The diagnostic accuracy of preimplantation genetic testing (PGT) in assessing the genetic status of embryos: a systematic review and meta-analysis.

Background: Preimplantation genetic testing (PGT) is widely used in assisted reproduction to assess the genetic status of embryos. However, increasing evidence suggests that the trophectoderm (TE) may not fully reflect the genetic status of the inner cell mass (ICM), raising controversy about the accuracy of TE biopsy. Research in recent years has focused on cell-free DNA (cfDNA) found in blastocoel fluid (BF) and spent culture medium (SCM), as these may contain genetic information from both the TE and ICM. Therefore, further research and validation are essential to determine the reliability and clinical applicability of these diagnostic methods in PGT.

Methods: Relevant studies published between January 2000 and August 2024 were identified through PubMed and Web of Science (WOS). Risk assessment and publication bias were evaluated using QUADAS-2 and Deek's test. Diagnostic meta-analysis was performed using a bivariate model to combine sensitivity and specificity, with results visualized through forest plots and summary receiver operating characteristic (SROC) curves.

Results: Out of 6,407 initially screened records, 36 studies involving 4,230 embryos were included. TE biopsy was identified as the best method for diagnosing the genetic status of embryos (sensitivity: 0.839; specificity: 0.791, AUC: 0.878), while SCM had slightly lower accuracy (sensitivity: 0.874; specificity: 0.719, AUC: 0.869). The effectiveness of BF (AUC: 0.656) was significantly lower than that of TE biopsy and SCM. Despite this, TE biopsy has not yet achieved ideal diagnostic performance. However, TE biopsies demonstrate a high level of accuracy in diagnosing PGT-SR (AUC: 0.957). Additionally, multiple TE biopsies (AUC: 0.966) or TE biopsies combined with SCM (AUC: 0.927) can enhance the diagnostic efficiency of PGT.

Conclusion: The findings of this study suggest that TE biopsy has yet to achieve optimal diagnostic accuracy, which may result in a significant number of missed embryo diagnoses and misdiagnoses. Our results confirm that SCM has the potential to serve as a supplementary test. Employing multiple biopsies or combining TE with SCM may enhance diagnostic efficiency and yield optimal results.