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.
- preimplantation genetic diagnosis (PGD)
- mitochondrial (mt)DNA mutations
- single-blastomere biopsy protocol
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Contributors SCEHS: analysed the data of the performed PGD cycles, studied the literature, counseled patients for PGD and wrote the article. JCFMD: coordinated and authorised the genetic laboratory work, documented the PGD data and reviewed the article. EC: involved in the IVF procedures, reviewed the article. ADCP: supervised and authorised the genetic laboratory work, reviewed the article. DMEIH: supervised and authorised the genetic laboratory work, reviewed the article. CEMdD-S: medical coordinator PGD, counselled patients for PGD, reviewed the article. HJMS: head of department Clinical Genomics at the time most analyses were performed, supervised and authorised the genetic laboratory work, supervised writing of the article. PL: performed the statistical analysis, supervised writing of the article. SCEHS, HJMS and PL are responsible for the overall content as guarantors.
Competing interests None declared.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Medical Research Ethics Committee azM/UM (reference number 03-199)
Provenance and peer review Not commissioned; externally peer reviewed.