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

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

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

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).

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

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

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.