Polymerase chain reaction-based detection of chromosomal imbalances on embryos: the evolution of preimplantation genetic diagnosis for chromosomal translocations.

Objective: To develop and assess a polymerase chain reaction (PCR)-based preimplantation genetic diagnosis (PGD) approach for detection of chromosomal imbalances in embryos.

Design: A prospective study of embryos derived from chromosome translocation carriers that have undergone PGD using a novel molecular-based approach.

Setting: A reference molecular genetics laboratory specialized in the provision of transport PGD services and a private IVF clinic.

Patient(s): Twenty-seven couples carrying 12 different reciprocal translocations and 2 Robertsonian translocations.

Intervention(s): Preimplantation genetic diagnosis from chromosome translocation carriers on blastomeres biopsied from cleavage stage embryos.

Main Outcome Measure(s): Embryo diagnosis rate, pregnancy rate (PR), implantation rate, take-home-baby rate.

Result(s): Overall, 241/251 (96.0%) embryos were successfully diagnosed for chromosome rearrangements. Preimplantation genetic screening was included in the protocol of 12 couples, involving analysis of 90 embryos, 84 (93.3%) of which were successfully diagnosed and 53 (63.1%) showed aneuploidies. Embryos suitable for transfer were identified in 24 cycles. Eighteen couples achieved a clinical pregnancy (75.0% PR/embryo transfer), with a total of 31 embryos implanted (59.6% implantation rate). Ten patients (1 triplet, 1 twin, and 8 singleton pregnancies) have delivered 13 healthy babies, and the other patients (3 twins and 5 singletons) have currently ongoing pregnancies.

Conclusion(s): The PCR-based PGD protocol for translocations has the potential to overcome several inherent limitations of fluorescence in situ hybridization-based tests, providing potential improvements in terms of test performance, automation, turnaround time, sensitivity, and reliability.