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5 reasons why 'Three Person IVF' is not really worth the trouble?

The introduction of 'In vitro fertilization' technique in the field of reproductive medicine came as a boon for thousands of couples who, until then, were left helpless by their inability to conceive. The hard work of Patrick Steptoe and Robert Edwards in developing this technique bore fruit in 1977, when Lousie Brown, the world's first 'test-tube baby' was born in Manchester.

This moment in history was glorified recently in the year 2010, when Edwards was given the Nobel Prize in Medicine. By now, the technique had helped thousands of families all over the globe and become simply known as IVF to one and all. But within a few years from this glorious moment, we are looking at yet another breakthrough in reproductive medicine, which goes much further than what IVF achieved. Instead of just fertilizing the eggs in a petri-dish, a 'The 'Three Person IVF' allows for fertilization of an egg, using DNA from three people, the father, the mother and a donor. The UK is pushing the draft of a regulatory framework that will allow them to become the first country to allow 'Three person IVF'.

How different is 'three person IVF'?

Normal IVF

In a normal IVF, the egg  (containing nuclear as well as mitochondrial DNA) from the mother and the sperm (containing nuclear DNA) from the father is usually taken in a petri-dish to facilitate fertilization. In case, the egg or the sperm is faulty, an egg or a sperm donor steps in (replacing the previous provider) and helps in the fertilization process. Fertilized eggs are then implanted in the woman's uterus, marking the beginning of her pregnancy.

Three person IVF

A 'three person IVF' will be taken up, when the mother has a mutation in her mitochondrial DNA that prevents the foetus from being healthy at birth. Since the mitochondrial DNA is present only in the egg, a donor will step into the picture, where in she will donate her egg, from which the nucleus will be removed and then be replaced by nucleus from the mother's egg. The resultant embryo that will be formed post in vitro-fertilization, will have nuclear DNA from both the father and the mother and mitochondrial DNA from the donor, thereby making this procedure a three person affair.

While this might be welcome news for women who happen to have mitochondrial mutations and cannot conceive normal healthy children, the question we need to ask is whether a 'three person IVF' is actually any significant development as such?

1. First and foremost, IVF, by itself, is a laborious process, especially for the mother, with a fair chance for failures. Since a three person IVF requires two egg donors, two women now, need to undergo the procedure.

2. IVF is not an easily affordable procedure. The addition of another person to the procedure, means additional medical expenditure for the couple or the state (depending on your location and the nature of medical services therein).

3. One simply cannot find a reason to justify this 'Three-person IVF', since the already existing option of a regular 'two person IVF', is also going to bear the same result - a foetus free from any deadly mitochondrial disease.

4. Our recent post on mitochondrial numts spoke on how mitochondrial DNA imprints itself on the nuclear DNA as well. In case of a 'Three person IVF,' the mitochondrial and nuclear genome are not going to be from the same person. Would this have any impact on the health of the foetus, is something, we need concrete data on. Certain studies have been done in chimps but the data was not really (a, b, c) conclusive and a thorough examination is still needed in this regard.

5. There is hardly any cutting edge technological development that is happening with a three person IVF. It is simply a matter of 'cutting and pasting' of the nucleus from one egg to another. If the researchers had managed to find a way to silence the mitochondrial mutations, that would be of real great help. Knowing how to do this, 'cut & paste' of nuclear genome, might be good from an academic viewpoint but rushing to do for a patient is not really necessary.

a. Tachibana, M., Sparman, M., Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., Li, Y., Ramsey, C., Kolotushkina, O., & Mitalipov, S. (2009). Mitochondrial gene replacement in primate offspring and embryonic stem cells Nature, 461 (7262), 367-372 DOI: 10.1038/nature08368

b. Tachibana, M., Amato, P., Sparman, M., Woodward, J., Sanchis, D., Ma, H., Gutierrez, N., Tippner-Hedges, R., Kang, E., Lee, H., Ramsey, C., Masterson, K., Battaglia, D., Lee, D., Wu, D., Jensen, J., Patton, P., Gokhale, S., Stouffer, R., & Mitalipov, S. (2012). Towards germline gene therapy of inherited mitochondrial diseases Nature, 493 (7434), 627-631 DOI: 10.1038/nature11647

c. Lee, H., Ma, H., Juanes, R., Tachibana, M., Sparman, M., Woodward, J., Ramsey, C., Xu, J., Kang, E., Amato, P., Mair, G., Steinborn, R., & Mitalipov, S. (2012). Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck Cell Reports, 1 (5), 506-515 DOI: 10.1016/j.celrep.2012.03.011

replacement of certain genes of the embryoa couple with a faulty set of mitochondrial genes to completely replace these genes from another donor looks at complete replacement of gene


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