High pregnancy rate after comprehensive chromosomal screening of blastocysts

Abstract

OBJECTIVE: Traditionally, preimplantation genetic screening has involved the biopsy of a single blastomere at the cleavage stage followed by limited chromosomal assessment using fluorescent in situ hybridization (FISH). The objective of this study was to clinically apply a novel strategy for aneuploidy detection, based upon comprehensive chromosome screening of trophectoderm (TE) cells biopsied at the blastocyst stage. DESIGN: Clinical evaluation of a new approach for embryo viability assessment. MATERIALS AND METHODS: All 23 pairs of chromosomes were screened for aneuploidy in 106 blastocysts derived from 17 patients. The patients were of advanced maternal age (mean 37 years), with a history of multiple failed IVF attempts and/or multiple abortions. 3-10 TE cells were biopsied from each blastocyst and subjected to whole genome amplification and comparative genomic hybridization (CGH). Blastocysts were cryopreserved using vitrification while CGH analysis took place. Chromosomally normal blastocysts were warmed and transferred in a subsequent FET. RESULTS: The CGH approach underwent extensive validation prior to clinical application, confirming accuracy and cytogenetic concordance between the TE and inner cell mass. Clinically, CGH succeeded in producing a full chromosome screen for 91% of blastocysts tested. The aneuploidy rate was 43.8%. Embryo survival after biopsy and warming were excellent (100%). To date, 10 patients have undergone blastocyst FET, resulting in an implantation rate of 55% per embryo and an ongoing clinical pregnancy rate (fetal heart) of 70% per cycle. Further transfers are in progress. CONCLUSIONS: We report the first clinical application of a novel approach for preimplantation genetic screening, involving assessment of all chromosomes at the blastocyst stage. The sampling of several cells resulted in a robust diagnosis and greatly reduces the risk of misdiagnosis due to chromosomal mosaicism. Implantation and clinical pregnancy rates were high (55% and 70%), especially given the poor reproductive history of the patients, and compare very favorably with non-PGS cycles matched for maternal age (30% and 60% respectively). Despite the high implantation potential of blastocysts it is clear that many still harbor lethal aneuploidies. It is likely that accurate, comprehensive chromosomal screening will significantly improve embryo selection and may be key to maintaining high pregnancy rates in cycles involving elective single blastocyst transfer.