A case-control study on the link between trace element exposure in follicular fluid and premature ovarian insufficiency

Premature ovarian insufficiency (POI), affecting 3.5 % of women under 40, significantly impacts reproductive health. The unknown etiology in over 50 % of POI cases impedes accurate diagnosis and treatment. Evidence shows that environmental agents can adversely affect health and reduce fertility. Trace elements are critical pollutants impacting human health. However, research on populations with POI and their links to these elements is limited. We enrolled 367 female patients, dividing them into a POI group and a control group. We employed ICP-MS to measure 25 trace elements in follicular fluid. Bayesian kernel machine regression analyzed combined exposure effects and restricted cubic splines evaluated the relationships between individual trace elements and ovarian reserve markers, focusing on anti-Müllerian hormone (AMH) and basal FSH (bFSH). Logistic regression assessed the association between specific element concentrations and POI occurrence, and the posterior inclusion probability model tested the robustness of key driving factors. The study identified 24 trace elements in follicular fluid samples, revealing significant differences in 23 elements between the two groups. There were positive correlations between Cu, I, Se, and Zn with AMH levels, while negative correlations were observed for Ca, Co, Li, and AMH. Nonlinear relationships were noted for Ba, Cd, Fe, Mg, Mn, Mo, and Pb. Ca, Li, and Ni showed a significant positive correlation with bFSH, while Cu, I, Mg, Se, and Zn demonstrated a significant negative correlation with bFSH. Additionally, Ba, Mn, and Pb exhibited a nonlinear correlation with bFSH. Individuals in the medium and high tertiles for Cu, I, Pb, Se, and Zn were less likely to develop POI. In contrast, those in the medium and high tertiles for Ba, Ca, Cd, Li, Mn, and Ni had an increased likelihood of POI. Our study addresses a crucial gap by examining trace element exposure in follicular fluid and its link to POI risk, enhancing understanding of their effects on female ovarian function. This study lays a foundation for monitoring female fertility and emphasizes the importance of environmental pollutants on reproductive health.