Objective To explore the effects of two types of type I interferon (IFN-I) receptor deletions upon the reproductive performance of mice. Methods In vitro fertilization (IVF) was performed using two types of IFN-I receptor- deficient mice (dificient in IFN-α and IFN-α/ β receptor signaling) and wild-type background ( C57BL/ 6) mice. Each group contained 5 superovulated mice and the assay was repeated in triplicate. The female and male gametes of two the types of IFN receptor-deficient mice and the wild-type mice were examined using IVF. The IVF conditions were optimized and method to increase the fertilization rate were explored. Results The average IVF rates ( number of 2-cell embryos as a percentage of oocytes) for the two types of IFN receptor-deficient mice were significantly lower (P < 0. 05) than that of wild-type mice. The IVF rate of mice with IFN-α receptor deficiency was higher ( P < 0. 05) than that of mice with IFN-α/ β receptor deficiency. The IVF rates using receptor-deficient sperm and C57BL/ 6 oocytes were significantly higher (P < 0. 05) than those using receptor-deficient oocytes and C57BL/ 6 sperm. The IVF rates were significantly increased (P < 0. 05) by extending the sperm capacitation time from 30 min to 1 h or adding glutathione to the capacitation and fertilization solutions form 0 mmol / L to1 mmol / L. Conclusions Deletion of the IFN-I receptor may reduce the fertility of mice, and the effect on oocytes appears more significant than that upon sperm. Extending the sperm capacitation time or changing the capacitation and fertilization fluid composition improved the fertilization rate.