Does blastocyst size matter? Exploring reproductive aging and genetic testing

“[…] when selecting non-PGT-A tested embryos for embryo transfer (ET) or frozen embryo transfer (FET), a small hatching blastocyst seems to be a better choice than a large expanded one, especially for advanced-age patients for whom the risk of aneuploidy is higher.”

BUFFALO, NY — April 9, 2025 — A new research paper was published in Aging (Aging-US) Volume 17, Issue 3, on March 5, 2025, titled “Reproductive aging, preimplantation genetic testing for aneuploidy, and the diameter of blastocysts: does size matter?”

In this study, a team led by first author Jakub Wyroba from the Malopolski Institute of Fertility Diagnostics and Treatment and Andrzej Frycz Modrzewski Krakow University, and corresponding author Pawel Kordowitzki from Harvard Medical School, Nicolaus Copernicus University, and Charité, found that the size of an embryo and whether it has started hatching can help predict its genetic health. This insight could help fertility clinics select better embryos during in vitro fertilization (IVF), especially in countries or situations where advanced genetic testing is not available.

As more women are choosing to have children later in life, fertility challenges related to age are becoming more common. Older maternal age is linked with a higher risk of chromosomal problems in embryos, which can reduce the success of IVF. To identify healthy embryos, many clinics use a test called preimplantation genetic testing for aneuploidy (PGT-A). However, PGT-A is expensive and not available in all countries. This study explored whether embryo quality could be predicted using physical features alone.

During IVF, embryos develop in the lab for several days before being transferred into the uterus. Around day five or six, the embryo reaches a stage called the blastocyst. At this point, it begins to break out of its outer shell, called the zona pellucida. This process is called hatching, and it is an important step before the embryo can attach to the uterus and begin a pregnancy.

The researchers examined 1150 embryos from women aged 26 to 45 who underwent IVF. They looked at whether the embryos were already starting to hatch and how big they were. They then compared these features with results from genetic tests. They found that smaller embryos that were already hatching were more likely to be chromosomally normal, also called “euploid.”

“Of the 1150 blastocysts that underwent PGT-A analysis in this study, 49% were aneuploid.”

For women over 35, 51% of small hatching embryos were euploid, compared to just 38% of larger ones that had not started to hatch. Among younger women under 35, the difference was even greater—73% of small hatching embryos were euploid, compared to 58% of large, unhatched ones.

The research team also looked at what happened after the embryos were transferred. When embryos were already known to be euploid, both large and small embryos led to similar pregnancy rates. This means the size and hatching behavior mostly matter when genetic testing is not done.

This study offers new guidance for IVF clinics. Choosing a small hatching embryo may improve the chances of success, especially for women of advanced age and in clinics that do not use PGT-A. This finding could help make fertility treatment more accessible and affordable. As fertility science continues to advance, insights like this provide practical tools to improve outcomes and bring new hope to individuals and families trying to conceive through IVF.

Read the full paper: DOI: https://doi.org/10.18632/aging.206215

Corresponding authors: Pawel Kordowitzki- p.kordowitzki@umk.pl

Keywords: aging, maternal age, embryo, blastocyst, preimplantation genetic testing, aneuploidy

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