Predictive Factors for Sperm Recovery after Varicocelectomy in Men with Nonobstructive Azoospermia

The ability of testicular histopathology to predict the success of microsurgical varicocelectomy in patients with nonobstructive azoospermia was investigated. We used a next generation sequencer to compare the transcriptomes of varicocelectomy responsive and nonresponsive testes to identify the factors that predict sperm in the ejaculate.

A total of 83 men with nonobstructive azoospermia and left varicocele underwent microsurgical varicocelectomy with simultaneous testicular biopsy. Transcriptome results using the Illumina® platform were expressed as the number of fragments per kb. Immunohistochemistry for proliferating cell nuclear antigen was performed on tissue samples from men with maturation arrest. Sperm recovery was evaluated with respect to patient age, testicular volume, varicocele grade, follicle-stimulating hormone level and testicular histology.

Mean age was 34 years and the mean follicle-stimulating hormone level was 12.3 IU/l. Sperm recovery was confirmed in 20 patients (24%) within 12 months after varicocelectomy, including 1 of 43 (2%) with Sertoli cell only, 10 of 27 (37%) with maturation arrest and 9 of 13 (69%) with hypospermatogenesis. Comparisons of 23,003 genes between the groups with and without sperm in the ejaculate of men with maturation arrest revealed a number of cell cycle related genes that were up-regulated and several antioxidant genes that were down-regulated in men with sperm recovery. Proliferating cell nuclear antigen expression was significantly higher in the 10 varicocelectomy responsive men than in the 17 nonresponsive men.

Transcriptome analysis of patients with maturation arrest revealed a distinct difference in the transcription of cell cycle regulation genes between varicocelectomy responsive and nonresponsive patients. Cell cycle assessment can predict sperm recovery and could improve our understanding of varicocele pathophysiology.