This study reveals the association between gene copy number variants (CNVs) and integrin expression in endometrial tissue, especially focusing on patients with repeated implantation failure and unexplained infertility. The CNV expression, integrin αVβ3 (by real-time quantitative polymerase chain reaction and protein immunoblotting), and related clinical indicators were investigated by analyzing endometrial samples from 48 patients with repeated implantation failures and 10 patients with infertility and with no history of implantation issues. The results revealed the presence of CNVs in approximately 31.04% of patients with infertility, mainly affecting chromosomes 2, 5, 6, 7, 10, 11, 15, 19, and X. Age was associated with CNV occurrence. Integrin β3 expression was significantly higher in the CNV group than in the non-CNV group among patients with repeated implant failure. Clinical indicators related to coagulation were significantly different between the CNV and non-CNV groups. The study indicated a potential association between CNVs, increased integrin β3 expression, and recurrent implant failure. The study provides new information for understanding the complex interactions between genetic variants, integrin function, and coagulation factors by integrating advanced molecular diagnostic techniques, thereby emphasizing the need for a personalized approach in reproductive medicine. These results may redefine the diagnostic paradigm for recurrent implantation failure, laying the foundation for future translational applications.