Impact of controlled ovarian hyperstimulation on endometrial gene expression profiles during the window of implantation

Abstract

Gene expression profiling of human endometrial receptivity has recently started and demonstrated that endometrial receptivity is an active process involving hundreds of up-/down-regulated genes. In the present work, we have investigated the impact of controlled ovarian hyperstimulation (COH) on endometrial gene expression in human endometrial receptivity. Endometrial samples were collected from ovum donors at days LH+2 (n=5) and LH+7 (n=5) as determined by urinary LH surge during a single natural cycle. Also, endometrial samples were obtained from the same patient at day LH+7 (n=5) of the natural cycle and at day hCG+7 (n=5) of the next cycle during COH used for IVF treatment. Genomic analysis of endometrial samples was performed using microarray technology. The protocol for ovarian stimulation consisted of a long protocol with leuprolide acetate with FSH/HP, hMG and hCG. Leuprolide acetate and gonadotropin injections were discontinued the day of hCG administration, and progesterone supplementation was not administered. Samples were hybridized onto the GeneChip HG_U133A (Affymetrix) encompassing more than 22,000 human DNA fragments, and the results were validated by RT-PCR and quantitative RT-PCR . Our study demonstrates that the gene expression in the COH hCG+7 samples is deregulated as compared to the natural cycle at LH+7. No luteal support was administered during COH for ovum donation, in order to get a clear comparison between natural and COH cycles. Genes regulated during the window of implantation in the natural cycle are more comparable with the LH+2 than with the LH+7 patterns in the COH cycle. This suggests a delay in the gene expression regulation that is required for the formation of a receptive endometrium in COH cycles. This remarkable finding justifies furthers research to identify COH protocols with minimal impact on endometrial development. Our study demonstrates that the gene expression in the COH hCG+7 samples is deregulated as compared to the natural cycle at LH+7. No luteal support was administered during COH for ovum donation, in order to get a clear comparison between natural and COH cycles. Genes regulated during the window of implantation in the natural cycle are more comparable with the LH+2 than with the LH+7 patterns in the COH cycle. This suggests a delay in the gene expression regulation that is required for the formation of a receptive endometrium in COH cycles. This remarkable finding justifies furthers research to identify COH protocols with minimal impact on endometrial development.