Environmental Factor, April 2011, National Institute of Environmental Health Sciences
Infertility linked to PCB exposure
Meeker is also the principal investigator on an NIEHS grant(https://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=R01ES018872) to research bisphenol A and phthalate exposure in relation to fetal growth and preterm birth. (Photo courtesy of John Meeker)
Hauser is principal investigator on an additional three NIEHS grants on the effects of environmental exposures on fertility and development, as well as children's health. (Photo courtesy of Russ Hauser)
In an NIH-funded study published in February, investigators report that polychlorinated biphenyls (PCBs), in concentrations representative among the general U.S. population, were associated with failed embryo implantations in women undergoing in vitro fertilization (IVF). Although PCB production was banned in the U.S. and other developed countries more than 30 years ago, they were used extensively and persist in the environment, making exposure a significant public health issue even today.
As far as they are aware, the researchers believe this investigation represents the first use of IVF to explore the association of PCBs and chlorinated pesticides with infertility and early pregnancy loss. "This study population," they write, "serves as a unique model to study early pregnancy endpoints that are not otherwise observable in women conceiving naturally."
The team of scientists was led by John Meeker, Sc.D.(http://www.sph.umich.edu/iscr/faculty/profile.cfm?uniqname=meekerj) , first and corresponding author, and Russ Hauser, M.D., Sc.D.(http://www.hsph.harvard.edu/faculty/russ-hauser/) , principal investigator. Meeker is an assistant professor at the University of Michigan School of Public Health, and Hauser is the Frederick Lee Hisaw Professor of Reproductive Physiology at the Harvard School of Public Health. The study was conducted in collaboration with Daniel Cramer, M.D., Sc.D., and Stacey Missmer, Sc.D., of Brigham and Women's Hospital in Boston.
PCBs in the environment
The general population is exposed to PCBs primarily through ingestion of contaminated food, such as fish, meat, and dairy products, but also through occupational, ambient, and indoor sources. The half-life of PCBs in the blood ranges from one to more than ten years. Exposure to PCBs has been associated with a range of adverse health effects, including adverse effects on reproduction and increased risk of pregnancy loss.
Animal studies have demonstrated associations between PCB exposure and endometriosis and altered menstrual cycles. Exposure impairs oocyte maturation and adversely affects blastocyst formation and embryo development.
Consistent with earlier findings
Analysis of serum samples of 765 women, with a mean age of 36, undergoing 827 in vitro fertilization cycles between the years 1994 and 2003 showed dose-dependent trends of PCBs with increased odds of failed implantation and reduced live births. Three PCB congeners - PCBs 118, 138, and 153 - were analyzed in relationship to IVF outcome, individually and in sum.
PCB 153 individually showed the strongest association with IVF outcome. The odds of failed implantations were doubled and the odds of live birth were reduced by 41% among women with the highest concentrations of PCB 153, compared to women with the lowest concentrations.
The authors explain that their results are consistent with epidemiological studies of PCB exposure and time to pregnancy (TTP), an endpoint that lacks specificity since it may represent one or more aspects of male or female reproductive health.
Looking to the future
Although this prospective study gains strength from its large sample size, and examination of exposure biomarkers and outcome measures collected at or near the likely time window of interest, the researchers acknowledge that it has some limitations.
Oocyte qualities were not included, nor were serum PCB levels of male partners. Reductions in semen quality have been reported in relation to PCB exposure, which may also contribute to the success of IVF. As with nearly all environmental epidemiologic studies, there remain questions of causality and confounding co-exposures. In addition, the generalizability of findings for women undergoing IVF to wider populations is unknown.
The etiology of infertility and early pregnancy loss remains largely unexplained. The results from this study will help to understand and identify potential environmental risk factors for this important public health challenge. "These findings may help explain previous reports of reduced fecundability and increased TTP among women exposed to PCBs," the researchers conclude.
The study was funded by an NIEHS grant(https://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=R01ES013967) and by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Citation: Meeker JD, Maity A, Missmer SA, Williams PL, Mahalingaiah S, Ehrlich S, Berry KF, Altshul L, Perry MJ, Cramer DW, Hauser R. 2011. Serum concentrations of polychlorinated biphenyls (PCBs) in relation to in vitro fertilization (IVF) outcomes. Environ Health Perspect; doi:10.1289/ehp.1002922 [Online 24 Feb 2011].
(Angelika Zaremba, Ph.D., is a visiting postdoctoral fellow in the NIEHS Laboratory of Signal Transduction Inositol Signaling Group.)