Danny Daphnis, PhD, Scientific Director at Mediterranean Fertility Institute in Greece, is discussing the 3-parent baby technique (mitochondrial transfer) and the surrounding controversy.
Dr Daphnis started his talk by explaining that IVF is an assisted reproduction technique that aims in helping infertile couples achieve a pregnancy. Oocyte donation or egg donation is part of an IVF procedure and is usually performed in patients who either have an ovarian failure or have problems accessing the ovaries. It’s used when there are some chromosome abnormalities, and there is a need to use the donor’s oocytes. If a woman has attempted many IVF attempts before and as her biological age has increased, it can become a necessity for that patient to perform oocyte donation or if the ovaries have been removed because of cancer treatment.
One of the main disadvantages and one of the main concerns that couples have is that the woman will not give any part of her DNA to the resulting baby. This causes patients distress, and it might give rise to religious and ethical issues, etc.
In 2016, in New Mexico, Dr Ihang reported the birth of a healthy boy after mitochondrial replacement therapy (MRT) by the spindle to prevent the transmission of mitochondrial disease. In a US-based clinic, they flew the patients to Mexico and did the procedure because it wasn’t allowed in the US at that time, the patients were suffering from a mitochondrial disease. Mitochondria are energy sources for the egg and are located in the egg’s cytoplasm. MRT is based on the fact that the nucleus of the mother’s egg, the one that carries the DNA, is fused with a healthy donor cytoplasm.
Types of MRT (Mitochondrial Replacement Therapy)
There are 4 types of MRT, the first is maternal spindle transfer (MST), that’s what Dr Ihang used.
It uses own genetic material removed from the eggs and transferred into donor eggs, which have their nuclear genetic material removed. The resulting eggs are then fertilized with sperm to create the embryos.
In Ukraine, another option was used, called Pronuclei Transfer (PNT) They fertilized the mother’s eggs with the father’s sperm, but they removed the two pronuclei (the embryo on day 1 of development) and inserted it into embryos created from donor eggs.
There is also Polar Body Transfer (PBT), there are two ways of doing that. Either removing the first polar body from an unfertilized egg and transferring it to an unfertilized donor egg, which has had its nuclear DNA removed or removing the second polar body after fertilization and transferring it to a newly fertilized egg (a zygote), which has had its maternal nuclear DNA removed.
The last method is called Germinal Vesicle Transfer (GVT). Very immature eggs are called Germinal Vesicles (GV), and they are usually not utilized in an IVF cycle. The technique entails the removal of the GV from a patient egg (it still has the DNA) and transferring it to an unfertilized donor egg which again, in turn, had its GV removed.
Maternal Spindle Transfer (MST)
MST involves using DNA from three people to prevent serious inherited diseases. The nucleus is removed from the mother’s eggs, then the donor’s eggs are taken, and the nucleus is removed and destroyed, the donor ‘vehicle’ which has normal mitochondria is transferred and fused with the DNA from the mother, following that, the fertilization with the father’s sperm occurs. This is the most common technique that is used and will be possibly used, but the possible effects that the baby might have when it gets born are yet unknown.
In 2019, in Greece, a woman gave birth to a boy using MRT. The difference was that this woman had no genetic disease, there was no life-threatening disease that had to be avoided to give birth to a healthy child. The woman had a history of multiple IVF failures and poor oocyte quality, therefore, it was done for other reasons. They used the same procedure as Dr Ihang, and they did it in collaboration with Spain and had a very good result.
Poor Oocyte Quality vs MRT
The quality of the egg is the most important aspect of an IVF to work. If you have poor-quality eggs, you won’t produce good-quality embryos or you won’t have a healthy pregnancy. We know that ovarian cytoplasmic function is very important as it reduces the chance of premature development, which is caused by deficiencies in the cytoplasm. Therefore, if you use the ‘vehicle’ donor egg, which does not have the nucleus but has everything else, in this case, the cytoplasm, it will help get a healthy baby. Improving mitochondrial function in the cytoplasm usually leads to the improvement of reproductive capacity. The idea of using MRT using the mother’s DNA is quite innovative, and hopefully, it will remove some ethical or religious stress. So far, this technique has been used either for patients who are suffering from mitochondrial genetic diseases or with a history of IVF failures due to poor oocyte quality.
There is still little information about problems that can be caused because of MRT. There are some concerns regarding designer babies by allowing partners to select traits. Another thing is the presence of 3 genetic parent babies as there is the nuclear DNA from the mother, sperm from the father and the donor who provides the cytoplasm that contains mitochondrial DNA (mtDNA). It is still unknown what that effect might have on the baby, although there is a low mutant mtDNA carry over to the embryo. Other controversies include the rights of the child, the future adults and the next generation, the status of the embryo also needs to be included, donors’ roles and interests and the community considerations because we still don’t know what this could cause to the resulting baby.
The HFEA in the UK was the first to regulate MRT and mitochondrial donation, and it is advisable to do MRT under specific circumstances, MST or PNT can be used cautiously in a specific situation where there is no other alternative because of inherited disease that is likely to cause the death of serious disease. It is not allowed to be used for women who have an ovarian failure or just want to do oocyte donation. The Australian Senate debate concluded that in special circumstances and when all aspects are controlled, MST can be applied, but the debate is not yet finished.
This method is still new, and it is still being researched. It’s very important to know where it can be done, who can do it, and if it’s safe.