Preimplantation exposure to high insulin-like growth factor I concentrations results in increased resorption rates in vivo

Background: Women with polycystic ovarian syndrome suffer increased rates of miscarriage. Elevated insulin and insulin-like growth factor I (IGF-I) concentrations have been implicated. Here, we hypothesize that the high concentrations of IGF-I result in miscarriage, represented by decreased normal pregnancy rates and increased resorption rates in a mouse model. Methods: In-vitro studies: 2-cell embryos were cultured in either 1.3 or 130 nmol/l IGF-I; or 500 nmol/l IGF-I receptor (IGF-IR) sense and antisense oligoprobes for 72 h. Embryos were then transferred into pseudo-pregnant ICR females. In-vivo studies: IGF-I-containing slow-release pellets or mock pellets were implanted within the uterine horn in ICR female mice. For both studies, the recipient females were killed on day 14.5 and the numbers of normal implantation sites versus resorption sites were recorded. Results: In-vitro studies: blastocysts cultured in low IGF-I exhibited significantly higher normal implantation rates than blastocysts cultured in high IGF-I concentrations (P<0.01). Blastocysts cultured in IGF-IR sense oligoprobes exhibited a significantly higher normal implantation rate than blastocysts cultured in antisense oligoprobes. In-vivo studies: mice implanted with IGF-I-containing pellets exhibited significantly lower normal implantation rates as compared with mock-pellet controls (P<0.01). Conclusions: High preimplantation IGF-I concentrations in vitro or in vivo lead to increased resorption rates in the mouse.