Embryo fragmentation in vitro and its impact on treatment and pregnancy outcome

113

Human preimplantation embryo development is prone to high rates of early embryo wastage, particularly under current in vitro culture conditions. There are many possible underlying causes for embryo demise, including DNA damage, poor embryo metabolism and the effect of suboptimal culture media, all of which could result in an imbalance in gene expression and the failed execution of basic embryonic decisions. In view of the complex interactions involved in embryo development, a thorough understanding of these parameters is essential to improving embryo quality. An increasing body of evidence indicates that cell fate (i.e. survival/differentiation or death) is determined by the outcome of specific intracellular interactions between pro-and anti-apoptotic proteins, many of which are expressed during oocyte and preimplantation embryo development. The recent availability of mutant mice lacking expression of various genes involved in the regulation of cell survival has enabled rapid progress towards identifying those molecules that are functionally important for normal oocyte and preimplantation embryo development. In this review we will discuss the current understanding of the regulation of cell death gene expression during preimplantation embryo development, with a focus on human embryology and a discussion of animal models where appropriate.

Section: Human In Vitro Fertilization and Embryo Wastagementioning

confidence: 99%

Deadly decisions: the role of genes regulating programmed cell death in human preimplantation embryo development

Jurisicova¹,

Acton²

2004

113

“…In cattle, early embryonic loss between days 8 and 18 accounts for w40% of all PL (Ayalon 1978, Diskin & Sreenan 1980. Similarly, the vast majority of human embryos cultured in vitro at fertility centers worldwide fail to develop in vivo following transferring to the uterus (Dobson et al 2004) with implantation rates of only 20% (Ebner et al 2001). However, in contrast to the bovine embryos, human embryos were transferred back to the oocyte donors and were transferred to the uterus at earlier stages of development.…”

Section: Introductionmentioning

confidence: 99%

Bovine blastocysts with developmental competence to term share similar expression of developmentally important genes although derived from different culture environments

Ghanem¹,

Salilew‐Wondim²,

Gad³

et al. 2011

This study was conducted to investigate the gene expression profile of in vivo-derived bovine embryo biopsies based on pregnancy outcomes after transferring to recipients. For this, biopsies of 30-40% embryos were taken from grade I blastocysts (International Embryo Transfer Society Manual) and the remaining 60-70% of the intact embryos were transferred to recipients. Frozen biopsies were pooled into three distinct groups based on the pregnancy outcome after transferring the corresponding parts, namely those resulting in no pregnancy (NP), pregnancy loss (PL), and calf delivery (CD). Array analysis revealed a total of 41 and 43 genes to be differentially expressed between biopsies derived from blastocysts resulting in NP versus CD and PL versus CD respectively. Genes regulating placental development and embryo maternal interaction (PLAC8) were found to be upregulated in embryo biopsies that ended up with CD. Embryo biopsies that failed to induce pregnancy were enriched with mitochondrial transcripts (Fl405) and stress-related genes (HSPD1). Overall, gene expression profiles of blastocysts resulting in NP and CD shared similar expression profiles with respect to genes playing significant roles in preimplantation development of embryo. Finally, comparing the transcript signatures of in vivo-and in vitro-derived embryos with developmental competence to term revealed a similarity in the relative abundance of 18 genes. Therefore, we were able to present a genetic signature associated with term developmental competence independent of the environmental origin of the transferred blastocysts.

“…Cellular fragmentation is a common feature during early development of mammalian embryos (Van Blerkom et al 2001), but is generally considered as indicative of poor embryo quality both in bovine (Lindner & Wright 1983) and human (Puissant et al 1987). Moreover, human embryos with a substantial amount of cellular fragmentation have a markedly reduced implantation rate (Ziebe et al 1997, Ebner et al 2001. For human in vitro fertilised (IVF) embryos, not only degrees (in percentage) but also distinct patterns of fragmentation, which are correlated with in vitro development, have been defined (Warner et al 1998a.…”

Section: Introductionmentioning

confidence: 99%

Porcine embryo development and fragmentation and their relation to apoptotic markers: a cinematographic and confocal laser scanning microscopic study

Mateusen¹,

Soom²,

Maes³

et al. 2005

Porcine embryo selection prior to transfer is mainly influenced by morphological criteria. However, the relationship between embryonic morphology, developmental potential and cell death by apoptosis in porcine embryos is still unclear. The aim of this study was to establish embryo quality parameters for in vivo fertilised porcine embryos based on timing of development in vitro, embryo morphology and the presence of apoptosis. The kinetics of development and morphological parameters were investigated in a time-lapse cinematographic experiment. Possible links between embryo morphology and apoptosis were examined via a confocal laser scanning experiment, analysing nuclear changes, annexin V and terminal dUTP nick-end labelling. The timing of early cleavages was firmly linked to embryo developmental competence in vitro. Attainment of at least the 5-cell stage before 77 h post insemination and attainment of the morula stage before 102 h post insemination significantly increased the odds for reaching the early blastocyst stage. Overall, a negative effect of fragmentation percentage and fragmentation pattern on subsequent embryonic development was observed, but the developmental potential of embryos experiencing slight fragmentation (0 -5%) was not different from embryos without fragmentation. Correlations detected between developmental arrest and fragmentation, and fragmentation and apoptosis were 0.60 and 0.87 (P < 0.05) respectively. Only a minority of the embryos arrested between the 1-and 4-cell stage displayed biochemical characteristics of apoptosis. Consequently, a significant correlation (0.57) between developmental arrest and apoptosis could only be established for embryos arrested after embryonic genome activation.