Do you Transfer Mosaic Embryos? An Interview with a Genetic Counselor

Jennifer
Jennifer "Jay" Palumbo
CEO of Wonder Woman Writer & Mom to two boys, one with autism.

Historically, in the early days of genetic testing, embryos were classified as either “normal” (euploid) or “abnormal” (aneuploid). Recently, however, a new kind of embryo has emerged. It’s called a “Mosaic Embryo”, and it means that it has both normal and abnormal cells.

Since its discovery, there has been much debate about whether or not mosaic embryos should be transferred as part of the IVF process. According to a study from Fertility and Sterility, approximately one-third of mosaic embryos have developed into a healthy baby. However, the study size was small, and the genetic testing of the children was not performed.

So, what should you do if you have mosaic embryos?

I spoke with Jennifer Garbarini, MS, CGC of CooperGenomics. Jen is a licensed and board-certified genetic counselor at CooperGenomics. She provides genetic counseling about all types of preimplantation genetic testing (PGT) and manages the PGT-A team of genetic counselors. She has a background in research and pediatric cardiovascular genetics and received her Bachelor of Science in Biology from Ursinus College and her Master of Science in Genetic Counseling from Arcadia University. Jen remains active as a clinical supervisor for several genetic counseling programs and has served as a clinical supervisor, instructor, and thesis advisor for Arcadia students. Below is our conversation:

 

GOSTORK: First, let’s start with the basics: On your fertility journey, are there certain patients you’d recommend to their doctors about whether genetic testing would be beneficial to them?

Every patient who is pursuing a pregnancy, whether spontaneously or through assisted reproductive technology, should discuss the option of carrier screening with their physician. Carrier screening identifies couples who are carriers of the same recessive disorder or women who are carriers of X-linked disorders. In these cases, there is an increased risk of having an affected child.  Carrier screening may be based on ancestry/ethnic background (as some diseases are more common in certain ethnic groups) or maybe universal (not specific to your ancestry). Individuals can be a carrier even with no family history of genetic disease, and most carriers are asymptomatic.

Another genetic testing that may be useful to couples pursuing fertility treatment is a karyotype (also called a chromosome analysis). This testing can identify if there is a rearrangement of your or your partner’s chromosomes that may increase the risk of miscarriage or to have a child with a chromosome abnormality. I would also add here that there may or may not be a suspicious history.

 

GOSTORK: For those who don’t know, how does genetic testing work?

Not all genetic testing is created equal, but it usually starts with either a blood sample or a saliva/cheek brush sample. Carrier screening looks for some of the more common genetic diseases in children or diseases where there is an effective treatment in infancy or childhood. It does not look for all genetic diseases. If there is a family history of a specific genetic condition, more targeted testing may need to be considered.

 

GOSTORK: Now that we know more about genetic testing, can you walk us through what mosaic embryos are?

Mosaicism describes the presence of two or more populations of cells with different genetic make-ups in the same individual (1). In plain terms, the sample isn’t completely normal or completely abnormal. A percentage of that sample is normal, and a percentage contains some abnormality.

For preimplantation genetic testing for aneuploidy (PGT-A), a sample of about 5-7 cells is removed from the trophectoderm (the outer cell layer) of the embryo. The cells that will eventually make the baby (referred to as the inner cell mass) are never sampled as part of the process. The result of the trophectoderm (TE)  biopsy sample are expected to be the same as the make-up of the entire embryo. Most of the time, it’s a correct assumption but not always (2,3). Mosaicism in the trophectoderm biopsy makes interpreting PGT-A results complicated!

Mosaicism in the TE biopsy can mean three possibilities for the inner cell mass; normal, abnormal, or mosaic. While the studies surrounding the transfer of mosaic embryos are still emerging, we are starting to observe some trends. In general, embryos with mosaic PGT-A results implant less often, miscarry more often, and have lower rates of ongoing pregnancies/live births than those with normal (euploid) PGT-A results. Additionally, long-term follow-up about the health of babies born from embryos with mosaic PGT-A results is lacking. While it appears to be rare, there is one case report of a mosaic embryo that resulted in the birth of a baby with the same mosaic finding (4). The bottom line is that there is a lot of uncertainty surrounding mosaic results.

 

GOSTORK: Many of GoStork’s readers come to the site because they are considering either working with a surrogate or using donor eggs. When it comes to surrogacy, for example, does having mosaic embryos make the process more complicated?

It can! The risks are higher for failed implantation and miscarriage with the transfer of an embryo with a mosaic PGT-A result, which should be discussed with the surrogate before transfer. Additionally, prenatal diagnostic testing, like amniocentesis, is recommended following the transfer of an embryo, even those with normal PGT-A results. There are several points to consider when using a surrogate. Would the surrogate consider having an amniocentesis? Would pregnancy termination be an option in the setting of abnormal results? These big questions need to be considered before a pregnancy is achieved so that the expectations are clear.

 

GOSTORK: Lastly, should a patient pursue genetic testing, how can a genetic counselor like yourself be helpful?

Genetic counselors are skilled at providing complicated genetic information in a more understandable manner. Genetic counseling may be useful either before the testing is performed, to help the patient understand the risks, benefits, and limitations of the testing, or after the testing is performed to help explain results in more detail. If you decide to pursue carrier screening, genetic counseling may help you understand the potential reproductive risks. For patients who seek PGT-A, genetic counselors can talk through the specifics of the results, such as which chromosomes are impacted and what that might mean. Genetic results are often complicated, and genetic counselors are here to help!

 

And as always, GoStork wants to help guide intended parents on their journey to baby. Please visit our Resources Page to learn more.

 

  1.   Nusbaum, RL, McInnes, RR, Willard, HF. Genetics in medicine. 7th ed. Philadelphia: Saunders, 2007.
  2.   Fragouli, E, Alfarawati, S, Spath, K, Babariya, D, Tarozzi, N, Borini, A, Wells, D. Analysis of implantation and ongoing pregnancy rates following the transfer of mosaic diploid-aneuploid blastocysts. Hum Genet 2017;136(7):805-819.
  3.   Munne, S, Blazek, J, Large, M, Martinez-Ortiz, PE, Nisson, H, Liu, E, Tarozzi, M, Borini, A, Becker, A, Zhang, J, Maxwell, S, Grifo, J, Babariya, D, Wells, D, Fragouli, E. Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing. Fertil Steril 2017;108(1):62-71.
  4. Kahraman, S, Cetinkaya, M, Yuksel, B, Yesil, M, Pirkevi Cetinkaya, C. The birth of a baby with mosaicism resulting from a known mosaic embryo transfer: a case report. Hum Reprod 2020; 35(3): 727–733.