Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis.

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.