GENETIC TESTING

GENETIC TESTING OF EMBRYOS 
PGT-A (PGS)/ PGT-M (PGD) 

New genetic testing technologies of the embryos have developed and include two different types:  

  • PGT-A (Preimplantation Genetic Testing for Aneuploidies), previously known as PGS (preimplantation genetic screening). 
  • PGT-M (Preimplantation Genetic Testing for Monogenic/Single Gene Defects), previously known as PGD (preimplantation genetic diagnosis). 

Genetic testing can only be performed on embryos created through IVF treatment. 

PGT-A is a type of embryo testing which can determine the number of chromosomes and detect any structural chromosomal abnormalities. 

Healthy embryos carry 46 chromosomes in their cells with half of the chromosomes derived from the sperm and the rest from the egg. However some embryos may have too few or too many chromosomes. Those embryos are associated with risks, as they often fail to implant, can cause miscarriage or result in the birth of a child with a genetic syndrome such as Down’s. 

PGT-A is a very useful selection tool for the identification of embryos with a normal set of chromosomes and its use can be particularly beneficial for some couples. Through this selection technique the risks associated with chromosomally abnormal embryos may significantly be reduced. 

PGT-M is a type of embryo testing which can identify specific genetic defects within the embryos. It is particularly useful for couples, which are at risk of transmitting a serious genetic disorder, such as cystic fibrosis or thalassaemia, to their children. It allows for the identification of the affected embryos thus protects the couples from future emotional and physical implications or moral dilemmas; consider the termination of the pregnancy or decide to have a child who will suffer with a severe disease. 

Genetic counselling is very important and is strongly recommended to couples meeting the criteria for PGT-A or PGT-M, receive advice from our geneticist before proceeding with the treatment. 

 

In line with the rules of the Greek National Authority of Assisted Reproduction genetic screening of the embryos is allowed and may be considered in the following categories of patients:  

  • Couples who have had more than 3 unsuccessful IVF cycles 
  • Couples who have had more than 3 miscarriages 
  • Couples who have had a previous miscarriage with confirmed chromosomal abnormality of the embryo  
  • Couples who are carriers of an autosomal recessive disease (i.e. Thalassaemia, Sickle cell anaemia, Cystic fibrosis, Tay Sachs) 
  • Individuals who are affected by an autosomal dominant disease (i.e. Huntington’s, Myotonic Dystrophy) 
  • Individuals who are carriers or have X-linked conditions (i.e. Haemophilia, Fragile X syndrome, Duchenne muscular dystrophy) 
  • Individuals who are carriers of mutations linked with cancer syndromes (i.e. BRCA associated with breast cancer) 
  • Individuals who are carriers of balanced chromosomal abnormalities 
  • Women over the age of 40 
  • Couples who have an offspring suffering from life-threatening blood disorders who need an exact match for stem cells or bone marrow transplantation. 

Most commonly genetic testing is performed once the embryo reaches the blastocyst stage on day 5 or 6. At this stage the embryo consists of approximately 100 cells. Half of these cells will form the baby and other half will form the placenta. The technique for either PGT-A or PGT-M is exactly the same. A small number of cells from each embryo are obtained through biopsy and are tested by the geneticist for chromosomal abnormalities or genetic defects. The removed cells are taken from the part of the embryo that will form the placenta, while the part of the embryo that will form the baby remains intact.  

In selected cases genetic testing may also be performed on D3 embryos. At this stage of development the embryo consists of approximately 8 cells and the procedure involves the removal of 1 cell only, which subsequently is tested. 

However genetic testing done on D3 embryos is more invasive for the embryo and the results are less accurate, compared to D5 embryos, therefore it is not favored as a routine practice. 

Since it takes approximately 3 weeks to receive the results of the test from the laboratory the embryos are kept frozen. Once the results are available the normal embryos or the embryos free from genetic disease can be thawed and transferred to the uterus. The timings and the preparations for the embryo transfer will be discussed with you. 

 How long does it take to get the results?
 What the results mean? 

It takes on average 3 weeks to receive the results of the test from the laboratory.  

The results from PGT-A will identify each embryo as: 

  1. EuploidAll cells have normal number of chromosomes. This embryo is suitable for transfer to the uterus or, 
  2. AneuploidAll cells have abnormal number of chromosomes. This embryo is not suitable for transfer or, 
  3. MosaicThere is a mixture of cells with normal and abnormal number of chromosomes. We do not transfer this embryo.  

The results from PGT-M will identify each embryo as: 

  1. Unaffected:  This embryo does not carry the genetic disease and is suitable for transfer to the uterus or, 
  2. Affected: This embryo carries the genetic disease and is not suitable for transfer. 

Yes. Screening of the embryos for chromosomal abnormalities (PGT-A) and genetic defects (PGT-M) can be performed concurrently. The same genetic material can be used and no additional biopsy is needed. 

Although genetic testing can be particularly beneficial for selected group of patients, the couples should be aware of the limitations of the testing.  

PGT-A can identify chromosomally normal embryos suitable for transfer, but unfortunately cannot guarantee a pregnancy and cannot eliminate the risk of miscarriage. Even in the presence of a chromosomally normal embryo, there could be other reasons for an unsuccessful IVF treatment, such as a “hostile” uterine environment. 

Furthermore the results from PGT-A are not 100% precise and there is a risk of false diagnosis, which is less than 1%. Therefore if a pregnancy occurs as a result of IVF with PGT-A, the couples would be advised to consider amniocentesis or chorionic villous sampling (CVS) during pregnancy, if they want to confirm the diagnosis. 

Another limitation, which needs to be taken into consideration, is that the test cannot guarantee the presence of normal embryos. The expected number of normal embryos is directly correlated to the maternal age and the total number of embryos, which are available for testing. 

If you are considering PGT- A, in addition to the tests required for your IVF treatment both you and your partner/ husband must do the Peripheral Blood Karyotype, which is a test to assess the number and structure of your chromosomes. 

If you are considering PGT- M a blood test to establish the type of your genetic defect will be needed, to allow our geneticist to develop a specific PGT-M test which is unique for each patient. It normally takes between 4-6 weeks for your test to be ready and the results need to be available before the commencement of your IVF treatment. 

Yes. The sex of the embryo can be identified with PGT-A. However, the law in Greece strictly prohibits sex selection for social or family balancing reasons. Permission to select embryos on the basis of their sex is only granted to couples, which are carriers or have a history of known, sex-linked, serious medical conditions.