Elevated levels of diabetes-associated peptide hormones in the follicular fluid and serum of obese polycystic ovary syndrome patients are associated with suboptimal ovarian response

Objective: To compare diabetes-associated peptide hormones (DAPHs) and inflammatory markers in the follicular fluid (FF) and serum among polycystic ovary syndrome (PCOS) patients as compared to controls undergoing in vitro fertilization (IVF). Study Design: Levels of DAPHs and inflammatory markers in FF and serum were measured and correlated to IVF cycle outcomes and clinical pregnancy rate in three IVF groups: obese PCOS (n = 8), lean PCOS (n = 12), and controls (n = 11). Methods: Follicular fluid and serum were prosectively collected from obese and lean pcos and control females undergoing IVF. BioFlex ® array was used to analyze all samples from subjects. IVF cycle outcomes were collected on all subjects. Results: Ten DAPHs were assessed. Obese PCOS had higher levels of C-peptide (194.4 ± 163.5 pg/mL, P< 0.03), insulin (172.6 ± 113.6 pg/mL, P< 0.01), and leptin (10,046.1 ± 4920.2 pg/mL, P< 0.05) in FF as compared to lean PCOS and controls. Obese PCOS patients had higher levels of serum leptin (5575.5 ± 1650.2 pg/mL), with a difference in leptin concentrations noted between obese PCOS and controls (P < 0.01) and between obese and lean PCOS patients (P < 0.01). Higher levels of C-peptide (P < 0.04) and leptin (P < 0.01) in the FF were associated with increased total gonadotropin drug usage. There was a trend toward fewer oocytes retrieved (P < 0.06) and significantly lower number of normally fertilized zygotes (P < 0.04), with higher C-peptide levels. A trend toward increased clinical pregnancy rates was noted with lower serum levels of leptin (P < 0.08). Conclusions: DAPHs may play a role in the suboptimal ovarian response seen in obese IVF patients with PCOS as compared to lean PCOS patients and controls. Further studies are needed to understand if the evaluations in DAPH are secondary to obesity itself or are specific to this subset of PCOS patients.