09/08/2022
Chromosome testing strategies, such as preimplantation genetic testing for aneuploidy (PGT-A), improve initial IVF outcomes by avoiding transfer of aneuploid embryos in morphology-based selection practices. Chromosome mosaicism has been observed commonly although usually in only a minority of embryos. Sensitive technologies such as array CGH and NGS based methods can variably distinguish uniform aneuploidies (affecting all cells in the biopsy) from mosaic aneuploidies (affecting only some of the cells in the biopsy). At the blastocyst stage, the incidence of reported mosaicism using NGS methods is highly variable amongst clinics, ranging from as low as 2% to as high as 40% with the vast majority of clinics reporting between 5-15% depending on age group being investigated (Fragouli et al., 2019; Munne et al., 2016; Rodrigo et al., 2020; Ruttanajit et al., 2016). A consistent high incidence of mosaic embryos in a selected clinic may be related to predominant patient age group, clinical treatment and/or specific embryology practices (Fragouli et al., 2019) while a high level of apparent mosaicism across all referral clinics may be indicative of poorer testing laboratory practices. Circumstantial evidence is emerging that suggests that NGS and associated data analysis pipelines used to measure chromosome copy number may at times incorrectly indicate mosaicism (Fragouli et al., 2019; Marin et al., 2021). Theoretically, mosaicism estimates could be exaggerated by the following:
(i) Poor biopsy technique
(ii) Poor sample handling/transport
(iii) Sub-optimal DNA amplification and library construction
(iv) Choice of algorithms used for normalizing the chromosome mapping bins
More to follow..
