The associations of serum metals concentrations with the intermediate and pregnancy outcomes in women undergoing in vitro fertilization (IVF)

Toxic and essential trace elements are reported to have impact on female fertility. However, studies on the potential synergistic or antagonistic effects of metal mixtures on IVF outcomes remain limited.To evaluate whether serum concentrations of metals, individually and as mixtures, are associated with pregnancy outcomes in women undergoing IVF.In a prospective birth cohort study about IVF from the First Affiliated Hospital of Anhui Medical University (n = 1184), we measured the concentrations of serum metals by ICP-MS according to a previously established method. Oocyte/embryo development indicators and follow-up results were also collected. The individual and joint effects of metals were estimated using logistic regressions and Bayesian kernel machine regressions (BKMR).At embryonic stage, we found negative associations between the serum lead (Pb) (β = -0.14, 95%CI: -0.32, -0.04) and cadmium (Cd) (β = -0.24, 95%CI: -0.39, -0.09) concentrations and the high-quality embryos rate; and positive associations between the serum cobalt (Co) (β = 0.18, 95%CI: 0.05, 0.31) and selenium (Se) (β = 0.17, 95%CI: 0.06, 0.41) concentrations and the MII rate. Regarding to the pregnancy outcomes, the serum Pb was negatively related with successful implantation (OR=0.85, 95%CI: 0.77, 0.94) and clinical pregnancy (OR=0.95, 95%CI: 0.91, 0.99); and positively associated with spontaneous abortion (OR=1.39, 95% CI: 1.02, 1.91). The BKMR analysis showed linear or parabolic associations between the metal mixtures and pregnancy outcomes, with Pb showing the highest posterior inclusion probabilities.The toxic (Pb, Cd) and essential (Co, Se) metals could be incorporated as simultaneous predictors of IVF outcomes including potential antagonistic effects, in which Pb exhibits major contributions.