Application of multi-technique integration in the prenatal diagnosis of mosaicism derived from an ICSI blastocyst: a diagnostic approach and clinical implications

To investigate the prenatal diagnosis following intracytoplasmic sperm injection (ICSI) and blastocyst transfer. By integrating multiple cytogenetic and molecular techniques, we characterized a mosaic duplication of chromosome 20p, evaluated its pathogenicity and clinical significance, and provided evidence for prenatal genetic counseling. Amniocentesis was performed in a pregnant woman identified as high-risk by non-invasive prenatal testing (NIPT), which suggested a 15q 26.3 deletion. Fetal amniotic fluid cells were analyzed using G-banding karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH). NIPT detected a 3.04 Mb deletion at 15q26.3.CMA showed a 20.51 Mb mosaic duplication involving 20p13p11.23, with an estimated mosaic proportion of approximately 50%, whereas G-banding karyotyping of amniotic fluid cells showed an unremarkable result. Mid-term FISH analysis performed in our hospital identified mosaicism for der(15)t(15;20)(qter;p13), indicating that a duplicated segment of 20p13 was translocated to the terminal region of chromosome 15. FISH analysis performed at an external hospital showed that 49% of cells carried an additional 20p13 signal. Peripheral blood karyotypes of both parents were unremarkable. This case illustrates how the integration of CMA, G-banding, and targeted FISH enables accurate characterization of complex chromosomal rearrangements in prenatal diagnosis. While these findings underscore the importance of thorough evaluation in ART-conceived pregnancies, they do not establish a causal relationship between assisted reproduction and the observed chromosomal abnormality. The high-level mosaic duplication of 20p13p11.23 is associated with significant pathogenic risk. Following comprehensive genetic counseling, the parents made an informed decision regarding pregnancy management. Couples with abnormal sperm parameters or repeated fertilization failure should be counseled about the potential risk of chromosomal mosaicism, and preimplantation genetic testing may be considered where indicated.