Increased Adiposity Enhances Intrafollicular Estradiol Levels in Normoandrogenic Ovulatory Women Receiving Gonadotropin-Releasing Hormone Analog/Recombinant Human Follicle-Stimulating Hormone Therapy for in Vitro Fertilization

Abstract

Body mass index (BMI) reflects the amount of insulin in the human follicle and may enhance insulin action as a cogonadotropin. This study examined whether increased adiposity enhances intrafollicular steroidogenesis in normoandrogenic ovulatory women receiving GnRH analog/recombinant human FSH therapy for in vitro fertilization. Study participants were from an institutional practice and comprised 30 normoandrogenic ovulatory women who were lean (n=17; BMI<25 kg/m2) or overweight (n=13; BMI>or=25 kg/m2). Women received GnRH analog after basal serum hormone determinations and oral glucose tolerance testing, followed by recombinant human FSH therapy and human chorionic gonadotropin administration when two or more follicles 18 mm or larger in diameter were present. Follicle fluid was aspirated at oocyte retrieval from the first follicle of each ovary. Follicle fluid was assayed for estradiol (E2), progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, insulin, glucose, and lactate. Overweight women had hyperinsulinemia (P=0.03) with decreased serum SHBG (P=0.001) and increased serum free testosterone levels (P=0.02). Elevated intrafollicular insulin levels in overweight women (P=0.004) were accompanied by normal glucose and lactate levels. Intrafollicular E2 levels were greater in overweight vs. lean women (P=0.03), whereas the remaining intrafollicular steroid levels were similar in both female groups. In normoandrogenic ovulatory women undergoing in vitro fertilization, increased adiposity elevates insulin and E2 levels in terminally differentiated follicles without altering intrafollicular androgen levels or luteinization. Additional studies are required to determine whether these abnormalities impair oocyte development.