What Causes Abnormal Embryos in IVF?

Chromosomal errors account for the vast majority of abnormal embryos in IVF, with up to half of all embryos flagged as aneuploid during preimplantation genetic testing. The causes behind those errors span a surprisingly wide range: the age of the eggs, the quality of the sperm, how the ovaries were stimulated, what happens during the embryo’s very first cell divisions, and even the conditions inside the lab. No single factor explains the whole picture, and in many cases, several of these influences overlap in the same cycle.

How Common Are Abnormal Embryos, and What Does “Abnormal” Mean Here?

When fertility clinics talk about abnormal embryos, they almost always mean embryos with the wrong number of chromosomes. A healthy human cell carries 46 chromosomes, and an embryo that ends up with too many or too few is called aneuploid. This can happen because of an error in the egg, the sperm, or the embryo’s own early cell divisions. Aneuploidy is the leading reason embryos fail to implant, miscarry, or are excluded from transfer after genetic screening.

The rates are striking. Research on preimplantation genetic testing finds that roughly half of IVF embryos are aneuploid overall, though the proportion climbs steeply with the age of the person providing the eggs.¹ Even among young couples with no known fertility issues, one study found that about 63% of high-quality embryos carried chromosomal abnormalities, including various forms of monosomy and trisomy.² That number surprises many patients, because it means that looking normal under the microscope does not guarantee an embryo is chromosomally healthy.

Egg Quality and Maternal Age

The single most influential factor in embryo aneuploidy is the age of the eggs. A person in their early 30s might see roughly a third of embryos come back aneuploid; by the early 40s, the proportion can exceed 80%. The biological reason centers on how eggs are made and stored. Unlike sperm, which are produced fresh on a continuous cycle, eggs begin their development before birth and then sit in a suspended state for decades. During that long pause, the molecular glue holding chromosome pairs together gradually breaks down.

That glue is a protein complex called cohesin. Its job is to keep paired chromosomes tightly bound so they separate cleanly when the egg completes its final division. Studies in mammals have shown that cohesin levels drop steadily with age, and a protective protein called Sgo2 that shields cohesin at critical attachment points is depleted alongside it.³ When the remaining cohesin can no longer hold chromosome pairs in place, chromosomes drift apart unevenly. One daughter cell gets an extra chromosome and the other loses one. Recent research supports the idea that this cohesin deterioration is a leading cause of the age-related rise in egg aneuploidy.⁴

This mechanism is important to understand because it is not something a patient or clinic can reverse. No supplement, lifestyle change, or stimulation protocol can replenish cohesin that has degraded over 35 or 40 years. It is the primary reason donor eggs from younger individuals produce dramatically higher rates of chromosomally normal embryos.

Obesity and Metabolic Health

While age dominates the conversation, metabolic health plays a real and underappreciated role. Obesity affects egg quality through several overlapping pathways. Elevated insulin, glucose, and free fatty acids all appear to impair how an egg matures and how well it can support early development after fertilization.⁵

Animal studies have added more detail. Eggs from obese mice contain a high number of abnormally shaped mitochondria with disorganized internal membranes, reduced energy output, and signs of cellular stress. Because mitochondria supply virtually all of the energy an early embryo needs, this kind of damage slows development and contributes to the poorer outcomes seen in IVF cycles among patients with higher body mass.⁶ The picture in humans is still being filled in, but the clinical pattern is consistent: metabolic dysfunction at the time of egg retrieval is associated with lower embryo quality independent of age.

Sperm Contribute More Than You Might Think

Conversations about embryo abnormalities tend to focus on eggs, partly because egg-related errors are more common. But sperm quality matters too, and its role is probably larger than the traditional framing suggests. There are two main ways sperm can contribute to an abnormal embryo: through DNA fragmentation and through chromosomal errors of their own.

Sperm DNA fragmentation refers to breaks in the DNA strands packaged inside the sperm head. High levels of this damage can cause embryos to arrest during development or trigger the activation of cell-death pathways.⁷ An embryo that stalls at the four- or eight-cell stage and never reaches the blastocyst phase may look like a generic “poor quality” outcome, but sperm DNA damage is often a hidden contributor.

Advanced paternal age also introduces risk. As men age, their sperm accumulate DNA mutations and chromosomal abnormalities, alongside epigenetic changes that can silence important genes.⁸ The age effect on sperm is less dramatic than on eggs, and it does not follow the same steep curve. But dismissing the sperm side entirely is a mistake, particularly for couples where the male partner is over 45 or where standard semen analysis looks normal but embryos consistently arrest or come back aneuploid.

