• early onset Alzheimer’s disease
• preimplantation genetic diagnosis
• in vitro fertilisation
• late onset disorders

I note with interest the Controversy regarding a baby born free of an inherited predisposition to early onset Alzheimer’s disease through the use of preimplantation genetic diagnosis (PGD).^1,2 As the medical geneticist for the PGD programme for single gene disorders in Melbourne, Australia, I have seen many couples who have considered PGD for a wide range of genetic conditions. My observation is that many couples look to PGD for “milder” conditions and adult onset conditions for which they are not comfortable to have traditional prenatal diagnosis and termination of pregnancy.

An example of this is that in the last 11 years our unit has undertaken 13 prenatal diagnoses for Huntington’s disease from nine couples, whereas in the two years that we have been offering it we have had six requests for PGD for Huntington’s disease and three couples have already had IVF cycles.

I have a number of concerns with the argument that the woman should not have a child utilising PGD because she is predisposed to Alzheimer’s disease.³ Firstly, do the commentators believe that the couple should not have a child by natural means because of this fact? If this were the case, what lengths should be gone to to prevent the woman becoming pregnant by natural means? If the commentators who make this argument agree that it is not appropriate to prevent couples where one is at risk of a genetic disorder from having children by natural means, then assisting them to have children not predisposed to a genetic disorder is in my view entirely ethically acceptable.

The concerns for the child of having a mother suffer from early onset Alzheimer’s disease are that they will not have a mother to bring them up and the impact this will have. While members of the woman’s family have developed disease in their 30s and 40s, this is by no means certain for the woman herself. The only other report of people with this mutation also had early onset Alzheimer’s disease,⁴ but the numbers affected are very few, perhaps too few from which to draw a definitive conclusion about the exact age of onset for those with this mutation. For example the average of onset of the Val717Ile mutation is 57 years.⁵ This is a mutation involving the same amino acid (valine at position 717) and the substitution is for a chemically very similar amino acid (isoleucine compared to leucine). If the destiny of this particular woman is to develop Alzheimer’s disease in her mid 40s or beyond then her child will be an adult by the time she is severely affected. Even if we assume that onset of symptoms will be when the child is about 10 years old, the family are aware of this risk and can take steps to be prepared and put in place plans for this. Are couples with other sociological risk factors that put a child at risk of emotional deprivation prevented from utilising reproductive technology? In Australia at least, those who are from low income brackets or who use illicit drugs are not precluded from assisted reproductive technology, yet both these factors are associated with a number of poorer outcome measures for children.^6,7

Finally, PGD is a major undertaking for families. It is a protracted, expensive, and very stressful process and ultimately there is no guarantee that a child will be born through using it. Many couples who consider utilising PGD do not go through with the process for these reasons and choose other reproductive options, including traditional prenatal diagnosis, and natural pregnancy with no intervention, or they decide against having children. Therefore families who undertake this process are generally highly motivated and, one intuitively feels that the resultant child is less likely to suffer social deprivation. This issue will only be resolved by long term follow up studies.

In conclusion, I believe that PGD is ideally suited to situations where families wish to avoid their child having a genetic disease, but where they feel uncomfortable about terminating pregnancies. This includes late onset conditions such as neurodegenerative diseases and familial cancer syndromes, as well as early onset diseases that are considered relatively mild, such as deafness.