JBRA Assist. Reprod. 2026 2026;00(0):00-00
ORIGINAL ARTICLE
doi: 10.5935/1518-0557.20260061
1Science for Everymind. São Paulo-Brazil
2Instituto Sapientiae. São Paulo-Brazil
3Fertility/FERTGROUP- Medicina Reprodutiva São Paulo-Brazil
CONFLICT OF INTERESTS
ABSTRACT
Recent advances in genomics technologies have facilitated the introduction of new tools that broaden the scope of applications for genetic data. Preimplantation genetic testing using polygenic risk scores (PGT-P), a technique based on the fact that complex traits are influenced by multiple genes, is one such technology. Polygenic risk scoring involves the analysis of many genes in a single embryo to assess the odds of expressing diseaseand non-disease-related factors. This technique could alleviate subsequent burdens on healthcare systems, as it could lead to a population with reduced polygenic risk scores, potentially resulting in a lower incidence of genetic conditions, such as cardiovascular disease and cancer. However, following the introduction of PGT-P, numerous ethical concerns regarding its use have been raised. As such, it is crucial to gain a deeper understanding of stakeholder viewpoints regarding the technique. Worries include the validity and utility of PGT-P, limitations related to the number of embryos and available choices, and the challenges faced by prospective parents in terms of understanding and making informed decisions. Recently, published surveys have indicated that PGT-P is well accepted by both the general population and assisted reproduction patients; however, experts are concerned about the premature implementation of the technique. These findings raise the question of whether the general population is aware of the risks of technologies that could potentially manipulate the traits of future generations. To conclude, the value of PGT-P is indisputable if applied with caution, especially if relevant limits are not exceeded.
Keywords: preimplantation genetic testing, polygenic risk scores, polygenic diseases, ethics, concerns
Since the first documented use of preimplantation genetic testing for monogenic diseases (PGT-M), many advances have been made in this technology. Notably, the scope of PGT has been extended to encompass the routine assessment of chromosomal aneuploidy (PGT-A) and structural rearrangements (PGT-SR). Its application has shown steady annual increases, and it is now used in approximately 10%, 15%, and 50% of all IVF cycles in Latin America, Europe, and the United States, respectively. More recently, researchers have proposed that as most human traits are determined by multiple genes, and many genes can be analysed in a single embryo, assessing the risk of an individual developing polygenic diseases through preimplantation testing of the embryo would be feasible.
According to the World Health Organization, noncommunicable diseases (NCDs) kill 41 million people each year, accounting for 74% of all deaths worldwide. Cardiovascular diseases account for the majority of NCD deaths, followed by cancers, chronic respiratory diseases, and diabetes, all of which are polygenic diseases.
The first clinical application of PGT using polygenic risk scores (PGT-P) was reported in 2019 (Treff et al., 2019). Since then, PGT-P has emerged as a commercially available service, despite the absence of any substantial public deliberation regarding its ethical, clinical, and societal implications. In the scenario where techniques such as genome editing are possible, PGT-P has reignited concerns surrounding “designer babies”. Indeed, while the pursuit of a healthy infant and the right of individuals to make the best possible treatment decisions have been recognized in numerous societies, the eminent biotechnological revolution appears to be irreversible.
Technologies focusing on detecting chromosomal and monogenic disorders and traits have been applied for decades, allowing parents to exert influence over the characteristics of their future offspring. However, the majority of human phenotypes are influenced by multiple genes and environmental factors. Thus, PGT-P employs polygenic indices to estimate the expected phenotypes of embryos resulting from in vitro fertilization (IVF), thereby allowing parents to utilize these predictions to choose which embryo to transfer. One important concern regarding this technique is whether the use of PGT-P will be restricted to unique individuals, or whether it could potentially trigger or contribute to widespread societal transformations and disparities.
Many technologies, including ultrasound, PGT-M/PGT-A, amniocentesis, and non-invasive prenatal screening, have been applied to detect and/or “prevent” the onset of certain diseases in offspring. Conversely, PGT-P uses machine learning applied to data from biobanks to estimate the risk of certain diseases, by relying on the estimated associations between common genetic variations and genetic diseases that are polygenic, or have a specific phenotype (Torkamani et al., 2018). This genetics-derived metric can subsequently be employed not only for disease prevention, but also to potentially enhance traits such as heightened cognitive prowess or increased educational achievements.
Unlike PGT-M, which addresses high-penetrance monogenic diseases, PGT-P generates probabilistic estimates based on multiple genes. The utility of this testing for low-penetrance or late-onset diseases, such as certain forms of cancer, remains a topic of debate. However, comparing these approaches could shed light on the limits of public acceptance for technologies such as PGT-P. However, in contrast to technologies such as genome editing, which can potentially manipulate the traits of future generations and is thus prohibited in several countries, PGT-P is already offered by numerous companies worldwide.
