Research indicates polygenic embryo screening in IVF provides limited predictive value for traits — Evidence Review
Published by researchers at Guy’s and St Thomas’ NHS foundation trust
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Table of Contents
Couples undergoing IVF in the UK are using a legal loophole to access polygenic screening of embryos for traits like IQ, but the study finds these predictive scores are very crude and capture only a tiny fraction of heritability. Most related studies agree that polygenic embryo screening has limited predictive value and is not yet robust enough for clinical use (3, 5).
- Multiple studies indicate that, while polygenic scores can identify some genetic risk, their predictive power for complex traits like IQ or height in embryos is minimal, often translating into only small average gains (e.g., ~2.5 IQ points or centimeters in height) and with considerable uncertainty (3).
- There is broad consensus that clinical utility for embryo selection based on polygenic scores is unproven and potentially unethical, with leading experts urging caution and calling for further research and debate (5, 10).
- Research consistently highlights significant limitations, including poor performance across diverse populations and even within ancestry groups, as well as the strong influence of environmental and non-genetic factors on complex traits (6, 8).
Study Overview and Key Findings
The emergence of rapid, affordable genetic sequencing in IVF has enabled couples to request genome data from their embryos, raising the possibility of using polygenic scores to select embryos for various traits—including intelligence. This practice exploits a grey legal area in the UK, as polygenic screening is not officially permitted for non-medical traits, but patients can access their own medical data. The study is timely given the growing interest in reproductive genetic testing and the ethical, technical, and regulatory uncertainties it introduces.
| Property | Value |
|---|---|
| Organization | Guy’s and St Thomas’ NHS foundation trust |
| Authors | Prof Frances Flinter |
| Population | Couples undergoing IVF in the UK |
| Outcome | Predictive scores for health, height, IQ, and other traits |
| Results | Polygenic scores are crude and capture a tiny fraction of heritable traits |
Literature Review: Related Studies
To understand the context and implications of this study, we searched the Consensus database, which covers over 200 million research papers. The following queries were used to identify relevant literature:
- polygenic embryo screening IVF effectiveness
- heritable traits polygenic scores limitations
- IVF outcomes polygenic risk assessment
Below is a summary of major research topics and key findings from the related literature:
| Topic | Key Findings |
|---|---|
| How effective is polygenic screening for predicting complex traits in embryos? | - Polygenic embryo screening for traits like height and IQ produces only modest average gains (e.g., ~2.5 IQ points) with wide confidence intervals and limited real-world predictiveness (3). - Polygenic scores capture only a fraction of heritability for complex traits, with prediction accuracy dependent on sample size and trait architecture (7, 9). |
| What are the limitations and risks of applying polygenic scores in embryo selection? | - Predictive accuracy of polygenic scores varies significantly by ancestry and even within ancestry groups, limiting their generalizability and clinical utility (6, 8). - The use of polygenic scores in pre-implantation genetic testing is widely regarded as unproven and raises ethical concerns; most experts recommend caution and robust societal debate before adoption (5, 10). |
| What is the current evidence for clinical utility of genetic embryo screening in IVF? | - Comprehensive chromosome screening (CCS) for aneuploidy improves IVF outcomes such as implantation and pregnancy rates, but polygenic screening for complex traits does not have similar clinical validation (1, 2, 4). - Patients are interested in polygenic screening, but the impact on actual health outcomes or trait selection remains unproven, and variation among siblings is limited but still significant (12, 13). |
How effective is polygenic screening for predicting complex traits in embryos?
Most related studies agree that polygenic screening has limited practical effectiveness for selecting embryos based on traits such as IQ or height. Gains from selecting the "top scoring" embryo are modest and subject to considerable uncertainty, with environmental and random factors playing major roles.
- The average predicted gain from selecting embryos with the highest polygenic scores for IQ or height is small—about 2.5 IQ points or 2.5 centimeters—accompanied by wide confidence intervals (3).
- Polygenic scores can only explain a small fraction of the heritability of complex traits, and their predictive power in embryos is even lower due to the small number of embryos available for selection (7, 9).
- Studies using real-world family data find that the embryo with the highest polygenic score is not necessarily the one who will express the trait most strongly (3).
- The effectiveness of polygenic prediction is limited by genetic complexity, gene-gene and gene-environment interactions, and current algorithmic constraints (3, 7).
What are the limitations and risks of applying polygenic scores in embryo selection?
Significant methodological and ethical limitations constrain the current use of polygenic scores in IVF. These limitations include ancestry bias, variable prediction accuracy, and the lack of clinical validation.
- Polygenic scores derived from European ancestry samples perform poorly when applied to individuals of other ancestries, and even within a single ancestry group, prediction accuracy can vary with age, sex, and study design (6, 8).
- The lack of robust clinical validation means there is little evidence that polygenic screening for complex traits results in meaningful health or trait improvements in practice (5, 10).
- Leading experts caution that patients need to be fully informed about the limitations and uncertainties of polygenic screening, and that broader societal debate is needed before such practices are adopted (5).
- Ethical concerns include potential discrimination, inequity, and societal pressure regarding the selection of embryos for non-medical traits (5, 10).
What is the current evidence for clinical utility of genetic embryo screening in IVF?
While screening for chromosomal abnormalities (aneuploidy) in embryos has been shown to improve IVF outcomes, there is little evidence supporting the clinical utility of polygenic risk scoring for complex traits.
- Comprehensive chromosome screening (CCS) improves implantation rates, reduces miscarriage, and increases live birth rates in IVF, but this benefit does not extend to the use of polygenic scores for complex traits (1, 2, 4).
- Polygenic screening is primarily driven by patient interest in additional information, rather than established health benefits (12).
- Sibling variation in polygenic traits is less than that seen in the general population, but there is still enough genetic variability for polygenic screening to potentially make a difference—although the magnitude of benefit remains small (13).
- Overall, there is a lack of evidence from clinical trials or real-world outcomes to support the routine use of polygenic screening for embryo selection in IVF (5, 10).
Future Research Questions
Despite growing interest and commercial availability, the predictive power and clinical utility of polygenic embryo screening for complex traits remain limited and controversial. Future research is needed to address the scientific, ethical, and societal implications as well as to improve the accuracy and applicability of polygenic scores in diverse populations.
| Research Question | Relevance |
|---|---|
| How accurate are polygenic scores for predicting complex traits like IQ in embryos? | Most studies show limited predictive power for complex traits; robust clinical validation is lacking and needed to inform ethical and regulatory decisions (3, 5, 7). |
| What are the long-term health and psychosocial outcomes of children born following polygenic embryo screening? | The long-term impacts on children and families remain unknown, including potential unintended consequences and societal implications (5, 10). |
| How does ancestry affect the predictive performance of polygenic scores in IVF embryos? | There is strong evidence that polygenic scores are less accurate in non-European populations, which may exacerbate health disparities and limit the generalizability of findings (6, 8, 10). |
| What ethical frameworks are needed to govern the use of polygenic screening in reproductive medicine? | As the technology becomes more available, ethical guidelines are urgently needed to address issues of equity, consent, and societal impacts (5, 10). |
| Can improvements in polygenic score calculation and diverse genetic databases increase the clinical utility of embryo screening? | Enhancing algorithmic methods and expanding genetic reference databases may improve prediction accuracy and applicability across populations (6, 7, 10). |