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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

National Primate Research Center (D.H.A., D.A.D.), University of Wisconsin, Madison, Wisconsin 53715; Department of Obstetrics/Gynecology (D.H.A.), University of Wisconsin, Madison, Wisconsin 53792; Reproductive Medicine and Infertility Associates (D.A.D.), Woodbury, Minnesota 55125; and Department of Biostatistics (T.G.L.), Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Daniel A. Dumesic, M.D., Reproductive Medicine and Infertility Associates, 2101 Woodwinds Drive, Woodbury, Minnesota 55125. E-mail: danieldumesic{at}aol.com.

Context: Body mass index (BMI) reflects the amount of insulin in the human follicle and may enhance insulin action as a cogonadotropin.

Objective: This study examined whether increased adiposity enhances intrafollicular steroidogenesis in normoandrogenic ovulatory women receiving GnRH analog/recombinant human FSH therapy for in vitro fertilization.

Design, Setting, and Participants: 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 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.

Intervention: Follicle fluid was aspirated at oocyte retrieval from the first follicle of each ovary.

Main Outcome Measures: Follicle fluid was assayed for estradiol (E₂), progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, insulin, glucose, and lactate.

Results: 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.

Conclusion: 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.