Another issue to be discussed pertains to which population may benefit from PGT-P. Polygenic predictors have primarily been developed using data from a single ethnic group, typically comprising those of European ancestry; as such, while predictions may be beneficial for Europeans, they may be less useful for other ethnic groups such as Africans and Native Americans. Additionally, it is crucial to address the financial aspects of PGT-P, as this technology may not be accessible to everyone. This would require a comprehensive economic analysis, taking into account both the immediate costs of implementation and the potential long-term benefits, such as the prevention of chronic diseases that may otherwise require ongoing treatment. For example, while PGT-P may reduce the costs associated with managing polygenic diseases such as diabetes and cardiovascular conditions by preventing their onset, the upfront cost of the test may be prohibitive for many families. Further, the issue of whether this technique should be covered by health insurance remains a subject of debate.
There is no doubt that PGT-P could benefit the population by preventing serious diseases. However, questions remain regarding whether the technology is ready for implementation and, more importantly, whether we will know when to stop and whether its use can be confined solely to disease prevention.
The issue of how to define and restrict the phenotypes that could be selected for by PGT-P is critical. Beyond disease prevention, this technique could potentially be used to select traits deemed socially desirable, such as intelligence or physical appearance, raising ethical concerns about what testing should be permissible. It is thus essential to consider how we define a ‘desirable phenotype’, and to clarify what ethical and societal boundaries should be imposed to prevent the manipulation of human traits, such as intelligence or aesthetic characteristics, which could exacerbate inequalities and drive harmful social pressures. Currently, there are no clear or well-defined metrics to assess the success and feasibility of PGT-P. It may therefore be beneficial to align the ethical and clinical guidelines of other established forms of PGT, such as PGT-M and PGT-A, with those for PGT-P, in order to ensure consistency in practice and patient care. Such a “harmonization” of guidelines with other PGT approaches could help to establish a clear set of principles for both healthcare providers and patients. Issues such as the genetic risk threshold for intervention and the acceptance of tests based on polymorphisms also require thorough discussion.
Recently, Chin et al. (2026) proposed several safeguards to mitigate the potential misuse of PGT-P, as follows: (i) limiting the use of PGT-P to the prevention of clinically significant polygenic diseases, understood as conditions associated with substantial morbidity, reduced quality of life, or significant healthcare burden, rather than traits with primarily social or cosmetic relevance; (ii) restricting patients’ access to the raw genomic DNA sequencing data of their IVF embryos; (iii) validating the diagnosis of polygenic disease traits in the prospective parents or grandparents of IVF embryos, to allow subsequent confinement of PGT-P to the prevention of specifically-diagnosed polygenic diseases; and (iv) requiring thorough and comprehensive genetic counselling for IVF parents contemplating PGT-P.
Historically, several reproductive technologies, such as in vitro fertilization (IVF), PGT, karyomapping, the creation of savior siblings, and nuclear genome transfer for mitochondrial disorders, were initially controversial but were progressively incorporated into clinical practice under robust ethical and regulatory frameworks. These advancements were achieved not only through pioneering scientific and medical research, but also through the implementation of a robust and prudent ethical and legal framework. Consequently, many issues which were previously contentious, such as the use of PGT-M, are now regarded as standard practice and socially acceptable. Implementing PGT-P, under stringent regulation and on a case-by-case basis, should thus follow a similar trajectory.
One extremely important point to address is that discussions regarding ethical issues related to new techniques in assisted reproduction, such as PGT-P, must be undertaken with considerable caution to ensure that the regulation of other assisted reproductive techniques does not regress.
Previous population-based surveys have examined public acceptance of emerging genetic technologies, showing broad support for health-related applications of gene editing and greater reluctance toward non-health-related uses (Riggan et al., 2019). A similar trend has been reported for PGT-P. In a nationally representative survey of the general adult population in the United States, Meyer et al. (2023), assessed attitudes toward PGT-P and gene editing under a standardized hypothetical scenario in which these technologies were assumed to be safe, free of charge, and used as add-ons to IVF, conferring a modest benefit. Within this context, PGT-P was associated with higher moral acceptance and greater willingness to use compared with gene editing. Importantly, the study was conducted in the general population and was not restricted to infertile individuals or patients undergoing assisted reproductive treatment, which limits direct extrapolation to clinical IVF settings.
