Clinical Significance of Abnormal First-Trimester Chorionic Villus Sampling After Mosaic Embryo Transfer: A Prospective Study with Confirmatory Amniocentesis

Background/Objectives: Prenatal outcomes after mosaic embryo transfer are generally reassuring. However, evidence remains limited on how an abnormal first-trimester chorionic villus sampling (CVS) result should be interpreted. We evaluated first-trimester CVS findings after mosaic embryo transfer and examined their relationship with the original preimplantation genetic testing for aneuploidy (PGT-A) results and subsequent amniocentesis. Methods: This prospective observational study included 183 CVS specimens obtained from placentas corresponding to PGT-A-designated mosaic embryos. Uncultured chorionic villi were analyzed using the same next-generation sequencing platform used for PGT-A. Abnormal CVS findings were compared with the original PGT-A results, and all nine pregnancies with an abnormal CVS result underwent diagnostic amniocentesis. Results: Of the 183 CVS specimens, 174 (95.1%) were euploid and nine (4.9%; exact 95% confidence interval, 2.27–9.13%) were abnormal. Among the nine abnormal findings, three involved the same chromosome or chromosomal region reported by PGT-A, whereas six involved a different chromosome or region. Amniocentesis showed a euploid result in eight cases, which were classified as confirmed confined placental mosaicism. In the remaining case, mosaicism was also detected in amniotic fluid and was classified as confirmed fetal mosaicism. Conclusions: This is the largest published series specifically evaluating first-trimester CVS after mosaic embryo transfer. Abnormal CVS findings were uncommon, and eight of the nine abnormal findings were confined to the placenta. Furthermore, six involved a chromosome or chromosomal region different from that reported by PGT-A. Therefore, an abnormal CVS result does not necessarily indicate fetal involvement or persistence of the original PGT-A abnormality. Amniocentesis is required to clarify the fetal chromosomal status.