Mitochondrial donation and human reproduction: Clinical, ethical and legal aspects

Women carriers of a disease caused by changes in mitochondrial DNA (mtDNA) seeking to achieve motherhood, currently have three options: (i) prenatal testing, via CVS or amniocentesis for women aiming to conceive naturally and test the health of the fetus during development; (ii) preimplantation genetic testing (PGT), which allows for the selection of embryos without mtDNA mutations or with the lowest possible chance of pathogenic mtDNA presence, and (iii) egg donation. The United Kingdom and Australia have approved two methods for replacing mutant mtDNA: maternal spindle transfer (MST) and pronuclear transfer (PNT). In MST, the maternal nuclear DNA is transferred from the patient's oocyte into an enucleated donor oocyte from which the maternal spindle has been removed. The reconstituted egg would then be fertilized by the intended father's sperm and the newly formed embryo implanted in the intended mother. In PNT, first mother's eggs are fertilized using the intended father's sperm, then the pronuclei of the embryo are transferred to a recipient embryo, from which the pronuclei have been removed. This paper will illustrate the basis of mtDNA-related diseases and the approaches to minimize transmission to offspring. Then, it will focus on the main ethical and legal/regulatory complexities as to various types of nuclear transfer to prevent mtDNA diseases, the risks to the child and future generations, and the issues related to germline changing. Our conclusion is that the two main methods developed to replace pathogenic mtDNA variants are morally approvable because they afford the newborn child quality of life.