Environmental Effects On Fertility

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

Data from the Early Pregnancy Study (EPS) (A.Wilcox, PI) provide a resource for ongoing research into reproductive hormones, fertility, & early pregnancy. During field work for this study in 1982-1985, women enrolled at the time they stopped using birth control in order to conceive. We followed them through their 8th week of pregnancy. They collected daily first morning urine specimens and these were analyzed for human chorionic gonadotropin and steroid metabolites. Women with known fertility problems were excluded, so the sample represents normal unassisted reproduction. We conducted a pilot study to test the stability of hormones in urines stored from the Early Pregnancy Study. Pilot work supported the validity of BPA and phthalate measurements in the EPS urines after long-term storage, so we have designed a study to look at the association of those exposures with fertility and pregnancy outcomes in EPS. We designed a sample selection protocol (pool of 3 separate daily specimens) to the assess levels in each participant menstrual cycle and each clinical pregnancy. These have been analyzed at CDC. Analysis of these data indicate no increased risk of early pregnancy loss with phthalate or BPA exposure. We have extended the analyses to examine the relationship between these exposures and corpus luteum rescue, initial rise of human chorionic gonadotropin, corpus luteum rescue, and length of gestation. Several associations were found, but all will need replication before considered of clinical significance because our sample was small and analyses did not account for multiple testing. Antimllerian hormone (AMH) is used as a biomarker for ovarian reserve which is measured in IVF clinics to assess the likelihood that a woman will produce enough eggs in a stimulation cycle to warrant IVF. It has been hypothesized to be a marker of fertility and has been used to crudely predict time of menopause among late-reproductive-age women. The majority of data on AMH come from fertility clinics and suggested that, with the exception of smoking, it is not perturbed by many of the normal factors associated with reproductive outcomes. We have been examining AMH in women with no known fertility problems and find that many factors affect it's concentrations including use of hormonal contraception and BMI. We also examined the association with time-to-pregnancy in a community based study of older-reproductive aged women. It was not predictive of how long it took women to become pregnant, nor were other markers of ovarian reserve including urinary FSH. Given the lack of association, women are unlikely to benefit from the commercial products that provide in-home testing for fertility based on urinary FSH concentrations. We continue to investigate the association between vitamin D (measured by the circulating biomarker for vitamin D status, 25-hydroxy vitamin D) and reproductive characteristics including ovarian reserve and bacterial vaginosis. A current analysis shows that women with higher 25-hydroxy vitamin D,have higher estrogen levels during the menstrual cycle. Early-life factors may have long-term effects on adult reproduction as classically demonstrated by studies of DES. We recently examined soy-formula as another estrogenic exposure of interest. Our finding support an association between soy formula feeding in infancy and elevated menstrual bleeding and pain as an adult. Additionally, if mom worked or lived on a farm during the pregnancy of interest the age-adjusted ovarian reserve was lower in the adults. Finally, in another study of menstrual pain, we used ultrasound to identify IUDs that are lying low in the uterus (either due to problems with initial placement or post-placement migration). We found BMI to be a risk factor for having a low-lying IUD, and the women who had a low-lying IUD were at higher risk of menstrual pain difficulties.