The Intersection of Disability and Pregnancy: Risks for Maternal Morbidity and Mortality.

It is estimated that 1 in 4 women in the United States live with a disability, and using population-based estimates, 10-12% of women of childbearing age have a disability. There are limited data to suggest that women with disabilities experience higher rates of or risks for adverse outcomes related to pregnancy, delivery, and access to appropriate postpartum care. Research on specific disabling conditions demonstrates variable risk for syndromes that threaten the health of the mother, such as preeclampsia, infection, and coagulation disorders. Much of the literature suggests that normal, healthy pregnancy is possible but points to the need for tailored information for patients and providers about the intersection of their condition with pregnancy and specific care needs. Given the lack of systematic evidence in this area across conditions and functional impairments, more research is needed to clarify the interaction of specific disabilities with pregnancy and provide evidence-based information to the field to decrease the risks to mothers and their infants. This article will provide an overview of conditions that contribute to maternal morbidity and mortality as they relate to pregnancy in women with disabilities and provide resources to the field to further the investigation of this area.

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.

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.

Embryonic fibroblasts enable the culture of primary ovarian follicles within alginate hydrogels.

Hydrogel-encapsulating culture systems support the consistent growth of ovarian follicles from various species, such as mouse, non-human primate, and human; however, further innovations are required for the efficient production of quality oocytes from early-stage follicles. In this report, we investigated the coculture of mouse ovarian follicles with mouse embryonic fibroblasts (MEFs), commonly used as feeder cells to promote the undifferentiated growth of embryonic stem (ES) cells, as a means to provide the critical paracrine factors necessary for follicle survival and growth. Follicles were encapsulated within alginate hydrogels and cocultured with MEFs for 14 days. Coculture enabled the survival and growth of early secondary (average diameter of 90-100 µm) and primary (average diameter of 70-80 µm) follicles, which developed antral cavities and increased in diameter to 251-347 µm. After 14 days, follicle survival ranged from 70% for 100-µm follicles to 23% for 70-µm follicles. Without MEF coculture, all follicles degenerated within 6-10 days. Furthermore, 72%-80% of the oocytes from surviving follicles underwent germinal vesicle breakdown (GVBD), and the percentage of metaphase II (MII) eggs was 41%-69%. Medium conditioned by MEFs had similar effects on survival, growth, and meiotic competence, suggesting a unidirectional paracrine signaling mechanism. This advancement may facilitate the identification of critical factors responsible for promoting the growth of early-stage follicles and lead to novel strategies for fertility preservation.

A macrophage and theca cell-enriched stromal cell population influences growth and survival of immature murine follicles in vitro.

Innovations in in vitro ovarian follicle culture have revolutionized the field of fertility preservation, but the successful culturing of isolated primary and small secondary follicles remains difficult. Herein, we describe a revised 3D culture system that uses a feeder layer of ovarian stromal cells to support early follicle development. This culture system allows significantly improved primary and early secondary follicle growth and survival. The stromal cells, consisting mostly of thecal cells and ovarian macrophages, recapitulate the in vivo conditions of these small follicles and increase the production of androgens and cytokines missing from stromal cell-free culture conditions. These results demonstrate that small follicles have a stage-specific reliance on the ovarian environment, and that growth and survival can be improved in vitro through a milieu created by pre-pubertal ovarian stromal cell co-culture.

Sex and sensitivity: the continued need for sex-based biomedical research and implementation.

The phrase 'women's health research' embraces women as part of the biomedical research engine while categorizing women as separate. Before personalized medicine can become a reality, we must first ensure that basic physiological differences between the sexes are clearly delineated. In this article we argue that research into sex differences should be encouraged at the most fundamental levels of the biomedical sciences. Moreover, appropriate representation of both sexes as participants in clinical studies is still critically needed. Academic and governmental organizations must continue to articulate strong policy in order to ensure inclusion and analysis of sex as a critical variable. Focused attention on sex as a contributing factor to health, disease and therapeutic activity will increase our fund of knowledge regarding our everyday health, increase the pace of clinical research and ensure a healthier population.

Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways.

More than half of the primordial follicles that are formed by Day 6 of postnatal life in the mouse will be eliminated from the ovary by the time of puberty. Apoptosis, a form of programmed cell death, is one mechanism by which these follicles could be actively lost. To investigate whether apoptosis is responsible for the loss of primordial follicles, follicular atresia was examined during the prepubertal period, when follicles die and are cleared from the ovary at an extremely high rate. Four hallmarks of classical apoptosis were measured in follicles present in prepubertal ovaries. The primordial follicle cohort was not positively associated with nuclear condensation or cell shrinkage, activation of caspase 3, cleavage of poly(ADP ribose) polymerase 1 (PARP1), or fragmentation of DNA. These data are consistent with a nonapoptotic pathway that is responsible for small follicle death.