Non-invasive biomarkers in assisted reproductive technologies, current evidence, clinical utility and future...

Although assisted reproductive technologies have significantly advanced the treatment of infertility, overall success rates remain limited by the lack of accurate and safe tools for assessing reproductive potential. Conventional embryo selection and endometrial evaluation rely largely on morphological and non-functional criteria, which provide only indirect insight into the underlying biological competence of the embryo oocyte and uterine environment. In this context the development of non-invasive biomarkers has emerged as a critical objective in modern reproductive medicine. This review discusses current evidence on non-invasive biomarkers in in vitro fertilization and assisted reproductive technologies with emphasis on embryo derived follicular fluid and endometrial indicators. Advances in time lapse imaging analysis of spent embryo culture media follicular fluid profiling and uterine fluid assessment are discussed in relation to their biological significance and association with clinical outcomes. The role of metabolomic proteomic transcriptomic and genetic signals is examined alongside emerging applications of artificial intelligence for data integration and outcome prediction. While numerous non-invasive biomarkers demonstrate promising associations with embryo viability implantation potential and surrogate pregnancy outcomes, with limited evidence in live birth rates, their clinical translation is constrained by methodological heterogeneity, limited validation, and challenges in standardization. Integrative multi parameter approaches rather than single biomarker strategies appear most likely to enhance predictive accuracy. Continued efforts toward data harmonization, large scale validation, and clinically oriented model development are essential for the successful incorporation of non-invasive biomarkers into routine IVF practice. Curated databases and relevant AI applications may facilitate and help progress non-invasive biomarkers in ART.