Methodology matters: IVF versus ICSI and embryonic gene expression

Abstract

The use of assisted reproduction treatment, especially intracytoplasmic sperm injection (ICSI), is now linked to a range of adverse consequences, the aetiology of which remains largely undefined. The objective was to determine differences in gene expression of blastocysts generated by ICSI as well as ICSI with artificial oocyte activation (ICSI-A) versus the less manipulative IVF, providing fundamental genetic information that can be used to aid in the diagnosis or treatment of those adversely affected by assisted reproduction treatment, as well as stimulate research to further refine these techniques. Murine blastocysts were generated by ICSI, ICSI-A and IVF, and processed for a microarray-based analysis of gene expression. Ten blastocysts were pooled for each procedure and three independent replicates generated. The data were then processed to determine differential gene expression and to identify biological pathways affected by the procedures. In blastocysts derived by ICSI versus IVF, the expression of 197 genes differed (P < 0.01). In blastocysts derived by ICSI-A versus IVF and ICSI-A versus ICSI, the expression of 132 and 65 genes differed respectively (P < 0.01). Procedural-induced changes in genes regulating specific biological pathways revealed some consistency to known adverse consequences. Detailed investigation of procedure-specific dysfunction is therefore warranted.

Effect of sperm entry on blastocyst development after in vitro fertilization and intracytoplasmic sperm injection — mouse model

“…In human ART, concerns remain about whether fertilization techniques influence the distribution and expression of key transcription factors responsible for the developmental program of embryogenesis [7,22,51]. One of them, the POU-family transcription factor Oct4, is expressed throughout early embryonic development and becomes progressively restricted first to the entire inner cell mass (ICM) and then to the epiblast (EPI) at the blastocyst stage [35,46].…”

Quality control and standardization of embryo morphology scoring and viability markers

“…Particular challenges arise from patients exhibiting high intra-and intervariability (Feuerstein et al, 2012;Maston et al, 2006;Sapey et al, 2008) and variations in gene expression, which have been linked to a number of patient and treatment characteristics (Bridges et al, 2011;Wathlet et al, 2011). Consequently, some biomarkers indicated as strong predictors of developmental potential in specific patient populations may not be appropriate to select between embryos in other patient populations or even between embryos produced by the same individual.…”

Assisted reproductive technology results: Why are live‐birth percentages so low?

“…For example, IVF-produced morulae in the domestic cat display higher relative levels of Dnmt1 mRNA than do ICSI morulae (Waurich et al, 2010). Similarly, all reports in mice indicate that the global gene expression profiles differ significantly among blastocysts derived from ICSI versus IVF (Bridges et al, 2011;Kohda et al, 2011); ICSI followed by artificial oocyte activation versus IVF and ICSI, respectively (Bridges et al, 2011); and ICSI versus in vivo development (Giritharan et al, 2010). Interestingly, Kohda et al (2011) showed that in mice, the relative changes in ICSI-versus IVF-associated transcriptomes observed at the blastocyst stage remain at the neonatal stage, but disappear at 8-weeks of age.…”