Genetic diagnosis and outcomes of intracytoplasmic sperm injection in South Chinese patients with congenital bilateral aplasia of the vas deferens.

Background: Obstructive azoospermia commonly is caused by CBAVD(Congenital Bilateral Aplasia of the Vas Deferens), mainly due to the cystic fibrosis transmembrane conductance regulator (CFTR) and adhesion G protein-coupled receptor G2(ADGRG2) mutations. The genetic landscape for Chinese CBAVD patients is unclear, leading to debates over genetic screening, counseling, and assisted reproduction strategies. This study investigates the prevalence of CFTR and ADGRG2 mutations in a southern Chinese cohort of CBAVD patients and evaluates the impact of CFTR mutations on intracytoplasmic sperm injection (ICSI) outcomes.

Results: CFTR mutations were identified in 71.4% (30/42) of CBAVD patients, with a total of 36 CFTR mutation sites across 13 types identified, including two novel mutations. A novel ADGRG2 mutation was also detected. Betweenthe CFTR mutation-CBAVD group and the non-CBAVD OA group, a significant difference was observed only in the 2 Pronuclei(2PN) rate (79.5% vs 86.2%, P = 0.0065), while fertilization rates, pregnancy rates, miscarriage rates, and live birth rates showed no significant differences. Between the CFTR mutation-CBAVD group and the CBAVD group without CFTR mutation, there were no significant differences in fertilization rates, 2PN rates, pregnancy rates, miscarriage rates, or live birth rates.

Conclusion: Chinese CBAVD patients primarily exhibit mutations in the CFTR and ADGRG2 genes. Therefore, targeted gene testing for CFTR and ADGRG2 is more suitable compared to WES for CBAVD patients. Considering that the genetic factors of approximately 30% of CBAVD patients remain unknown, it is recommended to perform massive parallel sequencing for patients who test negative for CFTR and ADGRG2 gene screening. Despite these genetic factors, ICSI outcomes were not adversely affected, except for the 2PN rate. However, genetic counseling remains crucial for Chinese CBAVD patients before undergoing assisted reproduction.