Association of Model-Predicted Epigenetic Age and Female Infertility.

Background: To date, there are no precise clinical and laboratory methods to accurately predict the onset of fertility decline in women, with chronological age being the ultimate predictor. This has led to increased interest in developing methods to determine biological age, as it provides a more accurate understanding of individual age-related physiological changes.

Methods: In this study, we developed a model for estimating biological age based on DNA methylation levels in the ELOVL2, TRIM59, C1orf132, FHL2, and KLF14 genes using pyrosequencing. The model was tested in 64 Russian women, aged 25-39 years, to find an association between epigenetic age, infertility, low anti-Müllerian hormone (AMH) levels, and assisted reproductive technology (ART) failure.

Results: The predictive performance of the model was evaluated. The mean absolute deviation of the model was 2.8 years; the mean absolute error was 2.6 years (R² = 0.95). In the studied cohort, 33% of women exhibited epigenetic age acceleration (EAA), while 45% showed epigenetic age deceleration (EAD). All women with an EAA of ≥3 years (n = 6) had a history of infertility.

Conclusions: In this study, no statistically significant associations were observed between EAA/EAD and AMH, body mass index, infertility, or ART failure in women.