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 genetic analysis by nested polymerase chain reaction (PCR) and heteroduplex formation. A total of 18 cycles resulted in 137 normally fertilized embryos, of which 115 developed to cleavage stages and 114 were successfully biopsied. Genetic analysis was successful in 83 embryos (73 per cent). With the remaining embryos, either results from two or more cells were discordant or amplification failed. In 15 cycles, one or two either normal or carrier embryos were transferred and five (33 per cent) clinical pregnancies were established. Five singletons have been born and at birth all five babies have been confirmed as homozygous for the normal allele. Our experience demonstrates that IVF and cleavage stage biopsy consistently provides sufficient embryos, diagnosed as unaffected, for transfer in this autosomal recessive disease and that pregnancy rates are comparable to those following IVF.
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Institute of Obstetrics and Gynaecology, RPMS, Hammersmith Hospital, London, UK.
Ray
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Harper
J
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Lesko
J
J
Paraschos
T
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Atkinson
G
G
Soussis
I
I
Taylor
D
D
Handyside
A
A
Hughes
M
M
Winston
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RM
D000328:Adult; D001706:Biopsy; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004624:Embryo Transfer; D047108:Embryonic Development; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011256:Pregnancy Outcome; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies
C505032:CFTR protein, human; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator