Is ovarian stimulation detrimental to the endometrium?

Ovarian stimulation in assisted reproduction technology produces lower implantation rates per embryo transferred than natural and ovum donation cycles, suggesting suboptimal endometrial development due to the abnormal concentrations of hormones used to recruit more oocytes. After the publication of several studies on the gene expression profile of endometrial receptivity in the natural cycle using microarray technology, researchers have investigated the impact of ovarian stimulation on the gene expression pattern of the endometrium. Ovarian stimulation cycles that use gonadotrophin-releasing hormone (GnRH) agonists and antagonists have been analysed in detail during the window of implantation to establish differences compared with the natural cycle. This paper reviews results obtained in different studies to elucidate the changes induced by the different protocols used in clinics. At the morphological level, no relevant alteration was observed in endometrial development in the early and mid-luteal phases in women undergoing ovarian stimulation following GnRH antagonist treatments. However, the gene expression pattern of the endometrium showed some differences. In addition, the endometrial development after GnRH antagonist mimics the natural endometrium more closely than after GnRH agonist at both the morphological (no relevant differences) and molecular level (only 23 genes dysregulated at high dose). Clinical implications of these differences should be analysed in more detail.