PGTA: The Promise, the Hype, and the Reality — Part II
Written by Helen Yang, PhD
Founder & CEO, OvaVision
Behind the reassuring language of PGTA reports lies a scientific debate that rarely reaches patients.
New research has challenged the assumptions the test was built on — revealing biological complexity that a single biopsy cannot capture.
Part II dives into what the science actually shows, and why those findings have sparked global controversy.
🧩 New Science About PGTA
When PGTA first entered the IVF world, it was built on a simple assumption:
if a few cells from an embryo had the wrong number of chromosomes, the entire embryo must be abnormal.
At first glance, that logic holds. Early embryos contain only a small number of cells; if you test several and find aneuploidy, it’s intuitive to assume the rest are the same. The field needed a practical way to interpret results, and this simple rule seemed to offer clarity.
But the first rule of any rigorous science is that every assumption must be tested — even the ones that seem obvious.
When researchers eventually examined human embryos more closely, those early assumptions didn’t always match what the biology revealed. And that’s where the science behind PGTA began to shift.
1. Mosaicism — the Rule, Not the Exception
In Part I of this article, we talked about mosaic embryos — embryos that contain a mixture of chromosomally normal and abnormal cells. What we didn’t say is how common this really is.
When PGTA was first developed, mosaicism wasn’t even part of the conversation.
Mouse models almost never show it. Early human testing methods weren’t sensitive enough to detect it. For years, the field assumed embryos were either uniformly normal or uniformly abnormal — a simple binary that made PGTA seem straightforward.
But when researchers eventually applied higher-resolution techniques to human embryos, they found something entirely different:
Mosaicism isn’t a rare bug or complication. It’s a normal feature of early human development.
Multiple studies have now shown that most human blastocysts exhibit some degree of mosaicism.
The exact percentages differ depending on the technology used, but the conclusion is consistent across labs:
Mosaicism is the rule, not the exception.
This changes everything about how PGTA results should be interpreted.
A PGTA report showing all euploid cells does not mean the embryo isn’t mosaic.
A report showing all aneuploid cells does not mean the entire embryo is abnormal.
It simply means:
the tiny cluster of cells sampled all looked the same.
It tells you nothing about the chromosomal makeup of the rest of the embryo.
This is the scientific reality that early PGTA assumptions missed — and it’s the discovery that forces us to rethink what a biopsy can actually tell us.
And it naturally leads to the next question:
What kind of chromosomal abnormalities matter — and which ones don’t?
That’s where the distinction between mitotic and meiotic aneuploidy becomes essential.
2. Mitotic vs. Meiotic Aneuploidy — Two Different Problems
To understand why PGTA results can be so confusing, we need to zoom out and look at where chromosome errors come from.
There are two main paths:
errors that happen before fertilization
errors that happen after
They may sound similar on a report. But biologically, they’re not.
Meiotic errors: when the starting material is wrong
Meiosis is the special kind of cell division that creates eggs and sperm, our reproductive cells. Its job is to cut the chromosome number in half and package the right set into each reproductive cell.
When meiosis goes wrong, the egg (or sperm) ends up with the wrong number of chromosomes. Once that happens:
every cell in the embryo that came from that egg (or sperm) inherits the same mistake
there is no way for later divisions to “rewrite” that original chromosome mistake
But eggs and sperm follow two very different biological processes, and that difference explains almost everything about age-related chromosomal errors.
Like we mentioned in our previous article:
You’re born with all the eggs you’ll ever have.
These eggs begin meiosis before you are even born, then pause for decades — literally sitting in the middle of that division process. Every month after you reach puberty, a small group is recruited to finish the job and prepare for ovulation.
As the years pass, the structures that keep their chromosomes aligned slowly weaken, simply because the cells are aging right alongside you. While meiosis does have quality control systems like all other cell divisions — but by your 30s and 40s, that machinery is no longer new.
Sperm are different. They’re made continuously throughout life, from fresh cell divisions, not decades-old precursors. They don’t sit paused in meiosis for 30 or 40 years. But it can absolutely still make mistakes.
This is why meiotic aneuploidy is strongly linked with maternal age. These are the errors PGTA was originally designed to catch:
if the starting material is wrong, the embryo is much more likely to fail.
Mitotic errors: fast, messy early divisions
After fertilization, the embryo switches to mitosis — the everyday kind of cell division that makes almost every cell in the human body (except for the eggs or sperm).
Under normal conditions, mitosis is slow and carefully controlled: Cells grow to the right size, build all the necessary proteins, and run strict quality-control checkpoints before dividing.
But in the very first days of embryonic development, it isn’t following the usual rulebook.
In early embryo mitosis,
Cells divide without growing.
There are no pauses to check the DNA.
The embryo isn’t making new proteins yet — it hasn’t activated its own genome.
It survives entirely on the egg’s built-in supply of nutrients and instructions.
There is no external nutrient supply until implantation.
The embryo is focused on one job:
make enough cells as quickly as possible to reach implantation — the point where it can finally tap into real nutrients and shift into a more stable mode of development.
