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. In preliminary analysis of the data, there is no evidence of any associations between BPA or phthalates and early pregnancy loss or time to pregnancy. A comprehensive analysis has been completed and published in EHP. Epidemiologic study of menstrual characteristics, fertility, and miscarriage relies on self-report because these outcomes are not systematically monitored by medical care protocols. Therefore, study validity depends upon the accuracy of self-report for these outcomes. We have evaluated the validity of self-reported cycle characteristics by comparing interview data to prospective daily recording of menstrual bleeding and pain. In another methodologic project, we are using available data to determine how well women can report the timing of their positive pregnancy test. Bias arises in spontaneous abortion & time-to-pregnancy studies when comparing exposed and unexposed groups that differ in timing of pregnancy testing. Those who tend to have delayed pregnancy testing will recognize fewer spontaneous abortions, and they will have longer times to pregnancy. In another analysis 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 has been published, and a manuscript is being revised for Epidemiology. Even after 25-30 years there was good agreement of self-report with the prospectively observed time to pregnancy, but poor recall of early pregnancy exposures. Antimullerian 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 may 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. To what extent it is associated with time-to-pregnancy in the general population is currently under investigation. In recent work with vitamin D we have found that low vitamin D, as assessed by 25(OH)D in plasma from women 35-49 is associated with lower ovarian reserve, as assessed by urinary FSH from specimens collected outside of the midcycle surge in FSH. Low vitamin D was also found to be associated with menstrual cycle length and regularity.
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