Split Decisions: Is Genetic Testing of Embryos for Mosaicism Good or Bad?

Normal, abnormal and what it means for your embryos

Close-up of female technician doing genetic testing for mosaicism | CU Advanced Reproductive Medicine | Denver & Colorado Springs, CO

For most in vitro fertilization (IVF) patients, the end all be all of the process is the quality of the embryos they have created. Will they survive cryopreservation? How many will I have? And many more questions we always take our time to answer.

But what do you do when you have the embryos, but they aren’t perfect quality?

Some of these imperfect ones are known as mosaic embryos and are identified through preimplantation genetic testing for aneuploid. This genetic testing is a relatively new technology that allows us to identify the best embryos for transfer.

Embryos with mosaicism have two groups of cells within the embryo, some of which have tested as normal, or euploid, and others that are abnormal, or aneuploid.

Have questions about preimplantation genetic testing? Contact us now or request an appointment.

Genetic testing to determine the extent of mosaicism

In order to determine if an embryo has mosaicism, a blastocyst, or embryo that has time to develop to the appropriate stage to transfer, is biopsied. These biopsies gather 5 to 10 cells to undergo genetic testing.

There is a scale our genetics lab looks at when it comes to mosaicism and the number of abnormal cells in an embryo. Currently we classify embryos as follows:

Embryo classification Percent of abnormal cells
Euploid (normal) Fewer than 20%
Low level mosaicism 20-40%
High level mosaicism 40-80%
Aneuploid (abnormal) 80%

 

Because the biopsy gathers so few cells, it can be difficult to see a full picture. A collection of cells gathered from one area may have more euploid cells than cells gathered from another portion of the embryo. It is possible for mosaicism to appear throughout an embryo or be confined to a specific part.

Additionally, the cells used in testing are taken from the trophectoderm, which goes on to form the placenta, and not from the inner cell mass. That inner cell mass is what develops into the fetus. Therefore, testing the cells taken from the trophectoderm may or may not indicate that the inner cell mass has mosaic cells.

Related Reading: A Day in the IVF Lab

Mosaic embryos do not mean there is no hope

However, a mosaic embryo does not mean it will not implant. Roughly 20% of all blastocysts have some degree of mosaicism. Forty percent of those blastocysts with mosaicism will still implant.

Before genetic testing was an option, mosaic embryos were transferred without knowing it. Additionally, a 2015 study published in the New England Journal of Medicine found that 6 out of 18 mosaic embryos resulted in healthy live births. This is an extremely small sample upon which to draw verifiable conclusions.

But there are some difficulties, like lower implantation rates and a higher rate of miscarriage compared with a normal embryo transfer. The risk of miscarriage and implantation failure seems to be linked with the percentage of abnormal cells in an embryo. The more aneuploid cells there are, the greater the risk for failure.

Are there solutions for mosaicism evaluation?

Many things can change the outcome of a mosaic embryo transfer. The preimplantation genetic diagnosis testing for aneuploid could be inaccurate. As previously mentioned, this can occur due to the limited number of cells gathered for testing.

It could also be that the trophectoderm tissue does not necessarily reflect the number of abnormal cells in the inner cell mass. The cells that go on to form the embryo may be euploid, or normal, despite the testing.

Self-correction, or the embryo resolving the issues with the abnormal cells on its own, is another possibility for the outcome.

While all of these are possibilities, the American Society for Reproductive Medicine still recommends that any normal embryos should be transferred first before moving on to embryos with mosaic properties. We agree with this practice and always recommend starting with the embryos that have the highest chance of resulting in a successful pregnancy and birth.

Our recommendations with mosaic embryos

While preimplantation genetic testing has allowed us to improve our success with assisted reproductive technologies, it is important to note that it is not infallible. Now with the ability to further evaluate embryo quality for mosaicism and its variables, we have developed guidelines to help our patients navigate these murky waters.

Limitations with mosaic embryos to consider

  1. Embryos diagnosed as mosaic appear to have lower implantation rates and a higher rate of miscarriage than euploid embryos.
  2. Pregnancies arising from the transfer of mosaic embryos may have a higher rate of prenatal and perinatal complications due to the mosaicism isolated within the placenta.
  3. There is the potential for delivery of a child with congenital anomalies (birth defects).
  4. The biopsy specimen’s trophectoderm cells may not accurately represent the cells from the inner cell mass, increasing the possibility of identifying a normal embryo as abnormal or an abnormal embryo as normal.

CU ARM policy for transfer of mosaic embryos

  • We encourage our patients to meet with a genetic counselor and/or geneticist prior to the embryo transfer, as the risks for failure are greater and so is the prospect of a child with a birth defect.
  • Our policy is that we do not transfer aneuploid embryos, which are those embryos containing more than 80% abnormal cells.
  • If there are no euploid (normal) embryos and after extensive genetic counseling, we can transfer mosaic embryos.
  • Prenatal screening, testing performed during the pregnancy, is advised for any IVF patient who transferred a genetically tested embryo, since the accuracy of the PGT-A tests to identify abnormal embryos is greater than 95% – but not 100% accurate.
  • The prenatal diagnosis testing should consist of an amniocentesis, which reflects information generated from the inner cell mass. Chorionic villus sampling is more likely to reflect genetic information from the outer trophectoderm cells.

Additionally, we regularly work with UCH Prenatal Diagnosis and Genetics Clinic for our patients’ genetic counseling. They are located at 1635 Aurora Court, Aurora CO 80045. Please call 720-848-1860 if you are interested in scheduling an appointment. They can assist with the difficult decisions that come along with mosaic embryos.