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.

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.

The function of BK channels extracted and purified within SMALPs.

Human BK channels are large voltage and Ca2+-activated K+ channels, involved in several important functions within the body. The core channel is a tetramer of α subunits, and its function is modulated by the presence of ß and γ accessory subunits. BK channels composed of α subunits, as well as BK channels composed of α and ß1 subunits, were successfully solubilised from HEK cells with styrene maleic acid (SMA) polymer and purified by nickel affinity chromatography. Native SMA-PAGE analysis of the purified proteins showed the α subunits were extracted as a tetramer. In the presence of ß1 subunits, they were co-extracted with the α subunits as a heteromeric complex. Purified SMA lipid particles (SMALPs) containing BK channel could be inserted into planar lipid bilayers (PLB) and single channel currents recorded, showing a high conductance (≈260 pS), as expected. The open probability was increased in the presence of co-purified ß1 subunits. However, voltage-dependent gating of the channel was restricted. In conclusion, we have demonstrated that SMA can be used to effectively extract and purify large, complex, human ion channels, from low expressing sources. That these large channels can be incorporated into PLB from SMALPs and display voltage-dependent channel activity. However, the SMA appears to reduce the voltage dependent gating of the channels.

Identifying Brigham and Women's Hospital stage T2a cutaneous squamous cell carcinomas at risk of poor outcomes.

BACKGROUND: Although most of the poor outcomes with cutaneous squamous cell carcinoma (CSCC) occur in high-stage tumors, 26% of nodal metastases and 8% of disease-specific deaths develop in Brigham and Women's Hospital (BWH) T2a tumors. OBJECTIVE: To determine risk factors associated with poor outcomes (nodal metastasis, distant metastases, and disease-specific deaths) in BWH T2a CSCC. METHODS: A 17-year retrospective multi-institutional cohort study of primary CSCC BWH T2a tumors. A predictive model based on tumor characteristics was developed to identify those at higher risk of poor outcomes. RESULTS: Presence of 1 major criterion (primary tumor diameter ≥40 mm, invasion depth beyond subcutaneous fat, poor differentiation, or large-caliber perineural invasion) and ≥ 1 minor criterion (invasion depth in subcutaneous fat, moderate differentiation, small-caliber perineural invasion, or lymphovascular invasion) was most predictive of developing poor outcomes (area under the curve, 0.53; C-statistic, 0.60). This model has a sensitivity of 7.7%, specificity of 97.4%, and a positive and negative predictive value of 33.3% and 86.1%, respectively. The 5-year cumulative incidence of poor outcomes in these tumors is 8.0% (95% CI, 5.1-13.7) compared to 2.8% (95% CI, 1.9-4.1) in other T2a tumors (sub-hazard ratio, 3.0; 95% CI, 1.5-5.8). LIMITATIONS: Multi-institutional cohort study was not externally validated. CONCLUSIONS: BWH T2a-high CSCCs have an 8% chance of developing poor outcomes.

Why Does Facial Eczema Differ From Body Eczema?

BACKGROUND: The pathophysiology of atopic dermatitis (AD) is multifactorial, influenced by genetics, skin barrier dysfunction, and environmental stressors. There is a lack of research comparing the etiologies and pathologic mechanisms accounting for differences in facial vs body eczema. OBJECTIVES: To explore reasons why facial eczema may differ from body eczema. RESULTS: There are key differences in the environments of the face and body that may lead to AD exacerbation. These include differences in the skin microbiome, sebaceous glands concentration, and levels of natural moisturizing factor. The face is exposed to more environmental stress compared with the rest of the body. These stresses include aeroallergens, ultraviolet radiation, and cosmetic products. Management of facial eczema also differs from that of body eczema due to the avoidance of high potency topical steroids on the face. Topical steroids increase microbiome diversity, and lack of topical steroid use on the face can lead to decreased microbiome diversity and increased AD severity. CONCLUSION: Facial and body eczema differ due to differences seen in anatomical structure and environmental exposures. These differences should be further researched and used in the management of facial vs body eczema and can also be used in the development of new AD treatments. J Drugs Dermatol. 2022;21(10): 1119-1123. doi:10.36849/JDD.6354.

Predictive factors for fertility preservation in pediatric and adolescent girls with planned gonadotoxic treatment.

