We know that the commonest cause of IVF failure is a failure of the embryo to implant, and that the commonest reason for implantation failure is a genetic defect in the embryo . The truth is that human reproduction is not very efficient, and this is the reason why every fertile couple does not get pregnant every month they have sex ( except in Hindi films !) This is Nature’s defense mechanism, to prevent the birth of an abnormal baby. While these defects are often random, they are commoner in older women. This is because these eggs have more genetic abnormalities, because they have “aged” and have genetic defects.
This is why it seems very tempting to do pre-implantation genetic screening ( PGS, aka as PGD = preimplantation genetic diagnosis) and PGT = preimplantation genetic testing) for all IVF patients, so that we can select the genetically normal embryos . Logically, this should increase the chances of implantation and reduce IVF failure. After all, what’s the point of transferring a genetically abnormal embryo back into the uterus ? It will just fail to implant, or even worse , end up in a miscarriage.
This makes rational sense, but unfortunately , in real life , biology is far more complicated. I think we need to remember that when we’re doing PGS , we’re really not doing genetic screening – we’re really just doing chromosomal screening, so a better name really would have been pre-implantation chromosome screening or PCS.
Why is this important ? All these new genetic tests for PGT ( for example, CCS – comprehensive chromosomal screening and NGS – next generation sequencing ) only allow us to make sure that the cell has a normal number of chromosomes. This means we can make sure it is euploid, so that we can screen out which embryos are aneuploid ( these have an abnormal number of chromosomes) . Aneuploidy is an important cause of failure of implantation as well as miscarriages, but we also need to remember that counting the number of chromosomes is not enough if we want to identify genetically normal embryos. After all, there are over 30,000 genes , and there are only 23 pairs of chromosomes. This means that even though an embryo may appear to be normal on a PGS, this does NOT mean that it is genetically normal. Thus, PGS normal embryos will have a normal chromosomal complement, but they will still have lethal genetic defects that prevent them from implanting.
Unfortunately , most patients don’t understand this difference. When they end up spending a lot of money in order to transfer a PGS-normal embryo , and then still end up with a failed IVF cycle or a miscarriage, they’re obviously very bitter and angry and feel they’ve been misled. This can create a lot of dissatisfaction.
Many patients come to us and ask that we do PGS/CCS for them. Typically, these are older women or those who have had failed IVF cycles elsewhere. They have read about this new technique online, and want us to do it for them, because it is supposed to improve IVF success rates.
Here are the medical reasons why PGS does not help.
Genes are not the same as chromosomes. Even if the embryo is chromosomally normal, an euploid “normal” embryo after PGT can still miscarry, because it may have a genetic defect that is incompatible with life, which we cannot screen for. Patients who miscarry after the transfer of a PGT normal embryo are often devastated, because they have been sold the belief that the miscarriage rate after doing PT is zero. This is clearly a lie. This is a false negative result .
2. The phenomenon of mosaicism. What does this mean ? It means that not all the cells of the embryo are genetically identical. This means that the 2-3 cells which are biopsied at the time of PGT are not representative of all the remaining 100 cells of the embryo. Thus, if the biopsied cells are abnormal, the embryo is discarded, even though the remaining cells are normal, and this transferred embryo could have become a completely healthy baby. This can cause heart-break for patients, when they realise they discarded a healthy embryo because of a misleading test result. This is a false positive result.
3. Also, an embryo can self-correct. This means that even if a few cells are abnormal, the remaining normal cells can multiply normally, and result in a normal baby. This is another reason for a false positive result, where the doctor discards an embryo which could have become a healthy baby !
4. Technical limitations of the test. Patients often underestimate the technical skills and complexity of PGS testing. Thus, most IVF clinics send the biopsied cells to an external genetic lab for testing. Often, the results are ambiguous and confusing, but because IVF doctors don’t understand enough genetics, they err on the side of safety, and tell patients to discard embryos which are not reported as being completely normal. Also, sometimes, the DNA of the biopsied cells is not processed properly, as a result of which the lab is not able to provide a result, and the result comes back as “inconclusive”, which confuses the patient and doctor even more . And because not all embryologists are good at doing an embryo biopsy, many embryos get killed and damaged during the biopsy process ( a fact which is often hidden from the patient).
5. The need for PND ( prenatal diagnosis) even after doing PGD. Finally, patients are not informed that irrespective of the PGT result being normal, they will still have to be subjected to prenatal diagnostic testing when they get pregnant. If you are going to do prenatal diagnosis anyways ( usually a CVS or chorion villus sampling at 8 weeks of pregnancy), then why waste money on doing the PGT in the first place. The PND is much more reliable, and will stop you from having a baby with a chromosomal defect in any case !
So why has PGT becoming so popular today ? The reason is simple – it’s because it allows IVF clinics to make more money – at your expense ! And since it’s the newest technology around, it’s being marketed very aggressively and cleverly !
Logically, we should be very happy to do PGT for patients who ask for it , because we can charge more for these additional services. However, as professionals, we also need to explain to them that while PGS will help us make more money, it will not help to improve their chances of success.
Sadly, most other IVF clinics do not bother to do so . And if a patient wants a new technology to be used for them, and is willing to pay for it, then why not pander to their request and comply ? It takes too much time and effort to say No to a patient’s request – and it’s hard to say No when you are turning away additional income. It’s true that we lose these patients to other clinics, but other than educating them, there’s nothing else we can do about this.
Because we are well off and very busy, we are in the fortunate position of being able to afford to say No when we don’t think the inappropriate overuse of technology is in the patient’s best interests !
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