Objective(s): Unexplained infertility (UI) is a multifaceted reproductive disorder with an ambiguous cause. Oxidative stress has arisen as a possible factor in its pathophysiology. This study sought to evaluate the significance of the equilibrium between oxidative and antioxidant levels, alongside thiol and disulfide levels, in women with UI.

Materials and Methods: Serum samples from 23 women with UI and 27 healthy fertile controls were analyzed for total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), paraoxonase-1 (PON), arylesterase (ARES), thiol-disulfide homeostasis (TDH), and ischemia-modified albumin (IMA). Hematological and routine biochemical parameters were also assessed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of selected biomarkers.

Results: The UI group showed significantly lower TAS and native thiol levels, and higher levels of TOS, OSI, disulfide, oxidized thiol ratio, and IMA (p<0.001). ARES activity was elevated, whereas PON activity and total thiol concentrations did not differ significantly. TAS (AUC = 0.848) and reduced thiol ratio (AUC = 0.799) demonstrated the strongest diagnostic utility among the tested biomarkers.

Conclusion: Oxidative imbalance appears to play a pivotal role in the pathophysiology of UI. Biomarkers such as TAS and TDH-related indices may offer valuable diagnostic insights and serve as potential targets for therapeutic intervention in infertility management.