Liquid Biopsy as a Screening Tool in Recurrent Implantation Failure During IVF: A Narrative Review.
- 1Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- 2Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- 3Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
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.
Related
- Beyond the Embryo: Rethinking the Genetics of Recurrent Implantation Failure in the PGT-A Era
- Recurrent implantation failure: a registry-corroborated, age-stratified definition and pragmatic five-tiered management algorithm.
- Autophagy as a potential link between progesterone responsiveness and endometrial immune function in recurrent implantation failure
- Altered IRE1α-Dependent Decidual Programming Links Impaired Inflammation and Angiogenesis in Recurrent Implantation Failure.
- Live Birth Outcomes Following subendometrial platelet rich plasma versus Intrauterine platelet rich plasma infusion in Women with Recurrent Implantation Failure: A Cohort Study
BibTeX
@article{saeedinia2026liquid,
title = {{Liquid Biopsy as a Screening Tool in Recurrent Implantation Failure During IVF: A Narrative Review.}},
author = {Reza Saeedinia and Ava Hemmat and Zohreh Heidary},
journal = {Journal of family \& reproductive health},
year = {2026},
month = jun,
doi = {10.18502/jfrh.v20i2.22610},
url = {https://europepmc.org/article/MED/42924260},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Liquid Biopsy as a Screening Tool in Recurrent Implantation Failure During IVF: A Narrative Review.
AU - Reza Saeedinia
AU - Ava Hemmat
AU - Zohreh Heidary
PY - 2026
DA - 2026/06/01
JO - Journal of family & reproductive health
DO - 10.18502/jfrh.v20i2.22610
UR - https://europepmc.org/article/MED/42924260
AB - 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.
SN - 1735-8949
SN - 1735-9392
ER -