Misdiagnosis of different types of aneuploidy in preimplantation genetic testing (PGT): a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: P < 0.001

• Effect Size: OR = 10.04 for segmental aneuploidy misdiagnosis in PGT-A population

• Primary Outcome: Discordance rates between trophectoderm biopsy and inner cell mass/whole blastocyst genetic analysis

• Nnt Or Sensitivity: Segmental aneuploidy discordance rate: 17.4% vs 2.6% for euploid embryos

• Confidence Interval: 95% CI: 7.60-13.27

Clinical Application

Highly feasible - requires modification of existing PGT-A interpretation protocols rather than new technology Directly relevant to Australian fertility clinics offering PGT-A. May influence NHMRC guidelines and RTAC standards for genetic testing interpretation. Cost implications for Medicare-funded IVF cycles if additional confirmatory testing recommended. Couples undergoing IVF with PGT-A, particularly those with embryos diagnosed with segmental aneuploidies

Abstract

PURPOSE: Recent studies have reported that embryos diagnosed as aneuploid by preimplantation genetic testing (PGT) can still result in successful live births after transfer. This suggests that, in addition to mosaic embryos, fully aneuploid embryos may also carry a risk of diagnostic error, potentially reducing the overall accuracy of PGT. Therefore, thoroughly investigating the risk and characteristics of aneuploidy misdiagnosis is crucial for optimizing PGT strategies and improving clinical outcomes in assisted reproductive technology (ART). METHODS: Relevant studies published from January 2000 to December 2024 were identified through PubMed and Web of Science. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A diagnostic meta-analysis was conducted using a random-effects model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs), combining sensitivity and specificity. Results were visualized using forest plots. RESULTS: A total of 22 studies were included to assess the discordance between trophectoderm (TE) biopsy and inner cell mass (ICM) or whole blastocyst (WB) results. The discordance rate for euploid embryo diagnosis was low (2.6%), whereas it was significantly higher for aneuploid embryos (9.2%). Segmental aneuploidies showed the highest discordance rate (17.4%). In the PGT-A population, misdiagnosis of segmental aneuploid embryos was particularly prominent (OR = 10.04, 95% CI: 7.60-13.27, I2 = 0%, P < 0.001). CONCLUSION: The results indicate that embryos with segmental aneuploidies have a significantly higher risk of misdiagnosis, especially in the PGT-A population. This highlights the need for caution when interpreting trophectoderm (TE) biopsy results involving segmental aneuploidies, to avoid misdiagnosis and the inadvertent discard of potentially viable embryos.

References

1. 1.Jiang, W., Hu, Z., Han, Y., Shi, J., Chen, K., Lian, Y., Li, W., Hao, P., Zhou, Z., Wu, Z., Li, Y., Wu, X., Li, M., Deng, L., Zheng, H., Bi, Z., Ding, L., Pan, X., Ma, R., Tang, Z., Mu, J., Xie, X., Li, Y., & Yan, J. (2026). Misdiagnosis of different types of aneuploidy in preimplantation genetic testing (PGT): a systematic review and meta-analysis. Archives of Gynecology and Obstetrics. https://doi.org/10.1016/j.fertnstert.2022.10.010