title: Rational approach to genetic testing of cystic fibrosis (CF) in infertile men.
abstract: Male infertility as a result of isolated congenital bilateral absence of the vas deferens (CBAVD) is one primary genital form of cystic fibrosis (CF) and occurs in 1-2% of infertile men. Assisted fertilization in patients with CBAVD increases the risk of transmitting mutations in the CF gene. We developed a rational approach to genetic CF testing in infertile men. A total of 282 infertile male patients were screened for the most common CF mutations (DeltaF508, R117H, IVS8-5T). Clinical data including medical history, examination, semen analysis, sweat tests, karyotypes and hormonal values were analysed. We identified 23 patients carrying mutations in the CF gene (DeltaF508: 10 patients; R117H: six patients; IVS8-5T: 11 patients). Two patients were compound heterozygote for DeltaF508/R117H, two others for DeltaF508/IVS8-5T. Correlating these molecular analyses with the clinical data pertaining to serum follicle-stimulating hormone concentration, semen pH, sperm count and total testicular volume, we were able to develop a score with a high specificity (98.4) for the presence of a cystic fibrosis transmembrane conductance regulator (CFTR) mutation, but only with a low sensitivity (positive post-test likelihood: 62.5%; negative post-test likelihood: 6.3%). With regard to the low sensitivity and the high number of CFTR mutations found in this heterogeneous group of infertile men, we still recommend genetic CF testing before assisted fertilization.
authors.affiliation: Human Genetics, University Clinic of Schleswig-Holstein, Lübeck, Germany. mennicke@paedia.ukl.mu-luebeck.de
authors.forename: K
authors.initials: K
authors.lastname: Mennicke
authors.forename: R D
authors.initials: RD
authors.lastname: Klingenberg
authors.forename: M
authors.initials: M
authors.lastname: Bals-Pratsch
authors.forename: K
authors.initials: K
authors.lastname: Diedrich
authors.forename: E
authors.initials: E
authors.lastname: Schwinger
mesh_terms: D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D017931:DNA Primers; D005818:Genetic Engineering; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male
chemical_list: C505032:CFTR protein, human; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator