Mosaic embryos

What happens when an embryo is neither good nor bad—but a bit of both?

Many people who are seeking help from fertility specialists will decide to test their embryos for quality before they have them transferred. That means taking a five- or six-day-old embryo, removing a half dozen or so of its cells, and examining their chromosomes.

Human cells should have 46 chromosomes each. But sometimes it doesn't end up that way. Some have fewer, and some have more. Some have pieces missing or pieces added. 

If the chromosomes in the biopsied cells are as expected, the embryo is deemed "euploid." If all the cells have problems, the embryo is called "aneuploid." Importantly, aneuploid embryos have a much lower chance of implanting and developing into a healthy child. But if some of the cells are fine and some are not—"mosaic"—it leaves doctors and patients in a quandary. 

For a long time, any sign of mosaicism would doom an embryo to the discard pile. But recently, doctors have begun to reevaluate. There is now evidence that mosaic embryos can develop into apparently healthy babies. 

Below, I list some of the issues I have heard people raise regarding mosaic embryos.

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About 20 per cent of biopsied embryos are mosaic.

Mosaic embryos are associated with a lower rate of implantation, a higher rate of miscarriage, a lower rate of ongoing pregnancy, a lower rate of live birth, a higher risk of intrauterine growth restriction, a higher risk of congenital abnormalities, a higher risk of intellectual disabilities, and a higher risk of long-term health problems. However, babies who appear to be healthy have been born from mosaic embryos.

Preimplantation genetic testing does not make an embryo better.

Preimplantation genetic testing does not increase the overall chance of pregnancy. 

Preimplantation genetic testing costs around $7,000.

Some labs consider an embryo to be euploid if fewer than 20 per cent of its tested cells are abnormal, and aneuploid if more than 80 per cent are. Anything in between might be considered mosaic. Different labs draw different lines.

Patients should ask their clinic how they define mosaic and aneuploid embryos.

Clinics typically don't transfer embryos if they are known to be aneuploid. The same embryos could have been transferred had the clinic not known.

Is it always better to know?

Patients with no euploid embryos may want to transfer mosaic embryos. One study found that of 98 patients offered a choice, 42 per cent chose a new cycle, 30 per cent chose to transfer a mosaic embryo, 20 per cent could not decide, and 6 per cent discarded their embryos and discontinued treatment. 

The people who chose to transfer a mosaic were older and had done more previous IVF cycles. 

Only half of the people who did a mosaic embryo transfer opted to do amniocentesis.

A different study found that the pregnancy rate from embryos that had fewer than 50 per cent abnormal cells was the same as for healthy embryos. So the extent of mosaicism appears to matter.

Different clinics draw different lines on how much mosaicism is too much.

Preimplantation genetic testing plucks cells from the trophectoderm which goes on to become the placenta. There is some evidence that abnormal cells are more likely to be found in that region than in the inner cell mass which becomes the fetus. So testing may not be representative.

Mosaic embryos may self-correct. 

Abnormal cells may naturally die off during embryonic development.

Which mosaic embryo should be transferred?

Who should decide which mosaic embryo should be transferred?

Two people in a relationship may disagree about whether to transfer a mosaic embryo.

Some clinics won't transfer mosaic embryos. 

Some clinics will transfer mosaic embryos created there, but will not receive mosaic embryos from other clinics. 

Patients should ask their clinics about their policies on transferring mosaic embryos.

Some clinics have not discarded mosaic embryos that patients indicated in the past could be discarded. Now that it is clear that mosaic embryos can lead to apparently healthy live births, some of those patients may now want to claim those undiscarded embryos.  

Will clinics allow patients to transfer embryos previously deemed unusable?

Some surrogates will only accept fully tested euploid embryos.

People may want to donate their mosaic embryos to others.

What does informed consent look like where mosaic embryos are concerned?

Counselling should come before treatment starts.

Should children born from mosaic embryos be told of this fact? 

People hoped that preimplantation genetic testing would make things more clear, but in some ways it has made things more muddy.

How many of us started out as mosaic embryos? 

Are we all mosaics? 

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Many thanks to the Canadian Fertility and Andrology Society (CFAS) for allowing me to attend their meetings. Many of these insights were drawn from a roundtable led by Julia Woodward, from Duke University Medical Center, at this year's CFAS annual meeting, and from "To Transfer or Not to Transfer—Consequences and Risks Surrounding the Transfer of Mosaic Embryos," a CFAS meeting held in January 2018.

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Contact me at alison.motluk@gmail.com.

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