Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder

Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease

“…Eight unfertilized oocytes displayed mutation loads ranging from 9% to 90% and eight arrested embryos encompassing cleavage and morula stages had mutation loads ranging from 7% to 91%. Comparison of blastomere genotypes from five cleavage-stage embryos with mean heteroplasmy levels of 24.8% to 85.5% revealed standard deviations ranging from 0.5% to 2.9% (Treff et al 2012).…”

Recent Advances in Mitochondrial Disease

“…This technique involves genetic testing of cells removed from early embryos obtained during in vitro fertilization procedures and allows the selection of embryos with a reduced risk of mitochondrial disease for implantation. Although experience is still limited, preimplantation genetic diagnosis has been used for a small number of different mtDNA mutations and has successfully identified suitable embryos for transfer with undetectable or low levels of mtDNA mutation (39,67,76,84,93). For the majority of preimplantation genetic diagnosis cases, the biopsy has been performed on cleavage-stage embryos at the eight-cell stage of development, which involves removing one or two blastomeres for testing.…”

“…For this technique to be reliable, the mtDNA mutation level in the biopsied blastomere must be representative of the mutation level in the remaining embryo, assuming that the mutant mtDNA segregates uniformly across all blastomeres during early embryo cleavage. Limited studies in human embryos have revealed that this is often the case, and although exceptions have been reported (76,95), there are generally low levels of variation in heteroplasmy among blastomeres of cleavage-stage embryos (67,76,93). Alternatively, the biopsy can be performed at the blastocyst stage of development, which involves removing a small number of trophectoderm cells.…”

“…Alternatively, the biopsy can be performed at the blastocyst stage of development, which involves removing a small number of trophectoderm cells. This technique requires that the mutation level is consistent throughout the trophectoderm and corresponds to the level in the inner cell mass, which limited data suggest is the case in human embryos (93). There are only two reported cases of blastocyst biopsy for mitochondrial disease caused by an mtDNA mutation (39,93), and the outcome of one is subject to some disagreement (66).…”

“…This technique requires that the mutation level is consistent throughout the trophectoderm and corresponds to the level in the inner cell mass, which limited data suggest is the case in human embryos (93). There are only two reported cases of blastocyst biopsy for mitochondrial disease caused by an mtDNA mutation (39,93), and the outcome of one is subject to some disagreement (66). Even so, preimplantation genetic diagnosis for mitochondrial disease has resulted in the birth of healthy children with a lower risk of mitochondrial disease and so provides a promising option for some affected families.…”