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.

Uterine Artery Embolization for Symptomatic Adenomyosis: Proceedings from a Society of Interventional Radiology Foundation Research Consensus Panel.

Adenomyosis poses an important diagnostic and therapeutic challenge in women's health because of a variety of clinical/imaging presentations and frequent coexistence with other benign gynecologic conditions. In recent years, uterine artery embolization (UAE) for the treatment of adenomyosis has shown encouraging and favorable outcomes and long-term symptom improvement. To expand the current understanding of adenomyosis pathophysiology, imaging diagnostic criteria, and treatment outcomes, the Society of Interventional Radiology Foundation gathered a multidisciplinary Research Consensus Panel with experts from diverse backgrounds. The topics addressed were centered around the following: (i) the clinical presentation and imaging findings to diagnose adenomyosis; (ii) the currently available medical, interventional, and surgical treatment options; and (iii) existing literature for and experiences with UAE in symptomatic disease. The panel acknowledged that before the pursuit of a clinical trial, it would be necessary to first evaluate the imaging criteria for adenomyosis and correlate them with pathology and symptoms to establish a noninvasive imaging classification system. Second priority was given to the development of a quality of life questionnaire to assess patient outcomes following treatment. The third priority was the performance of a prospective clinical trial comparing UAE with medical therapy, which would help establish UAE in the treatment algorithm and societal guidelines for symptomatic adenomyosis.

Report of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development-sponsored workshop: gynecology and women's health-benign conditions and cancer.

The Division of Cancer Prevention and the Division of Cancer Biology at the National Cancer Institute and the Gynecologic Health and Disease Branch in the National Institute of Child Health and Human Development organized a workshop in April 2019 to explore current insights into the progression of gynecologic cancers from benign conditions. Working groups were formed based on 3 gynecologic disease types: (1) Endometriosis or Endometrial Cancer and Endometrial-Associated Ovarian Cancer, (2) Uterine Fibroids (Leiomyoma) or Leiomyosarcoma, and (3) Adenomyosis or Adenocarcinoma. In this report, we highlight the key questions and current challenges that emerged from the working group discussions and present potential research opportunities that may advance our understanding of the progression of gynecologic benign conditions to cancer.

Antithyroid antibodies and parity: further evidence for microchimerism in autoimmune thyroid disease.

OBJECTIVE: Fetal microchimerism may have a role in development of autoimmune thyroid disorders. Using parity as a surrogate for increasing fetal cell exposure, we analyzed its association with thyroid peroxidase antibody levels. STUDY DESIGN: Secondary analysis of serum thyroid analytes determined in 17,298 women from a population-based prospective study between 2001 and 2003. Sera were assayed for thyrotropin, free thyroxine, and antithyroid peroxidase antibodies. We analyzed the relationship between thyroid peroxidase antibodies and increasing parity. RESULTS: The incidence of abnormally elevated thyroid peroxidase antibody levels (>50 IU/mL) increased with advancing parity, but was not significant after adjustment for maternal characteristics. However, at higher thyroid peroxidase antibody levels (>500 IU/mL), a significant relationship with advancing parity persisted after adjustments (P = .002). CONCLUSION: Advancing parity is associated with an increased risk for high serum concentrations of antithyroid peroxidase antibodies. This suggests fetal microchimerism may play a role in development of autoimmune thyroid disorders.

Eye to the Future in Adenomyosis Research.

Adenomyosis is a poorly understood and clinically underappreciated gynecologic disorder associated with substantial morbidity including dysmenorrhea, pelvic pain, heavy menstrual bleeding, infertility, and poor pregnancy outcomes. Substantial gaps persist in our understanding of essentially all aspects of this disorder - epidemiology, risk factors, pathogenesis, pathophysiology, diagnosis, and treatment. In this article, we summarize current thoughts on future directions in basic, translational, and clinical adenomyosis research.

Effect of preconception low dose aspirin on pregnancy and live birth according to socioeconomic status: A secondary analysis of a randomized clinical trial.

