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OBJECTIVE To analyze the transcriptomic profile of endometrial gene alterations during the window of implantation in infertile obese patients. DESIGN Multicenter, prospective, case-control study. SETTING Three academic medical centers for reproductive medicine. PATIENT(S) Infertile patients, stratified into body mass index (BMI) categories according to the World Health Organization guidelines, were included in the study. INTERVENTION(S) Endometrial samples were obtained from women undergoing standardized estrogen and P replacement cycles after 5 days of vaginal P supplementation. MAIN OUTCOME MEASURE(S) To identify endometrial gene expression alterations that occur during the window of implantation in infertile obese patients as compared with infertile normal-weight controls using a microarray analysis. RESULT(S) XCL1, XCL2, HMHA1, S100A1, KLRC1, COTL1, COL16A1, KRT7, and MFAP5 are significantly dysregulated during the window of implantation in the receptive endometrium of obese patients. COL16A1, COTL1, HMHA1, KRCL1, XCL1, and XCL2 were down-regulated and KRT7, MFAP5, and S100A1 were up-regulated in the endometrium of obese patients. These genes are mainly involved in chemokine, cytokine, and immune system activity and in the structural extracellular matrix and protein-binding molecular functions. CONCLUSION(S) Obesity is associated with significant endometrial transcriptomic differences as compared with non-obese subjects. Altered endometrial gene expression in obese patients may contribute to the lower implantation rates and increased miscarriage rates seen in obese infertile patients. CLINICAL TRIAL REGISTRATION NUMBER NCT02205866.