PURPOSE: To characterize female pediatric and adolescent patients seen for fertility preservation consultation at an academic medical center and to describe the association between demographic or clinical factors and the use of fertility preservation treatment (FPT). METHODS: This is a retrospective chart analysis of female pediatric and adolescent patients seen for fertility preservation consultation at an academic fertility center over a 14-year period from 2005 to 2019. RESULTS: One hundred six females aged 3-21 years were seen for fertility preservation consultation with a mean age of 16.6 years. Diagnoses included hematologic malignancies (41.5%), gynecologic malignancies (9.4%), other malignancies (31.1%), non-malignant hematologic disease (14.2%), and non-malignant conditions (3.8%). Overall, 64.2% of subjects pursued fertility preservation, including oocyte cryopreservation (35.8%) and ovarian tissue cryopreservation (23.6%). Overall, age, minority race, diagnosis, time since diagnosis, and median household income were not significantly associated with odds of completing an FPT procedure. Among all patients, those who underwent gonadotoxic therapy prior to consultation had a lower odds of receiving FPT (OR= 0.24, 95% CI 0.10-0.55). Among patients without chemotherapy exposure, no factors were associated with FPT. CONCLUSIONS: Among pediatric and adolescent patients at an academic center undergoing a fertility preservation consultation, there were no socioeconomic or clinical barriers to FPT use in those who had not yet undergone gonadotoxic therapy. The only factor that was negatively associated with odds of pursuing FPT was prior chemotherapy exposure.

Detection of subclinical disease with baseline and surveillance imaging in high-risk cutaneous squamous cell carcinomas.

BACKGROUND: There are limited studies on imaging for management of high-risk cutaneous squamous cell carcinoma (HRCSSC). OBJECTIVE: To evaluate the impact of baseline (ie, at diagnosis) and surveillance (ie, subsequent time points after diagnosis) imaging on management of HRCSCCs. METHODS: All primary CSSCs treated at Brigham and Women's Hospital Mohs Surgery Clinic and Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic from January 1, 2017 through June 1, 2019, were reviewed to identify tumors that underwent baseline or surveillance imaging. Tumors that underwent imaging were reviewed to determine the impact of imaging on management and ability of imaging to identify subclinical disease. RESULTS: Eighty-three patients underwent imaging for 87 primary HRCSCCs, of which 48 (58%) underwent surveillance imaging. A total of 146 (59%) abnormal results were obtained from 248 imaging studies. Management was altered by 42 (24%) studies. Imaging detected subclinical disease in 21% of cases studied. A majority (56%) of detections were not seen initially but rather during surveillance imaging in the 2 years after treatment. LIMITATIONS: Single institution retrospective design. CONCLUSIONS: Imaging identifies subclinical disease in HRCSCC. Prospective studies are needed to determine best practices for screening and surveillance in HRCSCC.

Does theFMR1 gene affect IVF success?

FMR1 CGG trinucleotide repeat expansions are associated with Fragile X syndrome (full mutations) and primary ovarian insufficiency (premutation range); the effect of FMR1 on the success of fertility treatment is unclear. The effect of FMR1 CGG repeat lengths on IVF outcomes after ovarian stimulation was reviewed. PubMed was searched for studies on IVF-related outcomes reported by FMR1 trinucleotide repeat length published between 2002 and December 2017. For women with CGG repeats in the normal (<45 CGG), intermediate range (45-54 CGG), or both, research supports a minimal effect on IVF outcomes, including pregnancy rates; although one study reported lower oocyte yields after IVF stimulation in women with lower CGG repeat lengths and normal ovarian reserve. Meta-analysis revealed no association within subcategories of normal repeat length (<45 CGG) and IVF pregnancy rates (summary OR 1.0, 95% CI 0.87 to 1.15). Premutation carriers (CGG 55-200) may have reduced success with IVF treatment (lower oocyte yield) than women with a normal CGG repeat length or a full mutation, although findings are inconsistent. Direct implications of the repeat length on inheritance and the risk of Fragile X syndrome have been observed. Patients may require clinical and psychological counselling, and further preimplantation genetic testing options should be considered. Thus, there are clinical and psychological counseling implications for patients and potential further patient decisions regarding preimplantation genetic testing options.

Planar lipid bilayers in recombinant ion channel research.

There are a number of methods of investigating the function of recombinant proteins such as ion channels. However, after channel purification there are few methods to guarantee that the protein still functions. For ion channels, reconstituting back into planar lipid bilayers and demonstrating preserved function is a convenient and trusted method. It is cell free and even inaccessible, intracellular ion channels can be studied. We have used this method to study the function of recombinant channels of known subunit composition and have found it convenient for investigating the mode of action of ion channel modulators.

