Is three-parent IVF therapy safe? Fears for controversial technique after study shows faulty DNA can slip into eggs

Fresh questions have been raised over the effectiveness of a controversial three-parent IVF therapy that promises to help parents carrying a debilitating disease to have healthy children.

The technique aims to replace the damaged mitochondria from a fertilised egg of a couple with those from a healthy donor - leading to what have been termed as 'three-parent babies'.

But a new study has found that, in some cases, the mother's faulty mitochondria can slip through the net during the process, which scientists say raises challenges for making the technique 'safe and effective'.

A new study has found that a pioneering technique which could be used to treat mitochondrial disease, can lead to faulty DNA slipping through the net. The nuclear transfer technique moves the genetic material from a fertilized egg (illustrated) to a new host cell with healthy mitochondria, but scientists say challenges remain for making the technique 'safe and effective'

The effects of mitochondrial disease can be devastating for affected families, leading to miscarriage and premature birth, and for deteriorating health for children born with the condition. 

But pioneering mitochondrial transfer techniques promise to intervene at the fertilization stage to provide healthy copies of mitochondria from a donor, offering hope for families.

The research from scientists in the US has found that in some instances the faulty mitochondria – which produce essential packets of chemical energy for cells – can be carried over, compromising the treatment.

They used embryonic stem cells to focus on a technique called nuclear transfer, in which the genetic material is transferred from one cell to another. 

As mitochondria are only inherited from a baby's mother – in the egg cell – it means the genetic material can be switched to an emptied donor cell, with healthy mitochondria.

Researchers found that in some instances, after the nucleus had been transferred to the new host cell, faulty mitochondrial were able to 'piggy back' into the new cell.

Using a number of cell lines the researchers were able to show that a small amount of mitochondrial DNA donated from the mother, was able to get a foothold.

While this faulty mitochondrial DNA was phased out in most cell lines – showing that successful transfer is possible – it persisted in one of eight cell lines, with the faulty mitochondria overriding the healthy donor copies.

Mitochondrial disease can be devastating for affected families, leading to miscarriage and premature birth, and deteriorating health for children born with the condition. But pioneering techniques are hoping to intervene at the fertilization stage, provide healthy copies of mitochondria (pictured) from a healthy donor

'We identified a challenge to making mitochondrial replacement therapy safe and effective,' explained Dr Dieter Egli, at the New York Stem Cell Foundation and a senior author of the study.

He added: 'We anticipate that the findings will inform decisions regarding when and how mitochondrial replacement in humans will be done clinically.'

The findings are published today in the journal Cell Stem Cell.

Dr Egli added: 'In order to prevent the transmission of mitochondrial diseases, we need to avoid competitive situations between mitochondrial genotypes of the parent and of the mitochondrial donor.

Pioneering mitochondrial transfer techniques hope to intervene at the fertilisation stage to provide healthy copies of mitochondria from a donor, offering hope for families carrying disease. Stock image

'The co-existence of the two-mitochondrial types within one cell must be avoided through minimizing or even eliminating carry-over during transfer.'

Experts have said that while the findings are of interest and will feed in to discussions on approval of the technique, they should not hold back mitochondrial transfer techniques from moving forward in clinical practice.

One form of mitochondrial transfer received approval in the UK in 2015, but has been held back from clinical use in the United States.

'Although mitochondrial transfer has been recently approved in the UK, no babies have been born yet using this approach,' said Dr Dusko Ilic, a stem cell researcher at King's College London.

'This study is a fair warning that one technical approach carries more risk than other, nothing else. It should not divert or postpone our efforts to move forward with mitochondrial transfer in clinical setting.'

Professor Robin Lovell-Badge, of the Francis Crick Institute, commented: 'Optimists would say that these experiments are encouraging, with the expected and hoped for result found in almost all cases.

'Pessimists would focus on the infrequent unexpected and un-hoped for result, which if carried out for real in an attempt to avoid mitochondrial disease would fail to do so. They may conclude that the methods are too unsafe to use clinically.

'Whether or not to go ahead with these odds might actually be a question that the patients should answer.'