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Home » News and Research » Genetics in the Media » Three-parent IVF: Why the controversy?

Three-parent IVF: Why the controversy?

A new reproductive technique, 'three-parent IVF', has recently appeared in the media amidst a great flurry of controversy. This technology has the potential to help women who are affected with severe mitochondrial diseases to conceive healthy children. The implementation of this is currently being considered by regulatory authorities in the US and UK.

What are mitochondria?

Mitochondria are tiny organelles with a small amount of their own DNA (representing 0.1% of total cellular DNA) that serve as the 'powerhouse' of cells. Mitochondrial DNA (mtDNA) is distinct from nuclear DNA. Normally, a child inherits their nuclear DNA from both their biological parents; half from the mother and half from the father. In contrast, all of a child's mtDNA is inherited solely from their mother. Each mitochondria carry several copies of mtDNA and each cell has several mitochondria, which results in around 1000 copies of mtDNA per cell. It is possible that a cell can contain two genetically distinct types of mtDNA (termed 'heteroplasmy') and it takes a certain proportion (or threshold) of mtDNA that carry a mutation for the disease to ocur in an individual. It is also possible that a mother with a low proportion of faulty mtDNA to have children with higher levels of faulty mtDNA due to a 'bottleneck effect'. This means that only a small proportion of the mother's mtDNA are copied when the egg is produced. If the copies are made from mostly faulty mtDNA; the child will end up with a greater proportion of faulty mtDNA and thus likely to be more severely affected than their mother. Selection also occurs in tissues as development progresses meaning that even a child with a low mutant load can be severely affected if the majority of their faulty mtDNA happen to segregate to susceptible tissues or organs. Mitochondrial diseases vary in severity, but in many cases individuals who have a mitochondrial disease live with debilitating illness with symptoms such as seizures, dementia, migraines, heart failure, diabetes, liver disease, muscular dystrophy and have a reduced life expectancy.

How does three parent IVF help avoid mitochondrial diseases?

Current options to assist women with mitochondrial diseases have an unaffected child have limitations. Women or couples can choose to have non-biologically related children through adoption or egg or embryo donation. They can also choose to fall pregnant naturally and have prenatal diagnosis. However, due to the nature of mitochondrial inheritance, prenatal diagnosis for mitochondrial diseases can never give a definitive negative result. Moreover, for some people prenatal diagnosis is not a realistic option because it means making choices about termination of pregnancies. Couples can also choose to have pre-implantation genetic diagnosis (PGD) and the selective transfer of embryos that have the lowest proportion of faulty mtDNA. However, as explained above, the bottleneck effect and selection during tissue development also lead to uncertainties regarding whether the child would be unaffected.

How does it work?

Mitochondrial replacement-assisted IVF involves the collection of eggs from both an unaffected egg donor and from a mother who has a genetic fault in her mtDNA. The mitochondria from the mother's egg are then 'swapped-out' with unaffected mitochondria obtained from the donor egg. The resulting egg will then have healthy donor mitochondria and the mother's nuclear DNA. This egg could then be implanted and fertilised if necessary using IVF techniques. These techniques therefore prevent any disease caused by faults in mtDNA from being passed on to the next generation.

3parent Table


Currently there are many uncertainties associated with mitochondrial replacement technologies. Clearly further studies need to be performed to examine feasibility and safety. Public discussion of potential ethical concerns is also an important part of the approval processes. However, some of the fears and concerns raised can be tempered with further informed debate and the clarification of any misconceptions.

References and further reading

Thorburn, D. R. and Dahl, H.-H. M. (2001), Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options. Am. J. Med. Genet., 106: 102-114. doi: 10.1002/ajmg.1380

Baylis, F. (2013) The ethics of creating children with three genetic parents. Reprod Biomed Online,26(6):531-4. doi:10.1016/j.rbmo.2013.03.006.

Cohen, J. and Alikani, M. (2013) The biological basis for defining bi-parental or tri-parental origin of offspring from cytoplasmic and spindle transfer. Reprod Biomed Online,26(6):535-7. dx.doi.org/10.1016/j.rbmo.2013.03.008.













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