Tuesday, September 25, 2012

Should we be doing PGD for everyone ?

When we make embryos in the IVF lab , our goal is to transfer a single good-quality ( top quality) embryo inside a receptive uterus , so that the embryo implants and becomes a baby . Part of the problem is that we still not very good at identifying which embryo will become a baby. Today, we judge the quality of the embryos based on what they look like under the microscope. We grade them , depending upon their morphological appearance – for example , whether the embryo has any fragments ; whether they cells are equal; and how quickly the cells are dividing. We then select the best looking embryo, and transfer this into the uterus. Unfortunately , even a top quality perfect looking embryo may be genetically abnormal,  and it's not possible to judge its chromosomal normality just by looking at its appearance.

This is why PGD ( preimplantation genetic diagnosis) in which we biopsy the embryo to remove one or more cells from it to check their chromosome copy number (using CCS ( comprehensive chromosome screening))  , offers  great promise . PGD will allow us to select genetically normal embryos, which have a much better chance of implanting, as compared to genetically abnormal embryos.

Not only would this theoretically help to improve IVF pregnancy rates , it would also reduce the rates of miscarriage ( which often occur due to chromosomal errors in the fetus) ; as well as babies with birth defects  such as Down syndrome). So, if PGD is such a great idea , why don't we routinely offer it across the board to every IVF patient ?

The fact is that even though PGD technology appears very seductive on a theoretical basis, when we actually try applying this in practice , things often don't work very well . This is partly because we are still on a learning curve as regards PGD . Not only does PGD require a lot of experience and expertise on the part of the embryologist, removing cells from the embryo may end up damaging the embryo and thus reducing pregnancy rates . There are also real life practical issues. For example , when we analyze a single cell , we may not get accurate information, because our technology is still imperfect. Remember that a normal CCS report does not guarantee that the embryo has no genetic defects whatsoever – after all, it’s still not possible to do a comprehensive screen to rule out all possible genetic defects ! After all, how many questions can you ask a single cell ? Also, because biology is so messy, issues such as mosaicism ( the fact that not all the cells of an embryo are exactly the same), means that this technology will never give 100% accurate answers. Also, such sensitive tests are also likely to be plagued by problems of false positive and false negative results , as a result of which interpreting them can be quite challenging.

The problem is that there are a lot of clinics who create a lot of hue and cry about how useful PGD technology can be. They publish lots of articles on the techniques – and because this is  new technology, they grab a lot of media attention, because reporters are only interested in what is new ( whether it’s useful or not is often a secondary issue, unfortunately !) When na├»ve patients read these optimistic articles ( which are full of positive spin), they want to use all the newest and latest technology for their own IVF cycle, as they feel this will help them improve their chances of getting pregnant.

This puts a lot of pressure on IVF doctors to do PGD for them – they are scared that if they do not, their patient will go off to someone who does.  IVF can be a very competitive field, in which doctors are always trying to play the game of one-upmanship ! Most conservative clinics will still take a “wait and watch approach “ – let’s see how this new technology evolves. Part of the reason is that if the embryo gets damaged as a result of the PGD , the doctor will feel much more guilty about this , as compared to an IVF cycle failing because of inherent biological problems with the patient. Fortunately most doctors prefer not to intervene when there is scope for doing harm. After all, the first rule in medicine is – Primum non nocere – First, do no harm !

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