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Follicle Luteinization in Hyperandrogenic Follicles of Polycystic Ovary Syndrome Patients Undergoing Gonadotropin Therapy for in Vitro Fertilization

Departments of Obstetrics and Gynecology (S.C.F., J.L.P.), Biostatistics (T.G.L.), and Experimental Pathology (M.A.Z.), Mayo Clinic, Rochester, Minnesota 55905; National Primate Research Center (D.H.A., D.A.D.), University of Wisconsin, Madison, Wisconsin 53715; Department of Obstetrics and Gynecology (D.H.A.), University of Wisconsin, Madison, Wisconsin 53792; and Reproductive Medicine and Infertility Associates (D.A.D.), Woodbury, Minnesota 55125

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: Polycystic ovary syndrome (PCOS) is a reproductive disorder of ovarian hyperandrogenism and insulin resistance characterized by abnormal luteinization of small follicles. After exposure to GnRH analog/FSH stimulation for in vitro fertilization (IVF), however, it is unclear whether such PCOS follicles remain abnormally luteinized during the resumption of oocyte maturation in vivo.

Objective: The aim of this study was to determine whether PCOS follicles exposed to GnRH analog/FSH stimulation for IVF show abnormal luteinization.

Design: This study was a prospective cohort.

Setting: The setting was an institutional practice.

Patients: Eleven PCOS and 30 normoandrogenic ovulatory women were included.

Intervention(s): All subjects received GnRH analog/FSH therapy after basal serum hormone determinations.

Main Outcome Measure(s): Follicle fluid aspirated at oocyte retrieval from the first follicle of each ovary was assayed for gonadotropins, steroids, insulin, and glucose. LH receptor mRNA expression was determined in granulosa cells of the same follicle.

Results: In PCOS patients with basal hyperandrogenemia and hyperinsulinemia, total oocyte number was increased and follicle diameter was decreased, despite normal maximal serum estradiol levels. Within PCOS follicles, progesterone levels were reduced (P < 0.01), despite comparable bioactive LH and insulin levels and granulosa cell LH receptor mRNA expression; estradiol levels were normal, despite diminished FSH availability (P < 0.004). Elevated androstenedione (P < 0.01), testosterone (P < 0.001), and glucose (P < 0.01) levels also occurred. In PCOS follicles containing mature oocytes, however, elevated androgen levels were accompanied by both normal progesterone concentrations and a normal inverse relationship between glucose depletion and lactate accumulation.

Conclusion: Hyperandrogenic follicles with mature oocytes from PCOS women receiving GnRH analog/recombinant human FSH therapy for IVF show sufficient glucose utilization for normal luteinization.

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