Objective:

To investigate the distribution of heavy metals and essential trace elements in follicular fluid (FF) and their association with diminished ovarian reserve (DOR).

Approach:

• Study Design: A hospital-based case–control study was conducted with 195 participants in the DOR group and 237 controls matched for demographic confounders.
• Data Collection: Baseline clinical data and FF samples were analyzed using inductively coupled plasma mass spectrometry.
• Statistical Analysis: Associations were evaluated using Spearman correlation analysis, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and least absolute shrinkage and selection operator (LASSO) regression.

Key Findings:

• FF concentrations of arsenic (As), strontium (Sr), and calcium (Ca) were significantly higher in the DOR group (P(As) = 0.001, P(Sr) < 0.001, P(Ca) = 0.002).
• Logistic regression demonstrated that As (odds ratio [OR] = 4.727, 95% confidence interval [CI]: 2.456–9.611) and Sr (OR = 1.984, 95% CI: 1.350–2.985) were associated with higher odds of DOR, whereas copper (OR = 0.552, 95% CI: 0.359–0.831), vanadium (OR = 0.366, 95% CI: 0.183–0.716), and zinc (OR = 0.497, 95% CI: 0.308–0.789) were associated with lower odds.
• WQS regression identified Sr, As, and Ca as the primary contributors to the mixture effect on DOR.

Interpretation:

Heavy metals and essential trace elements in FF exhibit joint mixture effects in the pathogenesis of DOR, with specific elements showing independent associations.

Limitations:

• The study was limited to women undergoing ICSI, which may not represent the general population.
• Potential confounding factors beyond age and BMI were not fully controlled.

Conclusion:

Maintaining local trace element homeostasis may be critical for preserving ovarian reserve.