Faisabilité et incertitude du diagnostic préimplantatoire appliqué aux mutations de l'ADN mitochondrial

Preimplantation genetic diagnosis (PGD) is an alternative procedure to prenatal diagnosis for couples at-risk to have children affected with a severe genetic disease, such as a mitochondrial DNA (mtDNA) disorder. It relies on the genetic analysis of one or a few cells sampled from in vitro fertilized embryos, between day 3 and day 5 of development. In the case of mtDNA disorders, quantification of the mutant load on these cells is performed in order to assess the risk for the embryo to develop a severe mitochondrial disease, either in utero or in childhood. Our 15-year experience supports the reliability of such procedure. Overall 15 heteroplasmic patients were included in our PGD program. A total of 26 cycles were started, 25 oocytes retrievals and 16 embryo transfers were performed, resulting in 3 pregnancies and birth of 3 children. The mutant load assessed on a single blastomere sampled from 94 embryos was very close to the mutant load of the remaining cell/embryo, for all mutations tested : m.8344A > G, m.3243A > G, m.8993T > G, m.8993T > C, m.9185T > C, m.10197G > A. Most of the transferred embryos (17/25) were heteroplasmic, and 2/3 neonates carried the maternal mtDNA mutation, questioning the long-term prognosis of these patients. PGD remains a cumbersome procedure with a low success rate, which cannot be applied to homoplasmic or critically homoplasmic patients. There is therefore a strong need to develop alternative procedures such as nuclear transfer.