Environmental Effects On Fertility

National Institute Of Environmental Health Sciences

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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 are continuing to examine the relationship between these exposures and corpus luteum rescue, initial rise of human chorionic gonadotropin, corpus luteum rescue, and length of gestation. Epidemiologic study of menstrual characteristics, fertility, pregnancy outcomes, and exposures during pregnancy often relies on retrospective self-report; these outcomes are not systematically monitored by medical-care protocols. Therefore, study validity depends upon the accuracy of self-report for these outcomes. In recent analyses we compared self-reported retrospective data on time to pregnancy and early pregnancy exposures with prospectively-collected data (documented for participants in the Early Pregnancy Study during their participation). Participants were traced and sent a self-administered questionnaire to collect their retrospective self-reports nearly 30 years after the pregnancy attempt. The time-to-pregnancy comparison indicates that even after 25-30 years there was good agreement of self-report with the prospectively observed time to pregnancy. For the early pregnancy exposures we found good reporting for maternal BMI, but poor recall of early pregnancy exposures such as vitamin and alcohol use. Antimllerian hormone (AMH) is used as biomarker for ovarian reserve which is measured in IVF clinics to assess the likelihood of a woman producing enough eggs in a stimulation cycle to warrant IVF. It has been hypothesized to be a marker of fertility and has can be 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. We continue to investigate the association between vitamin D levels and reproductive characteristics. A current analysis showing that women with higher 25-hydroxy vitamin D, the circulating biomarker for vitamin D status, have higher estrogen levels during the menstrual cycle.