Genetic testing in reproduction

Genetic testing of embryos

Genetic testing of embryos before implantation (PGT)

Genetic testing of preimplantation embryos (PGT) involves the analysis of cells extracted from embryos obtained by in vitro fertilization, before their implantation in the uterus.

Given the invasiveness of the technique, the high costs and the risk of reducing the number of viable embryos for embryo transfer, these tests are not routinely performed, but are recommended based on genetic counseling, when there is an increased risk of embryonic genetic abnormalities.

The tested embryos are not transferred to the uterus immediately after the biopsy but are frozen to wait for the test results.

What are the most used tests and what is the difference between PGT-M, PGT-SR and PGT-A? PGT-M

PGT-M

(Preimplantation genetic testing – for monogenic defects, of a single gene) is the technology used in case of hereditary diseases already detected in the couple’s family (for example, thalassemia or cystic fibrosis).

If one or both partners are carriers of genetic mutations, the child may be affected by that hereditary disease. Preimplantation testing allows the detection of mutations associated with hereditary disease and the removal of affected embryos.

How is genetic testing of embryos done?

During laboratory development, embryonic cells divide and multiply. The embryo is in continuous formation in the first weeks after conception, having the possibility to repair or eliminate certain defective cells. In the same embryo, at some point in development, normal and genetically abnormal cells can coexist (an aspect called mosaicism). To avoid genetic contamination of embryos, they are not obtained by standard IVF, but a micromanipulation technique is used – ICSI. Also, in order for the embryo test to give a relevant result, not a single cell is analyzed; several cells are extracted from each embryo for testing.

 

    

Does genetic testing of embryos increase the overall chance of success of the IVF procedure?

Genetic testing is an investigation, not a treatment. Embryos are not “improved”, but only further analyzed. The chance of success is not higher than in the case of IVF without genetic testing, it can be even lower, given that it involves invasive maneuvers on embryos and reduces the number of embryos available for embryo transfer. The selection of embryos based on genetic analysis does not guarantee that they will be implanted and further developed, nor does it exclude other genetic abnormalities that have not been tested.

Can genetic testing be done on oocytes only?

It is possible to test only the oocytes before fertilization. This test does not assess the father’s contribution to the formation of genetically abnormal embryos or abnormalities that occur after fertilization.

PGT-SR

(Preimplantation genetic testing – for chromosomal structural rearrangements) is addressed to known carriers of chromosomal rearrangements, usually balanced. PGT-SR is used to detect and eliminate abnormal embryos in an unbalanced form, in which parts of the chromosomes are affected or missing.

When is biopsy and embryo testing done?

In order not to affect the evolution of the embryo and to provide the most representative result, the biopsy (cell extraction) should be done at an advanced stage of development and only if there are enough cells left to allow the survival and further development of the embryo. .

Although it can be done at 72 hours, currently the genetic testing technique is recommended only for embryos in the blastocyst stage, after 5 days of evolution. The biopsied blastocysts are cryopreserved to wait for the result of the genetic analysis. The intrauterine transfer of the embryo selected on the basis of the test is done in another cycle, after thawing.

What are the limits of PGT?

The preimplantation embryo testing procedure does not guarantee pregnancy and does not rule out the risk of miscarriage, ectopic pregnancy, fetal malformations or other pregnancy complications.

As with any laboratory method, there are limits and risks, including:

  • In the case of mosaicism (normal cells and abnormal cells present in the same embryo), testing may result in inconclusive or difficult to interpret results.
  • False-positive or false-negative results are not excluded
  • For some embryos no results can be obtained from the tested cells (2-5% of embryos)
  • Stopping the embryo from evolving after biopsy and freezing / thawing cannot be ruled out

Before deciding to make the TMP, it is necessary to understand the following:

  • If the number of blastocysts is low, no embryo transfer embryo may remain after testing.
  • Some embryos, even if genetically selected, may not survive cryopreservation
  • There is a risk of unexpected discoveries for the couple and genetically related people, with the detection of a medically significant genetic risk.
  • Genetic testing of preimplantation embryos does not replace testing during pregnancy by standard prenatal techniques; this test is recommended even if PGT has been performed.
PGT-A

(Preimplantation genetic testing – for aneuploidies) allows the detection of changes in the number or size of chromosomes (structures containing several hundred genes), often associated with fetal diseases or miscarriage (such as Down syndrome).

It is addressed especially to couples with repeated reproductive failures and increased risk of chromosomal abnormalities.

Acquired genetic defects can occur spontaneously and randomly, the risk increasing significantly with the age of the parents.

What extra steps must a couple performing preimplantation genetic testing do?

In order to resort to preimplantation testing, a medical indication from a specialist, genetic counseling and genetic testing of both partners is required before the IVF procedure.

Last but not least, the costs of genetic testing of embryos, in addition to the IVF / ICSI procedure with embryo freezing and transfer of frozen embryos, must be taken into account.

Are there more methods of genetic testing of preimplantation embryos?

There are different technologies for detecting genetic abnormalities, each method having specific indications, advantages and limitations. The techniques used in preimplantation genetic testing are:

  • FISH (Fluorescent in situ hybridization)
  • aCGH (Array Comparative Genomic Hybridization)
  • NGS (Next-generation sequencing) – the latest technology in practice

Non-invasive methods of testing embryos without embryonic biopsy are currently being studied, but the technique is still experimental and requires refinement before it can be used routinely.

What alternatives are there for genetic testing of embryos?

Genetic testing can be done in the first months of pregnancy, by standard, non-invasive or minimally invasive methods.

  • In the 10-11th week of pregnancy, the pregnant woman can do a non-invasive prenatal blood test. Some fetal cells can reach the mother’s blood and can be identified and genetically tested. If a severe abnormality is detected, abortion may be recommended.
  • In the 12-13th week of pregnancy, the genetic test can be done by chorionic villus biopsy, from the placenta.
  • After the 15th week of pregnancy, the test is done from amniotic fluid, by amniocentesis.