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.

PGT may be particularly important for couples with:

a known inherited condition in the family,

recurrent miscarriage,

previous unsuccessful IVF treatment, or

an increased likelihood of embryos with chromosomal abnormalities.

Preimplantation genetic testing does not guarantee pregnancy or the birth of a healthy child. When clearly indicated, however, it can support treatment planning, more informed embryo selection, and reduction of specific genetic risks.

Preimplantation genetic testing: what it is and when it is used

Preimplantation genetic testing, or PGT, examines embryos created through IVF before they are transferred to the uterus.

In simple terms, PGT can assess whether an embryo has the expected genetic material or a specific genetic or chromosomal abnormality. This may help select embryos with a better chance of a healthy pregnancy or avoid transmission of a serious inherited condition.

The term PGT is now used instead of the older terms PGD and PGS, in line with current international terminology for infertility and IVF [1].

The main types of PGT

1. PGT-A: testing chromosome number

PGT-A PGT-A assesses whether an embryo has the expected number of chromosomes.

A chromosomally normal embryo usually has 46 chromosomes. An embryo with additional or missing chromosomal material is described as aneuploid. This can lead to implantation failure, miscarriage, or, less commonly, the birth of a child with a chromosomal condition.

PGT-A may be discussed in situations such as:

  • advanced maternal age,
  • recurrent miscarriage,
  • repeated unsuccessful embryo transfers,
  • severe male-factor infertility.

It is important to understand that PGT-A does not improve or treat an embryo. It does not correct chromosomal abnormalities; it helps identify embryos that appear chromosomally normal. Its value should be assessed individually, particularly when only a small number of embryos are available [5,9–11].

2. PGT-M: testing for a specific inherited condition

PGT-A PGT-M is used when a known genetic condition runs in the family or when the intended parents carry a serious inherited condition.

Examples include:

  • beta thalassaemia,
  • cystic fibrosis,
  • Duchenne muscular dystrophy,
  • Huntington’s disease,
  • selected hereditary cancer syndromes.

The aim of PGT-M is to identify embryos that are not affected by the specific condition. Depending on the condition and genetic counselling, an embryo that is an unaffected carrier may sometimes be considered [5–8].

3. PGT-SR: testing for structural chromosomal rearrangements

PGT-A PGT-SR is used when one intended parent has a chromosomal rearrangement such as:

  • a balanced translocation,
  • an inversion,
  • a deletion or duplication of part of a chromosome.

The parent may be healthy but produce embryos with unbalanced chromosomal material, which can lead to miscarriage or unsuccessful treatment.

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

How is PGT performed?

Embryos are usually cultured to the blastocyststage, approximately five or six days after fertilisation.

A biopsy is then performed: a small number of cells are taken from the embryo’s outer layer, called the trophectoderm. This layer mainly develops into the placenta rather than the fetus.

The cells are sent for genetic analysis, and the embryos are usually frozen while the results are awaited. Blastocyst biopsy is currently the most commonly used approach, particularly for PGT-A [13,17,18].

What are the limitations?

PGT is valuable, but it is not a perfect test.

Possible limitations include:

  • it does not detect every possible genetic condition,
  • mosaicism, where different cells from the same embryo may have different chromosomal results,
  • a small possibility of a false-positive or false-negative result,
  • additional IVF costs,
  • no guarantee of pregnancy or the birth of a healthy child.

Clear information and genetic counselling are therefore important before deciding to proceed [8,12].

What about non-invasive PGT?

Non-invasive methods are being studied in which genetic material in the embryo-culture medium is analysed instead of taking an embryo biopsy.

This approach is promising, but it has not replaced blastocyst biopsy because questions remain about reliability and possible contamination [23–35].

Is prenatal testing needed after PGT?

In most cases, prenatal screening or diagnostic testing should still be discussed during pregnancy.

PGT can substantially reduce a specific risk, but it cannot exclude every genetic or chromosomal condition. Decisions about NIPT, ultrasound screening, or invasive prenatal diagnosis should be individualised [52–54].

In simple terms

PGT is genetic testing of embryos before embryo transfer.

It may help to:

  • reduce the risk of transmitting a serious inherited condition,
  • identify chromosomally normal embryos,
  • reduce miscarriage risk in selected cases,
  • avoid embryo transfers involving embryos with no realistic developmental potential.

PGT is not a cure-all. It does not treat embryos and cannot guarantee pregnancy. Used appropriately and for a clear indication, it can support better-informed treatment decisions.

Ioannis A. Sklavounos MD MSc DFFP
Consultant Obstetrician and Gynaecologist
Specialist Training and Fellowship in the United Kingdom
T.Senior Clinical Fellow – Liverpool Woman’s Hospital UK

References

  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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