January 09, 2026
4 min read
Key takeaways:
- More research is needed for preimplantation genetic testing for polygenic disorders.
- Now, it cannot account for environmental and lifestyle factors that will become important as a potential disease develops.
The American Society for Reproductive Medicine published a report that concludes preimplantation genetic testing for polygenic disorders is not ready for clinical practice and should not yet be offered as a reproductive service.
According to a press release from the ASRM, it is not yet ready because of “the predictive uncertainties of the results and the substantial ethical considerations” that the practice raises.
“This analysis provides an ethics-based framework to guide clinicians, policymakers, patients and the public at large as they navigate the emergence of polygenic embryo screening,” according to the release.
Healio spoke with Sigal Klipstein, MD, chair of the ASRM’s Ethics Committee, to learn more about the report, what women’s health care providers need to know and what needs to happen next for clinical implementation.
Healio: Will you briefly describe preimplantation genetic testing for polygenic disorders? What is its potential use?
Klipstein: Preimplantation genetic testing (PGT) is a technique that was developed in the 1990s to screen embryos for specific genetic diseases. Embryos derived from IVF are allowed to develop in the lab for 5 to 6 days, at which point they have approximately 100 cells. A biopsy is performed directly on the embryo, which removes approximately 5% of the cells. These cells can undergo testing that looks at all 46 chromosomes, known as aneuploidy screening. They can also be screened for a specific disease whose genetics is known, such as cystic fibrosis or Tay-Sachs. Another use of PGT is to screen for the presence of specific mutations that increase disease risk. One example is the presence of mutations in BRCA genes, which increase the risk that the resulting child will develop breast or ovarian cancer over their lifetimes.
More recently, several companies have started offering preimplantation genetic testing for polygenic disorders (PGT-P), also referred to as polygenic embryo screening. With PGT-P, the biopsied cells are not tested for a specific gene mutation or chromosomal abnormality, but rather for their risk for developing diseases that are impacted by hundreds or thousands of genes. Embryos are assessed for a genetic predisposition to develop these multifactorial conditions, with the hope of decreasing the risk for passing along these polygenic conditions, disease predispositions or traits.
With PGT-P, the results indicate a potential increased risk for developing a disease that is influenced by the interaction of many genes and often also by environmental or lifestyle factors. These include CVD, diabetes and bipolar disorder. In theory, intended parents can undergo IVF, test their embryos for a panel of polygenic diseases, and score these embryos based on the risk that the resulting children will develop one or more of these polygenic diseases. It is important to note that PGT-P is not designed to determine whether a resulting child will develop a given disease, but rather to predict whether a child resulting from one vs. another embryo, created with sperm and egg from the same individuals, is at increased risk for developing a polygenic disease.
Healio: What are the pros and cons to PGT-P’s potential?
Klipstein: The potential benefit of PGT-P for individuals who have more than one embryo available for transfer to the uterus is the possibility that the resulting child will be healthier or at least will be at lower risk for developing certain polygenic diseases than “sibling embryos.” However, there is no guarantee that a child resulting from a lower-risk embryo will not develop these diseases. Many diseases are highly impacted by environmental and lifestyle considerations, and medical science continues to advance such that many chronic diseases are becoming ever more manageable and treatable. For example, it is not possible to predict how a child born today with an increased risk for heart disease will fare many decades into the future, when the disease is expected to manifest.
To use PGT-P, intended parents need to both undergo IVF and have more embryos than they plan to transfer. In many cases, only a limited number of embryos are available, such that selecting among them is not pragmatically an option. One issue to consider is that embryos that undergo PGT-P screening are ranked. Parents who wish to have more than one child will often be left with the decision of transferring a lower ranked embryo and need to navigate that decision from a practical and psychological perspective.
One criticism of this technology is that the algorithms for PGT-P were developed based on data largely derived from adults of Western European Caucasian origin, which might limit the generalizability of the data for diverse populations. Another concern is that this technology is expensive and would only be affordable for a small percentage of the population, raising concerns about distributive justice.
In theory, if enough people use this technology, it could decrease genetic diversity in the population and make individuals more susceptible to emerging diseases.
Healio: The report concluded that PGT-P is not yet ready for clinical practice. Why is that? How did you determine this?
Klipstein: At present, there is a lack of evidence to support the clinical utility, long-term safety and predictive validity of PGT-P. Our understanding of the interplay between genetic and environmental factors for disease development is incomplete, such that scores generated from PGT-P may not translate into meaningful data with which to make embryo transfer decisions.
Healio: What is needed to get it ready for clinical practice?
Klipstein: Additional research is needed that validates the findings. Does a given genetic profile ultimately lead to an increased disease risk? Is this valid across diverse populations? How will the development of new medications and disease management options affect the impact of polygenic diseases on a patient’s health and longevity in the future? These are all questions that need to be addressed before PGT-P is offered clinically.
For now, research on PGT-P should be performed under strict research protocols with close oversight and attention to the clinical utility of making decisions based on polygenic risk scores.
Clinical use should only occur after safety, efficacy, ethical and societal concerns have been addressed.
Healio: Are there any other technologies that could offer similar benefits as an alternative to this?
Klipstein: Currently, preimplantation genetic testing for aneuploidy, structural rearrangements, monogenic diseases, and specific genes that confer disease risk are clinically validated options that patients can utilize to decrease risk to their children.
Healio: What is the take-home message here?
Klipstein: There is no technology that can guarantee a healthy baby. While physicians, intended parents and society at large have an interest in improving the health and well-being of future children, we need to avoid placing too much hope on as yet unproven ways of doing so.
For more information:
Sigal Klipstein, MD, can be reached at primarycare@healio.com.
Sources/Disclosures
Source:
Healio Interviews
Reference:
Disclosures:
Klipstein reports no relevant financial disclosures.
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