One unpublished survey by our group analysed the attitudes towards the application of genetic risk scores among assisted reproduction patients (n=508). Following an explanation of polygenic scoring and PGT-P, patients were asked if they would support the use of this test at the expense of human reproductive autonomy. The findings were similar to those in the aforementioned studies, in which the majority of participants (85.2%) showed a favorable attitude towards PGT-P, irrespective of sex; however, a trend towards negative responses was observed among older participants. The average ages of participants in favor and not in favor of PGT-P were 38.1 and 40.6 years, respectively. Nevertheless. these findings reflect the views of specific populations and should not be interpreted as representative of society at large.
Compared with the general population, the opinions of health care professionals appear to be more conservative. In one prior study, Siermann et al. (2023) interviewed 31 health care professionals specializing in PGT, questioning them on their perspectives regarding PGT-P technology, including aspects such as its validity, utility, limitations, and potential advantages. The results showed that a majority of health care experts were concerned about the premature introduction of PGT-P into clinical practice.
Overall, prior studies have shown that PGT-P is well accepted by both the representative general population and assisted reproduction patients worldwide. However, while the surveys discussed here may not represent the entire population, the results are relatively concerning. For example, the potential unintended consequences of assessing polygenic scores, which include the selection of adverse traits, population demographic modifications, exacerbation of social inequalities, and the devaluation of certain characteristics, should be discussed and carefully considered. Moreover, it should be noted that the susceptibility to complex diseases is influenced by multiple factors. Although the genetic component is important, it is also intricate, with each genetic variant having a small effect across the genome; in this context, environmental factors and rare genetic variants with a significant impact also play a substantial role in disease development. For example, factors such as diet, radiation exposure, smoking, and physical activity may all influence the likelihood of developing cancer. Further, all individuals have a certain risk of developing these and similar diseases; indeed, the estimated lifetime risk of developing cancer is approximately 50% (Griffin & Gordon, 2023). Despite large Genome-Wide Association Studies and more common investigations, experts in clinical medicine have expressed concerns regarding the accuracy of these predictions and, more critically, their generalizability across different populations.
In addition to the above, the potential for incidental findings and pleiotropic effects must also be taken into account. Many genetic variants whose clinical significance remains unknown or only partially understood could be uncovered by PGT-P, potentially without adequate assessment. However, these traits do not exist in isolation; by selecting against the likelihood of a specific disease, we may inadvertently affect other traits. Furthermore, while PGT-P targets a specific polygenic phenotype, as our understanding of the interactions among genes associated with polygenic traits remains incomplete, such selection could result in the unintended selection of other, potentially undesirable, phenotypes. Conversely, it could be argued that embryos deemed viable for transfer in any PGT cycle have already selected based on various criteria. As such, incorporating an additional selection method, such as the assessment of polygenic risk scores, would merely represent another means of facilitating the selection process. In recent decades, embryos have been assessed for aneuploidy, morphology, and, more recently, polygenic risk scores related to multiple conditions. Ultimately, employing artificial intelligence to consider patient preferences and concerns could be a feasible approach to rank embryos for transfer.
Another consideration that could support the case for PGT is that widespread implementation of PGT-P might alleviate the burden on healthcare systems by creating a population with reduced polygenic risk scores, potentially resulting in lower incidence rates of burdensome conditions such as cardiovascular disease and cancer.
Despite the potential advantages of PGT-P, the following questions should be considered to ensure that the ethical lines of what is or is not permissible regarding the genetic selection of individuals are not crossed:
Should PGT-P be limited to certain characteristics, and if so, who should draw this line and how?
How can we address the burden on parents informed that their child has a certain risk of developing a specific disease, along with the anxiety, guilt, and fear that may accompany such information?
How do we navigate the selection of PGT-P scores deemed suitable for transfer versus those that are not, potentially prompting the consideration of an additional IVF cycle to generate more embryos?
Finally, could choices regarding PGT-P be regulated without further threatening the use of other assisted reproductive techniques?
In conclusion, while PGT-P holds potential value, it has not yet been directly validated, partly because such validation would require many years of follow-up after numerous embryo transfers. Additionally, the emotional burden-such as guilt or anxiety-associated with the receipt of information regarding this test, raises a concern regarding whether PGT-P may introduce more harm than tangible benefit. Overall, it is clear that the application of PGT-P should be guided by fundamental ethical principles, including equity in access to this technology, the prevention of genetic discrimination, and the need for continuous engagement with society to adapt the clinical and regulatory practices to technological advancements. However, when used with caution, this test could provide substantial benefits to society, particularly for governments, by significantly reducing healthcare costs by reducing the incidence of major diseases such as cardiovascular conditions and cancers.
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