A Mega-Analysis of Anti-Müllerian Hormone Levels in Female Childhood Cancer Survivors Based on Treatment Risk, Time since Treatment, and Pubertal Status.

Purpose: Female childhood cancer survivors (CCSs) risk infertility due to gonadotoxic chemotherapy/radiation. Anti-Müllerian hormone (AMH) helps evaluate ovarian reserve, and the 2020 Oncofertility Pediatric Initiative Network (O-PIN) risk stratification is utilized to counsel risk of gonadal dysfunction/infertility. This study analyzed how AMH levels after cancer treatment differ with age and correlate AMH with O-PIN risk level and clinical outcomes. Methods: A literature review and mega-analysis of individual patient data were performed. Females ages 0-20 years at the time of cancer diagnosis with AMH values post-treatment were included. AMH outcomes were compared by O-PIN risk stratification, age at diagnosis, cyclophosphamide equivalent dose (CED), and hematopoietic stem cell transplant (HSCT). Multivariable random effects mixed models correlated AMH with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and pregnancy. Results: In 13 studies with 608 CCSs, the median age (years) at diagnosis was 12.0 (interquartile range [IQR] 5.2-16.2) and 21.1 (IQR 17.1-30.0) at AMH measurement. AMH values were higher with time since treatment and correlated with the O-PIN risk level. Patients with HSCT had very low/undetectable AMH levels regardless of CED; when stratified by CED, AMH levels were lower if treated peripubertally or older. AMH was detectable in 54% (34/63) of patients with POI on hormone replacement. Pregnancy did not correspond to the gonadotoxicity risk level (p = 0.70). Conclusion: This study supports utilizing the O-PIN risk stratification system in estimating risk of DOR in CCSs and its categorization by pubertal status. AMH levels may return over time even after receiving the highest risk therapy. These findings may help counsel cancer patients pre- and post-therapy.

Single-nucleus and spatial transcriptomics of paediatric ovary: Molecular insights into the dysregulated signalling pathways underlying premature ovarian insufficiency in classic galactosemia.

BACKGROUND: Classic galactosemia (CG) is an inborn error of galactose metabolism caused by mutations in the GALT gene. Premature ovarian insufficiency (POI) is a later complication that affects 80% of women with CG due to a significant decline in ovarian reserve (primordial follicle pool). The definite mechanisms underlying the early onset of POI in CG patients are not fully understood. METHODS: In this study, we performed single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics on ovary tissue biopsies from prepubertal girls diagnosed with CG to investigate dynamic changes in gene expression and altered signalling pathways in granulosa cells, oocytes, and stromal cells. RESULTS: We generated single-nucleus and spatial transcriptomics atlas of human ovaries from prepubertal girls diagnosed with and without CG. snRNA-seq profiling of the paediatric ovary revealed a diverse ovarian microenvironment with seven distinct major cell types. Our transcriptomic analysis revealed an increase in the expression of several endoplasmic reticulum stress and oxidative stress associated genes, which can promote apoptosis of granulosa cells in CG. PTEN/PI3K/AKT signalling, which is crucial for primordial follicle activation and survival was dysregulated as supported by upregulated PTEN transcripts and a significant reduction in phospho-AKT levels in the granulosa cells and oocytes. We also found a marked increase in expression of phospho-H2A.X, LC3A/B and CASP9 in the primordial follicles of CG ovaries suggesting DNA damage, autophagy, and accelerated follicular atresia. Furthermore, we noticed genes participating in extracellular matrix organisation, integrin and gap junction signalling, essential for structural support of the ovarian stroma were profoundly altered. CONCLUSIONS: Our findings provide molecular insights into the dysregulated cellular signalling pathways essential for primordial follicle growth and survival that can explain the etiology of POI in CG patients. This study has implications in the development of future therapeutic interventions to preserve ovarian function and promote female reproductive health. HIGHLIGHTS: Created a comprehensive single-nucleus transcriptomic atlas and spatial landscape of paediatric ovary tissue from prepubertal girls diagnosed with classic galactosemia (CG). Our transcriptomic analysis revealed activation of genes associated with ER-stress signalling, oxidative stress response and ATM signalling/DNA damage response as shown by significant increase in expression of p-EIF2A, p-H2A.X and LC3A/B in the primordial follicles of CG ovary. PTEN/PI3K/AKT signalling pathways was dysregulated evidenced by a significant reduction in phospho-AKT expression in the primordial follicles of CG ovary, suggesting impaired follicle activation and survival.

