The association of PRM1/2 with male azoospermia is well-documented, but the relationship between TXNDC2 deficiency and the azoospermia phenotype, sperm retrieval, and pathology has not been elucidated. Here we identified the association of TXNDC2 and protamines in evaluating testis pathology and sperm retrieval. An extensive microarray meta-analysis of men with idiopathic azoospermia was performed, and after undergoing several steps of data quality controls, the data passing QC were pooled and batch effect corrected. As redox imbalance has been shown to have a variable relationship with fertility, our relative expression studies began with candidate protamination and thioredoxin genes. We constructed a logistic regression model of TXNDC2 with PRM1 and PRM2 genes, and collective ROC analysis indicated a sensitivity of 96.8% and specificity of 95.5% with a ROC value of 0.995 (SE = 0.0070, 95% CI 0.982-1.000). These results demonstrate that TXNDC2, PRM1, and PRM2 combined have a robust power to predict sperm retrieval and correlate with severe azoospermia pathology.