SynthesisFrontiers in endocrinology2026
Clinical potential of fluid-based biomarkers for recurrent implantation failure: a systematic review.
Synthesis in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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5 authors.
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Abstract
Background: Recurrent implantation failure (RIF) remains a significant challenge in reproductive medicine, with diagnostic approaches that are limited and widely debated. This systematic review evaluates whether fluid-based biomarkers from blood, uterine fluid, and menstrual fluid can provide more accessible and clinically informative alternatives. Methods: A systematic search of MEDLINE, Embase, Scopus, and Web of Science was conducted (2015-2025). Study quality was assessed using QUADAS-2 for diagnostic studies and PROBAST for prognostic studies. Due to substantial methodological heterogeneity, meta-analysis was not performed. Findings were synthesized narratively, and diagnostic performance was summarized using forest plots of reported AUC values without statistical pooling. Results: From 3,105 records, 18 studies met the inclusion criteria. The evidence base was dominated by blood-based biomarkers (n = 17). Multi-marker models consistently demonstrated higher diagnostic performance than single analytes, with immune-cell profiling panels and cytokine-clinical parameter models achieving AUC values up to 0.94. In contrast, individual biomarkers generally showed lower performance (e.g., lymphocyte count, AUC = 0.577). Prognostic evidence for blood biomarkers was limited, although plasma D-dimer (AUC ≈ 0.81) and immune-cell profiling models (AUC ≈ 0.72) showed potential for predicting pregnancy outcomes. Only one study evaluated uterine fluid biomarkers, identifying a four-protein panel with promising diagnostic performance, while no eligible studies assessed menstrual fluid. Conclusion: Fluid-based biomarkers, particularly multi-marker models, may have diagnostic potential in RIF; however, current evidence remains insufficient to support routine clinical implementation. Future research should prioritize prospective validation of blood-based multi-marker models in standardized, euploidy-controlled cohorts, alongside greater investigation of biologically proximal uterine and menstrual biofluids. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251068643.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.