Cryptozoospermia in the Shadow of Azoospermia: Accurate Diagnosis with Clinical Predictors and Extended Semen Analysis.

Objectives: To address the critical issue of cryptozoospermia misclassification as non-obstructive azoospermia (NOA), this study aims to highlight the importance of accurate cryptozoospermia diagnosis with extended semen analysis and to identify predictive clinical markers in men initially labeled as azoospermic.

Methods: We retrospectively analyzed men diagnosed with azoospermia at external centers who underwent extended semen analysis at our center between April 2021-April 2024. To investigate the clinical significance and potential predictors, clinical data were compared to 239 patients diagnosed with NOA who underwent micro-TESE during the same period.

Results: Extended semen analysis revealed cryptozoospermia in 74 of 372 patients (19.9%). Compared to the NOA group, patients with cryptozoospermia exhibited significantly lower FSH levels (p<0.001), higher total testosterone levels (p=0.002), larger testicular volumes (p<0.001), and a higher prevalence of AZFc microdeletions and parental consanguinity (p=0.029 and p=0.043, respectively). Multivariate analysis identified serum FSH level (<18.6 mIU/mL) and testicular volume (>11 mL) were found as independent predictors for the diagnosis of cryptozoospermia.

Conclusion: Our findings reveal that nearly one in five men initially diagnosed with NOA were, in fact, reclassified as having cryptozoospermia following extended analysis. Clinicians should maintain a high index of suspicion for missed cryptozoospermia in azoospermic patients presenting with favorable clinical profiles-particularly lower FSH, higher testosterone, and larger testicular volume- to ensure accurate diagnosis and guide individualized ART strategies.