Utilization and cost of cell salvage in minimally invasive myomectomy.

OBJECTIVE: To assess the utilization and cost of intraoperative cell salvage (ICS) in minimally invasive myomectomy. STUDY DESIGN: Retrospective cohort study of patients who underwent minimally invasive myomectomy at a quaternary care academic hospital. Patients were classified into: ICS setup vs no ICS setup, ICS setup with reinfusion vs ICS setup without reinfusion. RESULTS: Of 382 patients who underwent minimally invasive myomectomy, 67 (17.5 %) had ICS setup, 30 (44.8 %) of those patients reinfused. Median volume of reinfusion per patient was 300 mL (range 125-1000 mL). Patients who ultimately underwent ICS reinfusion, compared to those with ICS setup only, had significantly larger mean maximum fibroid size (9.8 cm vs 8.0 cm, p = 0.02), higher median total specimen weight (367 vs 304 g, p = 0.03), higher median estimated blood loss (575 vs 300 mL, p < 0.0001), longer mean operative time (261 vs 215 min, p = 0.04). No perioperative complications were associated with ICS. Higher costs are associated with universal use or complete lack of ICS; lowest cost is associated with ICS setup only for those ultimately reinfused. CONCLUSION: ICS might reduce requirements for allogeneic blood transfusions in patients undergoing minimally invasive myomectomy, and may contribute to cost savings. Uterine and maximum fibroid sizes are possible preoperative indicators for patients who require cell salvage reinfusion.

AKAP13 Enhances CREB1 Activation by FSH in Granulosa Cells.

Granulosa cells (GCs) must respond appropriately to follicle-stimulating hormone (FSH) for proper follicle maturation. FSH activates protein kinase A (PKA) leading to phosphorylation of the cyclic AMP response element binding protein-1 (CREB1). We identified a unique A-kinase anchoring protein (AKAP13) containing a Rho guanine nucleotide exchange factor (RhoGEF) region that was induced in GCs during folliculogenesis. AKAPs are known to coordinate signaling cascades, and we sought to evaluate the role of AKAP13 in GCs in response to FSH. Aromatase reporter activity was increased in COV434 human GCs overexpressing AKAP13. Addition of FSH, or the PKA activator forskolin, significantly enhanced this activity by 1.5- to 2.5-fold, respectively (p < 0.001). Treatment with the PKA inhibitor H89 significantly reduced AKAP13-dependent activation of an aromatase reporter (p = 0.0067). AKAP13 physically interacted with CREB1 in co-immunoprecipitation experiments and increased the phosphorylation of CREB1. CREB1 phosphorylation increased after FSH treatment in a time-specific manner, and this effect was reduced by siRNA directed against AKAP13 (p = 0.05). CREB1 activation increased by 18.5-fold with co-expression of AKAP13 in the presence of FSH (p < 0.001). Aromatase reporter activity was reduced by inhibitors of the RhoGEF region, C3 transferase and A13, and greatly enhanced by the RhoGEF activator, A02. In primary murine and COV43 GCs, siRNA knockdown of Akap13/AKAP13 decreased aromatase and luteinizing hormone receptor transcripts in cells treated with FSH, compared with controls. Collectively, these findings suggest that AKAP13 may function as a scaffolding protein in FSH signal transduction via an interaction with CREB, resulting in phosphorylation of CREB.

The role of Hippo pathway signaling and A-kinase anchoring protein 13 in primordial follicle activation and inhibition.

