10. COMPARISON OF VARIOUS ANEUPLOIDY TYPES AMONG TWO TROPHECTODERM BIOPSIES AND A REST OF THE EMBRYO

Abstract

Introduction With the introduction of next generation sequencing (NGS), preimplantation genetic testing of aneuploidies (PGT-A) has become a powerful tool for the selection of euploid embryos, increasing the implantation rate and reducing the risk of pregnancy miscarriage. Due to the higher resolution and dynamic range offered by NGS, the phenomenon of mosaicism and segmental aneuploidies has become challenging for clinical interpretations. Numerous studies have reported live-births after transfer of mosaic embryos, however, only a few studies focused on the clinical relevance of segmental aneuploidies. In our study, we compared various aneuploidy findings among two trophectoderm biopsies and a rest of the embryo. Material and methods In total, 89 embryos previously analyzed with the VeriSeq™ kit were de-vitrified and re-analyzed with the consent of the patients. A second trophectoderm biopsy (TE2) and the rest of the embryo including the inner cell mass (RE) was tubed separately. The TE2 and the RE as well as the amplification product from the original trophectoderm biopsy (TE1) were analyzed using the PG-Seq™ kit. After TE1 reanalysis, 18 biopsies were classified as euploid and the remaining 71 samples had the following aberrations, 62 whole chromosome aneuploid, 32 segmental aneuploid, 26 whole chromosome mosaic and 7 segmental mosaic. Concordance of various aneuploidy types was assessed between TE1, TE2 and RE. Results From the original group of 18 embryo biopsies classified as euploid with TE1, 17 (94.4%) were concordant with TE2 and 16 (88.9%) in RE. Whole chromosome aneuploidy was concordant in 95.2% of cases between TE1-TE2, 93.5% of TE1-RE and 92.3% of TE2-RE with nonconformance generally due to changes in the affected chromosome to segmental aneuploidy or whole chromosome mosaic. In contrast, from 33 individual segmental aneuploidies detected in the original TE1, only 14 of them were observed again in TE2 and RE (42.2%) with 13 changing to euploid. When the TE1 segmental aneuploidy was also manifested in the TE2, it was almost always observed in the RE, with one exception (1/19, 5.3%). Only 1 of 26 (3.8%) TE1 originally found to be whole chromosome mosaic was repeated in the TE2 and 7 in the RE (26.9%). No segmental mosaics were concordant between TE1-TE2 or TE1-ROE and only 1/8 was concordant between TE2-ROE. Conclusions Our study showed that euploid and whole chromosomal aneuploidies have a high predictive value towards the rest of the embryo. In contrast, mosaicism seems to have a low concordance rate between different parts of the embryo, which show us minimal predictive value of the mosaic findings. Interestingly, a 42.2% concordance rate between TE1 and other two parts of the embryo in the group of subchromosomal aneuploidies suggest their clinical potential for healthy live births since these errors may be of mitotic origin. Moreover, and in contrast to mosaics, second embryo biopsy helps to significantly increase the predictive value of segmental aneuploidies towards the rest of the embryo. Further clinical studies are needed, however, a second trophectoderm biopsy of embryos with segmental aneuploidies seems indicated, especially for patients where an euploid embryo is unavailable.