Preimplantation genetic diagnosis for complex chromosome rearrangements

Complex chromosome rearrangements (CCR) are structural rearrangements that involve more than two breakpoints. The most common ones involve three chromosomes and three breakpoints, but double translocations can also occur. Theoretically, the potential for chromosome imbalance in the gametes of CCR carriers is higher than for simple translocations, and thus they are at an even higher risk of recurrent miscarriage. Preimplantation genetic diagnosis (PGD) has been shown to significantly reduce the risk of repeated pregnancy loss in translocation carriers, and thus it is well indicated for CCR. Here we describe different approaches for PGD of CCRs. After PGD of five couples carriers of CCR, only 6.4% of embryos were found normal or balanced, but the transfer of these six embryos into four couples, resulted in two pregnancies, one with normal non-identical twins, and the other with a balanced karyotype. Thus the implantation rate was 50%, and the pregnancy per retrieval was 40%, with 0% spontaneous abortions and 0% unbalanced offspring. This compares favorably with a prior history of spontaneous abortions, unbalanced offspring, and low fertility.