Imagine a crystal ball - mystical gray and silver clouds floating around inside of it. Now, imagine that those clouds could paint you a picture of your future child’s health well into adulthood. If you are concerned about health conditions - perhaps diabetes, heart disease, or cancer - then this new crystal ball could help prevent your child from developing them.
Preimplantation genetic testing for polygenic disorders (PGT-P) proposes to be this crystal ball for parents going through In vitro fertilization (IVF). PGT-P is a new type of testing, and it uses information from polygenic risk scores (PRS)
to screen embryos for a variety of conditions and to quantify their risk of getting a disorder in the future. While other genetic tests mainly look at diseases with a singular genetic cause (examples include spinal muscular atrophy, cystic fibrosis, Huntington disease, and mutations connected to serious cancer predisposition, such as BRCA), PGT-P provides the risk of developing polygenic conditions. These conditions, as their name suggests, are caused by multiple genes. What makes PGT- P unique is that it can screen for multifactorial conditions that are caused by the interaction of multiple genes and environmental factors, as long as there is enough PRS data collected for that condition.
PGT-P, then, is much less restricted to "high risk" families. Now, even those with a family history of conditions but no identified causal gene can screen their embryos - as can anyone who is simply interested in seeing their embryo’s risk scoring, even if they don't have a family history of relevant conditions.
Health policy implications
Increased prenatal and preimplantation screening has been a widely discussed ethical issue in reproductive health and the larger medical community for decades. It is challenging to balance the impact of developing/preventing a disease against the risks/costs that the screening itself carries. This is health policy at its core, and it is a good idea for these ideas to come to the surface so that we can have informed debates with all stakeholders as we shape health policy for the genomics era. During the internship, we explored a recent paper
written by the founders and employees of one of the companies offering PGT-P to get a better sense of the future of this technology. Their paper considered both the technology
and the ethical considerations of PGT-P, and we used this paper as a springboard to consider the genetic counseling issues and social implications that this testing can present.
Ethics in genetics and reproductive medicine
As one consideration in health policy debates, an ethical lens gives treatment to the four pillars of medical ethics: autonomy, beneficence, non-maleficence, and justice, in the adoption and use of medical technologies. It's a necessary piece of a social discussion of healthcare innovation. But it's also a large task for this particular technology, and this paper merely scratched the surface of the arguments. The exemplified arguments that were posed for beneficence, non-maleficence, and justice merely accepted that the technology IS beneficial to at least the chosen embryo, and largely dismissed all the other, untold implications from the technology. Instead, the authors simply steered toward the simple conclusion that it is ultimately about autonomy instead of properly illuminating the complexities that this technology poses. And while we do not dispute autonomy's place in this discussion, clinical genetics and reproductive medicine are disciplines that pluck away at a simple meaning of autonomy.
In our internship program discussion of this paper, we chose to zoom out and see whose autonomy is at play in these decisions. Is it the child born from a screened embryo, is it the parent having the embryo testing performed, is it the family unit that is created out of such screening, or is it the society to which these individuals all belong? It is problematic to consider that there is a singular patient with singular interests at stake in the clinical practice of PGT-P, when the point of the test is to somewhat arbitrarily reduce risk for various polygenic conditions by allowing prioritization of embryos based on predicted polygenic risk. Serious discussion about the impacts has to go beyond simply reducing health risk for a single embryo or a single family. Ultimately, that single embryo and single family is a part of a larger social sphere and making a meaningful decision will mean facing those complex issues. . . for each patient. And, in a society where the testing is already clinically available without extensive social conversation, a genetic counseling session is the place that those conversations tend to happen.
