Cystic Fibrosis: Influence of CFTR Variants on Epididymal Sperm Recovery and ICSI Results

RESEARCH QUESTION:How do microsurgical epididymal sperm aspiration (MESA) outcomes in men with cystic fibrosis compare with those with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RD), and what is the impact of CFTR variants on MESA success rates and subsequent cumulative outcomes after ICSI? DESIGN:A retrospective cohort study, conducted from 2003 to 2023 at Lille University Hospital, involved 147 participants with congenital bilateral absence of vas deferens (cystic fibrosis, n = 70; CFTR-RD, n = 77) who underwent MESA. Epididymal sperm extraction outcomes were compared, followed by an analysis of ICSI results in 108 patients who used their cryopreserved epididymal spermatozoa (cystic fibrosis, n = 49; CFTR-RD, n = 59). RESULTS:MESA outcomes were significantly poorer in the cystic fibrosis group. Extraction failure rates were 18.6% for cystic fibrosis and 3.9% for CFTR-RD (P = 0.01), and good-quality extraction rates were 45.7% for cystic fibrosis and 75.3% for CFTR-RD (P < 0.001). Cystic fibrosis was associated with an increased risk of extraction failure (odds ratio 11.3) and a 60% reduction in the probability of good-quality extraction. Among cystic fibrosis patients, CFTR variants without residual CFTR activity led to poorer outcomes: higher extraction failure rates (27.9% versus 3.7%, P < 0.001), lower good-quality extraction rates (30.2% versus 70.4%, P = 0.002) and reduced sperm concentration (3.5 versus 18.0 million/ml, P = 0.014). Cumulative success rates of ICSI did not differ significantly across groups. CONCLUSIONS:Cystic fibrosis patients exhibit poorer MESA outcomes than CFTR-RD patients, with the absence of residual CFTR activity significantly affecting the results. Cumulative ICSI outcomes were highly favourable for cystic fibrosis patients, showing no significant differences from CFTR-RD patients.