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13 Nov 2023

Genetic Screening and Genetic Testing Explained

PGS, PGT-A, PGT-M, PGD… what does it all mean?

Allecia Swale, Board Advisor, Fertility NZ and Senior Embryologist, Repromed.

Within the IVF sector there are many different terms that all mean the same or similar procedure.  When clinics refer to PGS (Pre-implantation Genetic Screening) or PGT-A (Pre-implantation Genetic Testing – Aneuploidy) they are talking about the checking suitable embryos to see if they have the correct genetic make-up.  To really understand this though we first need to understand a little more about human genetics. 


We as humans contain 23 pairs of chromosomes, these chromosomes contain all of the instructions that the cells in our bodies need to be able to function normally.  Each of the chromosomes contain many thousands of genes which are the specific instructions.  When PGS or PGT-A is completed on an embryo we are checking to see the embryo contains a full set of chromosomes.  Sometimes the embryos can have extra copies (3 more more) of any one of the chromosomes.  There can also be copies missing or there can be additional/missing segments of the chromosomes.  These embryos would all be considered abnormal and not suitable for treatment.  This is because many would not be able to establish a pregnancy, some would result in a miscarriage, others in a still-birth.  Some of the embryos considered abnormal may result in a live birth however, the child would have a genetic abnormality that, depending on the chromosomes involved, will can have a range of impacts on the child.


The method of genetic laboratory testing that is performed when using PGS/PGT-A is a process called next generation sequencing.  This type of testing is looking for a very large amount of information on the embryo.  Due to the vast amount of genetic information that is analysed, very small changes in the embryo’s genetics are not able to be identified. Something called a single gene disorder (e.g., Cystic Fibrosis) is a very small change in one of the genes located on the chromosomes.  This type of genetic change is not able to be detected through standard next generation sequencing.  However, we do also have specific testing that can be done to identify these types of disorders, this type of testing is referred to as PGD (Pre-implantation Genetic Diagnosis) or PGT-M (Pre-implantation Genetic Testing – Monogenic).  Only patients that are known to be carriers or have a family history of a single gene disorder will be referred to have PGD/PGT-M.  Often these patients will also have PGS/PGT-A completed on the embryos at the same time as PGD/PGT-M.  These patients may have embryos that are affected by the single gene disorder, but no abnormalities detected by PGS/PGT-A.


How are embryos tested?


In order to explain this, we need to go back to the start.  In the IVF laboratory, eggs and sperm are put together to create embryos.  All of the normally fertilised embryos are cultured in the laboratory for five to seven days.  The embryos need to reach a stage called the blastocyst stage of development.  This stage of development can be observed from day five, however some embryos may take a day or two longer to reach the full blastocyst stage.  These blastocysts will have anywhere from 70-200 cells inside them.  There will be two types of cells identifiable in the blastocyst embryo, the first forms a tight ball of cells called the inner cell mass (ICM).  These cells go on to develop into the fetus.  The second type of cells are called the trophectoderm cells (TE).  These cells will go on to develop into the placenta.  The quality of these two types of cells will be graded from A to D with A being the best.  Blastocyst embryos need to be good quality (commonly A’s or B’s but each laboratory will have its own criteria) to be suitable to undergo genetic testing. 


At the blastocyst stage of embryo development both the ICM and TE cells will be representative of the embryo’s genetic make-up.  It is for this reason that the IVF laboratory is able to take a sample of cells (usually 5-10 cells) from the TE part of the blastocyst embryo.  The embryo is held in place using a holding pipet.  Looking down a high-powered microscope, the embryologist will then take the sample of TE cells into a biopsy pipet (using a device that can apply very controlled and small amounts of suction).  Once the correct number of TE cells are in the biopsy pipet, a laser is used to cut the connections between the cells – this process is called the embryo biopsy.  The biopsied cells will then be washed and transferred in a very small volume of solution to a small tube that is frozen and sent to the genetics laboratory for the genetic testing to take place.  The embryo is immediately frozen, following confirmation the cells are seen in the tube, and placed into storage to await the genetic results. 


But what are the risks?


With any laboratory procedure, even though every precaution and care is taken to protect the embryo/patient material, there are always risks associated with it.  The first hurdle that the embryo needs to overcome with any type of genetic testing is the biopsy procedure.  Even though only the ‘top quality’ embryos are selected to undergo embryo biopsy the embryos don’t always respond the way the embryologist would expect them to.  There is around a 2-5% chance that the biopsy procedure could damage the embryo and reduce the embryo’s potential for pregnancy (even if there are no abnormalities detected following genetic testing).