OBJECTIVE: To determine whether the mechanotransduction and pharmacomanipulation of A-kinase anchoring protein 13 (AKAP13) altered Hippo signaling pathway transcription and growth factors in granulosa cells. Primary ovarian insufficiency is the depletion or dysfunction of primordial ovarian follicles. In vitro activation of ovarian tissue in patients with primary ovarian insufficiency alters the Hippo and phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/forkhead box O3 pathways. A-kinase anchoring protein 13 is found in granulosa cells and may regulate the Hippo pathway via F-actin polymerization resulting in altered nuclear yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif coactivators and Tea domain family (TEAD) transcription factors. DESIGN: Laboratory studies. SETTING: Translational science laboratory. PATIENT(S): None. INTERVENTION(S): COV434 cells, derived from a primary human granulosa tumor cell line, were studied under different cell density and well stiffness conditions. Cells were transfected with a TEAD-luciferase (TEAD-luc) reporter as well as expression constructs for AKAP13 or AKAP13 mutants and then treated with AKAP13 activators, inhibitors, and follicle-stimulating hormone. MAIN OUTCOME MEASURE(S): TEAD gene activation or inhibition was measured by TEAD-luciferase assays. The messenger ribonucleic acid levels of Hippo pathway signaling molecules, including connective tissue growth factor (CTGF), baculoviral inhibitors of apoptosis repeat-containing 5, Ankyrin repeat domain-containing protein 1, YAP1, and TEAD1, were measured by quantitative real-time polymerase chain reaction. Protein expressions for AKAP13, CTGF, YAP1, and TEAD1 were measured using Western blot. RESULT(S): Increased TEAD-luciferase activity and expression of markers for cellular growth were associated with decreased cell density, increased well stiffness, and AKAP13 activator (A02) treatment. Additionally, decreased TEAD-luc activity and expression of markers for cellular growth were associated with AKAP13 inhibitor (A13) treatment, including a reduced expression of the BIRC5 and ANKRD1 (YAP-responsive genes) transcript levels and CTGF protein levels. There were no changes in TEAD-luc with follicle-stimulating hormone treatment, supporting Hippo pathway involvement in the gonadotropin-independent portion of folliculogenesis. CONCLUSION(S): These findings suggest that AKAP13 mediates Hippo-regulated changes in granulosa cell growth via mechanotransduction and pharmacomanipulation. The AKAP13 regulation of the Hippo pathway may represent a potential target for regulation of follicle activation.

Racial and ethnic differences in reproductive knowledge and awareness among women in the United States.

Objective: To evaluate if knowledge and awareness of concepts and concerns pertaining to reproductive health and fertility vary by race/ethnicity among reproductive-aged women in the United States. Methods: A 2013 cross-sectional web-based survey assessed reproductive health-related knowledge, awareness, and perceptions of 1,000 women (18-40 years). Multivariable logistic regression analyses, adjusting for age, education, income, marital status, employment, region, and pregnancy history, examined the association between race/ethnicity and subfertility-related risk factor awareness; knowledge of factors that may affect pregnancy susceptibility; and future fertility-related concerns. Results: Knowledge and awareness related to reproductive wellness and fertility differed by race/ethnicity in US women. Compared with Caucasians, Hispanic women were less likely to be aware of smoking-related harm to fertility (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.38-0.86); African American women were more aware of the implications of sexually transmitted infections on fertility (OR, 2.13; 95% CI, 1.15-3.94); and Asian women demonstrated greater awareness of a possible relationship between dysmenorrhea and subfertility (OR, 2.05; 95% CI, 1.09-3.86). Asian women consider fertility socially taboo to talk about and a private affair that is difficult to discuss (OR, 2.63; 95% CI, 1.32-5.29 and OR, 1.99; 95% CI, 1.05-3.75, respectively), were more concerned about their future fertility (OR, 2.36; 95% CI, 1.24-4.52), and more likely to perceive a need for future fertility treatment (OR, 2.36; 95% CI, 1.18-4.71). Conclusion: Among reproductive-aged women in the United States, knowledge, awareness, and perceptions relating to reproductive health vary by race/ethnicity. Our findings suggest race/ethnicity as potential modulators of population perceptions regarding reproductive health and infertility. Clinical Trial Registration Number: NIH ZIA# HD008985.

Apremilast in the Treatment of Plaque Psoriasis: Differential Use in Psoriasis.

Small molecule medications like apremilast are emerging as promising options for patients with psoriasis and other inflammatory conditions. Apremilast was approved by the Food and Drug Administration in 2014 for the management of both psoriasis and psoriatic arthritis. Apremilast inhibits phosphodiesterase-4, which increases the intracellular levels of cyclic AMP, thereby reducing inflammatory cytokine production. This review aims to discuss the published evidence and evaluate the differential use of apremilast in plaque psoriasis of the body and scalp, nail psoriasis, and palmoplantar psoriasis. In clinical trials, apremilast effectively reduced the severity of different dermatological manifestations of psoriasis and improved patients' quality of life. It has an acceptable safety profile and is generally well-tolerated. Oral medications like apremilast offer an alternative route of administration which can be more convenient and appropriate for some patients. Additionally, pharmacoeconomic analyses of available anti-psoriatic systemic agents favor apremilast as a cost-effective therapeutic option.

An intersectional analysis of contraceptive types chosen among sexual minority women: A nationally representative study.

