What Is Genetic Testing in Embryos and Why Is It Performed?

Embryo genetic testing is an important solution, especially for women of advanced maternal age. Also known as PGT, why is embryo genetic testing performed, how is it done, and for whom is it recommended? In this article, you will find everything you need to know about embryo genetic testing.

What Is Embryo Genetic Testing?

Definition of embryo genetic testing

The genetic examination of embryos created through IVF treatment is called preimplantation genetic diagnosis. Embryo genetic testing examines the chromosomes, number, and genes of embryos before they are transferred to the uterus.

During the test process, 5–10 cells are taken by biopsy from embryos that have reached day 5 and are sufficiently mature. The collected cells are evaluated genetically, and healthy embryos are identified. In this way, only genetically normal embryos can be transferred.

Other names for embryo genetic testing are PGD (Preimplantation Genetic Diagnosis) and PGT.

Its role in IVF treatment

The most common cause of IVF treatment failure is abnormalities in embryo genetics. When genetically normal embryos are transferred after genetic analysis, the chance of pregnancy increases.

Conditions required for the test

Embryo genetic testing is not routinely performed for every couple. It is done for couples who meet certain criteria. Genetic counseling before starting IVF treatment helps draw the right roadmap.

Expectant mothers over the age of 35 are among those who should have the test. Expectant mothers and fathers with known hereditary diseases, as well as expectant mothers who have experienced recurrent miscarriages, are also in this group. PGT testing is also recommended before embryo transfer for expectant mothers with abnormalities in egg cells and expectant fathers with abnormalities in sperm cells.

If either partner has a known genetic problem, genetic analysis should be performed on the embryos. It can also be applied in couples with recurrent IVF failures and recurrent pregnancy losses.

Before starting IVF treatment, the couple should always be evaluated in detail and the cause of infertility should be determined. Genetic screening should be recommended accordingly.

Embryo Genetic Test Types

PGT-A (Preimplantation Genetic Screening)

PGT-A testing is performed to detect chromosome number abnormalities in embryos. Even in a genetically normal couple, spontaneous chromosomal abnormalities may occur in the embryo. The test aims to identify these abnormalities.

A healthy embryo contains 23 pairs of chromosomes. One of each pair comes from the mother and the other from the father. Problems during cell division or fertilization can also cause numerical chromosomal abnormalities in the embryo.

Embryos with a deficiency or excess in chromosome number are called aneuploid embryos.

As maternal age increases, the rate of aneuploidy in embryos rises significantly. While the aneuploidy rate is 15–20% in a 25-year-old woman, at age 40 this rate reaches 60–70%.

PGT-A is especially recommended in the following situations: women over 35, cases with recurrent pregnancy loss, couples with recurrent IVF failures, and individuals with balanced chromosomal translocation.

The accuracy rate of the test is 98%. Because false-positive or false-negative results may occur, prenatal diagnostic testing is recommended to confirm PGT-A results.

PGT-M (Preimplantation Genetic Diagnosis)

PGT-M is used in couples in whom one or both parents have a hereditary genetic disorder. The purpose of this test is to identify the healthy embryo that does not carry the genetic disorder.

PGT-M is not a general screening test. It only investigates the presence of the disease-related gene in the family.

For PGT-M, first a detailed map of the gene region carrying the mutation that causes the disease is created. The mutation region and its surroundings are identified. DNA amplification is performed on the biopsy samples taken from the embryos. A healthy embryo is investigated.

Differences between the two test types

PGT-A and PGT-M serve different purposes. PGT-A screens for chromosomal abnormalities, whereas PGT-M is aimed at preventing hereditary genetic diseases.

PGT-A detects chromosome number abnormalities without a genetic problem in the mother or father candidate. It is recommended in cases of recurrent miscarriages, recurrent IVF failures, or advanced maternal age.

By contrast, PGT-M investigates whether a known genetic abnormality in the mother or father candidate is present in the embryo. This test is performed if there is a child affected by a genetic disease or if the couple are carriers of the same genetic disease.

Therefore, while PGT-A performs general screening, PGT-M performs targeted analysis. Both tests go through the same biopsy process, but the laboratory analyses are different.

Why Is Embryo Genetic Testing Performed?

Embryo quality at advanced maternal age

As a woman’s age increases, DNA errors accumulate in egg cells. Since eggs accumulate genetic errors over the years, the risk of developing an abnormal embryo increases. While 70% of embryos in women in their twenties are euploid, the rate of euploid embryos drops to 25% at age 40.

The decrease in the chance of natural conception after age 35, the increase in infertility rates, and the rise in aneuploidy rates are due to the decline in egg quality with increasing maternal age. Therefore, women over 35 are candidates for PGT-A.

A large proportion of embryos formed in older women may have genetic abnormalities. Embryo genetic screening is especially recommended for women over 40. Even an embryo that looks good on visual inspection may carry chromosomal abnormalities, and in that case implantation may not occur or an early miscarriage may happen.

Prevention of recurrent pregnancy loss

Recurrent pregnancy loss refers to 3 or more pregnancy losses before 20 weeks. It is often seen up to the 12th week of pregnancy, and most cases are due to aneuploidy in the embryo.

With transfer, the chance of continuing the pregnancy with IVF treatment increases significantly, and the risk of miscarriage also decreases significantly.

Detection of hereditary diseases

In couples in whom one or both parents have a hereditary genetic disorder, the purpose of PGT-M is to identify the healthy embryo that does not genetically carry this disorder. PGT-M is not a general screening test; it investigates only the gene related to the disease present in the family.

