, including: standardized peri-CAR T-cell fertility guidelines; long-term fertility outcomes after CAR T-cell therapy; impact of CAR T-cells on a developing fetus; and determining the relevance of studying fertility in patients who receive CAR T-cells. We identified a high degree of variability in peri-CAR T-cell guidance on avoidance of pregnancy/fathering a child, as well as a wide-range of practices surrounding referral for fertility preservation, the latter of which may be likely due to the fact that patients receiving CAR T-cells in the present era are likely multiply relapsed/refractory. In summary, this is the first report of several live-births following CAR T-cells, which highlights the important need for further research in CAR T-cell therapy and fertility, with a host of novel research questions identified.