Causes and Treatments of Recurrent Implantation Failure: A Systematic Review and Meta-Analysis

<ns3:p>Background Recurrent implantation failure (RIF) is a critical barrier in assisted reproductive technology, affecting a significant subset of women undergoing <ns3:italic>in vitro</ns3:italic> fertilization (IVF). This systematic review and meta-analysis aimed to systematically review and analyze the causes and treatments of RIF, providing evidence-based insights to enhance clinical management. Methods PubMed, EMBASE and the Cochrane database of systematic reviews were searched for articles published up to February 29, 2024. Studies were selected if they involved human subjects undergoing IVF, reported pregnancy outcomes, and addressed embryonic or extraembryonic factors influencing implantation. A total of 4,380 articles were screened, and 75 studies were included in the meta-analyses. Odds ratios and 95% confidence intervals were pooled using fixed and random effects models, with heterogeneity assessed via I<ns3:sup>2</ns3:sup>, τ<ns3:sup>2</ns3:sup>, and Cochran's Q test. Key factors analyzed included embryo euploidy, uterine abnormalities, thyroid function, and chronic endometritis, while treatments evaluated included antibiotics, heparin, platelet-rich plasma, and assisted hatching. Results Meta-analyses revealed that embryo euploidy significantly improves the odds of clinical pregnancy, while untreated hydrosalpinx and chronic endometritis significantly decreases the odds of pregnancy. Effective interventions include antibiotics for chronic endometritis, hysteroscopy for uterine abnormalities, and heparin for specific coagulation disorders. Other treatments, such as platelet-rich plasma and assisted hatching, require further evidence. Conclusions RIF management demands a tailored approach, emphasizing comprehensive diagnostics and personalized interventions. Despite the growing recognition of RIF, inconsistencies in its definition and limited high-quality evidence for certain treatments remain challenging. Further research is essential to standardize protocols and improve outcomes.</ns3:p>