Pre-implantation Genetic Diagnosis (PGD)
Aneuploïdie Screening (PGD-AS of PGS)
The usefulness of PGS
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Performing PGD in the lab. |
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The removal of cells from a three day old embryo. |
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Two blastocysts after PGD. |
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Aneuploïde screening on a normal male embryo: chromosomes X ('blue'), Y ("gold"), 13 ("red"), 18 ("aqua") en 21 ("green"). |
The same technique is used for PGD-AS (or PGS) as for PGD. First the (future) parents' chromosomes are examined (via a blood sample) for abnormalities. For PGS, blood is also drawn in order to try out the coloured DNA markers (see further).
The egg cells are always fertilized with sperm using the ICSI technique, in order to obtain an optimal fertilization. On the third day, two cells are removed from the eight cell embryos and genetically examined.
Target group for PGDThe purpose of PGD is to look for a well defined hereditory defect. We know in the lab what defects to look for on which genes.
If you are are at risk genetically of passing medical conditions on to your children, the technique provides you with the chance of becoming pregnant without your baby being affected by hereditory abnormalities. Examples of these are Haemophilia, Cystic Fibrosis and muscle diseases. Most people by which this technique is implemented are not infertile.
PGD can be considered a very early pre-natal diagnostic test. However, some pre-natal tests (performed on the already implanted and developing embryo) can, if they provide an unfavourable result, lead you to having to make the choice whether to terminate the pregnancy or not. This is not so with PGD. Embryos which are shown to be abnormal will not be used for embryo transfer.
How PGD differs from PGS
In PGS, genes are not evaluated, but rather a specific diagnosis is made concerning the chromosomal contents of a cell. This is done via specific flourescent markers, with which the the chromosomes in the nucleus of the cell can be counted. The technique allows embryos to be selected not only by their morphology, (how well they are formed) but also by their genetic contents.
In preparation for PGS, we take a blood sample from the parents, in order to be able to try out the coloured markers on the chromosomes of the man and woman. In this way, we can establish whether there may be a problem with the recognition of chromosome signals in the embryo.
Which chromosomes can be tested?
Because of a shortage of coloured markers, the number of chromosomes which can be tested in 48 hours is restricted. At the moment, we only test the chromosomes 13, 16, 18, 21, 22, X and Y. This is because a defect in any one of these can regularly lead to a miscarriage, or serious abnormalities in the child. For example, an extra chromosome 21 would mean that the child born from that embryo would have Downs Syndrome.
Target group for PGS
We know from studies, that there is a relationship between the age of the mother and the number of chromosomal abnormalities in embryos in IVF. This is why IVF is less successful in older women and why there are more miscarriages in this group.
This knowledge led to the idea of selecting only normal embryos for replacement in the uterus, to provide the greatest chance of an IVF treatment being successful.
The technique is relatively new. The few studies which have been performed, indicate that PGD-AS is best implemented in four groups of patients:
- women older than 37. Embryos from women in this group can be up to 60% abnormal;
- women who have had several unsuccessful IVF treatments, despite the fact that the embryos were morphologically normal. There must therefore be another reason for the failures;
- women who have had a series of miscarriages, one after the other;
- couples in which the man has a serious sperm production problem, where the sperms could be chromasomally abnormal.
For patients who are not especially at risk of developing abnormal embryos, PGD will be of little use.
The usefulness of PGS
Initial results in women over the age of 37, indicate that the embryos which test chromosomally normal, tend to implant better. The long term aim is that chance of a healthy pregnancy and baby will be greater in the group of patients that have PGD than if they had not have had it.
At the moment, the technique is still limited. We cannot yet examine all the chromosomes. It is therefore still possible that a chromosomally abnormal embryo could be replaced, without us being aware of it.
It is also true that about 4% of embryos are lost as a result of the test procedure. This could be due to the biopsy going wrong, or due to an uncertain result, meaning that the embryo cannot be replaced. We don't think that the biopsy itself is detrimental to the wellbeing of the embryo, but we cannot say for certain.
Conclusion
The available results suggest that PGD-AS is a valuable procedure in the selection of healthy embryos for transfer, for a certain patient group. We hope that as we gather more results over time, that more certainty can be placed on the indications that this method does indeed result in better chances of healthy pregnancies.
Finally, there is a chance that PGD-AS will in the future become more refined, so that the replacement of only one embryo will ever be necessary, thus eliminating the risk of multiple pregnancy in IVF treatment.