Comparison of intra-ovarian metabolic environment between women with or without PCOS undergoing in vitro fertilization

Abstract

Context: Evidence suggest that lipotoxicity can cause hyperandrogenesis, the main feature of polycystic ovary syndrome (PCOS), but little is known about the intra-ovarian environment of women with PCOS and whether it displays features associated with lipotoxicity. Here we present a secondary analysis of data collected in a cross-sectional study aimed at evaluating the associations between follicular fluid androgen levels and markers of dysmetabolism in women seeking in vitro fertilization. Objective: To compare follicular fluid concentrations of testosterone, markers of lipid, lipid metabolism and inflammation between women with PCOS and without PCOS. Design: Controlled cross-sectional study. Setting: A private fertility clinic and one academic centre. Patients: Eighty (80) participants were recruited during one of their scheduled visits for an in vitro fertilization procedure. Medical records were used to determine PCOS diagnosis: 13 women were identified as having PCOS, while 58 had a negative diagnosis of PCOS, and 9 had an uncertain diagnostic. Patients were eligible if they were between 18 and 40 years old with a body mass index raging between 18 and 40 kg/m². Exposure(s): Participants were defined as affected by PCOS or not. Main Outcome Measure(s): Follicular fluid retrieved at the time of oocyte aspiration was analysed for total testosterone, non-esterified fatty acids (NEFA), triglycerides, NEFA metabolites (acylcarnitines and C16/C13 ratio as a marker of ineffective NEFA beta-oxidation) and inflammatory cytokines. Results: When compared to women without PCOS, women with PCOS had increased follicular fluid levels of testosterone (by definition; 12.9 nM vs 0.29 nM; P<0.001), NEFA (0.27 nM vs 0.24 nM; P=0.051), triglycerides (0.30 nM vs 0.16 nM; P<0.001), acylcarnitines C16/C3 ratio (34.9 % vs 25.8 %; P=0.013), IL-6 (13.0 pg/mL vs 8.6 pg/mL; P=0.02), while TNF-α remained similar (2.22 pg/mL vs 2.11 pg/mL; P=0.78). These differences remained statistically different after adjustment for BMI, except for IL-6. These group differences were also confirmed in paired analyses of 13 BMI-matched pairs of PCOS vs non-PCOS women, except for C16/C3 ratio and IL-6. Conclusion: These results suggest a role for intra-ovarian inflammation, but more importantly, lipid overexposure and ineffective lipid oxidation, in the pathogenesis of PCOS, probably through lipotoxic effects.