This proposal will address 1) accurate assessment of environmental exposures during the earliest phases of human development, and 2) association of these exposures with semen quality and time to pregnancy in a community-dwelling cohort of 300 couples trying to conceive. The contaminants selected for measurement, disinfection by-products (DBP) and bisphenol-A (BPA), have been associated with adverse reproductive outcomes in animal models and in limited epidemiologic studies. Exposure to these and other environmental contaminants is not well measured via traditional epidemiologic means such as participant recall using questionnaires or environmental monitoring in early pregnancy, such as at the time of the first prenatal visit, or ecologic measures such as assignment of contaminant levels reported from drinking water system monitoring. Biomarkers can allow for more precise estimates of internal dose, but for transient exposures and chemicals with short half-lives, the biological specimen must be collected at the right time in order to properly classify individual exposure in relation to critical developmental windows. Biomarkers collected in early pregnancy may be too late to detect peri-conceptional exposure if the exposure was transient or if the relevant chemical had a short half-life. Peri-ovulational exposures that affect probability of conception would also be missed in this type of design, as couples who fail to conceive will not enter into prenatal care.
SPECIFIC AIMS 1. Conduct prospective, peri-ovulational biomonitoring for disinfection by-products (DBP) and bis-phenol-A (BPA) in a human preconception cohort using a novel strategy of self-collection of environmental and biological specimens triggered by observation of fertility signs in a community-dwelling population. 2. Evaluate the association between prospectively measured exposures in the male and the female and the reproductive outcomes of semen quality and time to pregnancy. 3. Quantify the degree of misclassification bias generated by retrospective exposure assessment methods in common use (participant self-report of past exposure using a recall questionnaire and/or archival environmental monitoring data) compared to prospective peri-ovulational biomonitoring and sampling. The proposal is to recruit a pre-conception cohort, conduct prospective exposure assessment via biomarkers and questionnaires, evaluate the association of exposure with time to pregnancy, and compare prospectively measured exposures with retrospectively estimated exposures. Collected biospecimens will be banked as a repository for future analyses. Creation of this cohort and specimen bank will launch the independent career of Principal Investigator (Early Stage) Porucznik.
Previous studies of environmental exposures and reproductive outcomes have relied on participant report of exposure around the time of conception from already pregnant couples or couples who have already delivered. This proposed project will recruit couples before they conceive, teach them to identify when pregnancy is likely (the fecund or fertile window) and conduct prospective exposure assessment around each estimated day of ovulation for true, peri-ovulational (peri-conceptional if conception occurs) exposure assessment. Participants will be asked later to report recalled exposures for the peri-ovulational period, and the prospective and retrospective values will be compared to determine the error introduced by recalled exposure assessment in common use.
