We Test Embryos, But We Do Not Test the Whole Embryo: An ESSI Perspective
Understanding Mosaicism and What a PGT-A Result Really Represents
By Emanuela Lazzaroni Tealdi, MS Senior Embryologist & Fertility & Reproductive Immunology Specialist, ESSI Fertility & Immunology Program
In modern IVF, embryo selection increasingly relies on genetic testing. Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to help prioritize embryos with the highest likelihood of implantation and live birth.
But an important question remains: How completely does a PGT-A result reflect the true biology of an embryo?
A 2024 study published in Cell Discovery by Zhai et al. provides important insight into this question, showing that early human embryos are biologically far more complex than a single test result can fully capture.
What the Study Examined: Single-Cell Resolution
The study applied single-cell sequencing to human embryos, allowing researchers to analyze chromosomal content at the level of individual, isolated cells.
This is fundamentally different from standard PGT-A testing performed in IVF clinics today. Standard PGT-A:
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Samples a small group of cells (typically just 5 to 10 cells).
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Pulls these cells exclusively from the trophectoderm (the outer layer of the embryo that eventually becomes the placenta), leaving the inner cell mass (which becomes the fetus) entirely untouched.
By evaluating embryos cell by cell, the Cell Discovery study aimed to better understand how chromosomes are distributed within embryos, whether embryos are genuinely genetically uniform, and how early developmental biology handles chromosomal variation.
Key Finding: Mosaicism Is a Feature of Early Embryos
One of the central findings of the study is that human embryos frequently exhibit mosaicism.
Mosaicism means that different cells within the exact same embryo can have different chromosomal compositions. Some cells may be euploid (having the correct, normal number of chromosomes), while others right next to them may be aneuploid (having an abnormal number of chromosomes).
This study demonstrates that embryos are not perfectly uniform, genetically identical structures. Rather, they are heterogeneous systems at the cellular level. Importantly, the study presents mosaicism not as a rare anomaly or a defect, but as a normal, inherent biological characteristic of early embryonic development.
Complex Chromosomal Patterns Within the Same Embryo
Beyond simply identifying mosaicism, the study also describes incredibly complex chromosomal patterns occurring within a single embryo, including:
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The peaceful coexistence of normal and abnormal cells.
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Complementary aneuploidies, where gains and losses of the exact same chromosome occur in different cells within the same embryo.
This means that different regions of the same embryo may carry completely different chromosomal information. As a result, the clinical interpretation of an embryo’s health can vary wildly depending on exactly which 5 to 10 cells happen to be pulled during the biopsy.
What This Means for PGT-A
PGT-A remains a highly valuable and clinically useful tool in reproductive medicine. However, its methodology must be understood within its biological context.
Because PGT-A analyzes a highly limited biopsy of cells from a very specific region of the embryo, it provides a representative snapshot, not a complete chromosomal map. This study reinforces that:
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A tiny biopsy may not fully reflect the entire embryo.
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Some biological variability will simply not be captured.
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Embryo biology is vastly more complex than a single “normal” or “abnormal” result implies.
This does not mean PGT-A is inaccurate. It simply means that its results require expert interpretation within a broader biological context.
The Clinical Reality Has Not Changed
Despite this increased understanding of embryonic complexity, one key principle remains unchanged in the fertility clinic: Euploid (chromosomally normal) embryos continue to have the highest implantation and live birth rates.
This is supported by extensive, decades-long clinical data and remains central to embryo selection in IVF. The 2024 study does not challenge this fact. Instead, it provides deeper insight into what a euploid classification actually represents at the cellular level—it means the snapshot we took looks excellent, which is our best predictor of success.
Moving Beyond a Binary Framework
Embryo assessment has traditionally been framed in strict, binary terms:
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Euploid versus Aneuploid
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Normal versus Abnormal
However, findings like these suggest that embryo biology is not strictly binary. Embryos are dynamic, living biological systems composed of multiple, shifting cell populations capable of exhibiting incredible variability and self-correction during early development. Understanding this complexity is absolutely essential for the accurate, nuanced interpretation of genetic testing results.
Why This Matters for Patients
For patients, genetic testing results can feel terrifyingly definitive. Receiving an “abnormal” or “mosaic” result can feel like the end of the road. But studies like this highlight an incredibly important perspective:
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A result reflects the cells that were tested, not necessarily the entire embryo.
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Embryos are biologically complex, resilient systems.
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Interpretation requires context, nuance, and clinical experience—not just raw data.
This does not reduce the immense value of PGT-A testing. If anything, it reinforces the importance of expert, individualized interpretation by a clinic that understands reproductive immunology and advanced embryology.
Conclusion
The 2024 study by Zhai et al. reinforces a fundamental concept in reproductive biology: Embryos are heterogeneous systems, and our current testing methods capture only a part of that breathtaking complexity.
PGT-A remains an essential tool in IVF. But its results should be understood as highly informative guides, not absolute, infallible judgments.
At Endometriosis Surgical Specialists International (ESSI), this perspective guides our approach to fertility. We do not rely on isolated findings or treat our patients like lab reports. We evaluate the entire clinical, immunological, and biological picture. Because in reproductive medicine, understanding the whole system is just as important as reading the report.
Reference
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Zhai, J., et al. (2024). Single-cell chromosome testing of human embryos reveals mosaicism and complex developmental dynamics. Cell Discovery.
