Legacy and Alternative Flame Retardant Exposures Among Couples Seeking Fertility Treatment and Their Fertility Relevant Outcomes

Abstract

Infertility, the inability to conceive after one year of unprotected intercourse, affects approximately one out of every seven couples in the United States (US). In the last decade, 7.3 million Americans reported using fertility services. Infertility limits the likelihood of a live birth, but has also been associated with other reproductive diseases, psychosocial stress, and economic hardship. An infertility diagnosis can arise from female or male factors, or a combination of both. Currently, the use of assisted reproductive technologies (ART) including in vitro fertilization (IVF) is steadily on the rise. Human reproduction is a composite of multiple biological responses which occur in phases, many of which occur without observation. Each phase is susceptible to exposures to various environmental toxicants, including flame retardants (FR) commonly found in furniture foams, carpeting, electronics, and plastics. Their lack of covalent bonds allows for leaching into the surrounding environment and thus lead to widespread exposure. Although some FRs have been phased out of production, they persist in the environment and the use of alternative compounds is increasing. Legacy FRs such as polybrominated diphenyl ethers (PBDEs) and alternative FRs like organophosphate esters (OPEs), have been widely detected among the US population. Laboratory studies suggest PBDEs and OPEs are reproductive toxicants, yet human data are lacking. Furthermore, studies suggest that some PBDE metabolites, such as hydroxylated brominated diphenyl ethers (OH-BDEs), may elicit greater toxic effects compared to their respective parent compounds. The three aims of this dissertation were executed using data from a subset of couples from the Environment and Reproductive Health (EARTH) study, an existing longitudinal pre-conception cohort assessing the impact of environmental, dietary and lifestyle factors on fertility among women from a fertility clinic in Boston. The first aim evaluated the relationships of serum PBDE congeners and OH-BDE metabolites with early developmental (intermediate) and pregnancy (clinical) IVF outcomes among women seeking fertility treatment. The second aim investigated the joint effects of PBDE and OH-BDE exposure of women and their male partners with intermediate and clinical IVF outcomes. The final aim evaluated (1) whether exposure to OPEs as determined by levels of their urinary metabolites, was associated with in-home exposures and (2) the associations of OPE metabolites with male fertility. We observed a steady decline in PBDE concentrations over the ten-year study period. Concentrations of all FRs were higher in women compared to their male partners. We observed unexpected positive associations between female PBDE and OH-BDE concentrations and clinical IVF outcomes. However, when also accounting for male exposure, effect estimates diminished lost statistical significance. We observed a slight increase in OPE metabolite concentrations in the final years of recruitment. The use of several personal care and household products were associated with elevated OPE metabolite concentrations among couples. However, associations of OPE metabolites with male fertility were weak and inconsistent. This dissertation highlights the persistence of PBDEs and their metabolites despite being phased out of production. Furthermore, our novel study design underscores the importance of considering male exposures when evaluating the relationships of environmental toxicants with fertility and pregnancy outcomes. This work highlights the persistence of FRs and suggests PCPs can be an important source of OPE exposure and warrants future investigations of their possible reproductive toxicity.