AN IMPORTANT PRESS RELEASE - Has the hypothesis of EMBRYO SELECTION been finally laid to rest? Announcing an important paper
The Reproductive Times here reprints a press release form the Center for Human Reproduction (CHR) in NYC in which the center announces the publication of a paper in Human Reproduction Open by some members of its research staff which argues that the hypothesis of embryo selection (beyond basic embryo morphology), which has been an undisputed dogma in IVF practice since the first birth from IVF, has basically proven to be a complete failure. The hypothesis suggests that in every IVF cycle’s embryo cohort there are significantly better and poorer prognosis embryos beyond what standard embryo morphology can detect, therefore, new tests and procedures must be pursued to “select” the best embryos for transfers. This hypothesis is still being aggressively pursued to this day, and can be best illustrated by the onslaught of artificial intelligence (A.I) studies being reported demonstrating some promise. All changes – without exception - introduced to IVF promising improvements in IVF cycle outcomes based on the hypothesis of embryo selection for over more than 40 years, including – to name only the two most impactful ones - routine extended embryo culture to blastocyst stage and preimplantation genetic testing for aneuploidy (PGT-A) – have, however, by now been demonstrated not to improve IVF outcomes in general IVF population and, to be detrimental for significant subpopulations. Besides explaining why, on a biological basis embryo selection makes little sense in a large majority of women, the publication, therefore, argues that the concept of embryos selection in IVF beyond standard morphology should be finally laid to rest and the overwhelming majority of resources dedicated to the task of improving embryo selection in IVF , must now be redirected toward more promising research.
New York City – based Fertility Center publishes an important article in Human Reproduction Open: “Why the hypothesis of embryo selection in IVF/ICSI must finally be reconsidered.”
Since almost its initial establishment, the success of in vitro fertilization (IVF) has been based on obtaining through use of so-called fertility drugs more than the usual single oocyte (egg) that a natural ovulatory cycle produces in a female. Multiple oocytes then allowed for the production of multiple embryos with improved cumulative pregnancy and live birth chances. Having multiple embryos available, however, immediately raised the question, which among them are the best embryos to transfer first, leading to the concept of “embryo selection,” which since has become a dogma of IVF practice.
The assessment of “embryo morphology” (how embryos look under the microscope) was the first method of embryo selection applied and—at least to a degree—proved valuable in ranking available embryos in their chances of leading to pregnancy and delivery. But IVF practice demanded more categorical results. The search for better embryo selection methods, therefore, became the most actively pursued research goal in worldwide IVF practice, to this day consuming otherwise unmatched resources in the IVF field.
On first impression, some of these efforts appeared to bear fruit, as investigators, for example, claimed that extended embryo culture from day-3 after fertilization (cleavage-stage) to days 5-7 (blastocyst-stage) improved IVF cycle outcomes. As a consequence, the embryos of almost all IVF cycles are now routinely—at significant added cost—cultured to blastocyst stage, even though many studies have since demonstrated that this practice in general populations does not improve pregnancy outcomes and in some patient sub-populations, indeed, reduces pregnancy and live birth chances.
Other investigators proposed testing of embryos for chromosomal abnormalities (aneuploidy) to deselect chromosomal abnormal embryos from transfers, as we now know wrongly claiming, that this would improve IVF outcomes for the remaining normal (euploid) embryos. This procedure, first introduced over 20 years ago and now called preimplantation genetic testing for aneuploidy (PGT-A), is currently—at an additional cost of at least $5,000 per cycle—still used in the U.S. in over half of all IVF cycles despite 2024 joined opinions of the American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) that none of the by proponent claimed outcome benefits from PGT-A have indeed, been confirmed. Somewhat unsurprisingly, PGT-A, therefore, has recently become the subject of several class-action suits in the U.S. In Australia, one such suit was in 2024 already settled.
Worldwide disappointing experience with these two IVF practices and several others relying on the hypothesis that better embryo selection would improve IVF cycle outcomes, now led a group of investigators from NYC’s Center for Human Reproduction—an internationally recognized fertility center—to publish a paper in Human Reproduction Open, a medical journal of the European Society for Human Reproduction and Embryology (ESHRE), in which they call for embryo selection attempts beyond embryo morphology to be finally laid to rest (1).
Because a majority of research dollars in the infertility field still are spent on embryo selection procedures—confirmed by the current boom in proposed A.I. offerings in the service of embryo selection—the authors of the paper, moreover, not only call for an end to clinical embryo selection procedures but also to an end to the excessive research funding of projects involving the hypothesis of embryo selection. IVF practice, indeed, could greatly benefit from switching this funding to more promising areas of potential exploration.
The authors in the paper also explain why—for basic biological reasons—embryo selection simply cannot work. The most obvious among those explanations is that every embryo cohort in a single IVF cycle acquires a predetermined maximal cumulative pregnancy chance once the number of available and transferrable embryos has been established which can no longer be approved (though it can be negatively affected by poor practice).
This group of investigators also already in 2020 noted the association of to this day declining live birth rates in fresh IVF cycles in the U.S., apparently associated with increasing PGT-A practice (2). Their argument of redirecting research dollars to other than embryo selection goals, therefore, appears logical and cost-effective.
References
1. Gleicher N, Gayete-Lafuente S, Barad DH, Patrizio P, Albertini DF. Why the hypothesis of embryo selection in IVF/ICSI must finally be reconsidered. Human reproduction Open;2025(2):hoaf011
2. Gleicher N, Kushnir VA, Barad DH. Worldwide decline of IVF birth rates and its probable causes. Human reproduction Open 2020