PGT-A Testing: could it be the key to your IVF success?

The risks are, you know, we have to balance. It’s not for everyone. That’s my personal opinion. Unfortunately, it has been commercialised a lot, for various reasons. On one hand, we have the patients believing that this is the holy grail of IVF diagnosis, which it is not. Other pieces of the puzzle are equally, if not more, important. And of course, there’s the commercial demand. IVF clinics are also commercial entities, and sometimes driven by forces other than pure science. We have to balance all that and remember that nothing is perfect. There’s no perfect world, there’s no perfect test. Even if our patients are prepared to go the extra mile and spend an extra thousand, as scientists, we have to hold off on providing a blanket approach. In my clear opinion, it’s not for everyone.

The value of PGT-A is mainly for couples where the woman is over the age of 35, and in couples where there’s an obvious chromosomal anomaly. I would also add perhaps patients where there’s been a history of recurrent implantation failure or miscarriages. Definitely not for donors. There is a question on the panel: if it’s 25% in younger women, why don’t we do it on the donors? Because this is considered a very low chance, and because PGT-A is not entirely free of risk. There is a risk of damaging the embryo through all the manipulation. There is the risk of storage. We know now that freezing and storage probably have equal, if not better, chances than the first embryo transfer cycle. There is an added cost to the patients. Extra cost means fewer chances in the future because all our couples have certain budgets. How many attempts can they have for the same budget? We need to be very careful when costing treatments and add-ons which do not offer clear advantages.

PGT-A is a screening test. It is diagnostic, really, but also screening because the accuracy is not 100%. Depending on the labs, you will read in the small print the disclaimer that they recommend an amniocentesis in order to confirm the finding. We have to be in a dialogue with the obstetrician, with the team looking after the antenatal care. Often, I’m called into a multidisciplinary team to decide. My opinion is very clear: do all the non-invasive tests first. I’m a very non-invasive person. I’ve been around long enough to be a huge fan of minimally invasive approaches. In terms of how we double check in pregnancy, scanning is very valuable and non-invasive, and prenatal testing like beta HCG testing, non-invasive prenatal testing by means of fetal measurement in the woman’s blood, and then, if there’s still doubt, amniocentesis may be an option.

Absolutely. Roughly, no matter whether it’s the UK, Europe or the US, the cost of PGT-A can be as high as the cost of IVF itself. I always keep that maths in my head: what is best for the benefit of my patient, if I offer them for the same amount of 2 cycles of IVF or if I offer PGT-A in one cycle. This is a very important discriminatory factor to understand what’s best for an individual patient.

How long is a piece of string? From my experience, I’ve been around for 35 years. I’ve worked in more than 10, maybe 12 clinics and visited more than 100. The most senior embryologist is performing the embryo biopsy. As it becomes more common, there are quite a few people around. This is a skill developed over the years. Patients, the same way they trust us to do everything else, the same way they trust our embryologists to do ICSI, they should trust the clinics. I haven’t seen a single IVF unit where no experienced person was performing PGT-A testing, and usually it is the most experienced embryologist in the lab.

It can be done, technically it can be done. The question is, is it worth considering? Is it worth doing? It requires very careful counselling. For me, the most important deciding factor about PGT-A is: is it valuable for the individual couple, the individual patient?

For a 35-year-old doing their first IVF, I would definitely not suggest PGT. For 36, 37, the same, doing their first or even second cycle. I like to analyse every cycle step by step and optimise things according to my experience and clinical judgment. I would only suggest PGT-A on someone under 38 if they’ve had more than 2 perhaps unsuccessful, or 3 transfers, and everything else felt perfect. If somebody had 2 unsuccessful transfers and everybody commented on a difficult embryo transfer, I would try to correct the difficult embryo transfer with hysteroscopy and dilatation before jumping onto PGT-A. PGT-A is a very advanced, complex procedure, and I would resort to that if I have excluded other factors.

For under-37, 38-year-olds, recurrent implantation failure or miscarriages would be an indication. For over 38- 39-year-olds, where the chance of a genetic anomaly is very near 40- 50%, I would consider that and definitely discuss with our patients. It depends on logistics, where they live, and whether they can go home and come back.

PGT-A has a very important place where the woman is over the age of 40, where she’s had multiple failures. Over the age of 40, I like to know for sure that what I’m transferring is genetically normal. Research published this year shows that up to the age of 42, 43, one genetically normal embryo at 42 has the chance of implantation of a 35-year-old. This explains the miracle babies we have at 42, 43, and 44-year-olds. Over the age of 40, I generally like to know that I’m transferring a genetically normal embryo.

PGT-A is prevention. We test the embryo before we implant it. If it’s good, we implant it. If it’s not good, we don’t. That’s prevention. The 12-week scan is early diagnosis, early detection, not prevention. One is that we don’t let bad things happen. The other is that we diagnose bad things that have happened early. Huge difference.

First of all, congratulations. You were proactive. Your eggs and embryos produced by those eggs have the health of a 38-year-old, not of a 48-year-old. If you don’t have a history of miscarriages or any adverse factors, I probably wouldn’t PGT-A test them. What I would do is be very careful in screening you, in particular your uterus, the endometrium, your blood tests, your hormones, and you as a whole person, before implantation. The sperm you’re mixing them with is precious.

Yes, absolutely. We quantify those and reach a conclusion on whether it qualifies for endometriosis or not. For women with recurrent implantation failure, I always check for CD56 and CD138, and for microbiome, microbiota testing, which is very valuable and treatable. NK cells, I’m sitting on the fence. If there’s heavy history, I would probably do it. If there’s no heavy history, I’m sitting on the fence. We can test NK cells, but there’s no solid science behind how to interpret the results. With CD138, things are straightforward, and with microbiota testing, they’re straightforward and treatable.

Generally, we prefer day 5 blastocysts, but it’s not uncommon to have a normal day 6 blastocyst. We’re playing with hours sometimes. There’s no huge difference between day 5 and day 6. Day 5 is a better quality blastocyst. With time-lapse, we know the morphokinetics are more regular on day 5. Having said that, there’s an early day 6 and a late day 5, so no huge difference.

Embryos day 3, no, I didn’t say that. What I said is that many units are not using day 5 embryos and are using day 3 embryos, which may be okay for the initial stages. But when the case gets difficult after 1 or 2 failures, we need to insist on culture to day 5. A day 5 embryo by itself is a better prognostic than a day 3 embryo. The implantation value of a day 5 embryo equals 2 day 3 embryos. The value of a tested embryo is the same as two untested embryos. One tested blastocyst stage embryo probably has a value of 3 or 4 day-3 embryos. This minimises the chance of twins. In the old years, we transferred 3 and 4 embryos because day 5 embryos were uncommon. Now our incubators are equally good. I have no problem with day two, day three embryos initially, but after two or three implantation failures, we have to insist on day 5 and perhaps PGT-A testing.

It’s the stage they reach that’s important, not how many days it took them to get to that stage. We culture embryos for six days if they haven’t become blastocysts on day five. By the time they became blastocysts on day 6, I would transfer them on a day 5 endometrium, perhaps a little bit later on day 5, on day 5 and a half.