Pre implantation genetic testing

Pre-implantation Genetic Testing for Aneuploidies (PGT-A)
One of the commonly asked questions during a fertility consult is how can we improve success rate of IVF?

The success of IVF depends on a number of factors including a woman’s age, fertility diagnosis, number of embryos produced, and embryo quality.

Pre-implantation genetic testing for aneuploidies (PGT-A) (formerly known as pre-implantation genetic screening (PGS)) is a test used alongside IVF to increase the chance of a healthy on-going pregnancy.

HOWEVER, It is not a guarantee of a pregnancy.

PGT-A provides important information about chromosomal health of embryos before transfer so we can select the embryo most likely to lead to a successful pregnancy.

Understanding genetics

Healthy people typically have 23 pairs of chromosomes in each cell.
Each of these chromosomes in a pair is inherited from the mother (purple) and the other from the father Genes are the building blocks of these chr.  Genes are the instructions that tell the body how to make proteins that allow the body to develop, grow and function and is responsible for our blood group,height,eye colour,hair colour etc.

What happens if an embryo has an incorrect number of chromosomes?

Research has shown that many embryos have an incorrect number of chromosomes in their cells, a condition known as aneuploidy (extra or missing chromosomes),wherein, the genetic instructions no longer make sense and the embryo is unable to form a healthy baby.

In this example there is an extra chromosome number 21. When there is an extra chromosome, this is known as a trisomy. This is what happens in Down’s Syndrome

Most aneuploid embryos fail to implant in the uterus or miscarry during pregnancy. However, there are very few situations where a pregnancy can reach full term and a baby is born e.g. Down’s Syndrome

An embryo with missing or duplicated chromosomes may grow at a normal rate in its early stages. It is therefore possible to select an apparently normal embryo for transfer but actually contains faulty chromosomes. This is an important reason why IVF treatment is not always successful.

How is it done?

A few cells are removed from each embryo created in an IVF cycle and the number of chromosomes in each embryo cell are counted. An embryo with a normal number of chromosomes can therefore be chosen to be transferred, and this is thought to give a higher chance of creating a healthy baby.

By excluding the abnormal embryos, PGT-A helps to prevent the possible transfer of embryos which would end up not implanting, miscarrying or resulting in the birth of a child affected by an abnormal number of chromosomes.
However, this screening may also result in no embryos being found that are normal so no transfer can take place.

Situations where PGT-A might help?

PGT-A may be offered to couples who have a higher chance of having a chromosomal problem in their embryos, as they are most likely to benefit. These are:

1.Couples with a history of recurrent miscarriages
2.Couples who have had several failed IVF attempts
3.Couples who have had previous pregnancies affected by chromosome abnormalities
4.Women over the age of 35 years requesting PGT-A

For women in their early thirties, about 35% of embryos are aneuploid  Over the age of forty years, it is typical for at least 75% of embryos to be aneuploid.)

The PGT-A Process

1.Appointment at careivf : A doctor will take a detailed fertility history and arrange fertility tests to check if IVF is suitable. PGT-A will be discussed.

2.If suitable,IVF cycle is commenced ,eggs are retrieved,and put together with partners sperms for fertilization .The laboratory allows the fertilised eggs, now called embryos, to grow under observation for five days, or sometimes six day

3.On their fifth or sixth day of development the embryo is called a “blastocyst”. Each blastocyst is assessed and those that have developed normally will be biopsied.

At this stage,  embryologist will discuss proceedings of embryo biopsy and option for number of embryos to be biopsied  with the couple.Following consent, embryologist carefully removes a small cell sample from each embryo and sends it to PGT lab for testing. Straight after the biopsy procedure the embryos will be frozen to await the result of the test. There will be no embryo transfer in that cycle.

In certain circumstances, where there are very few embryos available the embryologist may advise against biopsy and PGT-A testing and recommend a fresh embryo transfer.

