P-228 Reliability of blastomere versus trophectoderm biopsy in preimplantation genetic testing for mitochondrial DNA disorders

Abstract Study question Can a single blastomere or trophectoderm (TE) biopsy accurately reflect the heteroplasmy levels of whole embryo for mitochondrial DNA (mtDNA) disorders? Summary answer Heteroplasmy and TE are comparable to those rest embryo, including inner cell mass (ICM). What is known already Oocytes women carrying mtDNA mutations can display varying mutation loads – percentage mutated copies. Preimplantation genetic testing (PGT) aims at reducing risk having affected children by screening embryos with minimal heteroplasmy. The technique involves either on cleavage stage from blastocysts, followed analysis select suitable transfer. However, it remains unclear whether there uniform segregation heteroplasmic during early stages embryogenesis, therefore load biopsies representative embryo. design, size, duration We investigated suitability PGT disorders comparing between recovered eight-cell stage, cells same blastocyst (n = 15) in mouse model m.5024C>T mutation. also compared ICM human blastocysts 5) blastomeres arrested 4) donated two disease patients. Participants/materials, setting, methods To obtain embryos, we mated female mice tRNAAla (m.5024C>T) wild-type males. Whereas experiments, analysed preimplantation different carriers m.3243A>G mutation, associated MELAS syndrome, who showed 16% 32% their peripheral blood. After biopsy, NGS was performed three independent technical replicates profiles were samples assess levels. Main results role chance Analysis strong correlation corresponding (r2 0.76), 0.94) 15). Moreover, observed biopsied 0.90). ranged 55.3% 88.3%, mean overall 73.7 ± 7.9%. Development non-manipulated mutant 10) (blastocyst rate 85.7%). For 5), statistical portions 0.98). modest among 0.60) 24 4 embryos). 10.3% 57.4%, 42.8 12.2% 38.6 17.3% blastocysts. Overall, concordance blastomeres, established embryos. Limitations, reasons caution These should be further validated increasing sample size inclusion mutations. Furthermore, current data suggestive, but not definitive, guarantee that will remain constant throughout life. Wider implications findings Taken together, suggest may better than disorders. likely less harmful development. Following, investigate how segregates peri-implantation after resumption replication. Trial registration number Not applicable