Oxidative stress as a mediator of environmental exposure impacts on fertility endpoints

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Understanding the origins of infertility is an important area of environmental health research, as it impacts a substantial proportion of the population and leads to heavy economic burden of treatment and psychological stress. Identifying chemical exposures and underlying mechanisms of toxicant action may enable prevention of these consequences. Urinary phthalate metabolites have been associated with poor fertility outcomes in men, including semen quality parameters such as sperm count, morphology, and motility, as well as sperm DNA integrity. Further, phthalates have been linked to adverse in vitro fertilization (IVF) outcomes in men and women from infertile couples. The strongest associations observed in this body of literature are between phthalate exposure in men and decline in semen quality and increased sperm DNA damage, and between phthalate exposure in infertile women and poorer IVF outcomes (including oocyte yield, clinical pregnancy, and live birth). We hypothesize that oxidative stress is an important mechanism by which phthalates may adversely impact fertility and IVF success. To investigate this question, this study uses data from the Environment and Reproductive Health (EARTH) study, an ongoing prospective cohort begun in 2004 of couples seeking fertility treatment, conducted at Massachusetts General Hospital (MGH) in Boston, MA, USA. In this population recruitment is ongoing, and fertility measures include oocyte yield and antral follicle count, which will be examined in relation to female oxidative stress concentrations, and fertility and pregnancy outcomes (oocyte yield, antral follicle count, implantation, pregnancy loss, and live birth) which will be examined in relation to both male and female oxidative stress levels. In addition, we will investigate mediation of the observed associations between phthalate exposure and fertility and pregnancy endpoints by oxidative stress. Last years progress Over the past year we have completed analysis of urinary oxidative stress biomarkers and have begun statistical analyses to address our primary research questions. One paper is under revision and another is in progress.