Newborns derived from embryos showing low/moderate-degree mosaicism do not exhibit chromosomal aberrations or uniparental disomy profiles.

To define the association between putative low-medium-grade mosaicism detected in IVF/PGT-A blastocysts and the occurrence of chromosomal mosaicism or uniparental disomy at birth. This is a follow-up study of newborns derived from a prospective multicenter non-selection study involving five IVF clinics. Trophectoderm biopsies showing intermediate chromosome copy number (CN) values consistent with low mosaicism (20-50%) were blindly reported as euploid. Embryos were selected for Single Euploid Embryo Transfers (SEET) based on their morphological grade. The original clinical study involved the transfer of 897 blastocysts (484 uniformly euploid– Group A and 413 low-moderate mosaic- Group B) between Sept 2018 and Dec 2019, resulting in 498 implantations (270 and 228, respectively). Of these initial pregnancies, 60 were lost prior to ultrasound confirmation, while 52 were miscarried, resulting in a total of 386 live births (210 and 176, respectively). When possible, genetic results from prenatal diagnosis (i.e., amniocentesis or chorionic villi sampling, CVS) or from products of conceptions analyzed following miscarriage were collected. At later stages, the chromosomal status of ensued newborns was investigated using single nucleotide polymorphism arrays (SNPa genotyping) on saliva samples collected from the newborns and their parents (trios). Ethical committee approvals and patients’ consents were obtained at each site. Four of the 52 miscarriages underwent POC analysis by standard cytogenetic analysis, whilst only 26 of all sustained pregnancies derived (26/386, 6.7%) underwent prenatal diagnosis (PND) by amniocentesis (Group A = 15, Group B = 9) or CVS (Group A = 2). All PND displayed a euploid karyotype except in one pregnancy from Group A which showed a 20% mosaicism for chromosome 22 following CVS analysis. However, previous findings were not confirmed by subsequent amniocentesis where all of the 50 metaphases analysed showed euploid karyotypes (the case was defined as placental confined mosaicism). PNG of newborns was possible for 38 families (9.8% of all newborns derived from the study; 5.2% of Group A (n= 11/210) and 15.3% of Group B (n= 27/176), respectively). All PNG tests showed fully normal karyotypes and absence of UPD. No infants showed abnormalities associated with an aberrant karyotype attributable to prenatal mosaicism. One infant from Group B was born with a diagnosis of Beckwith-Wiedemann Syndrome caused by hypomethylation in the region KvDMR/IC2, which is not a diagnostic target of PGT-A and only detectable through SNPa trios analysis. No instances of mosaicism or uniparental disomy were detected in babies born following putative mosaic SET.