Clinical outcomes after the transfer of blastocysts characterized as mosaic by high resolution Next Generation Sequencing- further insights

Munne S, Spinella F, Grifo J, Zhang J, Beltran M P, Fragouli E, Fiorentino F,
Eur J Med Genet. Feb. 2020 doi: 10.1016/j.ejmg.2019.103741


OBJECTIVE: To determine the pregnancy outcome potential of euploid, mosaic and aneuploid embryos. DESIGN: Retrospective study. SETTING: Reference genetics laboratories. PATIENT(S): 2654 PGT-A cycles with euploid characterized embryo transfers, 253 PGT-A cycles with transfer of embryos characterized as mosaic, and 10 PGT-A cycles with fully abnormal embryo transfers. INTERVENTION(S): Blastocysts were assessed by trophectoderm (TE) biopsy followed by PGT-A via array CGH or NGS. MAIN OUTCOME MEASURE(S): Implantation, miscarriage, ongoing implantation rates (OIR), and karyotype if available, were compared between different embryo groups, and between the two PGT-A techniques. RESULTS: The Ongoing Pregnancy Rate (OPR)/transfer was significantly higher for NGS-classified euploid embryos (85%) than for aCGH ones (71%) (p<0.001), but the OPR/cycle was similar (63% vs 59%). NGS-classified mosaic embryos resulted in 37% OPR/cycle (p<0.001 compared to euploid). Mosaic aneuploid embryos with <40% abnormal cells in the TE sample had an OIR of 50% compared to 27% for mosaics with 40-80% abnormal cells in the TE, and 9% for complex mosaic embryos. All the karyotyped ongoing pregnancies (n=29) were euploid. Transfers of embryos classified as aneuploid via aCGH (n=10) led to one chromosomally abnormal pregnancy. CONCLUSION(S): NGS-classified euploid embryos yielded higher OIRs but similar OPRs/cycle compared to aCGH. NGS-classified mosaic embryos had reduced potential to reach term, compared to euploid embryos. If they did reach term, those with karyotype results available were euploid. Embryos carrying uniform aneuploidies affecting entire chromosomes were mostly unable to implant after transfer, and the one that implanted ended up in a chromosomally abnormal live birth.