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Assisted Reproduction and Infertility
higher pregnancy rates and better take-home-baby rates.
37
The higher the risk on promised benefits. Other examples abound and, because of their
for aneuploidy (i.e. the older the patient), the more effective PGS should be. considerable potential for lost chances to conceive, for the first time in the
history of IVF they endanger the steady and continuous improvement in IVF
Therefore, who would be surprised that PGS swept the world of IVF and pregnancy rates worldwide.
entered routine practice, even though a limited number of controlled studies
failed to demonstrate demonstrable benefits?
38
The overwhelming assumed Single-embryo Transfer
wisdom of the underlying concept resulted in all caution being thrown to the The most blatant example is the widely propagated concept of SET,
41
which
wind. Rather than demanding more and better studies, the profession reached similar to PGS is based on false assumptions and incorrect statistical
the almost unanimous conclusion that those early data had to be wrong. considerations and was initially proposed to improve IVF outcomes. The
However, data rarely lie. Re-analyzing early published data, for over two years principal arguments in favor of SET were:
we unsuccessfully attempted placement of a manuscript that criticized basic
premises of PGS and its worldwide utilization. We argued that the proposed • twin pregnancies represent higher outcome risk than singletons;
benefits of PGS would statistically hold up only if PGS (i.e. embryo biopsy) did • therefore, twin pregnancies should be avoided—even at the expense of
not negatively affect embryo implantation chances (not a likely premise), PGS reducing pregnancy chances; and
achieved a high degree of diagnostic accuracy in predicting embryo aneuploidy • SET avoids the risk for twins pregnancies.
(with currently available techniques really unachievable), and if PGS was used
to select embryos (i.e. requiring a large enough embryo pool to select from, While this line of thought on first impression (such as the rational for PGS)
thereby disqualifying most older women). Furthermore, we demonstrated in appears logical, on closer examination it actually proves statistically fatally
the manuscript that, barring full satisfaction of these three pre-conditions, PGS flawed. Nobody can argue with the fact that twin pregnancies carry higher
could actually adversely affect pregnancy chances. Our manuscript was finally risks than singletons. However, such comparative data reflect an obstetrical
accepted and published
38
after a Dutch study demonstrated that in older treatment paradigm of spontaneous conception and post factum risk
women PGS seems to reduce pregnancy chances with IVF.
39
Since then, analysis. Infertility treatment reflects a different treatment paradigm, where
many authoritative voices have spoken out against the uncontrolled a new infertility patient prospectively views cumulative risks of achieving
utilization of PGS, declaring the procedure ineffective in improving IVF desired goals. For a large majority of infertility patients, the desired goal is
pregnancy rates and reducing miscarriage rates with IVF.
40
However, what more than one child; therefore, those who want two children, theoretically
has not yet been properly addressed is how the worldwide premature at least, have the option of choosing one twin or two singleton deliveries.
introduction of PGS into routine IVF practice could have occurred in the first Controlling for desired outcome (i.e. two children), the statistically correct
place, and what lessons could be drawn from this unfortunate experience. risk comparison between twin and singleton deliveries in such patients is
not between one singleton and one twin, but between two singletons and
Our earlier noted calculations,
38
and the previously mentioned Dutch study,
39
one twin delivery.
42–44
leave little doubt that the utilization of PGS in inappropriately selected patients,
at least in some instances, reduces pregnancy chances. These data also When this is completed, twin pregnancies suddenly no longer demonstrate
demonstrate convincingly in many patients that PGS, does not deliver on clinically relevant excessive risks, thus depriving SET of alleged outcome
promised benefits of improvements in IVF pregnancy rates and decrease in benefits in comparison with two-embryo transfer (2ET) and, with it, of any
miscarriages. Consequently, the premature introduction of PGS into clinical rationale.
42
Indeed, since SET reduces pregnancy chances in comparison
routine practice breached the primary tenet of healthcare: to do no harm. By with 2ET,
45
it once again exposes IVF patients to reduced pregnancy
reducing pregnancy chances without offering any visible benefits, PGS caused chances without compensatory benefits and, therefore, breaches the ‘do
harm because it negatively affected the goal of infertility patients: to conceive. no harm’ covenant, paradoxically historically used by proponents of SET in
support of the procedure. Therefore, we consider SET contraindicated,
This goal appears increasingly endangered by systemic interventions into unless patients are desirous of only a single child and/or have obstetrical
standard IVF practices. It almost seems that parts of the medical profession no contraindications against twin deliveries.
longer believe that the primary goal of infertility treatment—and consequently,
the overwhelming obligation of physicians—is to protect a patient’s desire for In some European countries, the concept of SET is directly legislated
pregnancy. Instead, as described above, systemic interventions are introduced (Belgium), or indirectly through government-appointed bodies (UK). If the
under hypothetical assumptions of benefit willingly accept proven reductions medical establishment can be so obviously wrong in reaching
in pregnancy chances. In other words, once again the basic tenet of recommendations, how can one expect government to be wiser? However,
healthcare— to do no harm—is violated since a certain detriment (reduction in professional medical opinion can shift quickly. As the experience with PGS
pregnancy chance) is accepted based on an only hypothetical benefit that, as has demonstrated, publication of a single study can be decisive.
39
To reverse
PGS demonstrated, later may or may not be proved correct. The ethical legislation, in contrast, takes much more effort and time, suggesting once
conduct of medical practice, of course, prohibits such situations from more that medical practice patterns should not be subject to government
occurring. Treatments without confirmed appropriate risk–benefit interventions, but rather should remain under professional controls.
considerations should be considered experimental, and it is unethical to
introduce them into standard treatment protocols. Other Bad Ideas
In Europe especially (also the birthplace of SET), the increasing popularity,
Unfortunately, PGS is not the only recently introduced systemic intervention and untested introduction into practice, of so-called low-intensity, natural or
into standard IVF practice that reduces pregnancy rates without delivering patient-friendly IVF cycles
46
raises the specter of further declines in
30 US OBSTETRICS & GYNECOLOGY
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