Prevalence of CBAVD in azoospermic men carrying pathogenic CFTR mutations - Evaluated in a cohort of 639 non-vasectomized azoospermic men

Background: Men with obstructive azoospermia (OA) due to impaired development of the genital tract often carry at least one Cystic Fibrosis Transmembrane Conductance Regulator CFTR mutation. Objective: To determine the frequency of Congenital Bilateral Absence of Vas deferens (CBAVD) in men with azoospermia carrying CFTR gene mutations. Materials and methods: Non-vasectomized men with azoospermia referred to our andrological center were consecutively included. All men underwent palpation of the scrotal parts of the Vasa deferentia, ultrasonography of the testicles and hormone profile, and genetic analyses. Testicular biopsy was usually performed. A panel of 32 of the most important CFTR mutations was examined from genomic DNA isolated from blood lymphocytes. Either multiplex PCR analysis or a next-generation sequencing technique was performed. Results: Among the 639 men with azoospermia, 69 (10.8%) had at least one CFTR mutation. Of the 43 patients with at least one of the two CFTR mutations, Delta F508 and R117H, 19 (44.2%) showed CBAVD, 2 (4.7%) Congenital Unilateral Absence of Vas deferens (CUAVD), and 22 (51.2%) presence of the scrotal parts of the Vasa deferentia. In contrast, only 1/21 men (4.8%) with an isolated IVS8-5T variant showed CBAVD. Among the further 20 men with an isolated IVS8-5T variant, 11 had a history of cryptorchidism. Among the 570 men without CFTR mutations, CBAVD was found in only two men and CUAVD in one. FSH level was higher and testicular volume lower in men with present Vasa deferentia compared to those without (P < .001; Student's t test). Thirty-one men with either Delta F508 or R117H mutations, or both, had a testicular biopsy. Motile spermatozoa were found in 100% of 16 cases with CBAVD but in only 6 out of 15 cases with present Vasa deferentia (P < .01; Fisher's exact test). Discussion and conclusions: CBAVD was found in similar to 44% of men with Delta F508/R117H mutations. The data may support that CFTR mutations might affect male fertility through other mechanisms than obstruction of the genital tract. For a practical, clinical purpose analysis for only Delta F508, R117H and IVS8-5T seems sufficient until further research shows anything else.

Automated summary

The study found that 44% of men with Delta F508/R117H mutations had CBAVD, while only 4.8% of men with isolated IVS8-5T variant showed CBAVD. Testicular biopsy results showed that 100% of cases with CBAVD had motile spermatozoa among men with Delta F508, R117H, or both mutations.