PGT is a technique that can be used in a laboratory to check if an embryo has the genes for a severe disease.
This article is pending medical review.
Contributors
Written by Naisha Lalwani, Willemijn Bosschaert and Shukeea Alberto
Reviewed by Lea Dörner, Alessandra Papitto and Sophie Oppelt
Edited by Juliëtte Gossens
Pre-implantation genetic testing (PGT for short) is possible for people undergoing in vitro fertilization (IVF). It’s a screening procedure done in the laboratory. With it, the genetic profile of an embryo can be determined. It can also assess the probability of passing on a genetic abnormality to the embryo (1). This way, embryos can be selected that don’t carry the genes for a severe disease.
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What Is PGT?
If you plan to or are in the process of having a baby through in-vitro fertilization (IVF), you might want to know the health of the embryo, and if it is at risk for any possible diseases. That's especially if one already runs in the family. Or maybe you can have babies naturally, but there’s a severe disease that you or your partner are carriers of. Being a carrier means that you have genes that can lead to that disease in your baby. If so, you can consider pre-implantation genetic testing (PGT) for the embryo. Below, we explain what PGT is by summarizing the result of fertilization of an egg cell by a sperm cell.
Fertilization is a mostly random process, involving a sperm cell coming into contact with an egg cell, also known as an oocyte. We explain this process in more detail in this article. The result of fertilization is that the contents of the sperm cell and the egg cell (oocyte) fuse. The resulting cell is called a zygote, which divides itself lots of times to make more cells. It forms an embryo and, later, a fetus. The sperm cell and egg cell contain genetic material (chromosomes), which holds all the information that the zygote needs to grow.
Sometimes, this information has abnormalities in it. It could be that there are chromosome abnormalities, which affect lots of genes at once. It could also be that just one gene is affected, which can lead to a specific disease or syndrome. A sperm cell or an egg cell containing an abnormality is purely up to chance, because they’re made from half the genetic information of the rest of the cells in your body. Which half ends up in the sperm or egg cell can’t be predicted. This is also explained in this article. These abnormalities can include an oocyte being unable to complete maturation, which is needed to have successful fertilization. They could also lead to a problem that prevents the oocyte or embryo from developing further (2). Some egg cells can be fertilized regardless of having a genetic abnormality. This can later lead to development problems in the embryo, which could lead to a miscarriage. Finally, the abnormality in question could also lead to an embryo that can develop like normal in the womb, but leads to severe disease when the baby is born or when the child grows up.
In IVF (or ICSI), a sperm cell and an egg cell are brought together in the laboratory. The goal is that they form an embryo, which can then be implanted back into the uterus (womb). In PGT, one cell from the embryo is taken out, while the embryo itself continues to grow as normal. The removal of that cell is called an embryo biopsy. Depending on the stage of growth that the embryo is at, the extracted cell can be used to test for the presence of different genetic abnormalities. If the embryo doesn’t have the abnormalities that were tested for, it can be implanted into the uterus like in a regular IVF cycle (3). This also explains the name: the genetic testing of the embryo is done “pre” (meaning “before”) implantation.
What is the difference between PGD and the three different kinds of PGT?
Above, we talked about PGT. But you might have come across other acronyms and terms describing the same idea, but a little bit different execution.
PGD, also known as pre-implantation genetic diagnosis, used to be the “gold standard” when it came to pre-implantation testing possibilities. This term is often used in older textbooks and literature. It is used to describe the collection of different tests that we now have more specific terms for. These terms are PGT-SR, PGT-M and the PGT-A tests. The testing methods themselves remained the same or very similar (3). We’ll summarize these different tests below (4).
PGT-SR* is used to see if there are chromosomal abnormalities such as so-called translocations. In a translocation, one part of a chromosome is exchanged for a different part of the same or of a different chromosome. Sometimes, the part is lost altogether or re-attaches but upside down. In other cases, two chromosomes are fused together. All of these issues make it difficult or impossible for an embryo to develop normally and will, in many cases, lead to a miscarriage. This can happen as a one-off in that particular embryo, but it’s also possible that you or your partner carry such an abnormality in your cells without issues for yourself. That makes it more likely that many or all embryos created are affected.
