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Fertility and sterilityJournal Article

07 May 2025

Chaotic blastocysts in preimplantation genetic testing for aneuploidy: prevalence, characterization, and re-biopsy results.

Objective

To evaluate the reproductive potential of blastocysts designated as chaotic by preimplantation genetic testing for aneuploidy (PGT-A) through re-biopsy and re-analysis.

Design

Retrospective study of 1,442 PGT-A cycles from November 2017 to December 2023.

Subjects

Five thousand eight hundred one blastocysts from 22 in vitro fertilization clinics, including 93 chaotic blastocysts donated for re-biopsy. Chaotic embryos were classified as pure (≥5 uniform aneuploidies), mixed (combination of ≥5 uniform aneuploidies and intermediate copy number chromosomes), and mosaic (≥5 intermediate copy number chromosomes).

Exposure

Re-biopsy and re-analysis of chaotic blastocysts using next-generation sequencing.

Main outcome measures

Prevalence of chaotic embryos, survival rate after thawing, and concordance rate between initial and re-biopsy PGT-A results.

Results

The prevalence of chaotic embryos was 4.3% (251/5,801): 13.5% (34) pure, 53.0% (133) mixed, and 33.5% (84) mosaic. After thawing 93 donated chaotic embryos, the survival rate was 74.2% (69). Surviving embryos underwent re-biopsy, yielding the following PGT-A results: 24.6% (17) euploid, 37.7% (26) chaotic, 26.1% (18) aneuploid non-chaotic, 7.2% (5) mosaic, and 4.4% (3) non-informative. Outcomes varied substantially among sub-categories of chaotic embryos. In the pure chaotic category (n = 11), 72.7% (8) yielded results identical to the initial biopsy, whereas 27.3% (3) were re-classified as aneuploid non-chaotic. Within the mixed chaotic category (n = 24), 54.2% (13) retained their mixed chaotic classification, whereas 45.8% (11) were re-classified as aneuploidy non-chaotic. Embryos re-classified into the aforementioned categories had at least one aneuploidy in common with the initial biopsy. Mosaic chaotic category (n = 31) showed the most diverse outcomes: 54.8% (17) were re-classified as euploid, 16.1% (5) remained mosaic chaotic, 16.1% (5) were re-classified as mosaic non-chaotic, and 12.9% (4) as aneuploid non-chaotic. Concordance with the initial biopsy in terms of aneuploid result was 100% in the pure and mixed chaotic categories. However, over half of embryos initially categorized as mosaic chaotic were, in fact, euploid.

Conclusion

Re-biopsy can potentially identify embryos with favorable reproductive potential, particularly those initially classified as mosaic chaotic. However, pure and mixed chaotic blastocysts consistently show aneuploidy on re-testing, suggesting limited benefit from re-biopsy for these categories.

COI Statement

Declaration of Interests A.C. is the PGT laboratory manager of the Institute of Sciences in Human Reproduction Vida. A.V.M has nothing to disclose. C.G.O. has nothing to disclose. I.M.R. has nothing to disclose. A.A.R.M. has nothing to disclose. A.M.G.G. is the CEO of the Institute of Sciences in Human Reproduction Vida, which has a clinical preimplantation genetic testing laboratory.

Article info

Journal issue:

  • Volume: not provided
  • Issue: not provided

Doi:

10.1016/j.fertnstert.2025.04.001

More resources:

Elsevier Science

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ClinicalKey

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