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 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 factors that might influence ovarian reserve as measured by AMH in several populations. Current use of oral contraceptives or Depo Provera, as well as elevated BMI are associated with lower AMH. In addition, using NHANES public access data, we found that elevated blood cadmium was associated with reduced AMH. We continue to investigate the association between vitamin D (measured by the circulating biomarker for vitamin D status, 25-hydroxy vitamin D (25(OH)D) and reproductive characteristics including fecundability, ovarian reserve, and bacterial vaginosis. Women with high 25(OH)D have higher estrogen levels during the menstrual cycle, and in a separate sample, in several studies increased fecundability. However, benefits to reproductive endpoints appear to rely on higher concentrations of 25(OH)D than are required for bone health. 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 adult woman. The apparent adverse effects of prenatal farm exposures on ovarian reserve was replicated in a separate population. Perturbation in early development of the reproductive tract in infant girls may also have long-term adverse effects. We are using data from the NIEHS Infant Feeding and Early Development Study to investigate early ovarian development. Ovarian growth and follicle development based on six ultrasound examinations conducted in this longitudinal study between birth and nine months. On average there is rapid ovarian growth for the first four months, with subsequent ultrasound examinations showing stable ovarian volumes or even slight decreases in volume. Antral follicles are common by the peak of growth at four months. Further analyses reveal that there are some female infants with very low ovarian activity during the first 9 months of life, and this will be investigated further with longitudinal data on AMH.