Tehran University of Medical Sciences Journal of Family and Reproductive Health 1735-8949 20 2 2026 09 13 94 100 Reza Saeedinia Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Ava Hemmat Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Zohreh Heidary Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 2026 06 30 2026 08 16 Objective: Recurrent implantation failure (RIF) remains a multifaceted challenge in assisted reproductive technology (ART), affecting a subset of in vitro fertilization (IVF) patients despite transfer of high-quality embryos. Conventional diagnostics often require invasive procedures that may disturb endometrial receptivity. This narrative review critically synthesizes the evidence on liquid-biopsy strategies for RIF screening, emphasizing biofluids such as uterine fluid (UF), spent embryo culture medium (SCM), peripheral blood, cervicovaginal fluid (CVF), and seminal plasma. Materials and methods: Literature searches covered PubMed, Scopus, and Web of Science through August 2025, with inclusion of pivotal pre-2022 studies. Eligible works included observational studies, clinical trials, multi-omics analyses, and systematic reviews reporting molecular biomarkers relevant to endometrial receptivity or embryo competence. Results: UF-derived microRNAs (miRNAs) and extracellular vesicle (EV) cargo during the window of implantation (WOI) consistently differentiate receptive from nonreceptive endometrium, with predictive accuracies (AUC 0.75–0.90) in small validation studies. SCM-based noninvasive PGT-A (niPGT-A) shows moderate concordance (~65%) with trophectoderm biopsy PGT-A, constrained by contamination and low cfDNA yield; recent advances include blastocoel fluid integration and methylation-based decontamination. Peripheral blood, CVF, and seminal plasma biomarkers remain exploratory due to lower specificity. Pre-analytical standardization and harmonized outcome definitions are critical for translation. Conclusion: UF-miRNA/EV profiling holds the strongest promise for noninvasive RIF screening, whereas niPGT-A may serve as an adjunct for embryo competence assessment when biopsy is not feasible. Both approaches require multicenter validation and prospective trials demonstrating improved live-birth rates before routine clinical adoption. https://jfrh.tums.ac.ir/index.php/jfrh/article/view/3793 https://jfrh.tums.ac.ir/index.php/jfrh/article/download/3793/759