PGT-A** looks for an incorrect number of chromosomes (aneuploidy). Normally, a healthy body cell (except for gametes) has two sets of 23 chromosomes. That’s 46 chromosomes in total. If an embryo forms from a sperm cell or an egg cell with a chromosomal abnormality, its cells could have a different number of chromosomes. Most of the time, that embryo won’t survive. In some cases, the baby can develop, but with issues. How severe those issues are, depends on which chromosomes are affected. Aneuploidy is more common in older women, because egg cell quality decreases with age. You can read more about aneuploidy here.
PGT-M*** is used when you or your partner are carriers of an hereditary disease that’s caused by a single gene (monogenic disease). The technique checks if an embryo also has the gene for this disease. This way, only unaffected embryos can be implanted back into the uterus. Sometimes, it’s OK if the embryo carries only a single copy of the gene, because the disease only develops if the embryo has two copies (one from both parents, if you’re both carriers). In other cases, even one copy of the gene can cause the disease, so the embryo shouldn’t have any copies.
* Pre-implantation genetic test for structural chromosomal rearrangements (PGT-SR)
** Pre-implantation genetic test for the analysis of aneuploidies (PGT-A)
*** Pre-implantation genetic test for monogenic diseases (PGT-M)
In theory, PGT-M could be used to select embryos with specific characteristics or traits, if the specific gene for that trait is known. But that’s a topic of controversy, and it’s illegal in most countries. If you want, you can think about this issue yourself – what could go wrong? In which ways could the technique be misused? Do you think you should be able to select desirable traits in your child?
Who Can Consider PGT?
Which people are eligible for PGT depends on the country. Some countries don’t allow some or all PGT techniques, or only for specific issues (5). In principle, you can only do PGT if you’re doing IVF, because the embryos need to be created and handled in the laboratory. In the Netherlands, for example, PGT is allowed for IVF patients. Some clinics and hospitals in the country will only refer you for PGT for specific indications. This could be the case for couples that have an increased risk for a specific genetic disorder. This can include people with a history of a genetic disorder in their family, people with a genetic disorder themselves, or people who already have a child with a genetic disorder. A history of miscarriage will also sometimes be a reason to undergo PGT (3).
When Is PGT Done?
Before PGT can be done, you will have to undergo all preparatory steps of IVF. You can read more about those in this article and this article (up to embryo transfer). The first step of PGT is to obtain cells from the embryo that was created in the laboratory. This step is usually performed on day 3, 5 or 6 of embryo development (at that stage, it’s called a blastocyst). The cells will then undergo genetic analyses in the lab. Results from the analyses will typically be available within 7 to 10 days afterward, but it could take several weeks. If necessary, the embryos will be frozen in the meantime. PGT will help to choose a healthy embryo which can then be transferred to the parent for pregnancy (3).
Advantages and Limitations
It's reliable
One advantage of PGT is that it’s 95-98% reliable (sensitive) (6). This means that there is only a 2-5% risk that the test hasn’t detected the genetic abnormality in the embryo that was being tested for, even though the abnormality is actually present (a so-called false-negative result). That’s typically a much lower chance to have a baby with an abnormality than if you were to leave it up to chance during a completely natural pregnancy.
It's safe for baby
Another advantage is that there have been no documented adverse health effects of PGT on the embryos or, later, on the children. There is no evidence that embryos exposed to IVF and PGT are at a higher risk of genetic anomalies than those not exposed to it. Children exposed to PGT have also been reported to have the same rate of development as those who were not exposed to PGT (3). A review published in 2018 that studied 400 PGT pregnancies found no health problems among the embryos or children, either (7).
You're (more) in control
Of course, it’s also an advantage that parents have to worry much less about the health of their future children if they carry a genetic abnormality that can cause severe disease. Using PGT, they can have more control over their children’s health outcomes.