Low socioeconomic status (SES) is associated with adverse pregnancy outcomes and infertility. Low-dose aspirin (LDA) was shown to improve livebirth rates in certain subsets of women, and therefore, may impact pregnancy rates differentially by SES status. Therefore, the aim of the current study was to examine whether daily preconception-initiated LDA affects rates of pregnancy, livebirth, and pregnancy loss differently across strata of socioeconomic status (SES). This is a secondary analysis of The Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial, a multisite, block- randomized, placebo-controlled trial conducted at four U.S. medical centers (n = 1,228, 2007-2012). Women attempting spontaneous conception with a history of pregnancy loss were randomly allocated preconception to 81mg of aspirin + 400mcg of folic acid (n = 615) or placebo + 400mcg of folic acid (n = 613). Study medication was administered for six menstrual cycles or until 36 weeks' gestation if pregnancy was achieved. For this analysis, women were stratified by SES, which included income (low, mid, high) and a combined grouping of education and income (low-low, low-high, high-low, high-high). Log binomial models with robust variance estimated risks of pregnancy, livebirth, and pregnancy loss for LDA versus placebo. LDA increased pregnancy and livebirth rates (RR 1.23, 95% CI: 1.03, 1.45) in the high-income, but not mid- or low-income groups. LDA increased pregnancy rates in both the low education-low income group (RR 1.22, 95% CI: 1.02, 1.46) and the high education-high income group (RR 1.23, 95%CI: 1.06, 1.42), with no effect observed in mid-SES groupings. LDA, a low-cost and widely available treatment, may be particularly beneficial to women at the highest and lowest ends of the socioeconomic spectrum, though underlying mechanisms of this disparity are unclear. Confirming these findings and identifying factors which may modulate the effectiveness of LDA will ultimately facilitate personalized clinical care and improvements in population-level reproductive health. Trial registration number: ClinicalTrials.gov, NCT00467363.

Gynecologic Health and Disease Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development: A Scientific Vision.

In May 2016, the newly formed Gynecologic Health and Disease Branch in the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited experts to a 2-day meeting aimed at identification of emerging opportunities in gynecologic investigation. Four primary disorders were chosen for emphasis because they represent the majority of the current Gynecologic Health and Disease Branch portfolio: uterine leiomyomas, endometriosis, pelvic floor disorders, and gynecologic pain conditions. Discussions generated a set of seven cross-cutting themes, which encompass both gaps in our current knowledge and potential directions for further research. These themes formed a continuum for understanding these disorders beginning with the need for classification systems, improved understanding of the natural history and etiology of these disorders, development of novel diagnostics, identification of opportunities for prevention, and the generation of new treatments using cutting-edge approaches. Along with these themes, three broad strategies were proposed to facilitate future research. First, investigators should improve utilization of existing research resources and focus on developing new resources to include databases, biospecimen repositories, animal models, and patient cohorts. Second, multidisciplinary scientific partnerships should be strengthened to bring new insights and approaches to gynecologic research. Third, patient and health care provider education must be promoted to ensure timely and accurate diagnosis and optimize treatment of gynecologic disorders. This article provides a summary of the workshop themes and suggestions, several of which have already been implemented through the development of program priorities and funding opportunity announcements aimed at improving women's reproductive health.

Liver receptor homologue-1 regulates gonadotrope function.

Over the past decade, substantial advances have been made in our understanding of the transcription factors which regulate gene expression in gonadotropes. One of the most important of these factors, steroidogenic factor-1 (SF-1; NR5A1) is critical for gonadotropin and GnRH-receptor expression. Interestingly, a closely related nuclear hormone receptor, liver receptor homologue-1 (LRH-1; NR5A2) has recently been detected in the anterior pituitary gland; however, its functional significance in this tissue has not been investigated. For the experiments reported here, we hypothesized that LRH-1 plays a previously unrecognized role in gonadotrope physiology. Towards this end, we first demonstrate LRH-1 mRNA and protein expression in both primary pituitary cells and gonadotrope-derived cell lines. We next show that LRH-1 stimulates promoter activity of the GnRH-receptor and gonadotropin subunit genes. Within the LHbeta gene, this response appears to be mediated by DNA-binding and transactivation through previously characterized SF-1 cis-elements. To our knowledge, this is the first report demonstrating a functional role for LRH-1 in the gonadotrope population of the anterior pituitary gland.