Multiple exposures to persistent organic pollutants and diminished ovarian reserve: findings from a French case-control study

Abstract

BACKGROUND AND AIM: The main cause of female infertility after the age of 35 is diminished ovarian reserve (DOR). Several persistent organic pollutants (POPs) have been associated with an increased time-to-pregnancy but research on the effect of POPs on DOR is limited. METHODS: Our study included 139 cases and 153 controls from the AROPE case-control study. Study participants were women between the ages of 18 and 40 recruited amongst couples consulting for infertility in four fertility centres in western France. Cases were women with DOR (defined as anti-müllerian hormone levels 1.1 ng/ml and/or antral follicle count 7) and controls were women with normal evaluations, no malformations, and regular menstrual cycles. 41 POPs (including 15 organochlorine pesticides, 15 polychlorinated biphenyls and 9 polybromodiphenylethers) were measured in blood serum at inclusion. We conducted logistic regression adjusted on potential confounders to study the effect of each POP on DOR separately. In addition, we used Bayesian Kernel Machine Regression (BKMR) to measure the mixture effect of POPs on DOR. RESULTS:17 POPs were detected in over 20% of the serum samples. Individual multivariate logistic regressions showed that p,p’-DDE was associated with an increased risk of DOR (OR=1.50 [0.78 - 2.89] for the second tercile and OR=1.93 [1.00 - 3.73] for the third tercile) and Beta-HCH was associated with a decreased risk of DOR (OR=0.76 [0.42 - 1.40] for the second tercile and OR=0.45 [0.23 - 0.88] for the third tercile). BKMR showed similar associations for individual exposures but found no significant associations for the total mixture effect. In addition, BKMR results suggested an absence of interactions between POPs. CONCLUSIONS:Although BKMR indicated no interaction between POPs and no associations for POPs as a mixture, certain POPs could be individually associated with DOR. KEYWORDS: Reproductive outcomes, Female, Chemical exposures, Endocrine disrupting chemicals, Mixtures