You might be more at risk
It's important to note, however, that the health risks of the testing for the embryo are separate from the health risks for the pregnant person. Some studies have associated PGT with pre-term pregnancies and hypertension in the mother, in addition to the increased risks associated with IVF only (3, 8). The fact that PGT is only possible in combination with IVF is another disadvantage, because the process can be a strenuous one, both physically and mentally.
Some embryos may be lost
The process itself could also cause damage to the embryo through the preparatory processes, leading to approximately 3% of embryos being lost before the transfer (9).
Lower chance of pregnancy
Another disadvantage is that PGT has only a moderate chance of leading to a successful, healthy pregnancy. Each PGT procedure has a 20% success rate (6). That’s a bit lower than most people’s natural chances of becoming pregnant, which are around 30% every month (10). But if you were already infertile (or subfertile), this success rate might be higher than your natural chances. Your personal chances could be different still, so if you want to know more, you should talk to your doctor.
Ethical considerations
Lastly, PGT carries ethical and moral implications. That’s not a disadvantage or an advantage, but it is something to consider. Especially if you and your doctor are unsure of what a given genetic abnormality might mean for your child, selecting an embryo based on only this factor isn’t a guarantee that your child will be healthy. It’s possible that the embryo that doesn’t have that genetic abnormality, has other problems that weren’t tested for, for example. Or has problems that aren’t genetic. You’ll never know if a different embryo that did carry the abnormality would have been more or less healthy. It’s a good idea to think about these issues, talk to your partner and your doctor about it, and think it over before you make your decision. Whatever decision feels best to you, is the right decision!
References
Harper JC, SenGupta SB. Preimplantation Genetic diagnosis: State of the art 2011. Human Genetics. 2012;131:175-186. DOI: 10.1007/s00439-011-1056-z.
Hatırnaz Ş, Hatırnaz ES, Ellibeş Kaya A, Hatırnaz K, Soyer Çalışkan C, Sezer Ö et al. Oocyte maturation abnormalities - a systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina. Turkish Journal of Obstetrics and Gynecology. 2022;19(1):60-80. DOI: 10.4274/tjod.galenos.2022.76329.
Schattman GL, Xu K. Preimplantation genetic testing. In: Wilkins-Haug L, Barss VA (eds.). UpToDate. 2022.
Griffin DK, Ogur C. PGT-SR: A comprehensive overview and a requiem for the interchromosomal effect. DNA. 2023;3(1):41-64. DOI: 10.3390/dna3010004.
Ginoza MEC, Isasi R. Regulating Preimplantation Genetic Testing across the World: A Comparison of International Policy and Ethical Perspectives. Cold Spring Harbor Perspectives in Medicine. 2020;10(5):a036681. DOI: 10.1101/cshperspect.a036681.
Maastricht University Medical Center. PGT and IVF. https://info.mumc.nl/pub-1654 [Accessed May 24th, 2023].
Heijligers M, Montfoort A van, Meijer-Hoogeveen M, Broekmans F, Bouman K, Homminga I et al. Perinatal follow-up of children born after preimplantation genetic diagnosis between 1995 and 2014. Journal of Assisted Reproduction and Genetics. 2018;35:1995-2002. DOI: 10.1007/s10815-018-1286-2.
Zhang WY, Von Versen-Höynck F, Kapphahn KI, Fleischmann RR, Zhao Q, Baker VL. Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertility and Sterility. 2019;112(2):283-290.E2. DOI: 10.1016/j.fertnstert.2019.03.033.
Washington University School of Medicine. Preimplantation Genetic Testing - FAQ. https://fertility.wustl.edu/treatments-services/genetic-counseling/preimplantation-genetic-testing-faq/ [Accessed May 24th, 2023].
Taylor A. ABC of subfertility: Extent of the problem. BMJ. 2003;327(7412):434-436. DOI: 10.1136/bmj.327.7412.434.
Please note: the information we provide to you here is for educational purposes only. If you’re experiencing any discomfort or have any complaints or questions about your health, please contact your doctor or other relevant health professional. We don’t provide medical advice.