Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin

Abstract

Human chorionic gonadotrophin (hCG) has been used to induce ovulation and oocyte maturation. Although the most common dose of hCG used in IVF is 10,000IU, there are reports that suggest 5,000IU is sufficient to yield similar results. The objective of this study is to evaluate the dose dependent differences in gene expression of granulosa cells following various doses of hCG treatment. Patients with polycystic ovarian syndrome (PCOS) were stimulated for IVF treatment. The hCG injection was either withheld or given at 5,000 or 10,000IU. Granulosa cells from the follicular fluids have been collected for RNA isolation and analyzed using Affymetrix genechip arrays. Unsupervised hierarchical clustering based on whole gene expression revealed two distinct groups of patients in this experiment. All untreated patients were clustered together whereas hCG-treated patients separated to a different group regardless of the dose. A large number of the transcripts were similarly up- or down-regulated across both hCG doses (2229 and 1945 transcripts, respectively). However, we observed dose-dependent statistically significant differences in gene expression in only 15 transcripts. Although hCG injection caused a major change in the gene expression profile of granulosa cells, 10,000IU hCG resulted in minimal changes in the gene expression profiles of granulosa cells as compared with 5,000IU. Thus, based on our results, we suggest the use of 10,000IU hCG should be reconsidered in PCOS patients.