The reproductive technique known as “three-parent IVF” or mitochondrial replacement therapy has faced renewed scrutiny as emerging research complicates earlier optimism about its safety and effectiveness. The procedure combines genetic material from both biological parents with mutation-free mitochondrial DNA from a donor egg, and was heralded as a breakthrough following the birth of eight healthy children to affected mothers in the U.K. However, scientists and ethicists are now questioning whether preventing mitochondrial disease represents the best initial application for the technology.
Research has uncovered a phenomenon called “reversion,” in which defective mitochondria from the biological mother persist and multiply despite efforts to replace them with healthy donor mitochondria. When scientists at Oregon Health & Science University developed an alternative method called maternal spindle transfer, laboratory testing revealed that problematic mitochondria could accumulate with each cell division even when up to 99% of defective mitochondria were initially swapped for healthy replacements. Data published in 2016 suggested this reversion could cause the technique to fail in roughly 15% of cases.
The issue extends beyond laboratory findings. A small clinical study involving 25 women under 40 with repeated IVF failures showed that reversion occurred in actual clinical settings. Two of seven children born carried substantial amounts of maternal mitochondria—as high as 51% in one case and 35% in another. Additionally, researchers at Newcastle University, which holds the only U.K. license to perform the procedure, documented reversion in three of the eight infants born, with levels between 5% and 16%. A Ukrainian clinic similarly identified reversion in two of six children tested, with one case showing maternal mitochondrial levels as high as 72%.
Experts caution that public perception of the technique as safe and low-risk does not align with current evidence. Some researchers now suggest that carefully controlled studies examining severe infertility may offer a more ethical pathway for developing the technology safely, rather than its current application toward preventing inherited mitochondrial disease. Meanwhile, regulators in Australia are preparing to launch their own clinical program using the technique.
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