EC Gynaecology

Review Article Volume 12 Issue 1 - 2023

Preimplantation Genetic Testing for Aneuploidies (PGT-A): Baring Our Limitations

C Fatemi1, B Ata2.1, I Elkhatib1 and D Nogueira3,1*

1In-Vitro-Fertilisation (IVF) Department, ART Fertility Clinics, United Arab Emirates

2Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey

3Inovie Fertilité, France

*Corresponding Author: D Nogueira, In-Vitro-Fertilisation (IVF) Department, ART Fertility Clinics, United Arab Emirates, Inovie Fertilité, France.
Received: December 01, 2022; Published: December 12, 2022



The clinical value of PGT-A remains an area of debate. Most data produced so far demonstrate that the intervention of PGT-A is safe since they neither support nor refutes its efficacy. The clinical value of a test rests in its validity. A fair assessment and interpretation of results based on the original experimental design are key determinants of the accuracy of the reported outcomes. A significant issue concerning non-inferiority trials on PGT-A are flawed experimental set ups which invalidate many of the conclusions. We highlight and challenge some of these reports herein. Moreover, other relevant aspects related to the PGT-A reports concerns the discernment between technical and true biological mosaicism. This critical distinction is essential since reporting mosaicism may primarily come at the expense of euploid diagnoses. Other significant aspects impacting PGT-A outcomes are specifically related to the embryology laboratory. Technical manipulations for PGT-A need validation as well proved standardized results in order to substantiate clinical performances. These factors range from type of blastocysts biopsied, choice of biopsy procedure and individual performance. Overall, the controversies on the efficacy of PGT-A are, in part, due to the methodological limitations of studies which fail to consider the influence of the technical aspects on the outcomes.

Keywords: Preimplantation Genetics Testing for Aneuploidy (PGT-A); Trophectoderm Biopsy; Blastocyst; NGS; RCT

  1. Cornelisse S., et al. “Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation”. Cochrane Database of Systematic Reviews (2020).
  2. Simopoulou M., et al. “PGT-A: who and when? Α systematic review and network meta-analysis of RCTs”. The Journal of Assisted Reproduction and Genetics 38 (2021): 1939-1957.
  3. Tiegs AW., et al. “A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy”. Fertility and Sterility 115 (2021): 627-637.
  4. Wang J., et al. “Trophectoderm Mitochondrial DNA Content Associated with Embryo Quality and Day-5 Euploid Blastocyst Transfer Outcomes”. DNA and Cell Biology5 (2021): 643-651.
  5. Kung A., et al. “Validation of next-generation sequencing for comprehensive chromosome screening of embryos”. Reproductive BioMedicine 31 (2015): 760-769.
  6. Scott RT., et al. “Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study”. Fertility and Sterility 97 (2012): 870-875.
  7. Treff NR and Scott RT. “Methods for comprehensive chromosome screening of oocytes and embryos: capabilities, limitations, and evidence of validity”. The Journal of Assisted Reproduction and Genetics 29 (2012): 381-390.
  8. Yang Y-S., et al. “Preimplantation genetic screening of blastocysts by multiplex qPCR followed by fresh embryo transfer: validation and verification”. Molecular Cytogenetics 8 (2015): 49.
  9. Yan J., et al. “Live Birth with or without Preimplantation Genetic Testing for Aneuploidy”. The New England Journal of Medicine 385 (2021): 2047-2058.
  10. Abdala A., et al. “Day 5 vs day 6 single euploid blastocyst frozen embryo transfers: which variables do have an impact on the clinical pregnancy rates?” Journal of Assisted Reproduction and Genetics 39 (2022): 379-388.
  11. Tiegs AW., et al. “Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as Day 5 and Day 6 blastocysts”. Human Reproduction 34 (2019): 1632-1639.
  12. Munné S., et al. “Euploidy rates in donor egg cycles significantly differ between fertility centers”. Human Reproduction 32 (2017): 743-749.
  13. Popovic M., et al. “Implicit bias in diagnosing mosaicism amongst preimplantation genetic testing providers: results from a large multicenter analysis of 36395 blastocysts”. Human Reproduction Abstract book1 (2022): 075 i44.
  14. Munné S., et al. “Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial”. Fertility and Sterility 112 (2019): 1071-1079.e7.
  15. García-Pascual CM., et al. “Optimized NGS Approach for Detection of Aneuploidies and Mosaicism in PGT-A and Imbalances in PGT-SR”. Genes 11 (2020): 724.
  16. Leigh D., et al. PGDIS position statement on the transfer of mosaic embryos (2021).
  17. De Rycke M., et al. “Preimplantation Genetic Testing: Clinical experience of preimplantation genetic testing”. Reproduction 160 (2020): A45-58.
  18. Swain JE. “Controversies in ART: can the IVF laboratory influence preimplantation embryo aneuploidy?” Reproductive Bio Medicine 39 (2019): 599-607.
  19. Huang A., et al. “Prevalence of chromosomal mosaicism in pregnancies from couples with infertility”. Fertility and Sterility 91 (2009): 2355-2360.
  20. Paulson RJ and Treff NR. “Isn’t it time to stop calling preimplantation embryos “mosaic”?” F and S Reports 1 (2020): 164-165.
  21. Wiemer K., et al. “Comparison of IVF outcome from concurrent use of 3 different PGT-A laboratories”. Fertility and Sterility3 (2021): 275.
  22. Marin D., et al. “Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data”. Prenatal Diagnosis 41 (2021): 545-553.
  23. Capalbo A., et al. “Consistent and reproducible outcomes of blastocyst biopsy and aneuploidy screening across different biopsy practitioners: a multicentre study involving 2586 embryo biopsies”. Human Reproduction 31 (2016): 199 -208.
  24. Rubino P., et al. “Trophectoderm biopsy protocols can affect clinical outcomes: time to focus on the blastocyst biopsy technique”. Fertility and Sterility 113 (2020): 981-989.
  25. Yang H., et al. “Application of Two Blastocyst Biopsy Strategies in Preimplantation Genetic Testing Treatment and Assessment of Their Effects”. Frontiers in Endocrinology 13 (2022): 852620.
  26. Hovatta O. “Derivation of human embryonic stem cell lines, towards clinical quality”. Reproduction, Fertility and Development 18 (2006): 823.
  27. Aoyama N and Kato K. “Trophectoderm biopsy for preimplantation genetic test and technical tips: A review”. Reproductive Medicine and Biology 19 (2020): 222-231.
  28. Kelka DA., et al. “Does laser assisted biopsy introduce mosaic or chaotic changes to biopsied cells?” Fertility and Sterility 3 (2017): e88.
  29. Herrero Grassa L., et al. “Does the trophectoderm biopsy technique affect the result of the genetic analysis in PGT-A cycles?” Human Reproduction Abstract book1 (2019): O-248 i111.
  30. Zong C., et al. “Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell”. Science 338 (2012): 1622-1626.
  31. Treff NR and Franasiak JM. “Detection of segmental aneuploidy and mosaicism in the human preimplantation embryo: technical considerations and limitations”. Fertility and Sterility 107 (2017): 27-31.
  32. Cimadomo D., et al. “Inconclusive chromosomal assessment after blastocyst biopsy: prevalence, causative factors and outcomes after re-biopsy and re-vitrification. A multicenter experience”. Human Reproduction 33 (2018): 1839-1846.

D Nogueira., et al. Preimplantation Genetic Testing for Aneuploidies (PGT-A): Baring Our Limitations. EC Gynaecology 12.1 (2023): 01-06.