Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism.

The health risks associated with transferring embryos classified as mosaic by preimplantation genetic testing for aneuploidies (PGT-A) are currently unknown. Such embryos produce PGT-A results indicating the presence of both euploid and aneuploid cells and have historically been deselected from transfer and grouped with uniformly aneuploid embryos as 'abnormal'. In recent years, numerous groups have reported the intentional transfer of mosaic embryos in the absence of uniformly euploid embryos, largely observing births of seemingly healthy babies. However, it remains to be understood whether the embryonic mosaicism invariably becomes resolved during the ensuing pregnancy, or whether the placenta and/or fetal tissues retain aneuploid cells, and if so to what potential clinical effect. Here, we report two cases of mosaicism persisting from the embryonic stage to the established pregnancy. Case 1 involved an embryonic low-level segmental mosaic loss in Chromosome (Chr) 1, which was confirmed in amniocentesis as well as in brain tissue of the products of conception. This pregnancy was terminated due to the chromosomal pathologies associated with 1p36 deletion syndrome, such as severe intellectual disability. Case 2 involved a low-level mosaic Chr 21 trisomy, which was confirmed with chorionic villus sampling and amniocentesis. The ensuing pregnancy was terminated after ultrasound identification of severe abnormalities in the placenta and fetus. Together, these two cases should be taken into account for risk-benefit assessments of prospective mosaic embryo transfers.

Neonatal and clinical outcomes after transfer of a mosaic embryo identified by preimplantation genetic testing for aneuploidies.

RESEARCH QUESTION: Do clinical and neonatal outcomes differ between mosaic embryo transfers (MET) and euploid embryo transfers (EET)? DESIGN: This retrospective cohort study compared the implantation rate, live birth rate (LBR) and miscarriage rate between 513 euploid embryos and 118 mosaic embryos (72 whole chromosome mosaic [WCM], 40 segmental mosaic and six complex mosaic). Blastocysts were analysed using preimplantation genetic testing for aneuploidies with next-generation sequencing, followed by a single vitrified-warmed embryo transfer. Trophectoderm biopsies were classified as mosaic if they had 20-80% abnormal cells. RESULTS: Overall, EET resulted in a significantly higher implantation rate (47.0%) and LBR (40.7%) than MET (implantation rate 39.0%, P = 0.005; LBR 28.8%, P = 0.008) and WCM embryos (implantation rate 37.5%, P = 0.01; LBR 22.2%, P = 0.007) after covariate adjustment. Segmental mosaic embryos had an implantation rate (47.5%) and LBR (45.0%) comparable to those of euploid embryos. Mosaic embryos with a high percentage of aneuploid cells (≥60%) showed a significantly lower LBR (10.5% versus 40.7%, P = 0.03) than euploid embryos after covariate adjustment, with three of the five implantations of mosaic embryos resulting in miscarriage. Neonatal outcomes did not differ significantly between the mosaic and euploid groups. Of the 34 women with a live birth after MET, 13 had a prenatal or postnatal genetic testing result, and no abnormalities were found. CONCLUSIONS: Mosaic embryos were associated with a lower LBR, while segmental mosaic embryos had similar clinical outcomes to euploid embryos. Mosaic embryos with a high aneuploidy percentage (≥60%) should be assigned a low transfer priority. Neonatal outcomes did not differ significantly between the euploid and mosaic groups.