Human Reproduction, Vol. 8, No. 8, pp. 1259-1263, 1993
© 1993 European Society of Human Reproduction and Embryology
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Andrology: Cystic fibrosis mutations impair the fertilization rate of epididymal sperm from men with congenital absence of the vas deferens
1University of California at Irvine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, UCI Center for Reproductive Health 101 The City Drive, Pavilion 2, Orange, CA 92668 2St Luke‘s Hospital St Louis, MO, USA
Correspondence: 3To whom correspondence should be addressed
One of the limiting factors for the successful treatment of male sterility due to congenital absence of the vas deferens (CAVD) is the low (<20%) and extremely unpredictable rate of in-vitro fertilization of their epididymal spermatozoa. The recent demonstration that CAVD is a mild form of cystic fibrosis (CF) disease, almost exclusively involving the genital tract, has prompted us to investigate the hypothesis of whether there could be an association between particular CF genotype mutations and the in-vitro performance of epididymal sperm. In this study 63 patients with surgically confirmed diagnosis of CAVD undergoing microsurgical epididymal sperm aspiration (MESA) and in-vitro fertilization (IVF) were evaluated. The genetic screening was carried out on DNA extracted from peripheral lymphocytes and amplified by the polymerase chain reaction. A total of 12 mutations in the cystic fibrosis transmembrane regulator gene (CFTR), representing 
90% of the total known CF mutations, were tested. The presence or absence of mutations, as well as the type of mutation found, was correlated with the IVF and pregnancy rates. Of the 63 patients examined, 40 (64%) were positive to the CF screening and 23 were negative. In three cases no spermatozoa were found because of rete testis blockage. The difference in fertilization rates between patients testing positive and negative was highly significant (P = 0.000003), 13 versus 23%, respectively. In order to pinpoint which mutation could account for the most deleterious effect on the IVF results, we analysed these by keeping the patients separated by CF mutations. Three major groups were identified: group I was formed by 21 patients (52% of the positive) with Delta F508, the most common and lethal of the CF mutations, as the only detectable. Group II was formed by 18 patients with various other CF mutations, including four compound heterozygotes (three with Delta F508/R117H and one with R553X/R117H) and one homozygote (R117H/R117H). Group III was formed by 21 patients in whom no mutations could be detected. The results showed a very low fertilization and pregnancy rate per patient (7 and 10%, respectively), in group I, while in groups II and III the fertilization and pregnancy rates were similar (group II, 21 and 39%, respectively; group III, 23 and 48%, respectively). The differences in the fertilization and pregnancy rates between groups I and III were statistically significant (P < 0.000001 and P < 0.01, respectively), while there was no difference between groups II and III. In conclusion, this study demonstrates a correlation between CF mutations and IVF capacity of epididymal spermatozoa retrieved from men with CAVD. Men with Delta F508 not opposed to known CF mutations give the poorest IVF outcomes; also at repeated attempts their pattern of poor fertilization is maintained, perhaps reflecting sperm intrinsic biochemical defects (alteration of chloride channels). These data open a new avenue in the interpretation of the IVF results from men with CAVD.
Key words: congenital absence of the vas deferens/cystic fibrosis/epididymal spermatozoa
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