Errors During the Embryo’s First Cell Divisions

Not all chromosomal problems in an embryo originate in the egg or sperm. A significant share arise after fertilization, during the embryo’s earliest cell divisions. These mitotic errors produce embryos where some cells are normal and others are not, a condition called mosaicism.

Mosaicism is remarkably common in human embryos. Studies of preimplantation embryos have found that between 65% and 70% show some degree of mosaicism at the cleavage stage, meaning a majority of embryos contain at least a few cells with the wrong chromosome count alongside normal cells.⁹ Mosaic embryos are, by definition, caused by mistakes in chromosome segregation during these early mitotic divisions rather than by errors inherited from the gametes.¹⁰

One reason human embryos are especially prone to these early errors is the way the first cell division is organized. Sperm contribute the centrosome, a structure that orchestrates the machinery pulling chromosomes apart. Research has found that sperm-derived microtubule organizing centers are not always sufficient to fully enclose and separate the two sets of chromosomes during that first division, which helps explain the high frequency of errors right at the start of development.¹¹ Defects in sperm centrosomes, problems with chromosome alignment on the spindle, and the gradual depletion of regulatory factors carried over from the egg all contribute to mitotic instability in the earliest days.¹²

Can Embryos Fix Their Own Errors?

Given how widespread mosaicism is, you might wonder whether the presence of a few abnormal cells early on necessarily dooms the embryo. The answer is: not always. There is evidence that embryos can preferentially push abnormal cells out of the developing inner mass. Normal cells tend to divide faster than aneuploid ones, and some abnormal cells appear to be shunted into the outer layer or expelled entirely.

A small study examined pairs of blastocysts and the cell debris shed during culture. Among embryos that tested as chromosomally normal at the blastocyst stage, some had debris containing trisomies or monosomies, suggesting the embryo had contained aneuploid cells earlier and then effectively separated them out.¹³ This self-correction capacity is an active area of research and adds a layer of complexity to interpreting genetic test results from a small biopsy sample.

A meta-analysis comparing outcomes after mosaic versus euploid embryo transfers found that mosaic embryos had lower implantation and live birth rates, reinforcing the advantage of chromosomally normal embryos. However, once a mosaic embryo did implant, miscarriage rates were comparable to those of euploid embryos, and neonatal health outcomes were similarly favorable.¹⁴ This suggests that implantation itself is the main bottleneck for mosaic embryos. Those that clear this hurdle seem to develop normally from that point forward, likely because self-correction mechanisms continue working through early pregnancy.

Ovarian Stimulation Protocols

IVF involves stimulating the ovaries with hormones to retrieve multiple eggs at once rather than the single egg a natural cycle typically produces. A reasonable question is whether that aggressive stimulation pushes immature or lower-quality eggs to develop, introducing more errors. The evidence is nuanced. A systematic review found that more intense stimulation does appear to be associated with a higher proportion of aneuploid embryos. At the same time, the sheer volume of eggs retrieved means patients still end up with more chromosomally normal embryos available for transfer, translating into higher cumulative chances of a live birth across multiple cycles.¹⁵

There is also a related concern about eggs that mature outside the body. When eggs are collected at an immature stage and matured in the lab (a technique called in vitro maturation), they show notably higher rates of spindle and chromosome alignment problems compared with eggs that matured naturally inside the body. One study using confocal microscopy found that about 44% of in vitro matured oocytes had abnormal spindle configurations and about 33% had abnormal chromosome organization, compared with roughly 14% and 9% among in vivo matured oocytes.¹⁶ In standard IVF, most eggs are retrieved after they have already matured, but a fraction of eggs in any retrieval may still be immature and require some lab maturation, which may contribute a small share of abnormalities.

What the Lab Environment Can and Cannot Control

Embryos spend their first five to six days developing in an incubator, and the conditions inside that incubator matter. Variables such as the type of culture media, the pH and temperature of the environment, osmolality, and oxygen concentration could all influence whether an embryo develops normally or accumulates chromosomal errors.¹⁷ Most modern IVF labs use low-oxygen incubators, tightly controlled temperatures, and rigorously tested media, but lab-to-lab variation still exists and remains a known quality concern in the field.

