Three-parent IVF trialled

“Three person IVF trial ‘success’,” reports BBC News.

This headline is based on the results of a trial of a controversial fertility treatment called mitochondrial replacement. Mitochondrial replacement, which uses genetic material from three people, is described as being “at the cutting edge, both of science and of ethics”.

The technique is designed to help prevent children from developing what are known as mitochondrial disorders. Every cell in the body contains structures called mitochondria, which produce the cell’s energy. These contain genetic material but, unlike the rest of our DNA, this is passed to the child only from the mother. There are several rare diseases caused by mutations in the genes in the mitochondria. Women carrying these mutations will pass them directly to their child.

The so-called three-parent IVF technique that was trialled in this research looked at how to prevent these “mitochondrial diseases” by replacing the mother’s mitochondria with healthy mitochondria from a donor.

While this technique has been performed in monkeys before, and had previously been thought to be theoretically possible in people, this was the first time it has been successfully performed using human eggs.

The researchers found that, although some egg cells that had undergone this procedure were abnormal after fertilisation, others were capable of normal embryonic development. It is important to note that none was used to create a viable pregnancy.

This is exciting scientific progress, but many factors need to be considered before this technique can be used to prevent mitochondrial diseases in humans. While baby monkeys conceived using this process appear to be healthy, there may be as yet unknown factors that could mean the technique is not suitable for human use.

  

Where did the story come from?

The study was carried out by researchers from Oregon Health and Science University (OHSU) and Boston University School of Medicine. It was funded by the OHSU Center for Women’s Health Circle of Giving and other OHSU institutional funds, the Leducq Foundation and the US National Institutes of Health. The study was published in the peer-reviewed journal Nature.

The research was covered well by the BBC and The Daily Telegraph. However, the Telegraph’s statement that this is the “first time” embryos containing DNA from three parents have been created is incorrect. A UK-based research group previously transferred nuclei between human zygotes (zygotes are the cells formed when a sperm and an egg cell join) in 2010.

However, these zygotes would not have been able to form a normal embryo, as they had been abnormally fertilised. 

What kind of research was this?

This was laboratory and animal-based research. As this is preliminary-stage research, this is the ideal study design to test feasibility. However, there is still a long way to go before this technique is ready for human use.

The journal article mentioned that the researchers looked at the overall health of monkeys who were conceived using three-parent IVF techniques in 2009, and they found no obvious abnormalities. But, while similar, monkey biology is not identical to human biology. So it is still not certain whether using this technique could affect the subsequent development of a baby.

These techniques need to be tested further for safety and efficacy, but there are also ethical issues to consider, such as whether a child conceived using this method has the right to know who their ‘third parent’ is.

What did the research involve?

The researchers harvested oocytes (egg cells) from seven female human volunteers donating their eggs for research. They selected a total of 65 oocytes for reciprocal nuclear transfer. This is often referred to as ‘spindle transfer’. It involves transferring the nucleus of a mother’s egg with faulty mitochondria into a donor cell with healthy mitochondria and other cellular components. The researchers also used 33 oocytes as non-manipulated controls.

This technique is the new technique essential to any ‘three-person IVF’. It is performed before the fertilisation stage of IVF. The researchers then fertilised the eggs by injecting sperm into them, and analysed the embryos formed to see if they were normal.

They checked the origin of the DNA in the nucleus, and the mitochondrial DNA in the embryo cells.

The researchers then investigated whether it would be possible to freeze embryos before performing the spindle transfer. This is because the method used up to this point would require both the patient and the donor to have eggs harvested at the same time, which could limit the practical applications of the technique. They explored this possibility using oocytes from monkeys. The researchers reported on the health and development of monkeys that had developed from oocytes that had undergone the spindle transfer procedure.

What were the basic results?

The researchers found that:

• Spindle (nuclear) transfer was successful for 64 of the 65 oocytes (98%).
• Sixty of these manipulated oocytes survived sperm injection, and 44 were successfully fertilised and formed pronuclei (a term for the oocyte and sperm nuclei before they fuse).
• The ratio of cells that survived injection and were successfully fertilised was similar for both the manipulated and control oocytes.
• Fertilisation was normal for 21 of 44 manipulated oocytes (48%). In contrast, fertilisation was normal for 21 of the 24 successfully fertilised control oocytes (88%).
• A similar proportion of both the manipulated and control oocytes that had been fertilised normally then went on to develop normally into blastocysts (an early form of embryo).
• The researchers checked the origin of the nuclear DNA in the cells of the blastocysts formed from manipulated oocytes and found that it was all from the spindle (nucleus) donor oocytes. All of the mitochondrial DNA was from the additional donors (the ‘third parents’).
• The researchers found it was possible to freeze the spindle (nucleus) donor egg, but that the spindle transfer procedure was most effective when the donor mitochondria egg was fresh.
• The health and development of four monkeys, which had developed from oocytes that had undergone spindle transfer, was reported. All reported tests were normal.  
   

How did the researchers interpret the results?

The researchers report that the spindle (nucleus) transfer procedure “can be performed with high efficiency in human oocytes”. They go on to calculate that, if success rates were similar to those seen in this study, two embryos could be created per cycle (assuming that a cycle produces 12 oocytes). They conclude that scientists and clinicians need to improve spindle transfer methods and ensure that these procedures are safe.

Conclusion

This paper has demonstrated the feasibility of transferring nuclei between human egg cells, which could lead to scientists and doctors being able to prevent inherited mitochondrial diseases.

Scientists have been experimenting with preventing mitochondrial diseases by transferring the nucleus of a mother’s egg with faulty mitochondria into a donor cell with healthy mitochondria and other cellular components.

The researchers found that a proportion of egg cells that had undergone this procedure survived, were normal after fertilisation and were capable of normal embryonic development in the laboratory.

In the embryos formed, all the nuclear DNA came from the nucleus donor cell, and all the mitochondrial DNA came from the mitochondria donor cell.

This is exciting scientific progress, but many factors need to be considered before this technique can be used to prevent mitochondrial diseases in humans. These techniques need to be tested further for safety and efficacy, but there are also ethical issues to discuss. Just because something can be done, does not mean that it should be done. For this reason, a public consultation has been launched to discuss the ethics of using three people to create one baby. For more information visit the HEFA website.