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Epidemiology, Environment, & Reproduction

Research Summary

The Fertility and Reproductive Health Group (FRHG) is led by Anne Marie Jukic, Ph.D. FRHG research aims to improve female reproductive health with a focus on reducing the burden of menstrual dysfunction, subfertility and infertility. Difficulty conceiving a pregnancy is a pressing public health problem that affects millions of U.S. women. Factors that affect fertility are not well-understood. At the same time, menstrual cycles are a vital sign for reproductive-aged women, yet menstrual cycle research is lacking2. We investigate environmental exposures that can influence menstrual cycles, fertility, or early pregnancy. Our work is hypothesis-driven and translational.

Vitamin D (the sunlight vitamin) is produced in the skin in response to ultraviolet radiation. Our research group has published the first studies showing that lower levels of vitamin D are associated with prolonged menstrual cycles, delayed ovulation, and a lower probability of conception. This body of observational research led us to develop the Investigation of Vitamin D and Menstrual Cycles clinical trial (the inVitD Trial) which examines the effect of vitamin D supplementation on menstrual cycle hormones. Our primary hypothesis is that high dose vitamin D supplementation will lead to a higher frequency of ovulatory cycles in women with low levels of vitamin D. Vitamin D is easy to assess clinically and evidence from InVitD, if successful, would support a low-cost intervention for regulating menstrual cycles and improving fertility.

The inVitD Trial is also leveraging participant-collected menstrual effluent to evaluate this novel matrix for more proximate vitamin D biomarker assessment and examine the effects of vitamin D supplementation on the uterine endometrium which might explain vitamin D’s associations with improved implantation during early pregnancy.

In addition to vitamin D, the FRHG examines reproductive effects of other environmental exposures such as phthalates, phenols, air pollution, season, and ambient temperature. We develop and rigorously apply epidemiologic methods, including leveraging mobile app health data to explore and describe reproductive health endpoints that are not well-understood such as pregnancy duration, pregnancy loss, and anovulation (infertile menstrual cycles where ovulation doesn’t occur).

Other Data Sources

The Apple Women's Health Study
The Apple Women's Health Study is a research partnership between Apple, The Harvard T.H. Chan School of Public Health, and NIEHS and aims to gain a deeper understanding of how certain demographic and lifestyle factors could have an impact on menstrual cycles, infertility, pregnancy health, menopause, and polycystic ovary syndrome (PCOS). The study includes cycle tracking data and other data from iPhone and/or Apple Watch (optional) and participants’ survey responses.

The North Carolina Early Pregnancy Study
The North Carolina Early Pregnancy Study (EPS) (Jukic, PI) was conducted during the early 80s (1982-86). The EPS enrolled 221 women who discontinued contraception in order to become pregnant. Participants were healthy with no known fertility problems. Women completed daily diaries and collected daily first-morning urine specimens for six months, or through the 8th week past LMP if they conceived. Women who became pregnant were followed to determine their pregnancy outcome. Urine specimens have been analyzed for several biomarkers including phthalates, phenols, estrone-3-glucuronide, pregnanediol-3-glucuronide, and human chorionic gonadotrophin (hCG).

The Study of Environment Lifestyle & Fibroids (SELF) (Jukic co-PI) was designed to identify risk factors for uterine fibroid development. It is the first study to identify incident cases based on ultrasound screening with a goal to identify new preventative factors that could directly benefit women. In addition to fibroids, SELF also studies sleep quality, menstrual cycle characteristics and symptoms, reproductive aging, birth outcomes and environmental exposures such as vitamin D, metals, and endocrine disrupting chemicals. SELF participants (N=1693) contributed data from baseline through four follow-ups (2010 – 2023) which included questionnaires, urine, blood, vaginal swabs, ultrasound, anthropometry, and measured biomarkers. Participants are currently attending a 15-year follow-up visit. In addition to NIEHS researchers, SELF also includes investigators at multiple sites including Boston University and Henry Ford Health.

Jukic received a B.S. from the University of Notre Dame, an M.S.P.H. from Emory University, and a Ph.D. in epidemiology from the University of North Carolina at Chapel Hill. She completed a postdoctoral fellowship at NIEHS and was an Assistant Professor at the Yale School of Public Health before joining NIEHS as a Principal Investigator. She has a secondary appointment in the Reproductive and Developmental Biology Laboratory.

Recent Publications

More Recent Publications from PubMed