4.The PGT lab informs the number of chromosomes in each embryo and accordingly an unaffected embryo is defrosted or thawed and then transferred to the womb. Remaining unaffected embryos if available can also be kept frozen for future use.

ADVANTAGES OF PGT-A

1.INCREASED IVF SUCCESS: More recent research indicates that the chances of an embryo with a confirmed normal number of chromosomes producing a healthy baby is more than 25% higher than when an embryo is selected for transfer based on the look of the embryo (morphology). In most cases normal and abnormal (aneuploid) embryos look identical. Without genetic screening, an embryologist cannot tell the difference between them and it is possible that chromosomally abnormal embryos could be inadvertently transferred.

2.SHORTENED TIME INTERVAL TO ACHIEVING PREGNANCY PGT-A may also reduce the time it takes to get pregnant meaning that fewer IVF cycles are needed.

3.It may also reduce the number of IVF pregnancies that miscarry since we know the commonest cause of miscarriage is chromosomal fault.

4.By ensuring that embryos with a normal number of chromosomes are prioritized for transfer, the chance of conceiving a healthy child may increase with PGT-A.

DISADVANTAGES

1.PGT-A does NOT diagnose specific genetic disorders

PGT-A will only look at the numbers of chromosomes in the embryo and cannot detect genetic disorders. If either partner carries a specific genetic disorder that could impair the normal development of a child affected by the disorder, you will be referred for Pre-implantation Genetic Testing for single gene disorders (PGT-M) or Pre-implantation Genetic Testing for structural chromosomal changes (PGT-SR).PGT-A does NOT screen against genetic disorders and does NOT guarantee a child will not be born with a genetic disorder (e.g. Cystic Fibrosis) rather than a chromosomal disorder (e.g. Down’s Syndrome).

2.Additionally, there may be a technical failure for a small percentage (less than 5%) of embryos and no result is produced. This can be due to the chromosomes breaking up before testing, or some may not contain any genetic material, cells may be lost during the highly technical fixation process of the test, or may have suboptimal fixation meaning they cannot be used for this complex analysis.

3.Risk of having nothing available for biopsy

There is a chance that no embryos will be suitable for biopsy as they have not reached the correct stage of development. In these cases, it is highly likely that the embryos that have stopped developing are chromosomally abnormal and would not produce a viable pregnancy in any case.

4.Risk of no normal embryos : The test may find that none of the embryos are normal, in which case there may be no embryo transfer procedure. The likelihood that this will happen is influenced by a variety of factors; the most significant are advancing female age and having a small number of embryos to work with. If there are no normal embryos where all the cells have the correct number of chromosomes (euploid), we will consider transferring embryos that have a mixture of normal and abnormal chromosome numbers, whereby the majority of the cells are normal (low level mosaicism), as these have been shown to produce healthy pregnancies although at a lower rate than with euploid embryos. We will discuss this with you when we give you the biopsy results.

5.No scientific test is 100% perfect

There is a small chance that the test will report normal embryos as abnormal and happens up to 15% of the time. The consequence is that a normal embryo is nor transferred when it could have resulted in a healthy baby.  The chance of the test reporting ab abnormal embryo as normal is lower (5%). The consequence of this is that an abnormal baby may result. It is for this reason that prenatal testing during pregnancy is recommended, even after pgt-a as double check.

6.Risk of an unsuccessful outcome and miscarriage

By performing PGT-A and having a normal embryo transferred does not, unfortunately, guarantee a positive pregnancy test or a healthy live birth. PGT-A has large financial and emotional costs.As with all pregnancies, there is also a risk of miscarriage. PGT-A testing and replacement of a chromosomally normal embryo does not eliminate the risk of miscarriage; it can only serve to reduce the risk.

If an embryo is damaged by the procedure, it may not produce an embryo suitable for transfer. The risk of damaging an embryo is less than 1%.

Several thousand healthy babies have now been born from IVF with PGT-A. These babies do not have any more congenital abnormalities (birth defects) than occur naturally in the general population (3-5%).