Aims: The overall goal is to characterize the variability of toxic trace elements and anti-oxidant enzyme activities in ovarian follicular fluid (FF) and to identify predictors of variability. A secondary goal is to pilot home seminal plasma (SP) collection and to assess temporal changes in toxic trace elements. Significance: The results of the proposed project will allow us to modify the protocol and analytic strategy for our planned larger study intended to more definitively investigate the impact of trace exposures to toxic elements on in vitro fertilization (IVF) outcomes and race disparities. According to recently released NHANES data, Asians had higher average levels of toxic trace elements than other U.S. race/ethnicities in 2011-2012, including As, Cd, Pb and Hg. In addition, Asian women consistently demonstrate poorer IVF outcomes than white women in the U.S. One probable explanation that has received increasing attention is differential exposure to environmental reproductive toxicants associated with diet and health behaviors, including toxic trace elements. Identification of potentially modifiable toxicant exposures is necessary to design interventions that maximize the likelihood for live birth by IVF or to identify couples with a high risk of failure. However, physicians conducting IVF often collect multiple oocytes, leading to multiple embryos, which are transferred based on clinical factors to maximize the likelihood for a live birth. Investigators are thus unable to ensure oocytes from sampled follicles are transferred and lead to pregnancy and live birth, and so cannot directly link concentrations of analytes measured in FF. Preliminary data from our group and others indicate between-follicles variability for toxic trace elements in FF, and so an inability to implement a one follicle-one pregnancy/delivery investigational study design may reduce statistical power. In the absence of a prohibitively large number of study participants a methodologic solution is required. Innovation: The proposed project is innovative because it is the only study to characterize the variability of toxic trace metals in FF, and to assess their utility as biomarkers of exposure for studying IVF outcomes. Approach: Nearly 1/3 of our U.S. based study population is comprised of Asian women and so we will assess the disparity in relation to toxic trace elements in the normal clinical context of IVF procedures. We will recruit 50 IVF couples from our center, and collect FF from four individual ovarian follicles during oocyte retrieval. We will: 1) measure levels of As, Cd, Pb, Hg and six anti-oxidant enzyme activities in FF to characterize sources of variability between follicles, between ovaries, between women and from analytic factors; 2) consider FF volume, IVF treatment protocol, infertility diagnosis, age, race, body mass index, cigarette smoking, fish consumption and other factors as predictors of FF variability; and 3) pilot a home semen specimen collection strategy to allow evaluation of longitudinal changes in SP toxic trace elements. The likelihood of success is enhanced by the extensive collaborative experience and expertise of the research team.
This study characterizes the variability of toxic trace elements and anti-oxidant enzyme activities in human ovarian follicular fluid (FF) and seminal plasma (SP); demographic and clinical factors will be explored as predictors of variability. In 50 couples undergoing in vitro fertilization (IVF), we will measure arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg), as well as activity levels for six key anti-oxidant enzymes, in four individual ovarian follicles, and in two SP collections across time. The results will allow us to modify the protocol and analytic strategy for our planned larger study to more definitively investigate the impact of trace exposures to toxic elements on IVF outcomes and race disparities.
