Criteria to evaluate patterns of segmental and complete aneuploidies in preimplantation genetic testing for aneuploidy results suggestive of an inherited balanced translocation or inversion

Abstract

Objective: To define criteria for determining when preimplantation genetic testing for aneuploidy (PGT-A) results are suggestive of a potential balanced chromosomal rearrangement in the egg or sperm source and warrant karyotyping. Design: Performance evaluation of criteria developed to assess PGT-A results for patterns of imbalances suggestive of a balanced chromosomal rearrangement in the egg or sperm source. Setting: A single PGT-A laboratory and multiple in vitro fertilization centers. Patients: Reproductive couples who underwent routine PGT-A testing. Interventions: Karyotyping of reproductive couples for whom patterns of imbalances observed in PGT-A results suggested a balanced chromosomal rearrangement in the egg or sperm source. Main Outcome Measures: Correct or incorrect flagging of predicted translocation in either the egg or sperm source based on chromosome analysis. Results: Proposed criteria correctly predicted a balanced reciprocal translocation in 97% of cases (n = 33), a (13;14) Robertsonian translocation in all cases (n = 3), and an inversion in all cases (n = 2). Other criteria evaluated were determined to be ineffective because of relatively low occurrences that met the criteria and/or low predictive value. Conclusions: Our results showed that the proposed criteria were effective for evaluating patterns of imbalances observed in PGT-A results suggestive of a potential chromosomal rearrangement in the egg or sperm source. Our proposed criteria can be employed by clinicians in the in vitro fertilization setting in combination with a patient’s reproductive history to identify PGT-A patients who are likely carriers of balanced chromosomal rearrangements.

Keywords

• PGT-A results
• segmental aneuploidy
• translocations
• inversions
• pattern detection