Authors
Greenlee, A., Arbuckle, T., and Chyou, P.

Title
Risk Factors for Female Infertility in an Agricultural Region

Journal
Epidemiology. 14: 429-436. 2003.

Summary
Pesticides have undergone intense scrutiny for their potential role in a variety of health outcomes. Pesticide exposure has been associated with altered semen parameters in men, and recent studies have suggested that agricultural occupations or exposure to pesticides may also impair female fertility. Although the mechanisms through which pesticides influence female fertility have not been fully elucidated, there is some evidence from animal models which demonstrate effects consistent with endocrine disruption. Interference with hormone signaling at the hypothalamic-pituitary axis may disrupt critical stages in the preparation for conception such as attenuating lutenizing hormone surges and disrupting normal menstrual cycle patterns. The risk of female infertility as related to agricultural and residential exposures was examined retrospectively in patients seeking infertility treatment at a medical clinic in Wisconsin.

Greenlee et al. identified potential cases through a review of the electronic medical records of all patients seeking infertility treatment. Cases included women 18-35 years of age who did not conceive a pregnancy ending in live birth after at least 12 months of unprotected intercourse. It was required that a male partner of each case agree to participate in the study. Controls were selected from women seeking medical care during their first trimester of pregnancy. This group was comprised of women aged 18-35 years of age, who conceived within 12 months of trying and had a male partner who agreed to participate in the study. A total of 322 eligible cases and an equal number of controls were included in the study. Participants were asked to answer questions pertaining to the 2 years prior to their pregnancy attempt. This included information regarding demographics, tobacco and alcohol use, adult weight pattern, occupational history, pesticide use at work or around the home, drinking water source, milk consumption, and medical and reproductive history.

The author's found that exposure to herbicides in women at any time during the 2-year period before trying to conceive was associated with a significantly increased risk of infertility (odds ratio (OR) =26.9, 95% confidence interval (CI) =1.9-384.8). Risk of infertility was also associated with fungicide use by either partner (women: OR=3.3, 95% CI=0.8-13.2; men: OR=1.5, CI=0.7-3.2). These results were adjusted for level of education, smoke exposure, and per capita income. Conversely, farm or rural residency, and drinking water from private wells as opposed to the municipal water supply were associated with a decreased risk of infertility.

This study suggests that herbicide and fungicide exposure are related to the risk of female infertility. However, these results must be viewed cautiously due to the small number of subjects in each specific exposure category and the possibility of recall bias attributed to the self-reporting of risk factor information by the study participants. This study also highlights the difficulty of assessing the effects of exposure to multiple chemicals. The number of women in each risk factor category was not sufficient to examine pesticide exposures by individual products or by active ingredients. Due to the heterogeneous nature of endocrine disrupting chemicals, assessing the effects of mixtures is difficult, as exposure to mixtures of these compounds may produce additive, synergistic or antagonistic effects. Most of the current evidence demonstrating the effects of pesticides on infertility has been generated using single chemicals in animal models, whereas humans are exposed at a variety of levels to many different substances. In addition, most of the cases in this study had an infertility diagnosis of unspecified origin, further compounding the difficulty of comparing relevant pesticide exposures and specific outcomes.