Follicular fluid profiling unveils anti-Müllerian hormone alongside glycolytic and mitochondrial dysfunction as markers of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, yet the molecular mechanisms influencing its pathophysiology remain poorly defined. A comprehensive prospective case-control study was conducted to elucidate the follicular fluid (FF) hormone and metabolite profile in women with PCOS and its implications for oocyte maturation and fertilization. The study involved 40 age- and body mass index (BMI)-matched women undergoing in vitro fertilization (IVF), including 20 diagnosed with PCOS and 20 controls with infertility due to tubal or male factors. A distinctive hormone profile in the FF of women with PCOS was identified, characterized by significantly higher anti-Müllerian hormone (AMH) levels (24.90 ± 17.61 vs. 16.68 ± 17.67 pmol/L, p = 0.0039) and lower progesterone (8253 ± 4748 vs. 25362 ± 10862 ng/mL, p < 0.0001) and estradiol levels (388.23 ± 210.58 vs. 651.48 ± 390.79 ng/mL, p = 0.0208) compared to normoovulatory controls. Moreover, a metabolite fingerprint associated with glycolytic and mitochondrial dysfunction was observed, as evidenced by lower lactate (4575.44 ± 1507.76 vs. 5595.34 ± 1073.32 μmol/L, p = 0.0182) and formate (64.51 ± 16.06 vs. 75.81 ± 16.63 μmol/L, p = 0.0351) levels and higher citrate levels (136.93 ± 52.53 vs. 109.15 ± 24.17 μmol/L, p = 0.0409) in the FF of women with PCOS. These findings suggest that the molecular profile of the FF in women with PCOS might be related to granulosa cell glycolytic and mitochondrial dysfunction, which can have a negative impact on oocyte fertilization potential. The study provides an integrative analysis of the FF hormone and metabolite profile in women with PCOS, offering insights into the molecular mechanisms underlying the reproductive dysfunctions associated with this condition.