Ethical Considerations of PGT-P for Polygenic Risk Scoring

PGT-P (preimplantation genetic testing for polygenic risk scoring) is a relatively new addition to the range of genetic tests available during IVF. Unlike PGT-A (which screens for chromosomal abnormalities) or PGT-M (which targets specific single-gene disorders), PGT-P aims to estimate the likelihood that an embryo might develop certain common conditions, such as type 2 diabetes, heart disease, or some cancers, based on a combination of many genetic variants. While the technology is intriguing, it also brings a host of ethical considerations that you should understand before deciding whether to pursue it. This guide offers a balanced overview of the controversy, the limitations, and the questions you may want to discuss with your clinic.

At a glance: key ethical points

• PGT-P provides a risk score, not a diagnosis. It cannot tell you whether an embryo will definitely develop a condition.
• The predictive value of polygenic risk scores is limited and varies by condition and population.
• There are concerns about potential discrimination, both in insurance and in family dynamics.
• Genetic counseling is essential to help you interpret results and make informed decisions.
• Regulations and availability of PGT-P vary by country and clinic; you should confirm what is offered and under what conditions.

What is PGT-P and how does it differ from other PGT tests?

PGT-P is designed to assess the cumulative effect of many genetic variants that each have a small influence on the risk of developing a common, complex condition. This is different from PGT-A, which looks at the number of chromosomes in the embryo to identify aneuploidy (an abnormal number of chromosomes), and PGT-M, which targets a specific mutation known to cause a monogenic disorder. PGT-P uses a polygenic risk score (PRS), which is calculated by comparing the embryo’s genetic profile to data from large studies that have linked certain variants to a condition.

It is important to note that PGT-P is not a diagnostic test. A high PRS does not mean the embryo will develop the condition, and a low PRS does not guarantee that it will not. The score is a probabilistic estimate, and many environmental and lifestyle factors also play a role in the development of these conditions.

The controversy: limited predictive value

One of the main ethical concerns about PGT-P is its limited predictive value. For many conditions, the genetic variants identified so far explain only a small fraction of the heritability. This means that a PRS may not be very accurate in predicting an individual embryo’s future health. The predictive power also varies across different ethnic populations, as most genetic studies have been conducted in people of European ancestry. This can lead to less accurate scores for embryos from other backgrounds, raising questions about equity and fairness.

Furthermore, the clinical utility of PGT-P is still debated. Even if a score is somewhat predictive, it is unclear whether selecting embryos based on these scores will lead to healthier children. Some experts argue that the potential benefits are small and may not justify the costs and risks of the procedure, which include the possibility of discarding embryos that might have been healthy.

Potential for discrimination and psychological impact

Another ethical dimension is the potential for discrimination. If polygenic risk scores become widely used, there is a risk that individuals with high scores for certain conditions could face discrimination in insurance, employment, or even within their own families. While many countries have laws against genetic discrimination, these laws may not cover all situations or may not be consistent globally. It is important to consider how your genetic information might be used and protected.

There is also the psychological impact on parents and children. Knowing that an embryo has a higher risk for a condition might cause anxiety or lead to decisions based on fear rather than evidence. Conversely, a low score might create a false sense of security, leading to neglect of important lifestyle factors. The child, when grown, might feel that their life choices were predetermined by their parents’ selection, which could affect their sense of autonomy.

The need for genetic counseling

Given the complexity and ethical implications, genetic counseling is crucial when considering PGT-P. A genetic counselor can help you understand what the test can and cannot tell you, interpret the results in the context of your family history and personal values, and discuss the potential risks and benefits. They can also help you think through the emotional and ethical aspects, such as how you would handle uncertain results or whether you would be comfortable making decisions based on probabilistic information.

Before undergoing PGT-P, you should have a thorough consultation with a qualified genetic counselor who is independent of the IVF clinic, if possible, to ensure that you receive unbiased information. The counselor can also help you explore alternative options, such as not testing, or using the information for lifestyle modifications rather than embryo selection.

Regulatory and availability considerations

The availability and regulation of PGT-P vary widely. Some countries have restrictions on the use of PGT for non-medical traits or for conditions that are not considered serious. Others may allow it under certain conditions. It is essential to check the legal status of PGT-P in the country where you are considering treatment, and to ask your clinic about their policies and the evidence they rely on.

You should also ask about the laboratory’s quality standards and how they validate their polygenic risk scores. Not all tests are created equal, and the accuracy can depend on the specific algorithms and reference data used. A reputable clinic will be transparent about these details.

Questions to ask your clinic

• What specific conditions does your PGT-P test screen for, and what is the evidence for the predictive value of these scores?
• How is the polygenic risk score calculated, and what reference populations were used?
• What is the cost of PGT-P, and is it covered by any insurance?
• How will you handle embryos with high or low scores? Are there options for re-testing or additional counseling?
• What are the legal and ethical guidelines in your country regarding PGT-P?
• Can I speak with a genetic counselor who is not affiliated with your clinic?

Next steps: making an informed decision

If you are considering PGT-P, take the time to gather information and reflect on your values. Here is a short checklist to guide you:

1. Research the conditions you are concerned about and the current state of polygenic risk scoring for those conditions.
2. Consult with a genetic counselor to discuss your personal risk factors and the implications of testing.
3. Ask your clinic for detailed information about their PGT-P protocol, including validation and limitations.
4. Consider the ethical and emotional aspects: how would you use the information? Would it change your decisions?
5. Discuss with your partner and family to ensure you are aligned in your approach.

Remember, PGT-P is an optional test, and you are not obligated to use it. The decision should be based on your own circumstances and values, not on pressure from any external source.

Conclusion

PGT-P is a promising but controversial technology. While it may offer some insights into the genetic predispositions of embryos, its limited predictive value, potential for discrimination, and the need for careful counseling make it a complex choice. By staying informed and asking the right questions, you can make a decision that aligns with your ethical principles and your hopes for your family.

Frequently asked questions

Is PGT-P the same as PGT-A or PGT-M?

No. PGT-A screens for chromosomal abnormalities, PGT-M targets specific single-gene disorders, and PGT-P estimates the risk of common polygenic conditions. They are different tests with different purposes.

Can PGT-P guarantee that my child will not develop a certain disease?

No. PGT-P provides a risk score, not a diagnosis. It cannot guarantee that a child will or will not develop a condition, as many environmental and lifestyle factors also play a role.

Are there laws against genetic discrimination based on PGT-P results?

Laws vary by country. Some have protections against genetic discrimination in insurance and employment, but these may not cover all situations. It is important to check the laws in your jurisdiction and discuss privacy concerns with your clinic.

Do I need genetic counseling before considering PGT-P?

Yes, genetic counseling is strongly recommended. A counselor can help you understand the test's limitations, interpret results, and explore the ethical and emotional implications, ensuring you make an informed decision.

Continue your research

• PGT in Thailand overview
• PGT and IVF guides
• Frequently asked questions

Medical information notice: This article is educational and does not replace individual assessment, diagnosis, genetic counselling or treatment advice from a licensed clinician. Provider services, availability, fees and policies should be verified directly before booking.