David Seifer, MD

The major focus of my research effort has been ovarian follicular aging. This effort has been directed to developing new, novel diagnostic methods and treatment. For the last two decades, I focused on the discovery of novel granulosa cell proteins and defining their respective roles in the function of the normal aging human preovulatory follicle. This research led to two translational advances. The first has been a better understanding of the aging granulosa cell and in turn, the aging ovarian follicle responsible for diminished reproductive function. This fundamental information has allowed greater insight into cellular and molecular events that precede the perimenopausal transition. The second advancement has been the clinical use of granulosa cell proteins as serum markers (specifically, inhibin-b and anti-Mullerian hormone (AMH), which provide patients and clinicians with an assessment of a woman’s real-time egg count prior to choosing an infertility treatment. Over time AMH moved from a scientific curiosity to a daily diagnostic test, to becoming utilized in a therapeutic fashion to help determine a physician's choice of initial and ongoing fertility treatment. In addition, AMH is now being used to anticipate the onset of menopause, is clinically useful in making the diagnosis of polycystic ovarian syndrome and is a diagnostic marker in a number of other clinically important areas of reproductive medicine including oncofertility, fertility preservation and family planning. Interest is now being directed to exploring the production of AMH analogues for potential therapeutic applications.

I have also worked with collaborators investigating a family of ovarian growth factors, known as neurotrophins, that we discovered to be present in the adult human preovulatory follicle. The family of neurotrophins include brain-derived neurotrophic factor (BDNF), neurotrophin-4/5 (NT-4/5), neurotrophin-3 (NT-3), and nerve growth factor (NGF). We have utilized both human and mouse models to investigate the neurotrophin site of secretion and potential function in promoting oocyte maturation as well as their basic roles in ovarian physiology. These studies indicate that neurotrophins, if not obligatory, facilitate regulation of oocyte physiology, including oocyte development within the preovulatory follicle. Our basic research shows promise of translational applications in both in vitro maturation of immature oocytes and in pathophysiologic conditions such as polycystic ovary syndrome. These findings may eventually lead to new opportunities for treatment of infertility and to improved methods contraception.

I have also been privileged to participate in health outcomes research for the last 10 years, studying health care disparities as it relates to IVF success. Initial studies were directed at investigating if there were differences in outcomes based on ethnicity/race. We found that race and ethnicity are important correlates of IVF outcomes. Follow up studies examined if there were real trends in these disparities over time. Further investigation was directed to trying to understand possible reasons for such differences. The relative contributions of several presumptive reasons were explored. They included biological (pathology, genetic, AMH, BMI), environmental (vitamin D deficiency, smoking, toxins) and socio-cultural reasons. This has also lead to studying the impact of race and ethnicity on female reproductive aging. Our ultimate goal of identifying racial disparities in reproductive outcomes is to isolate the basic determinants of these disparities and formulate strategies to improve outcomes.

Another area of sustained interest has been in the role vitamin D impacts female reproduction. Focusing on the mechanisms by which vitamin D levels may influence folliculogenesis in the context of specific types of infertility.