Molecular and immunological predictors of outcomes in assisted reproductive technology programs

Despite substantial advances in assisted reproductive technologies (ART), the proportion of unsuccessful in vitro fertilization cycles remains considerable, highlighting the need for additional prognostic tools. In recent years, increasing attention has been directed toward molecular and immunological markers that reflect oocyte competence, embryo developmental potential, endometrial receptivity, and the patient’s systemic inflammatory status. This review summarizes current evidence regarding the diagnostic and predictive value of biomarkers identified in follicular fluid, peripheral blood, and endometrial tissue. Particular emphasis is placed on oxidative stress markers (malondialdehyde, advanced oxidation protein products), antioxidant enzymes (including glutathione peroxidase), microRNAs and other non-coding RNAs, as well as immunological parameters such as cytokines, complement components, and immune cell subsets. Data on circulating cell-free DNA as an indicator of follicular microenvironment status are also discussed. Available evidence suggests that disturbances in redox balance and alterations in local immune regulation may be associated with impaired embryo quality and reduced implantation rates. However, substantial methodological heterogeneity, small sample sizes, and the lack of standardized assessment protocols limit the clinical applicability for many proposed biomarkers. Integration of molecular markers with clinical parameters, supported by multi-omics approaches, offers promising opportunities for the personalization of ART strategies. Nevertheless, large prospective studies with robust validation and evaluation of cost-effectiveness are required before these biomarkers can be incorporated into routine clinical practice.

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