Endometrial preparation with etanercept increased embryo implantation and live birth rates in women suffering from recurrent implantation failure during IVF.

Recurrent implantation failure (RIF),  defined as ≥3 failed in vitro fertilization (IVF) cycles with the accumulated transfer of at least five embryos, plague many infertile women. The exact cause is unknown; however, evidence supports the immune system, specifically the Tumor Necrosis Factor (TNF) pathway. Etanercept (a TNFα antagonist) has been shown to improve pregnancy rates in women with rheumatoid arthritis or endometriomas; therefore, this study aimed to determine the effectiveness of etanercept for IVF in RIF women. Eighty-three RIF women were recruited from the Ingenes Institute in Mexico City for this single-arm, prospective study. All patients underwent a similar IVF protocol and received etanercept (4 × 25 mg every 72 h) after endometrial preparation, if applicable, and at embryo transfer. IVF endpoints assessed were embryo implantation (h-βCG >10 mg/dL at Day 14), the presence of a gestational sac, live birth, and birth weight. All women reported no side-effects associated with the etanercept treatment. 75.9 % of the cohort achieved embryo implantation, 74.7 % developed gestational sacs, and the ongoing pregnancy/live birth rate was at 62.7 %. However, 56.7 % of the live births were preterm (<37 weeks) and 60.5 % of the births were underweight (<2500 g). When stratified by fresh or frozen cycles or by the ova source (patient versus donor), the results were not significantly different with respect to the implantation rate, formation of gestational sacs, and the live birth rate. Here, we showed that using etanercept during endometrial preparation improves IVF outcomes in RIF women.