And these conversations are bound to be complex. For some, PGT-P is simply seen as beneficial. The testing is seen as a way to increase reproductive choice for parents and improve the future health and quality of life of children. Tellier et al. espouse this perspective. According to the authors, having this testing could help prevent conditions and lower health risks for a larger population. They posit that not allowing people to utilize such tests would be unethical, on simple utilitarian grounds. For others, though, the consideration of PGT-P may put them in an uncomfortable position of putting different values on different lives. And for many patients going through fertility treatment, this is not a simple math kind of situation. They often place a high value on the embryos they can create, and are often ambivalent about the moral status and meaning
of any embryos they don't use in a transfer cycle. This ambivalence often lasts for years after their family is seemingly complete, and often comes with emotional distress
and delayed decision-making about the options for disposition of their remaining embryos. (For a glimpse into the dilemma that many "successful" fertility patients find themselves in, check out the educational series at empowerwithmoxi.com
or Gina's personal blog post here
We don't believe it is doing fertility patients any favors to skip the thought experiment about what will happen when they are done with the prioritized embryo transfers. Or checking in to see how they’ll feel about balancing health scores as a first milestone in their family planning. This is not a challenge to their reproductive autonomy, but rather a clarification of how nuanced embryo selection fits into the rest of their life. How will this affect their family as a whole? Are there dangers to parental choice going this far? How much information is helpful to patients and how much information will actually make their lives more complicated?
As many leaders in the field of clinical genetics have articulated, it is also problematic to bypass the structural racism
or classism that predominates the data and availability of this technology. One problem is the efficacy of these tests. PRS have historically been calculated mainly using data from those of European descent. This means that the screening results from PGT-P may not be as precise for those with other ancestries, at least until researchers include diverse populations in their studies. PGT is also costly and not widely covered by insurance. If patients going through IVF, which in and of itself is expensive, want to screen their embryos using PGT-P, they would need to pay out of pocket. The lack of equitable access to PGT-P can further contribute to health and social inequity. These costs undercut the benefits of the screening that proponents have mentioned for why the test should be made available. The high prices make it so that reproductive autonomy mentioned previously is only available for those that are wealthy enough. The affluent would also be more easily able to improve the health of their children, which can have impacts not only right now, but for generations to come.
Beyond equity and access issues, we also need to consider how these tests impact those with disabilities and even simple health problems as we move to ever-larger nets for screening. Preimplantation and prenatal genetic screening, among other novel genomic technologies, can send the message that people with these conditions are not desirable and should not exist. Check out this video
and this opinion piece
for more perspective on these issues. There needs to be careful attention paid to how we decide which diseases and conditions to test for, and exploration of what that means for the greater community.
Decision-making in PGT-P
It may seem like a lot of thinking to do for someone just wondering if it's a good idea to test their embryos in their upcoming IVF cycle. And we couldn't agree more. It's actually really complicated. These patients, and society at large, have to grapple with the potential promise and peril of this testing in their lives before they can begin to make meaningful decisions about it. Many patients seeking IVF to conceive don’t go into their fertility treatment looking to intentionally optimize their future child’s health. They simply want to start their family and might need a little help to do it. But it can be a hard option to walk away from if it becomes a readily available test, something that seemingly could be beneficial in nature, a way to give your child the best chances for future health and happiness. But it invokes profoundly different questions than the first generation of PGT for single-gene diseases or chromosome abnormalities: should we actually select (or eventually design) the future of humanity?
Genetic counselors, of course, are happy to have these individual conversations and help patients come to their own answers for their own families. That’s what we do. But we also need to continue the social conversation. We have the opportunity and the responsibility to guide informed discussions and debates about the repercussions of technology that could impact generations to come. We need to better understand this crystal ball and how it will impact the future of our health, our families, and our society. And it would be wise to do this before it takes off as just another add-on to a complicated treatment plan.
For further reading on this topic: check out this NEJM article
Disclaimer: Please keep in mind that the information provided here is not meant to be a medical opinion about your specific case. The problems of every patient are unique and should be addressed by their physician or other health-care professionals in an individual conversation. You are welcome to bring up questions inspired by this blog post with your medical team. However, no one should use this blog as a source of medical care.