Preimplantation genetic diagnosis for mitochondrial DNA mutations: analysis of one blastomere suffices

J Med Genet. 2017 Oct;54(10):693-697. doi: 10.1136/jmedgenet-2017-104633. Epub 2017 Jul 1.


Background: Preimplantation genetic diagnosis (PGD) is a reproductive strategy for mitochondrial DNA (mtDNA) mutation carriers, strongly reducing their risk of affected offspring. Embryos either without the mutation or with mutation load below the phenotypic threshold are transferred to the uterus. Because of incidental heteroplasmy deviations in single blastomere and the relatively limited data available, we so far preferred relying on two blastomeres rather than one. Considering the negative effect of a two-blastomere biopsy protocol compared with a single-blastomere biopsy protocol on live birth delivery rate, we re-evaluated the error rate in our current dataset.

Methods: For the m.3243A>G mutation, sufficient embryos/blastomeres were available for a powerful analysis. The diagnostic error rate, defined as a potential false-negative result, based on a threshold of 15%, was determined in 294 single blastomeres analysed in 73 embryos of 9 female m.3243A>G mutation carriers.

Results: Only one out of 294 single blastomeres (0.34%) would have resulted in a false-negative diagnosis. False-positive diagnoses were not detected.

Conclusion: Our findings support a single-blastomere biopsy PGD protocol for the m.3243A>G mutation as the diagnostic error rate is very low. As in the early preimplantation embryo no mtDNA replication seems to occur and the mtDNA is divided randomly among the daughter cells, we conclude this result to be independent of the specific mutation and therefore applicable to all mtDNA mutations.

Keywords: mitochondrial (mt)DNA mutations; preimplantation genetic diagnosis (PGD); single-blastomere biopsy protocol.

Publication types

  • Evaluation Study

MeSH terms

  • Biopsy
  • Blastocyst
  • Blastomeres*
  • DNA, Mitochondrial / genetics*
  • Diagnostic Errors
  • Female
  • Genetic Testing / methods*
  • Heterozygote
  • Humans
  • Mutation
  • Pregnancy
  • Preimplantation Diagnosis / methods*


  • DNA, Mitochondrial