Successful pregnancy to a complex chromosome rearrangement carrier by next-generation cytogenetics and preimplantation genetic testing

Background Complex chromosomal rearrangements (CCRs) pose a significant challenge for preconception counseling. This study aimed to provide a precise molecular diagnosis for an infertile woman with CCRs and to assess her fertility risks within a framework of assisted reproduction. Methods An integrated diagnostic strategy utilizing karyotyping, optical genome mapping (OGM), and mate-pair sequencing (MPseq) was employed to delineate the chromosomal breakpoints at a high resolution. Sanger sequencing was used for validation. Preimplantation genetic testing (PGT) was subsequently applied to assist this infertile woman in achieving a successful pregnancy. Results A complex rearrangement involving nine breakpoints between chromosomes 1 and 6 was identified by OGM. MPseq further detected six additional breakpoints that were not identified by OGM, all of which were confirmed through Sanger sequencing. A successful pregnancy was achieved following PGT. Prenatal diagnosis at 18 weeks’ gestation via amniocentesis and MPseq revealed the fetus carried the same CCRs as the mother. At 38 weeks of gestation, a healthy male infant weighing 3100 g was delivered through cesarean section. Conclusions Both OGM and MPseq are reliable next-generation cytogenetic tools for detecting chromosomal structural variations, with MPseq potentially offering superior accuracy in breakpoints determination. For individuals with CCRs, PGT may significantly improve reproductive outcomes.