Histopathological Severity Is the Strongest Independent Prognostic Factor of Sperm Retrieval in Men With Non-Obstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction

Background: The most widely used method for obtaining sperm from men with non-obstructive azoospermia (NOA) is microdissection testicular sperm extraction (micro-TESE), although the mechanisms underlying sperm retrieval remain debated. This study aimed to investigate factors affecting sperm retrieval success in men with NOA undergoing micro-TESE, including clinical, hormonal, genetic, inflammatory, and histological parameters. Methods: This retrospective study included 135 male patients with NOA who underwent micro-TESE between 2014 and 2025. Testicular histology, systemic inflammatory markers, blood hormone levels, and genetic information were investigated. Histopathological severity was evaluated with the Johnsen scoring system. Univariable and multivariable logistic regression analyses were used to determine independent predictors of successful sperm retrieval. Results: A total of 71 patients (52.6%) achieved successful sperm retrieval. The Johnsen score was the strongest predictor of sperm retrieval success in both univariable analysis (odds ratio [OR] = 1.65, 95% confidence intervals [CI] = 1.40–1.95; p < 0.001) and multivariable analysis, in which patients with mild histopathology had markedly higher odds of retrieval than those with severe histopathology (OR = 26.95, 95% CI = 6.85–106.03; p < 0.001). Although serum LH levels were significantly lower in the sperm retrieval–positive group on univariable testing (p = 0.017), this association did not reach significance in logistic regression analysis (OR = 0.95, 95% CI = 0.89–1.01; p = 0.093). No independent correlations were identified between sperm retrieval outcomes and other hormonal levels, systemic inflammatory markers, genetic abnormalities, or the presence of varicocele. Conclusion: The Johnsen score was the strongest independent predictor of successful sperm retrieval in patients with non-obstructive azoospermia undergoing micro-TESE. These findings underline the crucial role of histology in postoperative counseling and in planning repeat surgical interventions in men with NOA.