It has been speculated that controlled ovarian hyperstimulation (COH), as performed during in vitro fertilization therapy, may negatively affect embryo implantation. The objective of this prospective and randomized study was to investigate gene expression profiles of the human endometrium during the window of implantation of gonadotropin-stimulated COH cycles compared with temporally matched natural cycles (d 21). Analysis was performed with high-density oligonucleotide microarrays. In addition, other structural and functional features of the endometrium were investigated. Results corroborated that COH cycles depicted advancement of pinopodes appearance, histological features, and steroid receptor down-regulation when compared with natural cycles. These changes were associated with significant, albeit small, variations in gene expression (18 genes/expressed sequence tags and -1.55- to +3.40-fold changes). Second, there were significant changes in gene expression when comparing cycles using a GnRH agonist vs. a GnRH antagonist (13 genes/expressed sequence tags and +1.42- to +2.10-fold changes). This is the first attempt to elucidate gene expression profiles of the endometrium during COH cycles. The observed differences in gene expression in COH cycles using state-of-the-art protocols may not have a major functional impact on embryo implantation.