Rethinking IVF: NYC Study Urges New Approach to Embryo Selection

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 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 fruits, 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 costs 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 and 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.

Norbert Gleicher, MD, lead author of the here announced paper, is available for further information regarding this subject. Please call 212-994-4400 at Center For Human Reproduction or request further information at [email protected]. He is the Medical Director and Chief Scientist of the CHR in NYC, a Visiting Scientist at Rockefeller University, and President of the not-for-profit Foundation for reproductive Medicine, all located in NYC.

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(3):hoz017