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.