Toxic trace elements in follicular fluid, oxidative stress, and in vitro fertilization (IVF) outcomes

Exposures to environmental contaminants, including non-essential toxic trace elements, may be associated with in vitro fertilization (IVF) outcomes. Follicular fluid (FF) envelops the developing oocyte, offering a “snapshot” of the oocyte microenvironment. FF may better estimate trace element concentrations associated with IVF outcomes than more commonly employed blood and urine biomarkers of exposure. Hence, FF concentrations of four widespread non-essential toxic trace elements (arsenic, mercury, cadmium, and lead) were investigated in relation to a spectrum of IVF endpoints in n=56 women undergoing IVF. Antioxidant activity was explored as an intervening variable and dietary exposure sources of non-essential toxic trace elements in FF were characterized. A reliability assessment was conducted to attribute sources of variability for trace elements. Variability between subjects (women) contributed the greatest proportion of variability measured for FF As and Hg, Cd, Cu, Se, and Zn concentrations compared to variability between ovaries, between follicles, and that attributed to analytic factors. Differences in the proportion of variability attributable to follicles by age, BMI (kg/m2), race, history of smoking, primary infertility diagnosis and stimulation protocol were detected, and FF was identified as an appropriate biomarker of As and Hg exposures for use in epidemiologic studies of IVF outcomes. Associations between non-essential toxic trace elements with several IVF endpoints (oocyte maturity, fertilization, measures of embryo quality, biochemical pregnancy, and live birth) were investigated. Statistically significant relationships were detected for FF Hg with biochemical pregnancy and live birth, and for FF Pb and live birth, in which higher concentrations were associated with a lower likelihood of successful outcomes. Finally, associations between consumption of select seafood and other dietary items with non-essential toxic trace elements were evaluated to identify patterns predictive of FF concentrations. Consumption of heavy seafood diets was associated with greater FF concentrations of As and Hg.