Although there seems to be a consensus on this point, there are good reasons - which I outlined in the Journal of Assisted Reproduction and Genetics earlier this year - to question this limitation in this stage of the development of the technique.
Imagine that a new technique needs to be introduced. There are two possible settings: setting A in which some harm may be caused by the technique but, based on preclinical research, the harm will likely be small. Or setting B in which some harm may be caused by the technique but in which there is also a high risk of serious harm because of another reason. Based on the moral duty to minimise harm, most people would conclude that we should start in setting A.
However, the UK and Australia decided that the technique (mitochondrial transfer) should be initiated, practised on and limited to those cases where there is a high risk of a serious and lethal genetic disease related to mitochondrial DNAmutations. The main concern for the technique's safety at the moment is that mutated mitochondrial DNA is transferred together with the nucleus. It turns out to be very difficult to transfer the intended mother's nucleus into the donor oocyte without taking any pathogenic mitochondria along. The higher the carryover levels, the higher the risk for the child to develop the mitochondrial disease.
Mitochondrial transfer could also be used as a technique to treat infertility. Just as ICSI has become a solution for male infertility, mitochondrial transfer (a misnomer for what is actually enucleated oocyte donation) could be a solution for some female-related infertility. According to the Human Fertilisation and Embryology Authority (HFEA), mitochondrial transfer should not be used for fertility problems 'because a strong causal link between infertility and impaired mitochondrial function has not been made'. Such a link would be needed if only mitochondria would be transferred, but this is not the case. In fact, the whole donor oocyte with the exception of the nucleus. That includes many other parts of the oocyte that may affect oocyte maturation, fertilisation and embryo development.
For every new technique, there is a learning curve. By applying the technique first in infertility cases, not only could practitioners learn more about the risks of applying the technique, they would also be more experienced by the time they started practising the technique on high-risk cases. If these methods are applied in patients with low-quality oocytes, changes to the protocol could be tested without creating high risks for the offspring, since the mitochondrial DNA of the intended mother is not pathogenic.
The technique could, for instance, be tried in people who have a history of failed IVF cycles. They, like the women considered by the HFEA, 'have no other option of having their own genetic child'. However, the evidence of its effectiveness in this group is very limited at the moment. The preliminary results of a study in Greece in 25 patients with poor oocyte quality, published in Fertility and Sterility, resulted in six live births after 25 maternal spindle transfer cycles. The mitochondrial DNA carryover levels were below one percent and almost undetectable in the children, apart from one child who carried up to 60 percent of the maternal haplotype in different tissues at the age of six months. This reversion would have been very worrisome if it had happened in patients with mitochondrial disease. The uncertainty about its effectiveness explains why the technique is not used for infertility patients. However, whether or not mitochondrial transfer is effective and safe should be shown through application in a research setting.
Other techniques, generally captured under the heading of 'add-ons', are applied in fertility treatment without proven effectiveness and safety. The regulatory authorities restrict themselves to a recommendation not to use these techniques. However, the reaction to mitochondrial transfer in the UK and Australia is much stronger: the application for fertility treatment is forbidden by law. It is unclear why the technique cannot be tested as an innovative technique within a clinical research setting, given the reassuring data from animal and preclinical stem cell research. Moreover, the HFEA and the Australian authorities have already decided that the risks linked to the application of the technique itself are acceptable, since this risk also applies to prevent mitochondrial diseases.
In the initial phase we are in at the moment, mitochondrial transfer should first be used to remedy infertility caused by poor oocyte quality or poor embryonic development. The expertise acquired during that learning period will allow researchers to improve their technical skills and the knowledge of the best procedure, before starting on high-risk cases.
Professor Guido Pennings
Professor of ethics and bioethics at Ghent University, Belgium
bionews.org.uk
Mitochondrial transfer: first for fertility treatment, then for mitochondrial diseases
Australia recently passed legislation explicitly allowing mitochondrial donation (see BioNews 1139). It is the second country after the UK to do so (see BioNews 826). Like in the UK, the technique is only allowed to prevent transmission of mitochondrial defects in children of mothers known to be carriers of such diseases.
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