Preimplantation genetic testing

Pre-implantation genetic testing is a specialized procedure applied to embryos created through IVF or microinsemination (ICSI). Its aim is to check the embryos genetically before the embryo transfer, so that they can be selected those that have the best conditions for transfer to the uterus.

This method can be particularly important for couples with:

- known genetic problem in history,

-repeated miscarriages,

-Previous failed IVF attempts or

-Increased chance of creating embryos with chromosomal abnormalities.

Pre-implantation genetic testing is not a guarantee of pregnancy or the birth of a healthy child. It is, however, a valuable tool that can help in better treatment planning, more targeted selection of embryos and reducing specific genetic risks when there is a clear indication.

Pre-implantation genetic testing: what is it and when it is used

The preimplantation genetic testing, or PGT, is an examination done on embryos created by IVF, before they are transferred to the uterus.

Simply put, it helps us see if a fetus has normal genetic material or if it carries a specific genetic or chromosomal abnormality. So we can choose for embryo transfer the embryos that have the best chance of leading to a healthy pregnancy or to avoid the transmission of a serious hereditary disease.

The term PGT used today instead of older terms PGD and PGS, according to the latest international terminology for infertility and IVF [1].

The Basics of PGT

1. PGT-A: chromosome number control

The Pgt-A Checks if the fetus has the correct number of chromosomes.

A normal fetus must have 46 chromosomes. When there is more or less chromosomal material, the fetus is called aneuploid. This can lead to implantation failure, miscarriage or, more rarely, the birth of a child with chromosomal syndrome.

PGT-A can be discussed in cases such as:

  • Increased age of woman
  • repeated miscarriages
  • Repeated failed embryo transfers
  • Severe male infertility factor.

But it is important to emphasize that PGT-A Does not improve the fetus itself. It does not "correct" chromosomal problems. It simply helps to select the fetus that looks chromosomally normal. Its usefulness must be individualized, especially when there are few embryos available [5,9–11].

2. PGT-M: Control for specific inherited disease

The pgt-m It is used when there is a known genetic disease in the family or when the parents are carriers of a serious hereditary condition.

Examples:

  • Mediterranean anemia
  • cystic fibrosis
  • Duchenne Muscular Dystrophy
  • Huntington's disease
  • Certain hereditary cancer syndromes, in selected cases.

The purpose of PGT-M is to select embryos that They do not suffer from this particular disease. In some cases, a fetus can also be chosen, which is a simple carrier, but does not get sick, depending on the disease and genetic counseling [5–8].

3. PGT-SR: Control for chromosomal rearrangements

The PGT-SR It is used when one of the two parents has a chromosomal rearrangement, such as:

  • balanced shift
  • inversion
  • Lacking or doubling of part of a chromosome.

In such cases the parent may be healthy, but produce embryos with unbalanced genetic material. This can lead to miscarriages or failed attempts.

PGT-SR helps to select embryos with normal or balanced chromosomal material [5,6,8].

How is the audit practically done?

Usually embryos are cultivated until the stage of blastomist, i.e. about the 5th or 6th day after fertilization.

Then a biopsy is done: few cells are taken from the outer part of the fetus, called trophy. From this part later mainly the placenta is formed, not the fetus itself.

The cells are sent for genetic analysis and the embryos are usually frozen until the results are out. Blastocyst biopsy is now considered the most commonly used method, particularly for PGT-A [13,17,18].

Are there any restrictions?

Yes. PGT is a valuable tool, but it's not perfect.

Possible limitations:

  • not detect all possible genetic problems
  • There is a possibility of mosaicism, i.e. different cells of the same embryo have a different genetic effect
  • there is little chance of a false positive or false negative result
  • Increases the cost of IVF
  • It does not guarantee pregnancy or the birth of a healthy child.

That is why proper information and genetic counseling is needed before the decision [8,12].

What about non-invasive PGT?

In recent years, non-invasive methods have been studied, where instead of a biopsy by the fetus, genetic material found in the embryo culture fluid is analyzed.

This method is promising, but at the moment it is not considered to have replaced the classic blastocyst biopsy, because there are still questions of reliability and possible contamination [23–35].

Should prenatal testing be done after PGT?

Yes, in most cases it is recommended to discuss prenatal screening in pregnancy as well.

This is because PGT significantly reduces the risk, but does not exclude any possible genetic or chromosomal abnormality. The decision for NIPT, ultrasound screening or invasive prenatal testing should be done individually [52–54].

In very simple words

PGT is a genetic testing of embryos before embryo transfer.

It can help:

  • reduce the risk of a serious inherited disease
  • Select chromosomal normal fetuses
  • in some cases reduce the risk of miscarriage
  • To avoid unnecessary embryo transfers with embryos that have no chance of development.

But it's not a panacea. It does not cure fetuses and does not guarantee pregnancy. It is a tool that, when used correctly and in the right cases, can significantly help make better decisions.

Ioannis A. Sklavounos MD MSC DFFP
Obstetrician Surgeon Gynecologist
Specialists & Retrained in Great Britain
T.Senior Clinical Fellow – Liverpool Woman’s Hospital UK

Bibliography

  1. Zegers-Hochschild F, Adamson GD, Dyer S, et al. The International Glossary on Infertility and Fertility Care, 2017. Human Reproduction. 2017;32:1786–1801.
  2. Eshre PGT Consortium Steering Committee, Carvalho F, Coonen E, Goossens V, et al. Eshre PGT Consortium Good Practice recommendations for the organization of PGT. Human Reproduction Open. 2020;2020:HOAA021.
  3. Xu CM, Lu SJ, Chen SC, et al. Preimplantation Genetic Testing Guidelines of International Society of Reproductive Genetics. Reproductive and Developmental Medicine. 2023;7:3–11.
  4. Giuliano R, Maione A, Vallefuoco A, Sorrentino U, Zuccarello D. Preimplantation Genetic Testing for Genetic Diseases: Limits and Review of Current Literature. Genes. 2023;14:2095.
  5. Simopoulou M, Sfakianoudis K, Maziotis E, et al. PGT-A: Who and when? A Systematic Review and Network Meta-Analysis of RCTS. Journal of Assisted Reproduction and Genetics. 2021;38:1939–1957.
  6. Munné S, Kaplan B, Frattarelli JL, et al. Preimplantation Genetic Testing for Aneuploidy Versus Morphology as Selection Criteria for Single Frozen-Thawed Embryo Transfer. Fertility and Sterility. 2019;112:1071–1079.
  7. Mahesan AM, Chang PT, Ronn R, Paul ABM, Meriano J, Casper RF. Preimplantation Genetic Testing for Aneuploidy in Patients with Low Embryo Numbers: Benefit or Harm? Journal of Assisted Reproduction and Genetics. 2022;39:2027–2033.
  8. Leigh D, Cram DS, Rechitsky S, et al. PGDIS Position Statement on the Transfer of Mosaic Embryos 2021. Reproductive Biomedicine Online. 2022;45:19–25.
  9. Eshre PGT Consortium Data Collection XVI–XVIII.
  10. Eshre PGT Consortium Data Collection XXI.
  11. Eshre PGT Consortium Data Collection XIX–XX.
  12. Studies on prenatal screening after IVF with PGT-A.
  13. Society of Obstetricians and Gynaecologists of Canada Recommendations.
  14. American College of Obstetricians and Gynecologists Guidance on Prenatal Screening After PGT.
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