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Meta-Analysis
. 2025 May 14;20(5):e0321859.
doi: 10.1371/journal.pone.0321859. eCollection 2025.

A systematic review and meta-analysis of the diagnostic accuracy after preimplantation genetic testing for aneuploidy

Vanessa Bacal  1   2 , Angela Li  1 , Heather Shapiro  1   2 , Urvi Rana  3 , Rhonda Zwingerman  4 , Lisa Avery  5   6 , Alina Palermo  2 , Eleni Philipoppolous  7 , Crystal Chan  1   8
Affiliations
Meta-Analysis

A systematic review and meta-analysis of the diagnostic accuracy after preimplantation genetic testing for aneuploidy

Vanessa Bacal et al. PLoS One. .

Abstract

Objective: Aneuploidy accounts for many pregnancy failures and congenital anomalies. Preimplantation genetic testing for aneuploidy (PGT-A) is a screening test applied to embryos created from in vitro fertilization to diminish the chance of an aneuploid conception. The rate of misdiagnosis for both false aneuploidy (false positive) and false euploidy (false negative) test results is unknown. The objective of this study was to determine the rate of misclassification of both aneuploidy and euploidy after PGT-A.

Data sources: We conducted a systematic review and meta-analysis. We searched Medline, Embase, Cochrane Central, CINAHL and WHO Clinical Trials Registry from inception until April 10, 2024. The protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO CRD 42020219074).

Methods of study selection: We included studies that conducted either a pre-clinical validation of the genetic platform for PGT-A using a cell line, studies that compared the embryo biopsy results to those from the whole dissected embryo or its inner cell mass (WE/ICM), and studies that compared the biopsy results to prenatal or postnatal genetic testing.

Tabulation, integration, and results: Two independent reviewers extracted true and false positives and negatives comparing biopsy results to the reference standard (known karyotype, WE/ICM, pregnancy outcome). For preclinical studies, the main outcome was the positive and negative predictive values. Misdiagnosis rate was the outcome for pregnancy outcome studies. The electronic search yielded 6674 citations, of which 109 were included. For WE/ICM studies (n=40), PPV was 89.2% (95% CI 83.1-94.0) and NPV was 94.2% (95% CI 91.1-96.7, I2=42%) for aneuploid and euploid embryos, respectively. The PPV for mosaic embryos of either a confirmatory mosaic or aneuploid result was 52.8% (95% CI 37.9-67.5). For pregnancy outcome studies (n=43), the misdiagnosis rate after euploid embryo transfer was 0.2% (95% CI 0.0-0.7%, I2=65%). However, the rate for mosaic transfer, with a confirmatory euploid pregnancy outcome, was 21.7% (95% CI: 9.6-36.9, I2=95%).

Conclusion: The accuracy of an aneuploid result from PGT-A is excellent and can be relied upon as a screening tool for embryos to avoid aneuploid pregnancies. Similarly, the misdiagnosis rate after euploid embryo transfer is less than 1%. However, there is a significant limitation in the accuracy of mosaic embryos.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA flow diagram.
Fig 2
Fig 2. Forest plots for whole embryo or ICM studies.
a. Negative predictive value of euploid embryos. b. Positive predictive value of aneuploid embryos. c. Positive predictive value of mosaic embryos.
Fig 3
Fig 3. Forest plots for pregnancy outcomes: misdiagnosis rate.
a. Euploid embryo transfer. b. Aneuploid embryo transfer. c. Non-selection embryo transfer. d. Mosaic embryo transfer.
See this image and copyright information in PMC

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