CLINICAL-EXPERIENCE WITH PREIMPLANTATION GENETIC DIAGNOSIS OF CYSTIC-FIBROSIS (DELTA-F508)

Preimplantation genetic diagnosis (PGD) was attempted in 12 couples in whom both parents carry the common Delta F508 deletion causing cystic fibrosis (CF). In vitro fertilization (IVF) was followed by cleavage stage biopsy on days 2 and 3 and removal of one or two cells for genet ic analysis by nested polymerase chain reaction (PCR) and heteroduplex formation. A total of 18 cycles resulted in 137 normally fertilized e mbryos, of which 115 developed to cleavage stages and 114 were success fully biopsied. Genetic analysis was successful in 83 embryos (73 per cent). With the remaining embryos, either results from two or more cel ls were discordant or amplification failed. In 15 cycles, one or two e ither normal or carrier embryos were transferred and five (33 per cent ) clinical pregnancies were established. Five singletons have been bor n and at birth all five babies have been confirmed as homozygous for t he normal allele. Our experience demonstrates that IVF and cleavage st age biopsy consistently provides sufficient embryos, diagnosed as unaf fected, for transfer in this autosomal recessive disease and that preg nancy rates are comparable to those following IVF.