The next hurdle is that the cells need to be able to give a result.  In less than 5% of cases there may be no, or insufficient genetic material (DNA) detected in the tube by the genetics laboratory.  This can arise because the quality of the DNA from the cells was poor, which can be caused by the cells starting to break down (lyse) prior to them being frozen and shipped. Unfortunately this is not something that can be predicted; the IVF laboratory tries to control for this by only performing biopsy on good quality embryos.  It can also arise because while every care is taken something has gone wrong with the cell transfer and the cells from the embryo have not survived the process, meaning the genetics laboratory cannot detect any DNA from the embryo.


The final hurdle for the embryo is that it needs to survive the freezing and thawing process.  While the majority of laboratories experience embryo survival rates of around 90-95%, there are still some cases where the embryo does not survive the freezing and thawing.  Again, the IVF laboratory will take every care to protect the embryo but sometimes for reasons that are not always understood even good quality embryos do not survive the process.


There is also risk associated with the genetic results:

  1. A patient may go through the process of PGT-A/PGS/PGT-M/PGD and result in no embryos that are suitable for transfer either because no embryos were suitable for biopsy or because all of the embryos biopsied had abnormalities detected.  This is a very upsetting result but is something all patients should be prepared for.  The risk of this occurring increases as maternal age increases. 

  2. A false positive/negative result may be given, which occurs in 1-2% of cases.  This is when the genetic laboratory reports that an embryo is abnormal, when in actual fact it has no detectable abnormalities.  This can also happen in the reverse where an embryo is reported as having no abnormalities detected but does contain abnormalities.

  3. The genetic condition called mosaicism may occur.  Mosaicism is a difficult concept to explain – however at its most basic explanation, it means that not all of the cells in the embryo contain the same genetic make-up.  This is reported by the genetics laboratory generally as a percentage of the embryo that has an abnormal genetic make-up (e.g., 40% mosaic for trisomy 21 – means 40% of the cells had an extra copy of chromosome 21).  Mosaicism can occur in the embryo in a few different ways as follows:


Type of Mosaicism

Reported as

  • The whole embryo is mosaic

Percentage mosaic e.g., 40% mosaic

  • Just the ICM carries abnormal cells but the TE has no detectable abnormalities

No abnormalities detected – Suitable for transfer

  • Just the TE carries abnormal cells but the ICM has no detectable abnormalities

Abnormal embryo – Not suitable for transfer


If an embryo is in the category of example two above, this embryo would be considered suitable for transfer.  However depending on the chromosome/s involved in the abnormality may not result in a healthy live birth.  If the embryo is in the category of example three, it would be considered abnormal and would be discarded; however could have resulted in a healthy live birth.  The embryos that arise from example one generally require further discussion with your clinician or a genetic counsellor to consider the possible outcomes that could occur and will be related to the level of mosaicism detected and the chromosome involved.


Due to all of the risks associated with genetic testing of embryos it is always strongly recommend that should an ongoing pregnancy be established, routine obstetric checks and testing is also completed to confirm the genetic results obtained from the embryo.


Why do genetic testing?


The reason to use genetic testing in an IVF cycle will vary from patient to patient.  It will depend on each patient’s fertility journey and family genetic history.  Genetic testing of embryos is not suitable for everyone and there are still conflicting scientific research papers that both support and rebut the benefits of genetic testing.  At our Auckland fertility clinic Repromed, we generally recommend it to any patients that have a known genetic condition, or those that meet a list of criteria suggesting testing will be beneficial. It is widely accepted in the IVF sector that PGD/PGT-M is beneficial to prevent the genetic condition being passed on to the future child.  There is also a subset of IVF patients that have had what is termed recurrent implantation failure (RIF) – where three or more good quality blastocysts have been transferred but no pregnancy has been achieved.  For RIF patients, genetic testing of embryos can help identify and eliminate one aspect that could be causing the failure of embryos to implant.


It is important to remember that the genetic makeup of the embryo is only one part of the puzzle to achieving an ongoing pregnancy and healthy live birth.  Careful consideration and discussion with your fertility specialist should be done before opting for genetic testing of embryos.Allecia Swale, Board Advisor, Fertility NZ and Senior Embryologist, Repromed


Within the IVF sector there are many different terms that all mean the same or similar procedure.  When clinics refer to PGS (Pre-implantation Genetic Screening) or PGT-A (Pre-implantation Genetic Testing – Aneuploidy) they are talking about the checking suitable embryos to see if they have the correct genetic make-up.  To really understand this though we first need to understand a little more about human genetics. 

Watch Allecia's webinar - Genetic Testing and What to Expect.

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