Abstract
Polycystic ovary syndrome is characterized by hyperandrogenism, insulin resistance and exaggerated luteinization of small ovarian follicles. The degree to which PCOS follicles luteinize after gonadotropin therapy for IVF is uncertain, however, because the terminally differentiated follicle requires normal amounts of aromatizable androgens and glucose for steroidogenesis and energy metabolism, respectively. This study examines whether 1) abnormal follicle luteinization, as measured by follicle fluid (FF) P levels and granulosa cell luteinizing hormone (LH) receptor messenger ribonucleic acid (mRNA) expression, occurs in PCOS women undergoing gonadotropin-releasing hormone (GnRH) agonist/ recombinant human (rh) follicle-stimulating hormone (FSH) therapy followed by human chorionic gonadotropin (hCG), and whether it is accompanied by 2) altered intrafollicular steroid or glucose levels. Prospective cohort Eleven PCOS and 30 normoandrogenic ovulatory (NO) women received GnRH agonist/ rhFSH therapy after basal serum hormone determinations and oral glucose tolerance testing. hCG was given when ≥ 2 follicles ≥ 18mm in diameter were present and serum estradiol (E2) levels were ≥300 pg/mL/follicle. At oocyte retrieval, FF was aspirated from the first follicle (>15mm) of each ovary and was assayed for bioactive (bio) LH, immunoreactive (i) FSH, P, 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), E2, insulin and glucose. Quantitative real-time polymerase chain reaction determined LH receptor mRNA expression in mural granulosa (MG) and cumulus cells (CC) of the same follicle. Data are mean ± standard deviation; P<0.05 is significant. Age and body mass index were similar between NO and PCOS women, the latter of whom showed hyperandrogenemia, hyperinsulinemia and 2-hour postprandial hyperglycemia. Degree of pituitary downregulation was similar between NO and PCOS women, as were amount and duration of rhFSH therapy, maximal serum E2 level and serum iFSH concentration at oocyte retrieval. FF E2 levels (NO 3.5±2.0, PCOS 5.0±2.6 ng/mg) were comparable between the two female groups, despite reduced FF iFSH concentrations in PCOS (2.7±1.0 ng/mg) versus NO women (4.1±2.1 ng/mg, P<0.004). With comparable levels of FF bioLH (NO 0.5±0.3, PCOS 0.4±0.2 ng/mg) and insulin (NO 0.1±0.1, PCOS 0.2±0.2 μU/mg), FF P levels were suppressed in PCOS (149.1±83.6) versus NO (220.9±110.1 ng/mg; P<0.01), despite normal MG and CC LH receptor mRNA expression. Conversely, FF glucose levels were elevated in PCOS (13.7±4.8 mg/mg) versus NO women (10.9±3.8 mg/mg, P<0.01). Intrafollicular A and T levels of PCOS women (A 0.9±1.7 ng/mg, T 65.1±65.4 pg/mg) also were greater than those of NO women (A 0.2±0.07 ng/mg, P<0.01; T 26.8±12.3 pg/mg, P<0.001), while FF 17OHP, DHT and DHEA levels were similar between female groups. Hyperandrogenic follicles of PCOS women receiving GnRH agonist/ rhFSH therapy for IVF show reduced P production in the presence of glucose excess, suggesting that their terminal differentiation is perturbed by local androgen excess and/or altered glucose utilization.
Published Version
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