Purpose: The goal of this study is to determine whether any balanced translocation (BT) had been missed by previous karyotyping in patients with unexplained recurrent pregnancy loss (uRPL).
Methods: This case series included 48 uRPL-affected couples with normal karyotypes. The embryos from these couples have all undergone preimplantation testing for aneuploidies (PGT-A). Based on the PGT-A's results, 48 couples could be categorized into two groups: 17 couples whose multiple embryos were detected with similar structural variations (SVs, segmental/complete) and 31 couples without such findings but who did not develop any euploid embryo despite at least three high-quality blastocysts being tested. The peripheral blood sample of each partner was then collected for mate-pair sequencing (MPseq) to determine whether any of them were BT carriers.
Results: MPseq analyses identified 13 BTs in the 17 couples whose multiple embryos had similar SVs detected (13/17, 76.47%) and three BTs in the 31 couples without euploid embryo obtained (3/31, 9.7%). Among the 16 MPseq-identified BTs, six were missed due to the limited resolution of G-banding karyotyping analysis, and the rest were mostly owing to the similar banding patterns and/or comparable sizes shared by the two segments exchanged.
Conclusion: A normal karyotype does not eliminate the possibility of carrying BT for couples with uRPL. The use of PGT-A allows us to perceive the "carrier couples" missed by karyotyping analysis, providing an increased risk of finding cryptic BTs if similar SVs are always detected on two chromosomes among multiple embryos. Nonetheless, certain carriers with translocated segments of sub-resolution may still go unnoticed.
Keywords: Cryptic balanced translocation; GTG-banded karyotype analysis; Mate-pair sequencing; Missed diagnosis; Preimplantation genetic testing for aneuploidies; Unexplained recurrent pregnancy loss.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.