This stripped-down mode of cell division is inherently noisy:
some cells pick up extra or missing chromosomes
others stay normal
different lineages can diverge
This is the biological basis of mitotic aneuploidy and mosaicism.
And importantly, several studies suggest that mitotic error rates do not rise in the same way with maternal age, because they arise from the developmental program itself, not from the age-related weakening of chromosome structures in eggs.
Some of those mitotic errors are cleared later or confined to tissues like the placenta, and do not show up in the baby at birth. That doesn’t mean mitotic errors are always harmless. But they are not equivalent to a meiotic error baked into every cell.
Why this distinction breaks the “one result = one truth” model of PGTA
PGTA cannot see any of these distinctions.
It can’t tell:
whether an abnormality came from aging eggs (meiotic)
or from the embryo’s fast, reductive early divisions (mitotic)
or whether the abnormal cells represent the fetus, the placenta, or a tiny patch of noise
This is why PGTA results often don’t line up with real developmental outcomes. On the report, they look the same.
This is why some embryos labeled “abnormal” still lead to healthy live births, and why new research is trying to separate meiotic from mitotic origin more precisely instead of treating all aneuploidy as equal.
For patients, the takeaway is simple: a PGTA result is not a direct readout of an embryo’s fate. It’s a small snapshot, from a few cells, layered on top of biology that is much more complex.
3. Error-mitigation mechanisms — how early embryos manage abnormal cells
A major reason PGTA often fails to predict actual outcomes is that early embryos aren’t static.
We still don’t have a complete map of how embryos respond to abnormal cells, but the evidence is growing: early development is dynamic, not binary. Embryos have built-in ways of mitigating, isolating, or removing abnormal cells — and PGTA only captures a single moment in that process.
These mechanisms are not about “repairing” chromosome errors. Embryos cannot rewrite an incorrect cell division. But they can reorganize themselves in ways that change the significance of early mitotic mistakes.
Here are the mechanisms scientists now believe play a role:
Apoptosis — the built-in self-destruct button
Apoptosis isn’t just a way for embryos to eliminate “unfit” cells.
It’s a normal sculpting mechanism used throughout mammalian development. Embryos use apoptosis to shape tissues, refine structures, and remove cells that are:
damaged
dividing poorly
poorly positioned
or simply no longer needed, even if they are perfectly healthy
It’s the same process that separates our fingers during fetal development and remodels organs throughout life.
In early embryos, apoptosis can remove cells that aren’t contributing properly, including some cells carrying mitotic errors. It doesn’t “fix” the chromosome problem — but it can reduce its impact by eliminating cells that the embryo doesn’t want to keep.
Lineage allocation — “placing” abnormal cells in less critical tissues
Several studies show that embryos may direct abnormal cells toward the trophectoderm (the future placenta, and where the cells are biopsied from in PGTA), preserving a more normal inner cell mass (future fetus).
This isn’t chromosome repair. It’s compartmentalization: steering abnormal cells into roles where they are less likely to affect fetal development. And it makes sense biologically: the placenta is a temporary organ with a single job — support the pregnancy — and it’s discarded after birth. So if the embryo has a choice, placing imperfect cells in a structure that won’t become part of the baby may be an evolutionary feature, not a flaw.
Developmental pruning — letting healthier lineages outcompete weaker ones
In early development, different lineages expand at different rates. Cells with stable chromosomes divide efficiently; unstable lineages often stall or fall behind.
Over time, the healthier lineage becomes the dominant contributor to the embryo, while abnormal ones contribute less or fade out.
This dynamic can produce normal development even when early divisions were chaotic.
Cellular fragmentation — packaging damaged material
Fragmentation is another way embryos can isolate or shed unwanted material. These small fragments often contain pieces of cells or damaged components that the embryo separates out during early divisions. Low-level fragmentation can be part of normal development, but when a large portion of the embryo becomes fragments, there simply isn’t enough intact cell mass left to support normal growth.
This is why embryos with very high fragmentation scores tend to have lower survival rates — not because fragmentation is inherently harmful, but because too much of the embryo has been discarded into fragments before it reaches implantation.
Why this matters for PGTA
These natural processes can dramatically change an embryo’s trajectory — but none of them are visible to PGTA, which samples only a few cells from the trophectoderm at one moment in time.
In short:
PGTA captures a snapshot. Early development is a movie.
And these error-mitigation mechanisms are one of the reasons the snapshot often misleads.
⚖️ The Controversy Behind the Scenes
In Part I, we talked about how PGTA is classified as a lab-developed test under CLIA, not an FDA-approved diagnostic — and how early marketing claims quickly outpaced the science.
But the controversy surrounding PGTA goes beyond regulatory loopholes and early optimism. Several deeper, less-discussed issues shape how PGTA is used today.
A global divide most patients never hear about
The United States stands nearly alone in its routine use of PGTA.
Across much of Europe:
PGTA is not recommended for most patients
guidelines consistently emphasize insufficient evidence of benefit
some countries restrict or ban routine embryo screening outright
This isn’t because Europe is behind. It’s because their regulatory frameworks require demonstrated clinical value before a test becomes mainstream. The U.S. moved in the opposite direction: widespread adoption before definitive evidence.
