avoided by using healthy donated oocytes. However, whilst this guarantees the disease is not transmitted, it also means that any resultant child will not be genetically related to the mother. The panel reviewed two other methods that allow the transmission of both parent‟s nuclear DNA but involve replacing abnormal mitochondria with normal mitochondria: maternal spindle transfer (MST) and pronuclear transfer (PNT). A third technique, cytoplasmic transfer, where some ooplasm containing mitochondria from a donor oocyte is injected into an oocyte with compromised mitochondria, was attempted clinically more than a decade ago with the intention of improving development of embryos from poor quality oocytes, but not specifically to overcome mitochondrial disease. The technique has been discontinued9. In mitochondrial disease, it is unlikely to allow sufficient substitution of abnormal with normal mitochondria and the panel did not consider this possibility further as a method to avoid mtDNA disease.
4.1.2 MST uses micromanipulation techniques to transfer the woman‟s nuclear genetic material (the spindle with chromosomes attached) from her oocyte into an enucleated oocyte donated by a woman with normal mtDNA (Figure 1). The reconstituted oocyte would then need to be fertilised with sperm from the patient‟s partner. PNT uses similar micromanipulation techniques to transfer the couple‟s nuclear genetic material (the maternal and paternal derived pronuclei) from a fertilised oocyte (zygote) into an enucleated donor zygote with normal mtDNA (Figure 2). MST takes place between mature metaphase II oocytes. PNT takes place between fertilised oocytes, after the stage where the egg has been penetrated by sperm but prior to the first embryonic division. Both techniques are therefore carried out prior to the formation of an embryo with the maternal and paternal chromosomes together within the same nucleus10. With either method, any resulting child would inherit nuclear genetic material from both parents, while the mitochondria would be derived from the egg donor. If efficient, so that
9 There was concern about a US clinical trial on cytoplasmic transfer, which was halted as it seemed to be associated with a high frequency of chromosome abnormalities in resulting embryos. However, this could have been due to the age of the mothers, and to poor egg quality, etc, rather than the method itself. Several children were born, but it has not been possible to obtain information about their health. (From written evidence submitted to panel by Dr Jacques Cohen)
10 MST occurs pre-fertilisation and PNT occurs after syngamy but prior to the breakdown of the pronuclear membranes
Page 14 of 45