Background and Objectives: Male infertility is a growing public health concern, with up to 50% of cases lacking a clearly identifiable cause. This study aimed to assess the epidemiological characteristics of male infertility in Lithuania and evaluate the clinical utility of oxidative stress assessment using the MiOXSYS system. Materials and Methods: A two-stage retrospective study was conducted between 2019 and 2023 at one of the largest fertility centers in Lithuania. The first stage involved an epidemiological analysis of 718 men who met the inclusion criteria. In the second stage, 261 men underwent oxidation-reduction potential (ORP) testing using the MiOXSYS system. Semen parameters were evaluated according to World Health Organization (WHO) 2010 guidelines. ROC curve analysis was used to assess the diagnostic value of ORP. Results: Male infertility was identified as the sole factor in 20.1% of couples, while unexplained infertility accounted for 24.4% of all cases. Among normozoospermic men, 48.5% exhibited elevated ORP levels (>1.34 mV/10⁶ sperm/mL). ROC analysis demonstrated moderate diagnostic accuracy of ORP (AUC = 0.634; sensitivity: 75.3%; specificity: 51.5%). The inclusion of ORP testing reduced the proportion of unexplained cases and supported their reclassification under the Male Oxidative Stress Infertility (MOSI) framework. Conclusions: This study provides novel epidemiological data on male infertility in Lithuania and highlights the potential of ORP testing as a supplementary diagnostic tool. Systematic evaluation of oxidative stress may help better identify cases previously labeled as unexplained and enable more personalized treatment strategies.

Background and Objective: Unexplained infertility is a major challenge in reproductive medicine and requires advanced diagnostic approaches to identify the underlying factors accurately. This study aims to evaluate the utility of risk factor analysis and a gene panel in diagnosing unexplained infertility using the next-generation sequencing (NGS) technology. Our study aimed to characterize and identify risk and genetic factors associated with unexplained infertility. Materials and methods: A cohort of patients with unexplained infertility was comprehensively screened for risk factors and genetic variations using a targeted gene panel (10 couples with unexplained infertility (UI) and 36 fertile couples). 108 articles were selected (58 on female infertility and 50 on male infertility) presenting genes that may be associated with unexplained infertility. A gene panel for unexplained infertility was compiled based on the literature data. A customized virtual panel was created from the exome sequencing data. Results: In the female group, controls had a higher mean age, while in the male patients, both groups were similar in terms of age. Both gender groups had comparable BMI values. No significant associations (p > 0.05) between risk factors and unexplained infertility were found when evaluating anthropometric parameters and other sociodemographic characteristics. In two male patients (20%), a molecular defect was detected in NGS variants classified aspossible benign and probably benign In particular, missense variants were identified in the UGT2B7 and CATSPER2 genes, A molecular defect classified as probably damaging was found in five female patients (50%). In particular, missense variants were identified in the CAPN10, MLH3, HABP2, IRS1, GDF9, and SLC19A1 genes. Conclusions: The study emphasizes that unexplained infertility is often related to mechanisms beyond causative mutations and highlights the need for integrative genomic research involving broader gene panels and multi-faceted approaches, including transcriptomics and epigenetics, to uncover latent genetic predispositions.