Increased frequency of cystic fibrosis transmembrane conductance regulator gene mutations in infertile males

ObjectiveTo investigate the frequency of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in males with reduced sperm quality before intracytoplasmic sperm injection (ICSI).DesignThe nine most frequent cystic-fibrosis-causing mutations in the German population and IVS8T alleles were analyzed.SettingUniversity-based centers for reproductive medicine and clinical genetics.Patient(s)An unselected group of 597 males with oligo-, astheno-, terato-, crypto-, oligoasthenoteratozoospermia, or azoospermia, which underwent pre-ICSI genetic counseling over a 5-year period.Intervention(s)Blood samples were collected from the patients during genetic counseling.Main Outcome Measure(s)Frequency of mutations of CFTR gene in infertile males.Result(s)A heterozygous CFTR mutation was observed in 34 of 597 patients (5.70%). None of the patients had two CFTR mutations. Given that our mutation panel recognizes about 82% of heterozygotes, it can be assumed that the frequency of CFTR heterozygotes in our cohort is about 6.94%. The frequency of CFTR mutations in our cohort did not correlate with a reduced sperm count.Conclusion(s)The frequency of cystic fibrosis in the German population is 1:3300. Thus, a CFTR heterozygosity of 3.42% can be estimated. This indicates that in our cohort of infertile males, the frequency of CFTR heterozygosity is twofold higher than in the general population (P<.0001).