By Sean Henahan, Access Excellence

BRUSSELS- A collaborative effort by medical geneticists and fertility specialists has allowed an infertile couple, both carriers of the same cystic fibrosis gene mutation, to have a healthy baby boy.

Congenital bilateral absence of the vas deferens is a common cause of infertility which occurs more often in carriers of the CF transmembrane conductance regulator gene than in the population at large. The genital form of CF is a rare phenotype of the disease associated with a specific CFTCR mutation, delta F508. It is an unusual form of CF inasmuch as the patient may not present with the typical respiratory manifestations.

Given the high rate of CF seen in association with the congenital lack of vas deferens, the researchers screened both parents for CF mutations to evaluate the risk of their having a child with severe CF . Both were found to have the delta F508 mutation, but no other mutations.

In this case, both members of the infertile couple were outwardly healthy. The medical team used a surgical technique called microsurgical epididymal sperm aspiration to obtain sperm from the testes of the patient. Next they performed an in vitro procedure called intracytoplasmic sperm injection in oocytes obtained from the future mother. This procedure tends to produce better results than regular in vitro fertilization techniques when sperm motility is impaired as is often the case in patients with the congenital lack of vas deferens.

Next, the researchers used polymerase chain reaction to test the two day old embryos for the delta F508 CF mutation prior to implantation in the uterus. Analyses of single blastomeres indicated that none were free of the mutant CF gene. However, while two of the embryos were homozygous for the mutation, the remaining three were delta F508 carriers. A single pregnancy was then achieved following transfer of the carrier embryos.

Subsequent amniocentesis confirmed the delta F508 CF mutation carrier status of the fetus. The final result, a healthy six pound boy with intact vasa deferentia. This is the first report of the combined use of microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection in conjunction with preimplantation genetic analysis.

Questions remain regarding patients with this phenotype of cystic fibrosis. It is possible that other rare CFTR gene mutations may be present along with the rare delta F508 mutation. Therefore, it is possible that the delta F508 carrier embryos in this case could have been compound CF heterozygotes. The combination of a delta F508 mutation from the mother and a rare CF allele from the father could produce a more severe CF phenotype than that of the parents.

The couple in this study underwent both extensive genetic testing and counseling before and during the fertility procedures. When tests showed that none of the embryos were non-delta F508 carriers, they opted to take the risk of bearing a child with CF, since the father was completely free of pulmonary and pancreatic symptoms, and the couple had been unable to conceive for ten years.

Subsequent testing was unable to find a second mutation in the father's CF gene. Since the new born was free of the congenital defect seen in the father and showed no other signs of CF, the researchers believe he inherited the delta F506 gene from his father and a normal CF gene from his mother.

For the complete details on this study see: Liu et al, JAMA, 12/21/94, v.272 , No. 23, pp. 1858-1860.

Transmitted: 94-12-27 21:33:26 EST

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