BMI and idiopathic infertility drive polarized redox phenotypes in human follicular fluid

Background: Oxidative balance within follicular fluid (FF) plays an important role in oocyte competence and female fertility. However, most previous studies have focused on isolated oxidative biomarkers rather than on the coordinated organization of the follicular redox system. This study aimed to identify system-level oxidative phenotypes within FF and evaluate their associations with infertility-related clinical and metabolic factors. Methods: Seventy-seven women undergoing IVF treatment were included. Nineteen oxidative and antioxidative biomarkers were measured in FF collected separately from both ovaries. Bayesian multivariable regression with Markov chain Monte Carlo inference was combined with directional indicator analysis and unsupervised taxonomic clustering to identify latent oxidative phenotypes. Results: Two structurally distinct and antagonistically organized oxidative phenotypes were identified within FF. Phenotype 1 comprised biomarkers representing the primary antioxidant defense system, whereas Phenotype 2 included enzymes involved predominantly in secondary detoxification pathways. Idiopathic infertility and BMI demonstrated significant and opposite directional effects across the two phenotypes. Specifically, increasing BMI and idiopathic infertility were associated with decreased activity of biomarkers belonging to Phenotype 1 and increased activity of biomarkers assigned to Phenotype 2 (p = 0.0177 and p = 0.0097, respectively). Conclusions: The follicular redox environment demonstrates a polarized and system-level biochemical architecture rather than uniform oxidative alterations. BMI and idiopathic infertility appear to selectively reorganize oxidative pathways within FF through opposite effects on two antagonistically structured phenotypes. These findings suggest a shared pathophysiological mechanism reorganizing the follicular antioxidant network in both conditions and challenge the single-biomarker paradigm in reproductive oxidative stress research.