Newer technologies aim to reduce the handling embryos undergo. Time-lapse imaging systems, for instance, allow embryologists to monitor embryo development through a camera inside the incubator rather than removing embryos to check them under a microscope. Artificial intelligence tools are now being developed to analyze the morphokinetic data from time-lapse videos, attempting to predict which embryos are most likely to be chromosomally normal and to implant successfully, without requiring a biopsy at all.¹⁸ These approaches are still being validated, but they represent a growing push toward less invasive ways of assessing embryo health.

Inherited Chromosomal Rearrangements

In some couples, one partner carries a structural rearrangement in their chromosomes, such as a reciprocal translocation, an inversion, or a Robertsonian translocation. These individuals are typically healthy because they have the right amount of genetic material, just reorganized. But when their eggs or sperm form, the rearranged chromosomes can segregate unevenly, producing a high share of embryos with too much or too little of certain chromosomal segments.

The impact varies by type of rearrangement. Among carriers of reciprocal translocations, roughly 64% of blastocysts were unbalanced, compared with about 28% for inversion carriers and 37% for Robertsonian translocation carriers.¹⁹ For these patients, preimplantation genetic testing is not optional but essential, since the majority of their embryos will carry unbalanced rearrangements incompatible with a healthy pregnancy. Knowing the specific type of rearrangement helps set realistic expectations about how many embryos from each cycle are likely to be transferable.

How Reliable Is the Testing Itself?

Preimplantation genetic testing for aneuploidy (PGT-A) works by removing a few cells from the outer layer of a blastocyst and analyzing their chromosomes. The test is powerful, but it has a fundamental limitation: it samples only a handful of cells from the trophectoderm, the layer that will become the placenta, not the inner cell mass that becomes the baby. In a mosaic embryo, those few biopsied cells may not represent the rest of the embryo.

Recent research has found that almost half of the false-positive PGT-A results in one case series involved mosaic aneuploidies, including chaotic patterns. When those embryos were re-examined more thoroughly, none of the mosaic findings were confirmed.²⁰ The investigators noted that the mosaicism detected in a small biopsy may reflect cells that were already being pushed to the periphery of the embryo, or it may reflect technical artifacts from the DNA amplification process. Either way, the clinical meaning of a “mosaic” PGT-A result remains frustratingly uncertain.

A non-invasive alternative is also in development. Rather than biopsying cells, researchers can analyze tiny fragments of DNA that embryos shed into their surrounding culture medium. Early studies have found concordance rates with standard PGT-A of around 82% in one report and about 56% concordance when both methods were compared against the embryo’s actual chromosomal makeup after extended culture.²¹²² The technology is promising but not yet accurate enough to replace biopsy-based testing in clinical practice. For now, both methods have real limitations, and a diagnosis of “abnormal” or “mosaic” does not always mean the embryo is truly non-viable.

When Mosaic Embryos Are the Only Option

For patients whose cycles produce no euploid embryos, the question of whether to transfer a mosaic embryo becomes intensely practical. The data offer some reassurance. Mosaic embryo transfers result in lower live birth rates compared with euploid transfers, with one study reporting about 47% versus 59%.²³ But a roughly one-in-two chance of a live birth is meaningful, especially for patients facing the alternative of starting over or pursuing donor gametes. Pregnancy loss rates after mosaic transfers do not appear significantly higher than after euploid transfers once the pregnancy establishes itself, and the babies born are healthy by standard measures.

The challenge is deciding which mosaic embryos to prioritize. Not all mosaicism is equal. An embryo with a single extra copy of a small chromosome may behave very differently from one with complex or chaotic patterns across multiple chromosomes. Genetic counselors typically help patients weigh these distinctions, but the field is still building the data needed to make these calls with real confidence.

Epigenetics and the Invisible Layer

Beyond the chromosome count, there is a subtler layer of potential trouble. Epigenetic marks, which are chemical modifications that control which genes are turned on or off, are extensively reprogrammed in eggs, sperm, and early embryos. If that reprogramming is incomplete or goes wrong, an embryo can have the correct number of chromosomes but still develop abnormally because key genes are silenced or inappropriately activated. Parental environmental exposures, including diet and metabolic state, can alter the epigenetic landscape of the gametes before they even meet. Research in livestock species has documented that these epigenetic effects can influence embryo viability and, in some cases, carry consequences into the next generation.²⁴ The clinical relevance in human IVF is still being mapped, but it is increasingly clear that a chromosomally normal embryo is not necessarily an epigenetically normal one, and this invisible layer may explain some of the unexplained implantation failures that frustrate patients and clinicians alike.