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expert reaction to study describing the regeneration of functional human oocytes from discarded genetic material

Scientists publishing in the journal Cell Stem Cell have reported the production of functional human oocytes from discarded genetic material, a process which they suggest could one day assist in fertility treatment or mitochondrial replacement therapy.

All our previous output on this subject can be seen here.

 

Dr Helen O’Neill, Embryology, IVF and Reproductive Genetics Group, Institute for Women’s Health, UCL, said:

“In no way should it be concluded that success rates will be “doubled” for infertility patients. This is a harmful exaggeration when each patient comes with a very individual set of circumstances; be that poor quality eggs, low number of eggs or no eggs. This technique would not help the latter group at all, and relies on donor eggs, which are not available in abundance.

“The authors have acknowledged that more work needs to be done to optimise protocols and this may be due to the number of eggs that were needed to generate a potentially viable embryo. The study started with 32 eggs (many times more than any patient would have access to) and, of those that were fertilised, only 8 reached the stage which would be capable of implanting.

“Furthermore, it has been concluded that aneuploidy rates are comparable between control blastocysts and test groups (normally fertilised PBNT blastocysts), but only two embryos were assessed in the test group. This is not a sufficient number to conclude “comparable rates”, as this may be due to chance.

“Finally, though not considered statistically significant, 186 genes (of 14,876) were differentially expressed between the two cell lines generated. Further work would need to be done to conclude if these genes had an effect on future offspring.

“While this is a useful study, in that it has shown that previous work done on mice can be applied to human oocytes, it is far from clinically applicable at this stage.”

 

Prof. Joyce Harper, Professor in Human Genetics and Embryology, UCL, and BFS spokesperson, said:

“I do not feel that this technique would make an impact on fertility treatment for women of advanced maternal age as their polar bodies are just as likely to have a chromosome abnormality as their eggs. It would create more eggs, but it will not improve the quality. The technique could be explored as a method for the treatment of mitochondrial replacement therapy.”

 

Prof. Daniel Brison, Honorary Professor of Clinical Embryology and Stem Cell Biology & Scientific Director of the Department of Reproductive Medicine, University of Manchester, said:

“The paper by Mitalopov and colleagues is intriguing as it shows that the genetic material which is discarded by nature during the process of egg maturation is of relatively high quality and can give rise itself to a normal embryo, in addition to the one which comes from the remaining egg following fertilisation.  The embryos coming from these discarded egg “polar bodies” appear to be relatively normal, based on an impressive array of genetic tests on the embryos and embryonic stem cell lines made from them. However there may be defects undetected here which would limit the use of polar bodies to make embryos for fertility treatment. In any case the technique is unlikely to be of benefit to most IVF couples as an egg from a healthy donor is required in order to make use of each polar body. This will certainly not double the success rate of IVF treatments, but does give us valuable information about the process of egg maturation.”

 

Prof. Darren Griffin, Professor of Genetics, University of Kent, said:

“The authors have pulled off an impressive technical feat of getting preimplantation embryos from polar bodies rather than oocytes. The community will watch with interest how the work progresses however the current low success rate of generating embryos from polar bodies compared to the usual way using oocytes potentially could indicate underlying problems with the approach.

“A note of caution should also be rung in terms of the claim that this would “double the number of gametes available.” The oocyte and polar body are genetic “reciprocals” and this means that if there was a problem with one (e.g. an extra chromosome) we might expect to see a problem (e.g. the same chromosome missing) in the other.”

 

Prof. Dagan Wells, Associate Professor at the NIHR Biomedical Research Centre, University of Oxford, said:

“The work is technically impressive and may, in the future, provide another option for patients hoping to avoid of conditions caused by the inheritance of defective mitochondria. It is particularly interesting that the scientists involved were able to use the genetic material from the polar body, a cell which is discarded by the egg as it matures and is traditionally thought of as being little more than a dustbin for the chromosomes that the egg needs to discard in order to make way for those that will be delivered by the sperm.

“I think it is very important not to overstate the possible benefits of this procedure. While it is true that some forms of infertility are caused by defects in the egg, by far the most common egg problem is chromosome abnormality, an issue that increases greatly with advancing age and has a profound impact on the chances of a successful pregnancy. Unfortunately, the chromosome abnormalities seen in the egg tend to be mirrored in the polar body, so most abnormal eggs will also have abnormal polar bodies. This is not to say the approach will be useless, but its clinical impact might be less than one might imagine. In terms of treating inherited mitochondrial disorders, there might also be a problem if the polar body receives a disproportionate number of abnormal mitochondria from the egg, which is something that has been suggested might happen. Methods that have previously been developed, and focus on transferring the mother’s genetic material to a healthy egg at a different stage, might be superior.”

 

Functional Human Oocytes Generated by Transfer of Polar Body Genomes’ by Ma et al. published in Cell Stem Cell on Thursday 10th November. 

 

Declared interests

Dr Helen O’Neill: None received

Prof. Joyce Harper: No conflicts of interest

Prof. Daniel Brison: “I have no interests to declare other than those previously, which is that I am Scientific Director of the IVF clinic at St Mary’s Hospital, Manchester, UK and involved in embryonic stem cell research.”

Prof. Darren Griffin: President of the International Chromosome and Genome Society http://www.icgs.info, Director of the Centre for Interdisciplinary Studies of Reproduction (CISoR) http://www.kent.ac.uk/cisor, and Treasurer of the Preimplantation Genetic Diagnosis International Society

Prof. Dagan Wells: Dagan Wells has conducted research into avoiding mitochondrial disorders but has no conflicts of interest.

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