Media Blog- PGD/PGS
CHR Blog: PGS finally on the front page
The media have finally caught on to the preimplantation genetic diagnosis (PGS) ruse that has been going on for much too long. In an excellent piece Gautam Naik in the Wall Street Journal on July 1, 2009 well demonstrated that the emperor, indeed, does not wear any clothes. PGS does not, as widely propagated by many so-called “experts” in the field, improve pregnancy rates with in vitro fertilization (IVF). Indeed, it may, especially in older women, actually reduce pregnancy rates. PGS also does not reduce miscarriage rates and, once again, at least in some patients may, indeed, reduce the chance to even conceive via IVF.
Peer review
The Wall Street Journal piece explained well most of the reasons why PGS so far has been such a failure. What the piece, however, failed to adequately address is the failure of the scientific peer review process that preceded the ultimate understanding reflected in the article.
Investigators at CHR, after reanalyzing PGS data, at that point published by various authors all over the world, already in late 2005 recognized that the superficially attractive concept of PGS improving pregnancy chances with IVF, and reducing miscarriages, was statistically flawed. PGS, of course, at that time was being widely touted based on the conceptionally attractive concept that selecting chromosomally normal from amongst many chromosomally abnormal embryos, and transferring only chromosomally normal ones into the uterus, would improve pregnancy chances per embryo transfer.
This concept appeared to make particular sense in older women since the percentage of chromosomally abnormal embryos increases with advancing female age. Indeed, the concept appeared so obviously correct that clinical trials to verify the idea before widespread introduction of PGS into daily clinical practice seemed almost unnecessary. The obviousness of the gospel also prevailed when some small-scale clinical trials were unable to confirm the expected benefits. In rejecting the results of these trials, proponents of PGS (as to this day !!) attacked the quality of the trials, but refused to reconsider their deeply flawed basic concept of PGS.
It was one of these early, and greatly criticized, trials by a Belgian group, which, on reanalysis of their data by CHR investigators, for the first time suggested that PGS not only may not improve IVF outcomes but, especially in older women, may actually reduce pregnancy chances with IVF, a fact later confirmed in a prospectively randomized study out of the Netherlands (Mastenbroek et al., N Engl J Med 2007;357:9-17) . CHR investigators summarized the results of their literature review in a paper and in early 2006 submitted it for publication to the leading general medical and specialty journals in the field.
One after the other, these journals rejected the paper, often, as the reviewers’ identical comments demonstrated, reviewed by the same small cadre of so-called PGS “experts.” Many amongst them, of course, in the meantime had developed strong financial incentives to keep PGS going. By developing PGS laboratories, they had established significant new income streams for themselves, but also for IVF providers. Any interruption in the continuous growth of PGS would, of course, have reversed this.
Only after the prestigious New England Journal of Medicine (which earlier had rejected the CHR manuscript) in 2007 published Mastenbroek’s paper (for reference see above), did the scientific atmosphere start to change. Suddenly, Fertility and Sterility, the official organ of the American Society for Reproductive Medicine (ASRM) accepted a resubmitted version of the previously rejected manuscript and, credit where credit is due, published it on fast track (Gleicher et al., Fertil Steril 2008;89:780-788).
Since then, the literature, of course abounds with data and opinion-driven papers, which conclude that PGS, in its current technical context, is at best useless and, possibly, harmful to IVF outcomes. Amazingly, there are still voices out there, which claim otherwise, and accuse published studies of, sometimes true, shortcomings. What they, however, during all of this controversy steadily have ignored is that it is up to proponents of PGS to prove the procedure’s clinical usefulness; it is really not up to opponents to prove, beyond reasonable doubt, that PGS is a waste of time, money and effort and potentially even reduces pregnancy chances with IVF.
Professional organization
The Wall Street Journal article also failed to address the utter failure of professional organizations in the PGS disaster. Neither ASRM in the U.S., nor its European counterpart, the European Society of Human Reproduction and Embryology (ESHRE), voiced for much too long any concerns with the world-wide spread of PGS as a routine clinical procedure. Both organizations, therefore, very obviously failed in their advisory responsibilities to the profession, even though they by now have caught up with the published data and, like the American College of Obstetricians and Gynecologists (ACOG), have published appropriate guidelines.
Paradoxically, this is, however, not yet the case for all professional organizations. For example, the International Federation of Fertility Societies (IFFS), in its spring 2009 newsletter, still gives exposure to a rather timid opinion about PGS. Its author, interpreting published data quite obviously incorrectly, in his concluding recommendations suggests that PGS “would be expected to benefit primarily women of advanced age (>37 years).” He then, however, immediately practically contradicts himself by concluding that “at least 6 and preferably 8 morphologically normal embryos should be available,” since older women, of course, hardly ever produce such embryo numbers.
In analogy to above discussed peer review process, the reasons for the failure of organized medicine in regards to establishing PGS recommendations in timely fashion are obvious: Within both organizations it is the “PGS experts” who control subcommittees and, therefore, policies of the entire organization. The same conflicts of interest, therefore, abound, and it would appear that both, medical journals and professional organizations, have lessons to learn.
Conflict statement
CHR is in a small minority of IVF centers world-wide, which performs PGS in house and does not send embryonic cells out for analysis to national PGS laboratories. CHR, thus, would have even more economic incentive to perform PGS than the vast majority of other IVF centers, which do not have the benefit of PGS laboratory revenues.
Nevertheless, CHR never recommended PGS for the purpose of improving pregnancy chances with IVF and/or reducing miscarriage risks. Very much to the contrary! As the pages of our website, CHR’s various publications and many patients who have come to CHR with a desire for PGS well document, CHR since 2005 recommended against the use of PGS for these indications.
When CHR decided to establish PGS in house, above noted review of the world-wide literature was initiated as part of CHR’s routine quality assurance process. This process then led to above noted manuscript by Gleicher et al., and an in-house policy to, contrary to then prevalent opinion, not support the use of PGS for above noted indications. Recent developments, of course, have validated CHR’s position!
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