A Complete Guide to Pre-Implantation Genetic Testing: PGT-A, PGT-M and Mosaic Embryos
Incredible advances have been made in genetic testing technology since the 1950s discovery that one extra copy of chromosome 21 can cause Down syndrome, especially for prenatal screening. Read more to learn how screening an embryo’s genetics before a transfer can maximize your chances of a successful pregnancy.
How do genetic abnormalities affect my chances of successful implantation and pregnancy?
One way to gather information about an embryo’s health is by examining its genetic content. More specifically, looking into the number of chromosomes each embryo contains during early development. A healthy embryo should contain 46 total chromosomes, 23 from the sperm and 23 from the egg. This is referred to as euploid. However, if the sperm or egg have an abnormal number of chromosomes, the resulting embryo will also have an abnormal number, known as aneuploid. Most aneuploidies are lethal to a developing embryo and result in a failed implantation or pregnancy loss1.
Aneuploidy can happen to anyone, regardless of age. However, it appears to be more common as we age. A 2013 study from Franasiak et al. determined that for women aged 26 to 37, approximately 2-8% of embryos were aneuploid. By age 42, this rate increased to 33% and at 44, 53%. With a significant impact on fertility, new technology has been developed that allows embryologists to check whether an embryo is aneuploid before transfer. This technique is known as Pre-Implantation Genetic Testing for Aneuploidy (PGT-A).
In addition to PGT-A, parents may opt to have Pre-Implantation Testing for Monogenic disorders (PGT-M) performed on the embryos to test for certain genetic disorders. For parents who are known to have conditions like cystic fibrosis, Huntington disease, Duchenne Muscular dystrophy, or sickle-cell anemia, PGT-M can be used to identify which embryos have received the gene associated with the condition2. Embryos that are unaffected by the disorders can then be safely transferred.
Normal and abnormal might not be so obvious – what about mosaicism?
Not all embryos are deemed “normal” or “abnormal.” Sometimes, PGT reveals that an embryo is a mix of both or mosaic. There has been widespread debate as to what to do about embryos that fall in this category.
When an embryo grows and develops, one cell doubles its genetic content and splits into two genetically identical cells. By the time an embryo reaches the blastocyst stage, it is composed of over 100 cells! However, sometimes errors occur during cell division within the embryo, resulting in some cells being “normal” and others “abnormal.” So, what does this mean for the health of the embryo as a whole and its likelihood of implanting? At Anova, when our partner geneticists at Igenomix encounter mosaic embryos, they grade them according to the following criteria:
If less than 30% of cells are abnormal, embryo is labeled “normal”
If 30-50% of cells are abnormal, embryo is “low-level mosaic”
If 50-70% of cells are abnormal, embryo is a “high-level mosaic”
If more than 70% of cells are abnormal, the embryo is labelled “abnormal”
Typically, mosaic embryos are considered for transfer only if there are no other embryos available. However, there are some exceptions to this rule. In cases where the mutations could lead to a child with significant congenital abnormalities or health issues, embryos are not transferred, even if they are low-level mosaic.
How does PGT work?
If you choose to have PGT-A or PGT-M performed on your embryos before your transfer, your IVF treatment protocol will largely remain the same. Retrieved eggs are fertilized using IVF or ICSI to create embryos and grown until the blastocyst stage. This occurs approximately 5 to 6 days after fertilization. At this stage, PGT can be performed on fresh or frozen embryos.
A tiny sample of cells is removed from the outer region of each embryo, which will form the placenta. Next, these cells are sent to a lab for genetic testing to determine which embryos are genetically normal. These embryos can then be used for an upcoming transfer.
How does PGT-A increase pregnancy rates?
For patients undergoing IVF treatments that have experienced recurrent pregnancy loss under 12-week gestation or recurrent failed implantations, there is a significant chance that it may be due to the transfer of aneuploid embryos. PGT-A allows aneuploidy to be removed from the equation, which typically results in significantly higher implantation rates.
Unfortunately, PGT is considered a fertility add-on and is not covered by the Ontario Health Insurance Plan (OHIP). As PGT adds extra steps to a typical IVF treatment plan, there are associated costs that the patient must pay for out of pocket. However, PGT is generally considered cost-effective, as it can decrease the number of failed IVF cycles, saving patients both time and money.
Pre-Implantation Genetic Testing is not required in every case but can be helpful for patients who are experiencing recurrent implantation failure or pregnancy loss. It is important to speak with your fertility physician to determine if PGT could help you on your fertility journey.
Chloe Graham (she/her)
Doctoral Student (University of Guelph, Biomedical Sciences)
About the author
Chloe is a Masters Student in Biomedical Sciences at the University of Guelph, who also works as a patient coordinator at Anova Fertility.
At Anova, she educates patients through creating online resources, manages patient flow and assists with administrative functions. Before joining our team, Chloe advocated for women’s health and reproductive rights as an executive member of Oxfam at Guelph, local branch of the international anti-poverty organization.
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