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Abnormal fetuses are highly unlikely to heal themselves

18 April 2016
By Professor Caroline Ogilvie
Professor of Cytogenetics, King's College London
Appeared in BioNews 847

Professor Magda Zernicka-Goetz and her colleagues recently published an elegant study (1) of early events in mouse embryo and fetal development (see BioNews 845). The authors fused normal mouse embryos with embryos that had been treated to create abnormal cells with the wrong number of chromosomes (aneuploidy). They found that, as development proceeded, the abnormal cells in the fused embryos gradually disappeared, by a process called apoptosis (programmed cell death). Some of these embryos developed into apparently normal pups, as long as there were sufficient numbers of normal cells at the start.

It is already known that, in humans, many early embryos produced via IVF have the wrong number of chromosomes in some or all of their cells (the phenomenon is called mosaicism when only some cells are affected). Identifying and discarding these embryos has therefore been suggested, and many centres follow this approach with the aim of improving IVF success.

However, recent studies have shown that at this very early stage of human development the abnormal cells may be lost, and mosaic aneuploid embryos can indeed give rise to normal babies (2,3). The Zernicka-Goetz mouse study models this very early stage aneuploidy, and gives some insights into the mechanisms by which these embryos may be 'rescued'. Screening human IVF embryos for aneuploidy at this very early stage may therefore result in the destruction of potentially viable embryos and may not be in the best interests of the patients.

Press coverage of the Zernicka-Goetz paper speculated that termination of human pregnancies diagnosed with aneuploidy at prenatal diagnosis could therefore be unnecessary because of the ability of the fetus to 'heal itself'. In fact, this mouse paper tells us very little that we didn't already know about human fetal development in relation to aneuploidy, and its findings are certainly not relevant to aneuploidy detected at prenatal diagnosis, which is carried out when fetal development is already quite advanced.

Approximately half of all miscarriages are found to have aneuploidy, usually involving one extra chromosome. These pregnancies miscarry because the genetic burden of the extra material is not compatible with further fetal development. An extra copy of a smaller chromosome can sometimes allow development to term, resulting in a baby with congenital problems such as Down's syndrome. Prenatal diagnosis by sampling the placenta (chorionic villus sampling, or CVS) at around 11 to 13 weeks' gestation is the earliest point in an ongoing pregnancy at which aneuploidy can be definitively diagnosed.

We know that in mosaic aneuploid pregnancies, the normal cells allow the pregnancy to proceed further than when all the cells are abnormal. In addition, the abnormal cells may be confined to the placenta (confined placental mosaicism, or CPM), or may be lost by preferential growth of the normal cells or by apoptosis, resulting in a normal baby. However, the outcome of any pregnancy with mosaic aneuploidy will depend on the proportion of the abnormal cells, the genetic content of the extra chromosome, and the presence or absence of the abnormal cells in different fetal tissues.

Laboratories finding mosaicism after CVS will recommend a follow-up amniocentesis test, which looks directly at fetal cells. However, there can be no generalisations as to the outcome – at amniocentesis low-grade mosaicism can be benign, depending on the chromosome involved and, similarly, the absence of abnormal cells in amniotic fluid does not exclude the possibility that mosaicism is present in some other fetal tissues.

It would certainly be dangerously wrong to tell a woman that her fetus will 'heal itself' and that she will have a normal baby. Many of the fetal structures that could be affected by the abnormal cells will already have been formed by the time the CVS is taken, and even if the abnormal cells decrease in number as the pregnancy progresses, the damage may already have been done.

The press coverage of the Zernicka-Goetz paper is therefore mostly misinformed and irresponsible and could lead to distress and confusion for women regarding their prenatal testing results. Detailed and expert ultrasound assessment, further testing and genetic counselling is offered to any woman with a mosaic finding at CVS. But in the end it is her decision as to how to manage the pregnancy – for some, any risk of fetal abnormality may be unacceptable.

15 August 2016 - by Dr Katie Howe 
Researchers have identified an enzyme that helps ensure egg and sperm cells contain the right number of chromosomes...
11 July 2016 - by Ayala Ochert 
A roundup of research stories from the annual meeting European Society of Human Reproduction and Embryology that hit the headlines this week...
3 May 2016 - by Professor Magdalena Zernicka-Goetz 
Although our recent findings on the fate of aneuploid cells in mosaic embryos have indeed been somewhat misrepresented in the press, our findings may still constitute a strand of hope for mothers who have had early test results showing mosaic aneuploidy...
4 April 2016 - by Dr Helen Robertson 
The presence of genetic abnormalities in cells taken from the placenta at the early stages of pregnancy does not necessarily mean that a baby will be born with a genetic disorder, a study in mice suggests....
22 February 2016 - by The signatories of the COGEN Consensus Statement 
It is clear from the reply of Mertes et al in BioNews 835 to the COGEN Consensus Statement on preimplanation genetic screening that some controversy still remains regarding the benefits of PGS...
18 January 2016 - by Heidi Mertes, Sjoerd Repping & Guido de Wert 
Under the auspices of the Virtual Academy of Genetics, COGEN recently issued a 'consensus statement' on preimplantation genetic screening, based on a scientific meeting held in Paris last September...
22 June 2015 - by Jane Fisher 
There has been much recent media interest in non-invasive prenatal testing for Down's syndrome, and this coincides with deliberations by the UK National Screening Committee on its potential inclusion in the NHS Down's syndrome screening programme...
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