Complex Reciprocal Translocations, More Complex Than Initially Thought: a Case Report

Objective: To present a case of a couple who experienced spontaneous abortion after the transfer of a preimplantation genetic testing for structural rearrangement (PGT-SR) normal/balanced embryo. The embryo was later determined to have significant paternally inherited chromosome deletion that was not previously identified as part of a complex translocation.

Design: Case report.

Setting: Single infertility practice.

Patients: A 35-year-old patient with a history of five spontaneous abortions and her 36-years-old partner, a carrier of a balanced reciprocal translocation.

Interventions: In vitro fertilization with PGT-SR and follow-up genetic testing.

Main Outcome Measures: Identification of a paternal reciprocal translocation, pregnancy outcome after PGT-SR, and follow-up genetic testing after the spontaneous abortion of a PGT-SR normal/balanced embryo.

Results: Karyotyping for a couple with a history of recurrent pregnancy loss identified a paternal reciprocal translocation between chromosomes 5 and 17 after G-banding analysis. In vitro fertilization with PGT-SR resulted in one normal/balanced embryo. The couple experienced a 9-week spontaneous abortion of the transfer of the embryo. Testing of product of conception identified a 3.2-Mb deletion on chromosome 17 resulting in the loss of 55 known genes and deemed likely pathogenic. Repeat karyotyping using G-banding and metaphase fluorescence in situ hybridization identified an additional chromosomal translocation, a segment of chromosome 17 translocated to chromosome 6, the same segment of deoxyribonucleic acid absent from the fetus.

Conclusions: Preimplantation genetic testing for structural rearrangement cases are complex. Genetic testing must be completed with the best available technology by a reliable testing center. We, therefore, recommend that all chromosomal translocations detected by G-banding be further investigated with metaphase fluorescence in situ hybridization. When unexpected results occur in this patient population, testing beyond the standard of care may be required, including advanced molecular testing.