Preimplantation Genetic Testing: PGTa / NICS / Ni PGS

Preimplantation Genetic Screening?

Preimplantation Genetic Testing (PGTa) is a test that carefully examines the chromosomal material of an IVF or in vitro fertilized egg before the process of implantation can begin. During this time, one or more cells are removed from the embryo to test it for numerical chromosomal abnormalities.

In this method, the screening allows for selective implantation of embryos that are chromosomally normal and also called EUPLOID embryos.

NICS stands for non-invasive chromosome study, in order to determine the genetic characteristics of the embryo, but it predominantly takes into consideration the spent culture medium of the embryo. This requires the laboratory to have critically good culture conditions as well as a time-lapse incubator, which minimizes the exposure of the culture medium to the external environment.

NICS is going to be the future of genetic testing of the embryo because a lot of research is being done in this direction.

PGT-M is another advanced test, which is done for monosomal disorders of the genes and is applicable only in certain special situations. After genetic counseling has been done for the couple.

PGT-A and NICS are not recommended or required for everyone.

Women over 37 have a higher chance of carrying eggs with an incorrect number of chromosomes. Thus, the screening process becomes necessary for them if they wish to conceive.

Studies suggest that abnormal chromosomes are among the leading reasons women of that age have trouble conceiving. They are also more likely to have a miscarriage or a baby with Down syndrome and other chromosomal abnormalities.

There are other situations when your doctor might recommend PGS. These include—

1) If your family has a history of chromosomal problems
2) If your sperm has a risk of carrying an abnormal number of chromosomes
3) If you have already had some failed miscarriages
4) If you have had failed IVF tries without any explanation

That said, PGT-A or NICS is not a guaranteed way to prevent a miscarriage or have a baby, but it drastically reduces the chances of you having a miscarriage, as it is believed that a chromosomally normal embryo, or a EUPLOID embryo, has the best chances of giving rise to a live birth rate.

You need the test for a variety of reasons since it can be used in different circumstances. They include—

1) PGT-M Testing for monogenic disease –

In this case, the specific gene mutation carried by both parents is analyzed. After all, a disorder in a particular gene is due to a mutation in the DNA sequence. It results in diseases like cystic fibrosis or sickle cell anemia. There can also be inherited genetic mutations that might eventually develop into breast or ovarian cancer.

Some of the most common diseases tested via this method include

• Huntington’s disease
• Sickle Cell Anemia
• Cystic fibrosis
• Muscular dystrophy
• Fragile-X syndrome
• BRCA1 and BRCA2 mutations
• Tay-Sachs disease
• Thalassemia

To perform this test successfully, there needs to be proper scheduling with something called pre-PGTA, where a specific type of probe has to be made for the couple before they undergo any form of stimulation for the procedure of IVF. This is routinely carried out by doing a specific blood test, and then the procedure for IVF is initiated for the couple.

2) Testing for chromosome structural arrangement—

It analyzes embryos of parents who have chromosomal structural rearrangements like inversion or translocation. If unaddressed, it could result in miscarriages. The most common disorders examined through this process include

• Reciprocal translocations
• Non-reciprocal translocations
• Robertsonian translocations

Thus, depending on your underlying condition, the PGS process will help you realize possible complications that might arise during childbirth.

In PGT-a, the biopsy is usually taken at the blastocyst stage, during the fifth or sixth day of embryo development. The embryos are frozen at the clinic, while the biopsies take place in the lab. PGT-a screens every embryo biopsy and then quantifies the number of chromosomes in each sample.

The result can either show an average number of chromosomes, which means that the chance of a healthy pregnancy is relatively high, or it can show an abnormal number of chromosomes, meaning that there might be a miscarriage or other complications.

After the embryos are analyzed, a genetic report is sent to the medical professional. Based on this, along with the embryos’ grading and morphology, the doctor recommends which ones should be used for couples trying to get pregnant.

While PGT-a is a typical process, there are some risks attached, which is the case with all medical procedures. They include—

1) To do this procedure, it is mandatory that the embryos need to be frozen; this becomes slightly impossible and practically non-viable for a couple who is staying outside India.

2) The risk of biopsies or freezing harming the embryo.

The main indications for the need for PGS arise when couples have single-gene disorders or structural aberrations in the chromosomes. On the other hand, there aren’t any fixed conditions for PGS, but it is mostly undertaken by women above 35 or if they’ve had failed IVF processes and miscarriages.

PGT-a is a biopsy of approximately 3 to 5 cells, which is carried out under strict aseptic conditions in the IVF laboratory by a person who is a super specialist; this involves the cost of taking the biopsy as well as the cost of performing the genetic test.

The average cost of doing this procedure comes to approximately ₹25,000 per embryo; this cost varies based on the expertise of the available doctor

On the contrary, NICS does not involve taking any form of biopsy, but it involves setting up strict culture conditions in order to make sure that the culture medium, which is extracted from the embryo, does not have any contamination; this procedure virtually eliminates any form of damage to the embryo.

Because such standardization and high-quality laboratories are not available across the country of India, NICS is not an option that is available across the country.

At this moment, NICS is also associated with a high amount of positive and false negative rates. If the technique is not done correctly, and as a result of this, if you are a patient, you have to choose your clinic in which you are doing the IVF with great amount of caution.

• EUPLOID

This means that the embryo has a normal chromosome structure, and these are the embryos that are best suited for implantation, with the highest success rates for a live birth. It is ideal to get an EUPLOID embryo for patients across all age groups, as well as for patients who have had previous IVF failures or previous abortions.

In fact, getting a normal embryo is the very basis for offering the patient any form of immunotherapy. If at all, it is indicated after a detailed reproductive immunological evaluation.

• LOW MOSAIC

These are the embryos in which the chromosome abnormalities are in the range of 30 to 50%, and the majority of these embryos have a high tendency to undergo something called auto-correction.

Once they are submitted to the uterine microenvironment, an option is always given to the patient to go ahead and transfer the low mosaic embryos if they wish to do so

• HIGH MOSAIC

These are embryos in which the chromosomal abnormalities are in the range of 50 to 70%., The tendency to undergo auto correction of these embryos is extremely debatable, and very few of the patients ultimately end up having a healthy life birth if these embryos are transferred into their uterus

• ANEUPLOID

These are embryos in whom the risk of chromosomal abnormality is extremely high, and as a result, they are not suitable or recommended for transfer into the patient. Though it is highly debatable, an option is provided to the patient for discarding these embryos; should the patient decide to do so, my clinic will go ahead and ethically discard these embryos.

• CHAOTIC EMBRYOS

These are embryos in whom there are six or more proven genetic abnormalities, and they are absolutely not recommended for an embryo transfer.

In my practice, I have always found that combining genetic testing in the form of NICS along with advanced incubator conditions like time-lapse greatly helps in annotation and selection of the embryos for the patient and ultimately provides us with a live birth rate exceeding 40% in the majority of the selected cases.