Gene expression profile of the human endometrial receptivity: comparison

26 27 Background: The adjunction of exogenous hormones for controlled ovarian stimulation 28 (COS) may alter endometrial receptiveness. In order to identify the genes mis-regulated under 29 COS, we compared the endometrium gene expression profiles, from the same patients, in a 30 natural cycle and in a subsequent COS cycle. Methods: For the same normal-responder 31 patients (n=21), endometrial biopsies (n=84) were collected during the pre-receptive (LH+2) 32 and receptive stages (LH+7) of a natural cycle and, subsequently, on oocyte retrieval day 33 (hCG+2) and on transfer day (hCG+5) of a stimulated cycle. Samples were analyzed using 34 DNA microarrays. Gene expression profiles and biological pathways involved in the 35 endometrial receptivity were analyzed. Results: Although endometrium transition profiles 36 from pre-receptive to receptive phases are similar between patients, COS regimens alter 37 endometrial receptivity in comparison with natural cycle. Under COS conditions, two 38 endometrial profiles were identified and were associated either with a moderately altered 39 receptivity profile for the majority of the patients or a strongly altered profile for a sub40 category of patients. The receptive endometrium transcription profile under COS was 41 defective for biological functions such as TGF signalling, leukocyte transendothelial 42 migration and the cell cycle. In addition, several biological functions specifically activated 43 under COS regimens were identified. Conclusion: Gonadotropin treatments in COS cycles 44 led to disruptions of the transcriptional activation of genes involved in normal endometrial 45 receptivity. We propose that when the receptiveness of the endometrium is seriously 46 compromised by the COS protocol, fresh embryo replacement should be cancelled, the 47 embryo frozen, and thawed embryo replacement should be performed under natural cycles. 48 49