Can Preimplantation Genetic Screening (PGS) Improve IVF Pregnancy Rates?
Although the use of PGS to improve IVF success rates became more popular in recent years – Dr. Gleicher raises caution. Recent data suggests that PGS can actually reduce pregnancy chances, especially in women with diminished ovarian reserve (DOR). Click on the video below to listen to the the full explanation form Dr. Gleicher.
Dr. Gleicher considers the difficult question of whether Preimplantation Genetic Screening (PGS) can improve IVF success rates.
Title: PGS and IVF Success Rates
Speaker: Dr. Norbert Gleicher
Does Preimplantation Genetic Screening (PGS) Improve IVF Pregnancy Rates? Does using PGS during IVF cycles improve pregnancy rates?
That is a question which, in our opinion here at CHR, is a basically incorrect question because we have a very hard time finding a rationale in doing PGD to improve IVF outcomes. PGD has been once before very aggressively promoted to improve pregnancy outcomes in association with IVF. Approximately 5, 6, 7 years ago, when this was done, the commercial term was not PGD, “preimplantation genetic diagnosis”, but PGS, “preimplantation genetic screening”, and PGS in those days was very widely propagated. Thousands of women worldwide were told that it would improve their IVF pregnancy chances. And then, after it had been used for a good number of years on a very wide scale, it was finally recognized that PGS not only did not improve a pregnancy’s chances in association with IVF, but in a selective patient population, particularly in older women and in women with diminished ovarian reserve, actually reduces pregnancy chances.
Some centers are still using PGS to presumably improve pregnancy rates in IVF. What’s happening?
Once that was finally recognized, the utilization of PGS plummeted — though, surprisingly, it was not completely stopped. There are still some programs, or there have been programs over the past three years, that still continue utilizing it for reasons which I, frankly, do not understand. Indeed, we here at CHR were probably amongst the earliest voices 6, 7 years ago, trying to convince our colleagues in publications that PGS very unlikely would give the positive IVF outcome results everybody was expecting, and we came to that conclusion by analyzing some published data from European colleagues. And by reanalyzing those data, we actually also concluded that especially older women, and women with with diminished ovarian reserve, were actually at risk for worse outcomes if they used PGS. You know, we at some point published that in a paper, but the big change, the widely accepted recognition of that opinion, came after some Dutch colleagues published a paper in the New England Journal of Medicine, where they prospectively randomized patients to PGS and no PGS, and showed exactly what we had predicted, namely that the older women that they studied actually ended up worse off than others. The utilization of PGS then greatly declined — though it never stopped — and then, over the last year or two, we are seeing a resurgence, and this resurgence, in our opinion here at CHR, is it’s very unfortunate, because it seems to be repeating the same mistakes that were made during the initial first introduction of PGS.
Why is PGS ineffective in improving IVF pregnancy rates? Are there patients who might benefit from PGS?
The reason why the same mistakes are being made all over, and why the same, in our opinion, misrepresentations are being made all over again to patients, inducing them to go through PGS and pay for PGS, is that our colleagues believe that newer techniques to accurately diagnose chromosomal abnormalities will make the difference — and we don’t. There is no question that over the last 4 or 5 years, the technique to diagnose an embryo accurately has improved. But we never believed that the inaccuracies in diagnosing a given embryo — whether it is chromosomally normal, or chromosomally abnormal — was the reason why PGS didn’t work in the first place. We always thought that that contributed a little bit to it — obviously, one wants to be as accurate as possible in diagnostic methodology — but we always felt that mathematically, the concept didn’t work, especially for older women and women who have very few embryos, like women with prematurely diminished ovarian reserve, because women with very few embryos have to value each embryo very highly. In contrast, if a woman has lots of embryos, if one embryo gets a little damaged or loses pregnancy chances, it’s not a big deal because she has so many embryos. And therefore, we always argued that if there were patients where PGS may make sense and may work out as a mathematical model (meaning where selection of normal embryos would make sense) was in young women who had lots of embryos, and that was always counterintuitive to what the specialty, what the field, believed, because chromosomal abnormalities increase with advancing female age. And so, intuitively, our colleagues always believed that the patients who would most benefit from the procedure are older woman or women with premature ovarian aging, because they have so many, such a high degree of chromosomal abnormalities. But they also have the fewest number of embryos, and when you calculate this mathematically through, and when you accept the logic and the obvious fact that manipulating an embryo more doing a biopsy for diagnostic purposes, will, to a minor degree, reduce pregnancy chances, and when you add all of this up, the mathematical modeling shows you that you can expect overall outcome benefits only, at best, in patients that have large embryo numbers, and that’s not the older patient, in whom most of those procedures have been recommended. Now, our colleagues who are now bringing back PGS are ignoring this whole thing, and they think that simply by having a more accurate diagnosis of embryos, they are ahead of the old PGS and that will make the difference. There is already data in the literature — and we have recently published a few papers on that — that show that our point of view is correct, and so we feel very, very strongly that PGS not only is a waste of time, money, and effort for the overwhelming majority of women going through IVF, but it actually, in many women, unfortunately will reduce their chance of conception, and so we caution from the use of PGS, even the new PGS, whatever is being represented.
What must be overcome for PGS to be effective in improving IVF pregnancy rates?
As we sit here, I think nobody can tell with certainly whether the whole idea of PGS really works. The idea of PGS is a very attractive idea because we know that a lot of embryos that humans produce — even young women — are chromosomal abnormal. And therefore, the basic concept to select out chromosomal normal embryos before transferring embryos back into the uterus sounds wonderful. Except, a theory does not always transfer into good clinical practice. And that’s why we need clinical trials, because otherwise we can be very smart, think, have great ideas, and solve all the problems in the world. That’s not how medicine works. PGS, in its first incarnation and now in its second incarnation, in our opinion has failed to improve pregnancy chances. And it has failed to improve pregnancy chances because it is used, we believe, in the wrong patient population. We have some experimental data, which we published last year, from patients who went through PGS not in order to improve their pregnancy chances, but for other reasons, for example sex selection, so they did not have routine infertility, and they were not the youngest, but also not as old as our infertility patients. And in those patients, when we did a case control study (which is not the perfect way to do a study but a quite well controlled way of doing a study), we indeed found some outcome benefits from doing PGS. But that is not your average infertility patient. And those data, as I said, are preliminary. So we believe that there is a patient population probably out there that may benefit from doing PGS in their IVF cycles. But it definitely is not the patient population in whom PGS is now recommended. In our opinion, it is probably a young patient population. And whether they want to do it and spend the additional money for it is, of course, questionable. So that’s as far as we can go today. Otherwise, we have still to do a lot of studies to really define the right patient population for PGS.
- Use of preimplantation genetic screening (PGS) to improve pregnancy chances is becoming more prevalent in recent years with technical improvements in diagnostic accuracy.
- Because data suggest that PGS actually reduces pregnancy rates, CHR cautions against routine PGS for the purpose of improving IVF pregnancy rates, especially in women with diminished ovarian reserve.
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