OBJECTIVE: The purpose of this study is to use an intersectional approach in which race, insurance, care setting, and disclosure of sexual orientation to a provider are used to assess patterns of contraceptive use in sexual minority women. STUDY DESIGN: This study analyzes cross-sectional data from the 2011-2019 National Survey of Family Growth (NSFG). Sexual orientation of 21,075 respondents' data was used to investigate contraceptive use in sexual minority women, specifically lesbian and bisexual women, as compared to heterosexual women, controlling for variables such as race, age, and socioeconomic factors. RESULTS: Black and Hispanic lesbian women (adjusted odds ratio [aOR] = 0.39 confidence interval [CI] 0.20-0.76 and aOR = 0.44 CI 0.23-0.82, respectively) and Hispanic and Other Race bisexual women use hormonal contraceptive methods less than their White lesbian and bisexual peers (aOR = 0.45 CI 0.29-0.69 and aOR = 0.43 CI 0.20-0.94). Care setting was not correlated with long-acting reversible contraceptive methods (LARC; such as intra-uterine device, hormonal implants) or prescription-based hormonal methods (such as oral contraceptive pills, injectables, vaginal rings, and patches) in lesbian women (aOR = 2.92 CI 0.60-14.2 and aOR = 1.43 CI 0.47-4.38, respectively) or bisexual women (aOR = 0.90 CI 0.48-1.58 and aOR = 0.83 CI 0.37-1.86), but it was for straight women (aOR = 1.28 CI 1.03-1.59 and aOR = 0.68 CI 0.53-0.86). Similarly, insurance status did not correlate with contraceptive patterns in sexual minority women. Importantly, adjusting for nationally representative data did not impact the results; in other words, the odds ratios after adjusting yielded the same results as before adjustment. CONCLUSIONS: Insurance and care setting are important determinants of straight women's contraceptive use patterns with fewer effects seen among sexual minority women. These findings support previous work and indicate that known advantages of insurance coverage or use of public clinics may not positively impact sexual minority women as much as they do straight women. Provider awareness of sexual identity and sexual orientation is important for adequate contraceptive care. IMPLICATIONS: While prior research has presented findings on sexual minority women contraceptive use, to our knowledge there are limited studies that address the social and demographic implications for contraceptive use in this population.

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.

Fertility after Curative Therapy for Sickle Cell Disease: A Comprehensive Review to Guide Care.

Curative therapy for sickle cell disease (SCD) currently requires gonadotoxic conditioning that can impair future fertility. Fertility outcomes after curative therapy are likely affected by pre-transplant ovarian reserve or semen analysis parameters that may already be abnormal from SCD-related damage or hydroxyurea treatment. Outcomes are also likely affected by the conditioning regimen. Conditioning with myeloablative busulfan and cyclophosphamide causes serious gonadotoxicity particularly among post-pubertal females. Reduced-intensity and non-myeloablative conditioning may be acutely less gonadotoxic, but more short and long-term fertility outcome data after these approaches is needed. Fertility preservation including oocyte/embryo, ovarian tissue, sperm, and experimental testicular tissue cryopreservation should be offered to patients with SCD pursing curative therapy. Regardless of HSCT outcome, longitudinal post-HSCT fertility care is required.

Case report: two cases of mature oocytes found in prepubertal girls during ovarian tissue cryopreservation.

OBJECTIVE: To report two cases of mature oocytes found in prepubertal girls undergoing ovarian tissue cryopreservation (OTC). DESIGN: Case report. SETTING: Large tertiary care children's hospital and a private fertility clinic. PATIENTS: An 8-year-old prepubertal girl with ß-thalassemia and a 2-year-old girl with sickle cell disease who both underwent OTC before bone marrow transplantations. INTERVENTIONS: Laparoscopic right oophorectomy was performed in each patient. The ovarian cortical tissue was processed for slow freezing and long-term storage, and all oocytes were subsequently vitrified. MAIN OUTCOME MEASURES: Oocytes found at the time of OTC processing for fertility preservation. RESULTS: After a complete right oophorectomy, one mature metaphase II oocyte was discovered on tissue processing for OTC in each patient. Neither patient has yet returned for use of tissue or oocytes. CONCLUSIONS: To our knowledge, this is the first report of mature oocytes found during prepubertal OTC processing. These findings may indicate the need for increased research regarding prepubertal oocyte development and suggest that the technique of examining the media for both mature and immature oocytes at the time of OTC should become more widespread and perhaps recommended in prepubertal patients to optimize fertility preservation methods.