Studies raise doubts about three-parent IVF for mitochondrial disease
The United Kingdom last year reported eight healthy births to mothers carrying disease-causing mitochondrial mutations after mitochondrial replacement techniques, or “three-parent IVF,” combining nuclear DNA from the intending parents with mutation-free mitochondria from a donor egg. The results raised hopes that other countries might follow, including the United States, where the procedure remains banned. Australia, the second country to legalize MRT explicitly, is preparing a national experiment even as scientists and ethicists revisit whether preventing mitochondrial disease is the best first use of the technology.
Bert Smeets, a clinical genomics professor at Maastricht University who studies mitochondrial disease and sits on the oversight committee for the only U.K. clinic licensed to perform MRT, Newcastle University, said the public may wrongly assume the method is very safe and low-risk. Pushback had mainly targeted infertility marketing: a STAT investigation published on Monday found IVF clinics worldwide pitching MRT to older women seeking genetically related children despite scant evidence it works for them. Some researchers now argue that carefully run studies of severe infertility may be the most ethical path to develop MRT safely.
Newcastle pioneered pronuclear transfer in the early 2000s, creating embryos from the mother and a donor then swapping nuclear DNA. 2010 lab data showed less than 2% of the mother’s mutation-bearing mitochondria in reconstructed embryos, but many embryos did not survive. Shoukhrat Mitalipov of Oregon Health & Science University developed maternal spindle transfer, transferring a mother’s genetic material into a healthy donor egg before fertilization. In 2009 his lab reported the first monkeys born this way, healthy and without leftover original mitochondrial DNA. In human eggs, even after swapping up to 99% of defective mitochondria, remnants clinging to the spindle could overtake healthy mitochondria as cells divided—a problem they called reversion. Their November 2016 paper suggested reversion could cause MRT to fail in roughly 15% of cases.
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