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This version published online on January 23, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2161
A more recent version of this article appeared on April 1, 2007
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Submitted on October 3, 2006
Accepted on January 17, 2007

Increased Adiposity Enhances Intrafollicular Estradiol levels in Normoandrogenic Ovulatory Women Receiving GnRH Analog/Recombinant Human FSH Therapy for In Vitro Fertilization

Daniel A. Dumesic*, Timothy G. Lesnick, and David H. Abbott

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

* To whom correspondence should be addressed. 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 examines whether increased adiposity enhances intrafollicular steroidogenesis in normoandrogenic ovulatory women receiving GnRH analog/recombinant human (rh) FSH therapy for in vitro fertilization (IVF).

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 rhFSH therapy and human chorionic gonadotropin administration when ≥ 2 follicles ≥ 18mm in diameter were present.

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

Main Outcome Measures: FF was assayed for estradiol (E2), progesterone (P4), 17-hydroxyprogesterone (17OHP4), androstenedione (A4), testosterone (T), dihydrotestosterone (DHT), insulin, glucose and lactate.

Results: Overweight women had hyperinsulinemia (P=0.03) with decreased serum sex hormone binding globulin (P=0.001) and increased serum free T 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 versus lean women (P=0.03), while the remaining intrafollicular steroid levels were similar in both female groups.

Conclusion: In normoandrogenic ovulatory women undergoing IVF, 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.


Key words: obesity • steroidogenesis • glucose metabolism • folliculogenesis-ovarian function







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