Introduction, scope and objectives
Mitochondrial malfunction has been recognised as the significant cause of a number of serious multi-organ diseases. The underlying defects can be due to mutations in nuclear DNA affecting gene products required within mitochondria, or to mutations in DNA carried within the mitochondria themselves. Table 1 at Annex A lists clinical disorders that are associated with mutations in mitochondrial DNA (mtDNA). Although relatively rare, the seriousness of these diseases and the unusual inheritance pattern of mtDNA mutations have made them a focus for research into preimplantation methods to reduce or avoid a disease in offspring.
Preimplantation genetic diagnosis (PGD) can be used to test embryos that might be carrying mutations in their nuclear DNA so that only unaffected embryos are selected for implantation. Unlike most nuclear DNA mutations, mtDNA is solely maternally inherited, and any mutations it acquires are therefore likely to be passed on to all offspring. This presents particular challenges when it comes to avoiding transmission of disease to subsequent generations. For some women who are known to carry mtDNA mutations, current methods of diagnosis including PGD, can reduce, but not eliminate, the risk of a child being born with mitochondrial disease. However, these methods are not applicable to all cases. Moreover, even if unaffected themselves, girls born after the use of this procedure may themselves still be at risk of having affected children, as some abnormal mitochondria may be present in their oocytes (eggs). It is against this backdrop that recent research has explored alternative methods of maternal spindle transfer (MST) and pronuclear transfer (PNT) that have the possibility of eliminating, and not just reducing, the risk of disease due to mtDNA mutations.
Scope and objectives of this review
The terms of reference for the panel are “to collate and summarise the current state of expert understanding on the safety and efficacy of methods to avoid mitochondrial disease through assisted conception”. Accordingly, this review focuses exclusively on Page 5 of 45