Routine addition of human insulin-like growth factor-I ligand could benefit clinical in-vitro fertilization culture

Animal studies suggest that the insulin-like growth factors play an important role in preimplantation embryo development. Human preimplantation embryos express mRNA for insulin-like growth factor-I receptor (IGF-IR) but the ligand, insulin-like growth factor-I (IGF-I), is not expressed by the embryo until after implantation. We tested the hypothesis that IGF-I produced by the female reproductive tract may bind to these receptors, augmenting embryo survival, growth and development. Transcripts of mRNA for IGF1 were detected using reverse transcription-polymerase chain reaction in midcycle human Fallopian tube. Immunohistochemistry localized immunoreactive IGF-I to the cytoplasm of all the major structures of the Fallopian tube, with the most intense staining seen in the tubal epithelial lining. Maternally produced IGF-I was present in the fluid found in the human tube and uterus at concentrations of 8.0 and 10.9 nM respectively. Supplementation of culture medium with IGF-I increased the proportion of embryos developing to the blastocyst stage from 35% in controls to 60% in the presence of IGF-I. In addition the total number of cells in day 6 blastocysts was increased by 19% (64.44 versus 54.08% in control, not significant), due entirely to a statistically significant 59% increase (25 versus 15.75%, P = 0.020) in the number of cells in the inner cell mass. The effect of IGF-I was mediated through the IGF-I receptor. Immunocytochemistry using an alphaIR3 antibody confirmed the presence of IGF-I receptor in human blastocysts and the same antibody completely inhibited the stimulation of blastocyst formation by IGF-I. These data suggest that human preimplantation development is enhanced by maternal IGF-I. Mimicking this in-vivo paracrine relationship may improve clinical in-vitro embryo culture and IVF pregnancy rates.