Clinic-level variation and ethical friction
Even within the U.S., there is no standardization in how clinics interpret or act on PGTA results.
Some clinics:
refuse to transfer embryos labeled “aneuploid,” even if the patient requests it
treat “mosaic” as a near-absolute contraindication
handle “low-grade mosaics” differently than “high-grade”
Others are more flexible and will consider transferring certain categories after counseling.
The result is a system where the same embryo may be considered non-transferable at one clinic and acceptable at another.
This creates real ethical tension, especially given that some embryos labeled as abnormal have resulted in healthy live births.
The class-action lawsuits
Several lawsuits have emerged in recent years from patients who discarded embryos based on PGTA results and later learned that:
the test did not diagnose genetic disease
the “abnormal” result could have represented a viable embryo
the lab’s reporting practices were inconsistent or poorly explained
These lawsuits reflect a broader concern: patients are making irreversible decisions based on a test whose limitations they were not fully told.
🔍 Looking Beyond PGTA: Alternatives, Innovations, and What’s Next
PGTA has real value in specific scenarios — especially when clinicians need information about true meiotic aneuploidy, which affects the entire embryo. But the problem is not the tool itself. It’s how broadly and confidently it’s often applied.
A more accurate conversation includes the alternatives and emerging approaches that better align with the biology we now understand.
Polar body testing — a clean way to assess meiotic errors
Polar body biopsy samples the tiny cells discarded during egg formation.
It gives information about the egg’s chromosomes only, which makes it uniquely suited to identifying meiotic errors — the type that do matter everywhere.
It is non-invasive and avoids disturbing the embryo and it bypasses the mitotic “noise” of early cleavage.
However, it cannot assess paternal or post-fertilization errors, so it’s not a complete picture — but it is far more biologically coherent for studying maternal-age–related abnormalities.
PGT-AO — focusing on origin, not just outcome
Some researchers have proposed PGT-AO: Preimplantation Genetic Testing for Aneuploidy Origin, an updated framework that distinguishes:
meiotic-origin aneuploidy (high clinical relevance)
mitotic-origin aneuploidy (variable, often compatible with healthy development)
This approach reflects the consensus emerging from the science we talked about.
PGT-AO remains primarily a research-driven framework at this stage, proposed by scientists working to align embryo testing with the underlying biology, but it has not yet been adopted in routine clinical practice.
Non-invasive embryo assessment — the direction the field is moving
A growing body of research is moving away from embryo biopsies altogether. Instead of removing cells during the most unstable phase of early development, non-invasive methods try to observe what the embryo is already telling us:
cell-free DNA released into the culture media
metabolic and biochemical signatures
cumulus cell profiling (the cells surrounding the egg at retrieval)
non-invasive chromosomal analysis
AI-assisted morphokinetics
data-driven models of developmental timing and embryo behavior
These approaches aim to capture the embryo’s developmental trajectory without disturbing it — a model that aligns far more closely with the biology we now understand.
My thesis lab — the Needleman Lab at Harvard was at the cutting edge of this shift, working on multiple non-invasive strategies, including metabolic assays and cumulus cell analysis.
My own PhD research focused on AI-assisted morphokinetic analysis and Bayesian developmental modeling — building non-invasive tools that assessed embryos using time-lapse imaging, computer vision, and quantitative developmental features rather than removing a single cell. (BlastAssist: a deep learning pipeline to measure interpretable features of human embryos)
Some of these methods are still experimental and others remain debated, but the larger trend is unmistakable:
the future of embryo assessment is dynamic, non-invasive, and grounded in real-time biology — not static snapshots taken at the most chaotic moment of development.
🌱 Beyond Snapshots: Rethinking Fertility Through a Dynamic Lens
PGTA wasn’t built on bad intentions. It was built on the best assumptions we had at the time — assumptions that seemed reasonable, simple, and intuitive. But as the science caught up, those assumptions cracked. Early development is dynamic, not static. Embryos reorganize, allocate, discard, and adapt. Biology rarely behaves in clean categories, and a single biopsy from a few cells can never capture the full story.
That same principle extends far beyond embryo testing. Across reproductive medicine, we keep relying on snapshots — one hormone value, one ultrasound, one test strip, one label — and treating them as destiny. But human biology never works in single moments. It works in trajectories, patterns, and change.
This is the philosophy behind the work we’re building at OvaVision. We’re not developing embryo-evaluation tools, but we are committed to the same scientific truth: people deserve insights that reflect how biology actually behaves — continuously, dynamically, and with context. Whether it’s early pregnancy, IVF cycles, or hormone changes, real understanding comes from watching the system over time, not from one static measurement.
Fertility is too important, too personal, and too complex for binary answers or oversimplified tests. Patients deserve transparency, nuance, and tools that honor the real biology underneath their care.
And as the field finally begins to move toward that reality, the hope is simple:
more clarity, fewer assumptions, and science that truly reflects the way life begins.
About the Author
Dr. Helen Yang, PhD, is a Harvard-trained scientist with years of experience in cutting-edge fertility research. She founded OvaVision to bring people AI-driven insights into their fertility journey, with a focus on clarity, emotional support, and science that actually makes sense.
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