Cleavage stage embryo biopsy significantly impairs embryonic reproductive potential while blastocyst biopsy does not: a novel paired analysis of cotransferred biopsied and non-biopsied sibling embryos

Abstract

Recent advances in molecular genetics provide the opportunity to more accurately assess the reproductive potential of embryos. These technologies require embryonic DNA which necessitates embryo biopsy. Amongst the most critical questions surrounding these technologies are the risks associated with embryo biopsy itself, and whether biopsy is safest at the cleavage or blastocyst stage. This study uses a novel paired design to accurately assess the impact of biopsy on day 3 and day 5 of development. Paired randomized controlled trial. Patients received routine care inclusive of embryo selection. Once the 2 best embryos were selected for transfer, one was randomly selected for biopsy and the other to control. The embryos were then transferred together. With resulting pregnancies, DNA fingerprinting of the conceptus was used to determine whether it was derived from the biopsied (self) or non-biopsied (sibling) embryo. Analysis was done using a paired test of proportions. 103 patients were studied - 32 at the cleavage stage and 71 at the blastocyst stage. There was a dramatic reduction in implantation rates amongst biopsied cleavage stage embryos compared to the non-biopsied controls (31% vs 53%;P=0.035) - a loss of reproductive potential of more than one third. In contrast, the implantation rate of biopsied and non-biopsied blastocysts was equivalent (52% vs 54%; P=0.80). Trophectoderm (TE) biopsy of blastocysts does not adversely impact embryonic reproductive potential. In contrast, biopsy at the cleavage stage was clearly detrimental with a 22% reduction in implantation rate. Optimizing clinical outcomes following PGD might be best realized by performing biopsies at the blastocyst stage. Potential explanations as to why blastocyst biopsy is safe when cleavage stage biopsy is not include the removal of a smaller proportion of the embryo, certainty that only TE cells are biopsied, and better embryonic tolerance of manipulation after genomic activation.