Carriers of cystic fibrosis among sperm donors: complete CFTR gene analysis versus CFTR genotyping

Abstract

Objective: To determine the frequency of cystic fibrosis (CF) carriers among sperm donors in Spain studied through a complete analysis of the CFTR gene and to compare the results with those that would have been obtained by the 4 genotyping panels of the CFTR gene most commonly used as a carrier test in the context of assisted reproduction in our country.

Design: Descriptive observational study.

Setting: Private center.

Patients: Nine hundred thirty-five sperm donors, from January 2014 to June 2019.

Intervention: None.

Main outcome measure: Presence of pathogenic variants in the CFTR gene.

Results: 17% of the donors were carriers of at least 1 pathogenic variant in CFTR, with 39 different pathogenic variants detected. Only 4 of these 39 variants (10.27%) would have been detected by the 4 genotyping tests considered, and 22 variants (56.41%) would not have been detected by any of the genotyping tests. The pathogenic variants of the CFTR gene included in the different genotyping tests analyzed vary widely, and <50% are common to all of them.

Conclusions: Although the was not based in the general population, these results show that the use of genotyping tests is associated with a high reproductive risk, because the rate of detection of CF carriers was lower when these panels were applied, in comparison with the complete study of the CFTR gene. We recommend that complete sequencing of the CFTR gene by next-generation sequencing be performed as a screening method for CF in sperm donors.

Keywords: Allelic heterogeneity; CFTR gene; carrier screening; cystic fibrosis; genotyping test; sperm donor.