Oxidative stress biomarkers in assisted reproductive technologies: From follicular redox biology to clinical translation

Reactive oxygen species (ROS) are important regulators within the ovarian follicle microenvironment and are increasingly recognized as mediators of impaired oocyte competence in assisted reproductive technologies (ART). Beyond established factors such as aging, metabolic imbalance, and environmental exposures, redox dysregulation within the follicle may contribute to variability in ART outcomes that is not explained by conventional morphological assessment. ROS are generated across multiple subcellular compartments, including mitochondria, endoplasmic reticulum, lysosomes, plasma membrane, and peroxisomes. Their compartmentalized production, together with localized antioxidant defenses, creates spatially confined redox microdomains that regulate follicular physiological activity. Disruption of this finely tuned redox balance within the follicle may result in oxidative damage affecting oocytes. Identifying oxidative stress-related biomarkers within the follicle has therefore become an attractive non-invasive approach to infer oocyte competence, as these markers may reflect integrated redox dynamics. However, accurate quantification of ROS remains challenging due to their short half-life and subcellular confinement. Most current approaches rely on measuring stable oxidative by-products or antioxidant capacity in follicular fluid or granulosa cells. However, such markers may not accurately capture follicle-specific or compartment-specific redox status, and many oxidative modifications do not directly indicate functional impairment. Although numerous biomarkers have been associated with ART outcomes, methodological heterogeneity and limited biological resolution restrict their clinical translation. Further studies using standardized methodologies and higher-resolution measurements are required to clarify their prognostic relevance.