In this episode of DNA Today's series about infertility, certified genetic counsellor Jennifer Eccles, head of genetic counselling at Genomic Prediction, put her case for a new type of preimplantation genetic testing (PGT) called PGT-P. The term PGT-P has been coined to describe how polygenic risk scores are used to assist with embryo selection. Eccles explained that PGT-P is proposed as an additional test result for patients already undergoing PGT for diagnosing embryos with a genetic disease or screening embryos for chromosome balance.
Eccles opened with an overview of the different types of PGT available, explaining that the letter hyphenated to PGT signifies the type of testing reported for an embryo. For example, PGT-M tests for monogenic genetic disease designed for single-gene disorders such as cystic fibrosis. It was explained that polygenic testing has been around for some time for conditions influenced by multiple genes such as schizophrenia, type one diabetes and certain types of heart disease. Eccles emphasised that unlike established types of PGT, PGT-P 'is a whole different ball game, new in terms of the IVF world', with the first treatment cycle reported in 2019.
The concept of 'risk' is fundamental to understanding PGT-P. Embryos are not scored on attributes such as height or intelligence, but instead they are assessed clinically for a handful of health conditions including type one and two diabetes, schizophrenia, certain cancers, coronary heart disease and high cholesterol. The technology does not sequence the code of individual genes, but identifies over 800,000 small gene changes called single nucleotide polymorphisms (SNPs) tiled across the genome. Bioinformatic algorithms calculate a risk score from the similarities and differences in SNP profiles associated with certain conditions. Eccles clarified that the source of the data associating specific SNPs with a disease risk originated from the UK biobank.
It is important to emphasise that PGT-P is best characterised as a form of screening rather than testing. It does not provide a definitive test result, but instead offers a method of assessing the 'risk' of disease for embryos. According to Eccles, the objective is 'to provide patients with information they can use to prioritise embryos for transfer that have the lowest risk of developing the diseases scored for during their lifetime'. Eccles explained that although some families may have a family history of a specific polygenic condition which they wish to avoid, the second iteration of PGT-P will provide a single generalised number, that combines the scores of different polygenic conditions to evaluate risk. Eccles claimed this score would provide a more comprehensive figure for embryo triage.
Eccles illuminated the benefits of complementing traditional forms of PGT with PGT-P, however, the reality of integrating PGT-P into the IVF cycle is complex. For example, for patients who have underlying polygenic risk in their family history, PGT-P may be an additional concern during complex IVF treatment. Further, the psychological impact on patients with only one or two embryos with high PGT-P scores was not acknowledged. Eccles highlighted though, that the emergence of these additional considerations adds weight to the importance of genetic counselling services, consideration of family history and the patient's situation. All patients having PGT-P currently speak with Eccles to discuss the benefits and limitations for informed consent.
Eccles explained that as testing needs to be incorporated into the IVF cycle, patients who are already having embryos biopsied can opt to add PGT-P to the reporting. Adding PGT-P does not require an additional invasive measure, only saliva DNA samples from the egg and sperm providers. Controversially, Eccles suggested that couples who are not experiencing infertility or at risk of passing down genetic disease might choose to undergo IVF solely to reduce polygenic risk.
Eccles claimed that, in time, increased data from biobanks would identify SNPs that give more accurate risk scores or new associations of particular SNPs with specific diseases. She advised data currently indicates that a combined risk score appears to be stronger than separating the score for individual disease. General good health, for one thing, may impact good health for another. Looking to the future, Eccles explained it is not known if the implantation potential of embryos with better 'P' scores is improved. A study to investigate this has been approved and will start this year.
The podcast concluded with a question from the host about the cost of PGT-P. Eccles explained this is variable. Currently, the clinic does not charge if a patient is already having PGT-M. However, there is a cost for the test design for patients having PGT-A. US health insurance does not cover PGT-P. Nevertheless, Eccles is keen to work with insurance providers to fund it, arguing the long term cost saving due to reduced disease burden. The Scientific and Clinical Advances Advisory Committee (SCAAC) of the Human Fertilisation and Embryology Authority (HFEA) in the UK, noted in February 2020 that PGT-P is on the horizon. The adoption of PGT-P in the UK, with its marketing and regulation, is a topic that will require careful consideration, consultation of the evidence base and fervent discussion.