Written by Dr. Phoebe Howells, with added insight from Jenny Wordsworth. 

Preimplantation genetic testing (PGT) is a type of procedure used in IVF in order to identify atypical fertilisation. The goal is to identify embryos with the correct number of chromosomes (euploid embryos) and avoid transferring embryos that are chromosomally atypical (aneuploid embryos). This can potentially reduce the risk of miscarriage and improve the chances of a successful live birth.

The different types of PGT tests

• PGT-A (Aneuploidy) This type of PGT screens embryos for certain chromosomally atypical embryos. Human embryos typically have 23 pairs of chromosomes (46 total) in each cell.  One chromosome in each pair is contributed by the egg, and the other is contributed by the sperm.  It is common for embryos to have random chromosome atypicalities such as a missing or extra chromosome, which is called aneuploidy.  In the majority of cases, these chromosomally atypical embryos happen by chance and are not inherited from a parent or donor.  Embryos with aneuploidy are more likely to result in miscarriage or a failed transfer.  Some types of aneuploidies may result in the birth of a baby with a chromosome condition such as Down syndrome or Turner syndrome.

• PGT-M (Monogenic) This is an option for those patients with an increased risk of a single gene disorder such as cystic fibrosis or sickle cell anaemia.

• PGT-SR (Structural rearrangements) This type of PGT is performed when a patient or their partner has a rearrangement of their own chromosomes such as a translocation or inversion.  A person with a translocation or inversion is at increased risk to produce embryos with missing or extra pieces of chromosomes. Embryos with missing or extra pieces of chromosomes are more likely to result in miscarriage, stillbirth, or a child with serious health issues.

How does PGT work?

The patient goes through the IVF cycle and egg collection process. Once the embryo is created by combining with the sperm, a few cells (usually 5-10 cells) are taken from the embryo. The cells are taken from a part of the blastocyst called the trophectoderm, which will eventually form the placenta.  These cells are expected to be representative of the rest of the embryo, however, this may not always be the case due to circumstances such as mosaicism which we will talk about later. Whilst waiting for the result the embryos will be frozen. Once an embryo has been classified as euploid it can then be defrosted and transferred in a frozen embryo cycle. 

For PGT-M, there may be an extra wait whilst the laboratory confirms if they will be able to reliably detect the specific genetic condition in the patient’s embryo(s).  The test development phase can take up to 6-12 weeks after all required DNA samples are received.  This process must be fully completed before an IVF cycle (stimulation medications) can be started.

Who Might Benefit from PGT?

The decision to have testing is complex and should be made after careful discussion with a fertility specialist and counsellor. PGT is particularly beneficial for women and people over the age of 37, as the likelihood of chromosomally atypical embryos increases with age. It may also be helpful for those with a history of recurrent miscarriages or those who have recurrent implantation failure. Some individuals come to the clinic with a history of a personal or family history of a genetic disorder therefore they may require PGT to check which embryos have a specific condition. 

Age brackets and the percentage rates of Aneuploid:

• 30 years old – 33%

• 30-34 years old – 38%

• 35-37 years old – 47%

• 38-40 years old – 60%

• 41-42 years old – 76%

• 43 years or older at the time of egg retrieval – 84%

Limitations of PGT

Whilst PGT has its advantages in that it can increase the likelihood of a successful pregnancy by transferring a euploid (normal number of chromosomes) embryo, it does not guarantee a pregnancy. There is also a small risk of damaging the embryo when undertaking the biopsy. Additionally, since the embryo must be frozen while PGT is being performed, they must also undergo a thawing procedure prior to transfer. The survival rate varies between centres but is around 97%.

Along with PGT also come the ethical and emotional considerations, that it is a complex decision deciding which embryos will be discarded and which will be implanted. 

There is a small (1%-2%) chance the lab may get inconclusive results for an embryo meaning they are unable to determine whether the embryo is chromosomally normal or atypical. 

Finally, although uncommon, inaccurate PGT results (i.e. false positives and false negatives) may lead to the transfer of a chromosomally atypical embryo that was not detected or the decision not to use an embryo with the potential to result in a healthy pregnancy.

Why Some Clinics Wait Before Discarding Embryos

One area of active discussion in fertility clinics is how many embryos are tested and when. Some clinics may biopsy embryos at day 5 regardless of their development, while others prefer to give embryos longer to grow before making decisions. A “keep everything and allow them to grow” approach can sometimes mean embryos that might otherwise have been discarded are given a chance to develop further and self-correct. This is particularly relevant for embryos that develop more slowly, or for those that initially show signs of atypical fertilisation. Waiting a little longer before testing or discarding may lead to better outcomes for some patients, but again, it depends on the clinic and the individual case.

Understanding your Results

When you get your results, it will either tell you if the embryo is Euploid (genetically normal) and these can be considered for transfer. Alternatively, they may be aneuploid (genetically atypical) or that they have a mosaic result. Aneuploid embryos are not recommended for transfer as they will have a low chance of resulting in a successful pregnancy. 

Mosaicism refers to a mixture of two or more types of cells within the same embryo. Some of the cells may be chromosomally normal (euploid) and some atypical (aneuploid). The 5-10 biopsied cells may not represent the whole embryo therefore could result in false positive or negative results. If you do receive these results, then you will need to have a detailed discussion with a genetic counsellor.

Questions to ask your clinic about PGT and atypical fertilisation

If you've had embryos with atypical or unexpected fertilisation results, or you're considering PGT, these questions can help you better understand your clinic's approach. It’s okay if their answers don’t align with your needs. Every clinic is different.

• What happens to embryos that don’t appear ‘normally’ fertilised? Are they discarded straight away?

• Do you offer PGT-A, and in which situations would you recommend it?

• Does your clinic use time-lapse imaging to monitor embryo development?

• Is your genetics lab able to perform molecular checks to confirm whether fertilisation was normal?

• Will you freeze and grow embryos that don't meet standard fertilisation criteria?

• Do you ever re-biopsy embryos or offer further testing if results are inconclusive?

• How do you approach mosaic embryos? Are they automatically excluded, or discussed case-by-case?

• What is your lab’s threshold for transferring embryos with lower grading or developmental delays?

A parting thought about PGT-A and the HFEA

Currently, the HFEA (the UK fertility regulator) classifies PGT-A as a treatment that is “uncertain whether it’s effective”, and that’s after reviewing the available evidence in detail. It’s a reminder that while this is a promising technology, it’s not a silver bullet. Success still depends on many factors: the quality of eggs and sperm, the embryo’s development, the clinic’s expertise, and a whole lot of biology we still don’t fully understand.

Jenny’s note: From our conversations with fertility experts, it’s clear that PGT-A can be helpful in specific scenarios, especially when guided by an experienced lab and a personalised approach. But it also has the potential to reduce your embryo pool unnecessarily. If you're considering it, we’d recommend speaking with your clinic to understand their philosophy around embryo development, how they interpret PGT-A results, and whether they offer embryo re-biopsy or mosaic embryo transfers.

Key Takeaways on PGT

PGT represents a significant advancement in fertility treatment, offering hope to many patients. However, it’s crucial to have thorough discussions with your fertility specialist to understand whether PGT is the right choice for your unique circumstances. Every fertility journey is personal, and making informed decisions is key.