Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each microg/dL increase in blood Pb concentration (relative risk (RR)=0.25, 95% confidence interval (CI) 0.03-2.50, P=0.240). For 15 male IVF partners, each microg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR=0.19, 95% CI 0.03-1.35, P=0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses.

We measured toxic metals in seminal plasma collected from 30 men using vitro fertilization (IVF), to evaluate associations with semen quality and IVF outcomes. A doubling in Hg-adjusted Pb concentration was associated with 47% lower total motile sperm. Positive associations were suggested for Hg with pregnancy and live birth, adjusted for Cd or Pb. A negative association was suggested for Hg-adjusted Cd with pregnancy. These data add to evidence indicating that toxic metals impact IVF.

Low-level environmental exposure to Hg, Pb and Cd may interfere with pregnancy during in vitro fertilization (IVF). The aim of this study was to generate hypotheses concerning associations between background exposures and pregnancy. In modified Poisson regression models including 24 women and adjusted for urine Cd and creatinine, blood Pb, age, race and smoking, 1 μg/L increases in blood Hg are associated with decreases of 35% (P=0.03) and 33% (P=0.01) in clinical and biochemical pregnancies, respectively. In alternate Poisson models including 26 women and adjusted for blood Pb, blood Hg, age, race and smoking, 1 μg/L increases in blood Cd are associated with decreases of 94% (P=0.01) and 82% (P=0.04) in clinical and biochemical pregnancies, respectively. No effects are detected in 15 men, although inverse associations are suggested for urine cadmium and pregnancy. These data suggest that low-level, background exposures to Hg and Cd may interfere with pregnancy following IVF.

Here we assess bisphenol A (BPA) in couples undergoing in vitro fertilization (IVF) and indicators of embryo quality; embryo cell number (ECN) and embryo fragmentation score (EFS). Twenty-seven couples provided serum on the day of oocyte retrieval. Unconjugated BPA was measured by HPLC with Coularray detection. Odds ratios (OR) were generated using ordinal logistic regression including female and male BPA concentrations, age and race, and day of embryo transfer for ECN. Inverse associations are suggested for male BPA with ECN (OR=0.70, P=0.069), and EFS (OR=0.54, P=0.009), but not for women. Male BPA exposure may affect embryo quality during IVF.

Are follicular fluid (FF), arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) concentrations associated with IVF outcomes among women undergoing IVF?

We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure.

Persistent organic pollutants (POPs) are ubiquitously distributed among the U.S. population and adversely impact human reproduction. These compounds have been detected in human ovarian follicular fluid (FF), where they directly contact a developing oocyte. As a pilot investigation, we measured 43 polychlorinated biphenyl (PCB) congeners, p,p'-dichlorodiphenyltrichloroethane (DDT), and its persistent metabolite p,p'-dichlorodiphenyldichloroethylene (DDE) in residual FF collected from 32 women undergoing in vitro fertilization (IVF). We identified significant inverse associations between higher levels of PCB congeners and indicators of ovarian reserve (e.g., antral follicle count), follicular response to administered gonadotropins (e.g., peak estradiol, number of oocytes retrieved, endometrial thickness), intermediate IVF endpoints (e.g., oocyte fertilization and embryo quality), and clinical IVF outcomes (e.g., embryo implantation and live birth), after adjusting for body mass index, cigarette smoking, race, and age. Our results suggest that ongoing exposure to POPs impacts IVF and merit confirmation in a larger and more definitive future study.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.

Human exposure to non-essential toxic metals such as cadmium (Cd), mercury (Hg), and lead (Pb), and metalloids such as arsenic (As) commonly occurs through diet. Toxic trace element exposures have been reported in association with fertility and fecundity in epidemiologic studies even at low to moderate levels. While most previous studies employed blood and urine biomarkers of exposure, few have assessed toxic trace elements in ovarian follicular fluid (FF), which surrounds the developing oocyte and hence may better reflect concentrations potentially affecting reproductive outcomes. Our objective was to identify dietary predictors of FF toxic trace elements in n = 56 women (mean age: 38.3 years) undergoing in vitro fertilization (IVF) at the University of California at San Francisco. We determined As, Hg, Cd, and Pb in 197 FF specimens, collected on the day of oocyte retrieval, using inductively coupled plasma tandem mass spectrometry. A comprehensive food frequency questionnaire was used to assess the weekly and annual dietary "patterns" of participants. Consumption of specific seafood items and turkey were correlated with individual FF toxic trace elements. We also found that each unit higher seafood consumption in the past week dominated by mollusks, shrimp, and bass was associated with 60% higher FF As (95% confidence interval (CI): 25%, 105%) and FF Hg (95%CI: 7%, 136%) concentrations. Higher annual seafood consumption dominated by urchin, crab, and trout was associated with 16% higher FF As (95%CI: -2%, 38%) and 31% higher FF Hg (95%CI: 7%, 60%) concentrations per unit intake. No associations were noted between diet and Cd and Pb levels in FF. Overall, our results suggest that higher seafood consumption contributes to elevated levels of As and Hg in FF. These findings are consistent with previous IVF studies that assessed toxic trace element exposures in blood and urine. To our knowledge, this is the first study to report that diet might be a source of As, Hg, Cd, and Pb in FF.