Background <p>Chronic endometritis (CE) has been associated with implantation failure and recurrent reproductive failure. Antibiotic therapy is widely used as a first-line treatment for CE, and previous studies have suggested that successful treatment may improve subsequent reproductive outcomes.</p> Methods <p>A total of 6,371 women who experienced their first implantation failure after IVF/ICSI treatment at Henan Provincial People’s Hospital between May 2019 and December 2023 were initially identified. Following the application of stringent exclusion criteria, 2,555 frozen-thawed embryo transfer (FET) cycles were ultimately included in this retrospective cohort study. This study aimed to evaluate the association between antibiotic treatment and pregnancy outcomes in subsequent FET cycles among women with first implantation failure.</p> Results <p>Among the 2,555 women included in the analysis, 383 (15.0%) were diagnosed with CE at the initial assessment, whereas 2,172 had no evidence of CE (NCE group). After one course of oral antibiotic therapy, 309 were classified as having cured CE (CCE group) and 74 as having persistent CE (PCE group) on repeat histological evaluation. Analysis of pregnancy outcomes in the subsequent FET cycles revealed significant differences in both the live birth rate (LBR) and clinical pregnancy rate (CPR) among the three groups, with the highest rates observed in the CCE group and the lowest in the PCE group.</p> Conclusion <p>In women with first implantation failure, cured CE after antibiotic treatment was associated with improved reproductive outcomes, whereas persistent CE remained associated with poorer subsequent outcomes; however, these associations should be interpreted cautiously given the retrospective design and the possibility of residual confounding. Our findings suggest that post-treatment reassessment to confirm histological resolution may be clinically informative in the management of CE.</p>