If one of the couple has a known genetic problem, genetic analysis should be performed on the embryos. Since the baby’s genetic basis comes from the mother and father, if one of them has a problem, it may also be passed on to the baby.

Increasing the chance of a healthy pregnancy

It is expected that transferring a theoretically and genetically normal embryo reduces the risk of pregnancy loss and the complications that arise from it, and increases the chance of a healthy ongoing pregnancy.

According to a large-scale study conducted in the United States, the IVF success rate in IVF treatment with genetic screening was found to be approximately 65%, and the rate of having a healthy child was approximately 55%.

Transfer of a chromosomally normal embryo positively affects clinical pregnancy rates, especially in the older age group. Eliminating genetically abnormal embryos may reduce early pregnancy loss rates.

How Is Embryo Genetic Testing Performed?

Biopsy procedure and timing

In the IVF process, embryos fertilized in the laboratory are followed until day 5 or 6. During this process, a biopsy is taken from embryos that reach the blastocyst stage.

The total cell count of the blastocyst-stage embryo varies between approximately 60 and 125. At this stage, the embryo has separated into two different cell groups. The fetus develops from the inner cell mass, while the placenta develops from the trophectoderm cells.

The timing of the biopsy procedure is important for success. If PGT is performed on day 3 of embryonic development, the embryo, which is still in the division phase, may be damaged by this procedure.

Cell collection process

On day 5 or 6, 5–10 trophectoderm cells are separated from the blastocyst through the opening made using a micro-scale thin glass biopsy pipette. In blastocyst biopsy, cells are taken only from the trophectoderm cells, and the inner cell mass is not touched.

The advantage of this approach is that trophectoderm cells are sampled without causing any damage to the cells that will form the baby. Because the number of cells obtained by biopsy is high, the success of making a diagnosis in genetic examination increases. After the biopsy procedure, the rate of maintaining the embryo’s viability is close to 100%.

Laboratory analysis stage

The biopsied embryo is frozen while waiting for the result. The collected cells are isolated and prepared for genetic analysis.

Different analysis methods are used in the laboratory. The NGS method enables DNA sequencing in order to examine chromosome structures and abnormalities. aCGH can screen the embryo’s entire chromosome map for numerical and structural losses. SNP microarray analyzes genetic variants one by one.

Evaluation of test results

It takes an average of 14 days for the results to be processed and reported. Based on the genetic analysis results, healthy embryos are identified and selected for transfer.

The average clinical error margin of PGT tests worldwide is around 2%.

When a healthy embryo is identified by the genetic test, the uterus is prepared. Then the frozen healthy embryo is thawed and transferred. The fact that the transferred embryo is chromosomally normal increases the chance of pregnancy, but does not guarantee it.

Frequently Asked Questions

Many questions come to mind for couples considering embryo genetic testing during IVF treatment. Obtaining clear information about the safety, cost, and success rates of these tests helps you make the right decisions during the treatment process.

Does the test harm the embryo?

Thanks to modern biopsy techniques, it is a safe procedure for the embryo. When performed in experienced centers, it does not affect embryo development. The biopsy is taken from the outer cell mass of the embryo, which has more than 100 cells on day 5 or 6.

In experienced hands, biopsy does not harm the embryo. The rate of the embryo continuing to remain viable after biopsy is close to 100%.

However, as with any medical procedure, there are some risks. Even if at a very low rate, the embryo may be damaged during the procedure for technical reasons. This rate is less than 0.1%. An embryo observed to have been damaged is not used in analysis or treatment.

Which patients is it recommended for?

PGT is not routinely recommended for every IVF patient. Potential benefits are anticipated in certain patient groups. It is especially recommended for women of advanced maternal age, particularly expectant mothers aged 35 and over.

It is directed toward couples with recurrent pregnancy losses in order to achieve a healthy pregnancy. It increases the success rate in patients with recurrent IVF failures. It is especially beneficial for couples with a family history of genetic disease.

It may also be recommended for couples carrying chromosomal abnormalities, in cases of severe male factor infertility, and if there is a history of aneuploid pregnancy. In addition, it is applied when planning an HLA-matched sibling for a child who requires bone marrow transplantation.

What are the success rates?

Success rates are high in IVF treatment with genetic screening. According to a large-scale study conducted in the United States, the IVF success rate is approximately 65%, and the rate of having a healthy child is approximately 55%.

When a chromosomally normal single embryo is transferred, the average pregnancy rate is 70%. The pregnancy rate after 3 transfers reaches 95%, and after 5 transfers it can increase to 98%.

If chromosome screening is performed due to advanced maternal age or translocation, when a euploid embryo is identified, the chance of pregnancy can rise to 70–74% even above the age of 40. The risk of pregnancy loss also decreases from 25–40% depending on age to 8%.

How reliable are the test results?

Genetic tests have a high level of accuracy. They provide over 95% reliability in detecting chromosomal abnormalities and certain genetic diseases. Most genetic tests have high accuracy rates of 95% to 99%.

However, although the tests are very sensitive, there is a small margin of error. With the PGT method, the margin of error in diagnosis is 1–3%.

For this reason, routine pregnancy screenings and check-ups must definitely be carried out when pregnancy is achieved in those who have undergone PGT-A screening.

In summary, embryo genetic testing

Not every couple needs to have genetic testing. First, you should receive detailed genetic counseling. Discuss your situation with your doctor and evaluate whether these tests are appropriate for you.

Although the test results have a high level of accuracy, do not neglect routine check-ups during pregnancy. After all, the goal is to have a healthy baby, and it is important to evaluate each step correctly during this process.