Accuracy of preimplantation diagnosis of single-gene disorders by polar body analysis of oocytes

J Assist Reprod Genet. 1999 Apr;16(4):192-8. doi: 10.1023/a:1020312823155.


Purpose: A number of pitfalls in single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation genetic diagnosis of single-gene disorders.

Methods: Preimplantation genetic diagnosis was performed by sequential first and second polar body analysis of oocytes in 26 couples at risk for having children with various single-gene disorders. Mutant genes were amplified simultaneously with linked polymorphic markers, and only embryos resulting from the mutation-free oocytes predicted by polar body analysis with confirmation by polymorphic marker testing were transferred back to patients.

Results: Overall 529 oocytes from 48 clinical cycles (26 patients) were tested, resulting in the transfer of 106 embryos in 44 clinical cycles. As many as 46 (9.6%) instances of allele dropout were observed, the majority (96%) of which were detected. Seventeen unaffected pregnancies were established, of which nine resulted in the birth of an unaffected child, and the rest are ongoing.

Conclusions: A high accuracy of preimplantation genetic diagnosis of single-gene disorders is achieved by application of sequential analysis of the first and second polar body and multiplex polymerase chain reaction.

MeSH terms

  • Alleles*
  • Cystic Fibrosis / genetics
  • Female
  • Gaucher Disease / genetics
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Oocytes / physiology*
  • Oocytes / ultrastructure
  • Polymerase Chain Reaction / methods
  • Pregnancy
  • Preimplantation Diagnosis*