Pre-implantation genetic screening, or PGS, is when we analyze individual cells of embryos prior to embryo transfer.
It holds great promise for maximizing pregnancy rates. Most IVF failures can be attributed back to embryo quality.
Is PGS right for you? Perhaps, but it’s a highly personal choice. It depends a lot on your circumstances and needs to be explored with your doctor.
PGS is expensive and complicated. Neither of these things are great to hear, of course, but the promise inherent in this level of testing is profound and, for some couples, it can be an extremely beneficial solution.
Why is it so difficult? To understand the science, I recommend starting with www.chromosome-screening.org. The short version is, the process is a part of IVF.
As you know, IVF is when your eggs are retrieved and inside a laboratory introduced to sperm. Some days later, the fertilized eggs are placed back into the womb. Before that happens, PGS can be done.
To do PGS, we remove one or more cells from the embryo. These cells are then analyzed in the laboratory or they’re shipped to an external lab. We look at the number of chromosomes that those cells carry. The idea is, that the cells accurately represent the embryo about to be implanted.
There are two kinds of lab analysis done on the cells: The laboratory can look for specific and known genetic diseases or can count the number of chromosomes.
Most people choose to count chromosomes. Most people aren’t looking for any specific disease because both partners aren’t predisposed to any diseases that are inheritable. What they’re looking for is to find out if their embryo is going to be of sufficient quality to be consistent with an ongoing pregnancy.
The most common reason that embryos are not healthy is something called aneuploidy – that means the embryo has too many or too few chromosomes. PGS checks to make sure the embryo has the correct number of chromosomes or anything else that would be abnormal or not suitable for transfer.
PGS is not all that new but the techniques involved have been changing over time.
One aspect that has not changed – you will need to do ICSI and assisted hatching as part of the process. ICSI is the placement of the sperm into the eggs, and it is necessary rather than traditional fertilization (where many sperm are placed around the egg), as with traditional fertilization there are going to be extra sperm stuck to the edge of the zona pellucida (egg shell). That means when the biopsy is done, an extra sperm could accidentally come along with the cell and the test will appear to be abnormal when, in fact, the cells were just fine. Doing ICSI, where we place the sperm into the egg, negates that risk.
Assisted hatching is where a laser penetrates the zona pellucida, at least partially in this case, so that the biopsy needle can be placed against the cells for removal.
Before PGS is even started, you are looking at the costs and complications implicit in IVF with ICSI and assisted hatching. But there are other expenses too. Most laboratories will charge a biopsy fee, the lab will also charge a diagnostic fee for the genetic testing and there can be some shipping charges when external labs are used.
Are the added expenses worth it? Well, in select circumstances, absolutely! If the technology can deliver on its promise, I’m willing to guess most of our patients would be more than happy. After all, many couples who have completed IVF without success can become frustrated by the apparent transfer of high-quality embryos into a healthy woman and still no pregnancy.
This happens because many so-called healthy-looking embryos, in fact, are aneuploid. Depending on the age group, only 30%-70% of apparently healthy, day-five embryos are, in fact, normal (and the ratio is even less for day-three embryos). Any technique that allows us to find the best embryo could be highly advantageous.
Historically, we have looked at cell number and the relative fragmentation of embryos to guess at an embryo most likely to be consistent with ongoing pregnancy. In more recent years, many labs strongly favour growing embryos to the blastocyst stage, which is five days of growth in the lab, to further differentiate the best-growing embryos. Finally, some laboratories are using “embryo scopes”, camera systems to allow constant visualization of the developing embryo. Huge amounts of data are being generated with such techniques, though it is difficult to say, of all this data, which of it is actually useful to predict who is going to have a baby.
And there’s the appeal of PGS: It gets right to the heart of the matter as we confirm whether or not there are the right number of chromosomes to be consistent with an ongoing pregnancy.
It is not that a euploid embryo is guaranteed to result in pregnancy, but some labs are reporting pregnancy rates in the range of 80% when euploid embryos are transferred. So, this is not a guarantee, but a far higher pregnancy rate than any other therapeutic approach to date.
But of note, I also mention the technical complications.
The chief amongst the complications are this: The biopsy and embryo manipulation.
Does the biopsy harm embryos? It may: There are some data suggesting embryos biopsied on day three do not fare as well as those biopsied on day five. Like any ongoing scientific processes, there remains debate on this point, but at this time, based on what information is available right now, I believe day-five biopsy makes the most sense. I may have to change my mind again in the future, the subject really is changing that quickly!
Though the day-five biopsy appears to be safe – cells are taken from the outer trophectoderm (cells that will eventually become the placenta) rather than from the inner cell mass (cells that will become the baby) – the challenge is deciding how best to handle the embryo from that point forward. There is going to be, after all, a waiting period while we look to the results of the PGS. This can be as short as twenty-four hours, or up to a week, depending on how the technique is done; but it necessitates for a day-five biopsy, either day six embryo transfer, or a freeze-all technique. Freeze-all meaning the embryos are frozen to be transferred in a future cycle (this will also add to the expense).
So, which is better? A day-six transfer or vitrification and transfer on a future cycle? I favour the latter, but again, this is lab dependent and you can get various opinions depending on which clinicians you speak to and the latest paper on the subject.
Lastly: The results that come from the laboratories regarding PGS are not always as reliable as we would like. There are some reports of embryos being retested and having completely different results than they did the first time around. Could this happen to you? Well, yes, it could and it is partly a limitation of the nature of the process: We are biopsying so few cells. This has to be contrasted with an amniocentesis, for example, done at sixteen weeks of pregnancy when literally hundreds of cells could be tested at a single time. It is much more accurate and you will find that even as PGS purportedly can rule out, for example Down’s Syndrome, you will be asked to have a definitive test later in pregnancy, regardless. PGS cannot be and is not definitive.
I like to write articles that discuss complicated subjects in transparent and easy-to-understand ways. PGS is a topic that is changing, at the information becomes more settled, I will continue to post information that I feel will be useful to a wider population.
At this time, the best I can say is that an educated conversation with your clinician is going to provide you the best sense for whether PGS is going to be helpful to you. That said, if you do not have confidence that you can generate a good number of blastocysts that PGS probably is not going to be helpful. After all, it is a sorting mechanism, and if you only have one or two embryos for transfer, sorting is not required. Careful transfer of your embryos may be all that is necessary.