Clinical Application of Preimplantation Genetic Diagnosis (PGD) for Carriers of Chromosome Rearrangements—What Should You Expect?

Abstract

Background: Preimplantation genetic diagnosis (PGD) for couples with structural chromosome rearrangements is an accepted and effective alternative to prenatal diagnosis of an ongoing pregnancy and possible pregnancy interruption. This type of specialized diagnostic procedure is now available to most IVF centers through the use of “transport PGD,” where the sample is sent to a specialty genetics laboratory able to perform this high-tech testing. Clinicians in the referring center, however, are often left wondering how to counsel patients and manage expectations in complex situations such as chromosome rearrangements. Objective: The aim of this study was to determine if the overall percentage and therefore the expected number of normal/balanced embryos per case differed in PGD cycles performed for various structural chromosome rearrangements (Robertsonian translocations, balanced reciprocal translocations, and inversions). Materials and Methods: In this retrospective study, the number of normal/balanced embryos per cycle and the overall percentage of normal embryos were assessed from PGD cycles performed for chromosome rearrangements in our laboratory. Of these 52 cycles, 35 (67.3%) were from patients in our center and 17 (32.7%) were transport PGD received from an outside center. Results: During the study, 408 embryos were biopsied and tested for known structural rearrangements. On average, there were 1.98 normal/balanced embryos per case. The number of normal/balanced embryos per cycle available for transfer was higher for Robertsonian translocations than for other structural chromosome rearrangements (3.0 vs. 1.4). Overall, the percentage of normal/balanced embryos for cycles performed for Robertsonian translocations was higher than for balanced reciprocal translocations and inversions (35.6% vs. 18.5%). In comparison, during the same time period we observed an average of 32.5% normal embryos (2.9 normal embryos per cycle) in our patients who had PGD for aneuploidy screening, primarily for advanced reproductive age. Conclusions: PGD for chromosome rearrangements is a unique class of testing that requires specialized patient counseling. In general, fewer normal embryos should be expected when PGD is performed for balanced reciprocal translocations and inversions than for Robertsonian translocations and aneuploidy. To manage patient expectations, this information needs to be discussed with them by a variety of different providers, including reproductive endocrinologists, embryologists, and genetic counselors.