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This version published online on March 21, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2142
A more recent version of this article appeared on June 1, 2006
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Submitted on September 27, 2005
Accepted on March 15, 2006

Follicle Luteinization in Hyperandrogenic Follicles of Polycystic Ovary Syndrome (PCOS) Patients Undergoing Gonadotropin Therapy For In Vitro Fertilization (IVF)

Shu C. Foong, David H. Abbott, Michael A. Zschunke, Timothy G. Lesnick, Jennifer L. Phy, and Daniel A. Dumesic*

Departments OB/GYN (S.C.F., J.L.P.), Biostatistics (T.G.L.) and Experimental Pathology (M.A.Z.), Mayo Clinic, Rochester, MN, 55905; 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; and Reproductive Medicine and Infertility Associates (D.A.D.), Woodbury, MN, 55125

* To whom correspondence should be addressed. 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. Following 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: To determine whether PCOS follicles exposed to GnRH analog/FSH stimulation for IVF show abnormal luteinization.

Design: Prospective cohort

Setting: Institutional practice

Patients: 11 PCOS and 30 normoandrogenic ovulatory women

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 (E2) levels. Within PCOS follicles, progesterone (P4) levels were reduced (P < 0.01), despite comparable bioactive LH and insulin levels and granulosa cell LH receptor mRNA expression; E2 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 P4 concentrations and a normal inverse relationship between glucose depletion and lactate accumulation.

Conclusion: Hyperandrogenic follicles with mature oocytes from PCOS women receiving GnRH analog/rhFSH therapy for IVF show sufficent glucose utilization for normal luteinization.
Key words: polycystic ovary syndrome • intrafollicular steroidogenesis • glucose utilization • follicle differentiation




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