Bacal Vanessa, Li Angela, Shapiro Heather, Rana Urvi, Zwingerman Rhonda, Avery Lisa, Palermo Alina, Philipoppolous Eleni, Chan Crystal
Department of Obstetrics and Gynaecology, University of Toronto, Canada.
Mount Sinai Fertility, Mount Sinai Hospital, Toronto, Canada.
PLoS One. 2025 May 14;20(5):e0321859. doi: 10.1371/journal.pone.0321859. eCollection 2025.
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.
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).
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%).
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.
非整倍体是导致许多妊娠失败和先天性异常的原因。植入前非整倍体基因检测（PGT-A）是一种应用于体外受精产生的胚胎的筛查测试，以降低非整倍体受孕的几率。假非整倍体（假阳性）和假整倍体（假阴性）检测结果的误诊率尚不清楚。本研究的目的是确定PGT-A后非整倍体和整倍体的错误分类率。
我们进行了一项系统评价和荟萃分析。我们检索了从创刊至2024年4月10日的Medline、Embase、Cochrane Central、CINAHL和世界卫生组织临床试验注册库。该方案已在国际前瞻性系统评价注册库（PROSPERO CRD 42020219074）中注册。
我们纳入了以下研究：使用细胞系对PGT-A基因平台进行临床前验证的研究；将胚胎活检结果与整个解剖胚胎或其内细胞团（WE/ICM）的结果进行比较的研究；以及将活检结果与产前或产后基因检测结果进行比较的研究。
制表、整合与结果：两名独立评审员提取了将活检结果与参考标准（已知核型、WE/ICM、妊娠结局）相比较的真阳性和假阳性及阴性结果。对于临床前研究，主要结局是阳性和阴性预测值。误诊率是妊娠结局研究的结局。电子检索共获得6674条文献，其中109条被纳入。对于WE/ICM研究（n = 40），非整倍体和整倍体胚胎的阳性预测值分别为89.2%（95%CI 83.1 - 94.0）和阴性预测值为94.2%（95%CI 91.1 - 96.7，I² = 42%）。确认性嵌合或非整倍体结果的嵌合胚胎的阳性预测值为52.8%（95%CI 37.9 - 67.5）。对于妊娠结局研究（n = 43），整倍体胚胎移植后的误诊率为0.2%（95%CI 0.0 - 0.7%，I² = 65%）。然而，确认性整倍体妊娠结局的嵌合移植率为21.7%（95%CI：9.6 - 36.9，I² = 95%）。
PGT-A得出的非整倍体结果准确性极佳，可作为胚胎筛查工具以避免非整倍体妊娠。同样，整倍体胚胎移植后的误诊率低于1%。然而，嵌合胚胎的准确性存在显著局限性。
