Although the use of polychlorinated biphenyls (PCBs) and many of the chlorinated pesticides, including DDT, are now prohibited or restricted, there remains concern over their potential human health effects because they persist in the environment, concentrate up the food chain, and are stored in adipose tissue. Laboratory studies show associations of environmentally relevant levels of PCBs and chlorinated pesticides with infertility and pregnancy loss through mechanisms that disrupt embryo development. Epidemiologic studies report associations of PCBs and DDE (stable DDT metabolite) with pregnancy loss. In the proposed study, we will explore the developmental toxicity of chlorinated compounds in women undergoing in vitro fertilization (IVF), which can be used as a model to assess early development, normally unobservable. Developmental endpoints that will be measured include oocyte production, fertilization, and pre- and post-implantation embryo development. Failure at these developmental stages results in infertility and pregnancy loss. Other measured endpoints include clinical pregnancy loss (spontaneous miscarriage and stillbirth) and peri-natal outcomes, such as birth weight. The proposed study is cost-effective because it uses data and specimens from a recently completed NICHD funded multi-center study on epidemiologic predictors of IVF success. In the multi-center study there is data on 2494 couples undergoing 5071 IVF cycles between 1994 and 2003. Serum and ovarian follicular fluid were collected and archived from the female partner and will be used to measure PCBs and chlorinated pesticides such as DDE, hexachlorobenzene, mirex, and the chlordane metabolites, trans-nonachlor and oxychlordane. Subjects completed detailed health and lifestyle questionnaires and information on IVF protocols and pregnancy outcomes were abstracted from patient medical records. The study design is novel because it uses IVF as a model system to study the associations of PCBs and chlorinated pesticides with failure of early development, which manifests clinically as infertility and early pregnancy loss. Early developmental failure represents the majority of losses of pregnancy and is considered the most sensitive developmental stage to PCB and chlorinated pesticide exposure. Since the etiology of infertility and early pregnancy loss remains largely unexplained, the identification of potential environmental risk factors will have large public health significance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES013967-04
Application #
7647423
Study Section
Special Emphasis Panel (ZRG1-IRAP-Q (01))
Program Officer
Dilworth, Caroline H
Project Start
2006-09-25
Project End
2012-06-30
Budget Start
2009-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$566,886
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Maity, Arnab; Williams, Paige L; Ryan, Louise et al. (2014) Analysis of in vitro fertilization data with multiple outcomes using discrete time-to-event analysis. Stat Med 33:1738-49
Benedict, Merle D; Missmer, Stacey A; Ferguson, Kelly K et al. (2012) Secondhand tobacco smoke exposure is associated with prolactin but not thyroid stimulating hormone among nonsmoking women seeking in vitro fertilization. Environ Toxicol Pharmacol 34:761-7
Johnson, Paula I; Altshul, Larisa; Cramer, Daniel W et al. (2012) Serum and follicular fluid concentrations of polybrominated diphenyl ethers and in-vitro fertilization outcome. Environ Int 45:9-14
Mahalingaiah, Shruthi; Missmer, Stacey A; Maity, Arnab et al. (2012) Association of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) with in vitro fertilization (IVF) outcomes. Environ Health Perspect 120:316-20
Humblet, Olivier; Sergeyev, Oleg; Altshul, Larisa et al. (2011) Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009. Environ Health 10:62
Benedict, Merle D; Missmer, Stacey A; Vahratian, Anjel et al. (2011) Secondhand tobacco smoke exposure is associated with increased risk of failed implantation and reduced IVF success. Hum Reprod 26:2525-31
Meeker, John D; Maity, Arnab; Missmer, Stacey A et al. (2011) Serum concentrations of polychlorinated biphenyls in relation to in vitro fertilization outcomes. Environ Health Perspect 119:1010-6
Missmer, Stacey A; Pearson, Kimberly R; Ryan, Louise M et al. (2011) Analysis of multiple-cycle data from couples undergoing in vitro fertilization: methodologic issues and statistical approaches. Epidemiology 22:497-504
Benedict, Merle D; Missmer, Stacey A; Vitonis, Allison F et al. (2011) Cotinine concentrations in follicular fluid as a measure of secondhand tobacco smoke exposure in women undergoing in vitro fertilization: inter-matrix comparisons with urine and temporal variability. Chemosphere 84:110-6
Meeker, John D; Missmer, Stacey A; Altshul, Larisa et al. (2009) Serum and follicular fluid organochlorine concentrations among women undergoing assisted reproduction technologies. Environ Health 8:32

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