Non-invasive biomarkers in assisted reproduction: a comprehensive review for predicting IVF success

Infertility affects a significant portion of couples globally. In vitro fertilization (IVF) is a widely utilized assisted reproductive technology (ART). Despite significant advancements, IVF success rates remain suboptimal, which necessitates innovative approaches to improve embryo selection and predict the outcomes. Traditional methods, including morphological grading and preimplantation genetic testing (PGT), possess limitations, necessitating the development of innovative, non-invasive biomarkers. This narrative review sought to investigate novel biomarkers, such as oxidative stress (OS) indicators like malondialdehyde and advanced oxidation protein products, antioxidants including glutathione peroxidase and catalase, cell-free DNA (cfDNA), immunologic markers, and microRNAs (miRNAs) extracted from follicular fluid (FF), blood, and endometrial tissue, which may serve as predictors of ART outcomes. A narrative review of published studies investigating non-invasive biomarkers in human ART was conducted. Literature was sourced from databases including PubMed, Scopus, and Web of Science, focusing on studies reporting oxidative stress markers, antioxidant enzymes, miRNAs, cfDNA, and immunologic markers in FF, blood, or endometrial samples. Elevated OS markers were linked to low-quality embryos, while high levels of antioxidants were linked to higher quality of oocytes and embryos. Moreover, certain miRNAs in FF exhibited potential as indicators of embryo viability and implantation success, potentially enabling more precise and personalized IVF approaches. Incorporating these emerging biomarkers into standard clinical practice can improve prediction methods. Future research should focus on confirming these biomarkers in various populations and creating standardized protocols to promote their integration into reproductive medicine which can lead to better fertility treatments and help couples deal with the emotional and psychological problems caused by infertility.