The problem with PGS - overpromising and underperforming

One of the most frustrating problems in IVF today is implantation failure . We know that the commonest reason for failed implantation is a genetic problem in the embryo , which is why preimplantation genetic screening ( PGS) was considered to be a big advance when it was first introduced 20 years ago. The technology offered the hope that if we could test the embryos to ensure they were genetically normal before transferring them , the IVF pregnancy rate would improve dramatically. After all, selectively transferring only those embryos which are genetically normal would allow us to both increase the IVF pregnancy rate and also reduce the risk of miscarriage after IVF .

Sadly, what appears to be true in theory often does not work well in real life, because human  biology is so complex . I5 years ago, the only technology to check if embryos were genetically normal or not was using a technique called FISH ( fluorescent in situ hybridisation) . FISH allowed us to check whether the embryo’s chromosomes were normal or not. However, because it used to fluorescent dyes to  label the chromosomes, the number of chromosomes we could check with FISH was very limited. As a result, even embryos which appeared to be normal on FISH had  chromosomally abnormalities, which led to IVF failure and miscarriages.

PGD using FSIH was hyped up a lot when it was first introduced. The clinics which offered this marketed themselves as offering cutting edge advanced technology, and lots of patients were lured into doing PGD with the hope that their pregnancy rates would improve.  However, controlled clinical trials clearly showed that PGD / FISH did not increase IVF pregnancy rates – and in fact, could cause them to drop ( because the embryo biopsy procedure could damage the embryo). However, lots of patients had wasted a lot of money unnecessarily on false hope.

Of course, the same IVF scientists then claimed that the problem was not with the PGD , but with the FISH technology. Genetic technology had improved considerably, and they believed that using more advanced technology such as CCS ( comprehensive chromosomal screening ) or NGS (next-generation sequencing ) for genetic testing would allow us to select the normal embryos with greater accuracy. They labeled FISH as being old-fashioned and unreliable, and started selling the benefits of array technology, which allows us to check all the chromosomes – not just  the 6 or 7 which FISH allows us to screen for.

While it's true that CCS is better than FISH, the fact still remains that it has its own limitations. However, we are now seeing a new marketing blitz , with lots of hype about how PGS/CCS will improve IVF pregnacy rates and should be offered routinely to all IVF patients.

The one fact which a lot of doctors will still not share with patients is that a chromosomally normal embryo is not always a genetically normal embryo. This might seem confusing , but even an embryo which appears to be chromosomally normal ( euploid) may still have lethal genetic defects which we cannot pick up. These may cause the embryo to arrest after transfer ( leading to a failed IVF cycle); or result in a miscarriage.

The problem is that when doctors misuse words , patients get confused between genetically normal and chromosomally normal embryos. When they fail to get pregnant even after doing PGS/CCS; or if they miscarry after a PGS/NGS cycle, they feel cheated .

This is why it's important that doctors learn to use words precisely ; and that patients have realistic expectations as to what the technology can offer them. Other wise we will end up with the old problem of overpromising and under delivering , which plagued PGS in the past, and caused a lot of patient unhappiness because of shattered dreams.

Not sure if you need PGS or not ? Please send me your medical details by filling in the form at http://www.drmalpani.com/free-second-opinion so I can guide you sensibly ?