The three-parent IVF process aims to replace or reduce the DNA mutation effects in mitochondria to overcome infertility or prevent the potentially debilitating mitochondrial diseases to their offspring.
Three-parent IVF is the assisted reproductive technology in which genetic material of one male and two females used for generating human offspring.
Mitochondrial manipulation technologies are specifically used in three-person in-vitro fertilization.
A small amount of cytoplasm from donated egg cells collected from healthy women is injected into the mother’s egg. This process is termed ooplasmic transfer.
After the ooplasmic transfer, the genetically modulated mother’s egg fertilized with the father’s sperm and then created an embryo implanted into the mother’s womb by using the IVF process.
The risk of hereditary disease transmission is significant in the ooplasmic transfer.
Therefore, the application of this process to treat infertility or mitochondrial disease has declined.
Apart from the ooplasmic transfer, the maternal spindle transfer and pronuclear transfer are the two most significant supplemented processes.
In maternal spindle transfer, the nucleus from the mother’s egg cell has collected and inserted into the donor egg by removing the nucleus with leaving behind the cytoplasm.
Then the egg is fertilized with the father’s sperm and then transferred to the mother’s uterus for further gestation, similar to other IVF procedures.
In pronuclear transfer, fertilization is performed by combining the mother’s egg with the father’s sperm to produce a zygote.
Then, the collected pronuclei are inserted into a donor egg from which the nucleus is removed and has been fertilized to produce a zygote.
Then the created zygote from the donor egg is implanted into the mother’s uterus.
In the mid of 1990s, the first ooplasmic transfer was introduced at a reproductive medical center in the United States to treat women infertility who had over 35 years of age and failed to get the successful result after repeated attempts of traditional IVF techniques.
However, during the initial phase of discovery, long-term safety data lacked and no animal testing was conducted.
Moreover, the impact of heteroplasmy involving donor mtDNA on health was also uncleared.
Later, in the early 2000s, an animal test result of mitochondrial replacement was conflicting.
Some of the tested animals had a cognitive decline in adulthood or accelerate the aging process, whereas other animals were apparently healthy and could breed well.
Initially, ooplasmic transfer was applied for infertility treatment, but later the aim was shifted and considered as the preventing treatment for mitochondrial disease transmission.
However, the safety and efficacy of ooplasmic transfer to prevent the inheritance of mitochondrial disease were uncertain.
Still, now, the impact of mitochondrial manipulation on heredity remains unknown.
However, researchers assumed that the possibility of potential alteration of family ancestry is high with involving donor mtDNA.
In 2001, the application of mitochondrial manipulation technologies was banned to use in reproductive clinics.
In 2014, the agency had taken into consideration that the three-person IVF is an improved technology that could be potentially used for preventing mitochondrial disease.
But the three-parent IVF is a debatable topic in the United States.
A special-permission requires from the US FDA to the use of mitochondrial manipulation technologies.
Reproductive clinics could not only use this technique without issuing explicit authorization from the FDA.
However, in 2012, after conducting clinical trials to test the efficacy of these technologies, the United Kingdom concluded that the use of mitochondrial manipulation technologies was ethical.
In 2015, United Kingdom introduced laws to guide the use of three-parent IVF after members of Parliament of this country voted in favor of allowing three-parent babies.