Heavy metals and diminished ovarian reserve: single-exposure and mixture analyses amongst women consulting in French fertility centres

Research question Do heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age? Design We included 139 cases and 153 controls between 2016-2020. The participants were aged 18-40 and consulted for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count < 7 and/or anti-müllerian hormone levels ≤ 1.1 ng/ml. Controls were frequency matched on age groups and centres and were women with normal ovarian reserve evaluations, no malformations, and menstrual cycles between 26-35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR). Results We observed non-significant increased risks of DOR for cadmium (OR 1.89, 95% CI 0.98 - 3.67, for the second tercile of exposure and OR 1.18, 95% CI 0.55 - 2.52, for the third tercile) and chromium (OR 1.24, 95% CI 0.65 - 2.39, for the second tercile of exposure and OR 1.77, 95% CI 0.84 - 3.70, for the third tercile). Quantile g-computation and BKMR both yielded a non-significant increased risk of DOR for the mixture of metals, with no evidence of interaction. Conclusions We detected weak signals that some heavy metals could be associated with DOR. These findings should be replicated in other studies.