Concordance of repeat biopsy results among embryos with 6 or more aneuploidies

Chaotic embryos have copy number variations in 6 or more chromosomes and subsequent transfer is typically not recommended. Yet, recent reports detail a healthy live birth following chaotic embryo transfer (1) and demonstrate that 40% of re-biopsies resulted euploid following initial ‘chaotic’ biopsy result (2). The objective of this study is to assess chromosome concordance in embryos found to be ‘chaotic’ on repeated biopsy. Secondary outcome was to evaluate for associations with maternal age and/or day of blastocyst biopsy. This repeated measures study compared the initial and the repeat biopsy results analyzed by Next Generation Sequencing (NGS) at the same reference laboratory. Analysis of concordance between first and second biopsies was stratified by patient age and day of blastocyst biopsy. Concordance was defined as a re-biopsy result of either chaotic (“concordantly chaotic”) or aneuploid. For embryos with concordantly chaotic results on both biopsies, per pair chromosome concordance was assessed. Non-random associations were assessed by Fisher’s Exact Test. A total of 64 embryos initially reported as chaotic were re-biopsied. Overall concordance was 67% (44% concordantly chaotic,23% aneuploid) (Table). A total of 11 embryos were reclassified as euploid on repeat biopsy (17%) (Table). While chaotic embryos biopsied on day 7 were more likely than day 5 or 6 chaotic embryos to be concordant this did not achieve statistical significance (P=0.067). Further, concordance in chaotic embryo diagnosis was not associated with maternal age. Concordantly chaotic embryos (n=28) showed a Median of 100% (IQR 96-100%) of having the same aneuploidy per pair of 23 chromosomes. In our hypothesis-generating observational study, 17% of chaotic embryos were reclassified as euploid at re-biopsy. A trend toward higher likelihood of concordantly chaotic result was observed among late-developing embryos. Interestingly, concordantly chaotic embryos demonstrated copy number variations in the same chromosomes in nearly every instance. Additional study will lend credence to observations and allow for insight into the clinical relevance of findings presented herein.