Mosaic embryos are embryos that have a combination of normal and abnormal cells (with chromosomal abnormalities). This occurs because, during the early cell division process, some of the embryo’s cells accidentally lose or duplicate chromosomes.

In recent years, the term “mosaic embryo” has raised questions among both patients and assisted reproduction professionals. This has been quite frequent, particularly in the context of embryo chromosome analysis and in relation to the reproductive potential of mosaic embryos.

The most recent scientific studies by IVI and the laboratory Juno Genetics indicate that detecting and reporting mosaic embryos does not yield a significant clinical benefit in terms of reproductive outcomes. This has led to a rethinking of their role in routine in vitro fertilization (IVF).

In this article, we explain what a mosaic embryo is and, more importantly, what its true relevance is today, based on the latest scientific evidence.

Mosaic embryo: definition and types

All of the genetic information of the human species is organized into a total of 46 chromosomes (grouped into 23 pairs). Half come from the father and the other half from the mother. The number of chromosomes must be normal for the embryo to develop properly. If this is not the case, there is a risk that the embryo will not implant in the uterus. This leads to miscarriage or chromosomal syndromes (such as Down syndrome, which occurs when there are three copies of chromosome 21). 

The genetic analysis of embryos to assess the number of chromosomes is known as preimplantation genetic testing for aneuploidy (or PGT-A). Thanks to PGT-A techniques performed on embryos, the risk of chromosomal abnormalities of this type can be minimized. By using these techniques, it is possible to identify embryos with an abnormal number of chromosomes.

At the blastocyst stage, an embryo already has two distinct parts:

• The inner cell mass: the inner part of the embryo that will give rise to the future fetus (i.e., the baby).
• The trophectoderm: the outer layer of the embryo, which will give rise to the tissues that will eventually form the placenta.

Mosaic embryos have two or more cell lines with different chromosomal content. This means they have a combination of healthy and abnormal cells. These abnormal cells may be present throughout the embryo, or only in one of the two parts (in the inner cell mass or in the trophectoderm).

What types of mosaic embryos are there?

Depending on the proportion of abnormal cells in the embryo, it is possible to distinguish between two types of mosaic embryos:

Low-grade mosaic embryos 

In PGT-A, an embryo is classified as a low-grade mosaic when the result indicates that most of the cells are chromosomally normal. Only a small percentage exhibit abnormalities.

Generally, an embryo is considered low-grade when the PGT-A result indicates that between 20% and 40–50% of the cells analyzed are abnormal. These embryos display an implantation potential and a likelihood of resulting in a viable pregnancy similar to those observed in chromosomally normal embryos.

High-grade mosaic embryos

In PGT-A, an embryo is considered a high-grade mosaic when the result indicates the presence of a high percentage of cells with chromosomal abnormalities. It is considered high-grade when more than 40–50% of the cells analyzed are abnormal. Some studies suggest that these embryos may have reduced reproductive potential (lower likelihood of implantation and higher risk of miscarriage or developmental abnormalities).

How is a mosaic embryo detected?

Preimplantation genetic testing for aneuploidy (PGT-A) makes it possible to assess the chromosomal makeup of embryos using a sample (biopsy) of their  trophectoderm, through next-generation sequencing (NGS) techniques.

Embryos in which PGT-A detects the correct number of chromosomes for each type are considered chromosomally normal (euploid). Those in which extra or missing chromosomal material is detected are classified as chromosomally abnormal (aneuploid). A gain of a chromosome is called a trisomy. A loss is called a monosomy. In turn, these gains or losses can affect an entire chromosome (whole-chromosome aneuploidy) or only a portion of one (segmental aneuploidy).

When a gain or loss has an intermediate value that does not reach the threshold to be considered an abnormal result, the laboratory classifies that embryo as “mosaic.” Depending on the percentage of deviation from the normal result, some laboratories may subclassify the result as “low-grade mosaic” or “high-grade mosaic.”

It is true that the presence of embryonic mosaicism can lead to these types of intermediate results. However, there are also other factors that can produce this result (such as technical or biological artifacts). Thus, the European Society of Human Reproduction and Embryology (ESHRE) recommends not referring to these intermediate results as “mosaic embryos”. It advocates instead using more neutral terminology, such as “intermediate result” or “possible mosaic.”

Do mosaic embryos have clinical value?

The most recent scientific studies have shown that reporting embryonic mosaicism does not improve reproductive outcomes, particularly with regard to the birth of a healthy baby.

A large, multicenter, double-blind, independently validated study conducted by IVI and Juno Genetics, which analyzed thousands of single-embryo transfers, assessed whether reporting the presence of mosaicism added value to traditional clinical and embryological predictive models.

The results showed that, although certain mosaic embryos could be associated with a slight reduction in the live birth rate (especially those classified as “high-grade mosaic”), their low clinical impact and poor predictive value do not justify their use as an embryo selection criterion. Furthermore, incorporating this information did not improve the predictive models when compared to those based solely on clinical and morphological factors.

Consequently, current scientific evidence indicates that embryonic mosaicism detected through PGT-A using IVI and Juno Genetics technology should not guide clinical decision-making in routine IVF practices.

Why are mosaic embryos not reported at IVI?

In light of the latest scientific evidence, IVI decided to stop reporting embryonic mosaicism as a separate clinical category, and to include it within the results considered negative for aneuploidy (or normal) in PGT-A.

This decision is based on several key considerations:

• The absence of a significant clinical benefit from reporting mosaics.
• The lack of improvement in live birth rates.
• The need to avoid providing ambiguous genetic information that could cause patients unnecessary anxiety.
• A commitment to embryo selection based on criteria with demonstrated predictive value.

In this way, IVI’s clinical practice remains aligned with the best available scientific evidence and with a focus on patient safety and well-being.

Dr. Josep Pla

Josep Pla is the lead genetic counsellor and coordinator of the Reproductive Genetics Unit for the IVI RMA clinics. He graduated got his degree in Biomedical Sciences from Universitat Autònoma de Barcelona in 2013 and obtained his MSc in Genetic Counselling from Universitat Pompeu Fabra in 2015.

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