Screening and identification of endometrial proteins as novel potential biomarkers for repeated implantation failure.

Inadequate endometrial receptivity may be responsible for the low implantation rate of transferred embryos in in vitro fertilization (IVF) treatments. Patients with repeated implantation failure (RIF) impact the clinical pregnancy rate for IVF. We collected endometrial tissue during the implantation window of hysteroscopy biopsies from September 2016 to December 2019 and clinical data were collected simultaneously. Patients were divided into RIF and pregnant controls group according to pregnancy outcomes. A total of 82 differentially expressed endometrial proteins were identified, including 55 up-regulated proteins (>1.50-fold,  < 0.05) and 27 down-regulated proteins (<0.67-fold,  < 0.05) by iTRAQ labeling coupled with the 2D LC MS/MS technique in the RIF group. String analysis found interactions between these proteins which assembled in two bunches: ribosomal proteins and blood homeostasis proteins. The most significant enriched Gene Ontology terms were negative regulation of hydrolase activity, blood microparticle, and enzyme inhibitor activity. Our results emphasized the corticosteroid-binding globulin and fetuin-A as the specific proteins of endometrial receptivity by Western-blot. Our study provided experimental data to establish the objective indicator of endometrial receptivity, and also provided new insight into the pathogenesis of RIF.