The couples' distinct effects of metals exposure on intermediate and pregnancy outcomes of in vitro fertilization treatment: A prospective cohort study.

Currently, studies on the effects of metal exposure on in vitro fertilization (IVF) outcomes mostly focus on single-metal exposure. To explore the associations based on couples' co-exposure of multiple metals, we enrolled 665 couples. The metal levels in the gamete microenvironment were evaluated by ICP-MS using follicular fluid (FF) and seminal plasma (SP) as specimens, respectively. Generalized linear models (GLMs) and restricted cubic splines (RCS) were utilized to assess the associations between single-metal exposure and IVF outcomes; Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) were used to evaluate the combined effects of metal mixtures. Copper and molybdenum levels in FF were associated with a higher chance of live birth (p for trend: copper, 0.019; molybdenum, 0.043) and lower miscarriage risk (p for trend: copper, 0.025; molybdenum, 0.011). Selenium levels in FF and SP show different trends regarding IVF outcomes. Higher selenium levels in FF (p for trend = 0.015) were related to a lower miscarriage risk, while higher levels in SP were associated with lower chance of clinical pregnancy (p for trend = 0.028) and live birth (p for trend = 0.020). The metal mixtures in both matrices were not significantly related to the likelihoods of the above pregnancy outcome. Regarding intermediate outcomes, lead and barium in FF and vanadium in SP seemed to be detrimental. While, titanium, manganese and copper in FF exhibited beneficial trends. The findings enhance the evidence that heavy and trace metals in the microenvironment of gametes affect IVF outcomes and demonstrate distinct effects from each partner.