Association between serum elementomics of 48 elements and female fecundity: evidence from a nested case-control study in China

Infertility is an increasingly global issue, with exposure to various elements linked to female fertility; however, comprehensive studies on the effects of simultaneous exposure to multiple elements are lacking. In this research, we used a nested case-control design within a pre-pregnancy cohort, examining serum samples from 142 infertile women and 139 controls who attempted conception between 2019 and 2022. The study assessed 48 elements using inductively coupled plasma-mass spectrometry and identified key elements affecting infertility risk through advanced statistical techniques, including Elastic Net Regression and Bayesian Kernel Machine Regression (BKMR). The interaction effects of elements were further explored using Generalized Additive Models (GAM), and their impacts on time to pregnancy (TTP) were analyzed through Kaplan-Meier and Cox regression analyses. The findings reveal that higher levels of Cd are positively linked to infertility, while elements like Fe, Cs, Sb, and Y may offer protective effects. Further BKMR analysis indicated that the mixture of identified elements had a combined effect on infertility risk in a nearly linear manner, with Fe and Cd being major contributors. A notable interaction between Cd and Fe was found, where low Fe and high Cd levels were associated with a higher risk of infertility and a longer TTP. Our results suggest that Fe supplementation and reducing Cd exposure could decrease the likelihood of infertility. This study underscores the complex interactions of elemental exposures on reproductive health. These findings highlight the potential need for public health interventions to reduce Cd exposure and promote Fe supplementation for women preparing for pregnancy. Additional research is required to investigate the underlying biological mechanisms and confirm these findings across various populations.