Biochemical study of individual zonae from human oocytes that failed to undergo fertilization in intracytoplasmic sperm injection

Successful intracytoplasmic sperm injection (ICSI) is dependent upon the competence of the oocyte to respond to the injection of a spermatozoon in the presence of calcium. This study determined if oocytes that failed to become fertilized (absence of any pronuclei) failed to undergo cytoplasmic activation, as ascertained by an electrophoretic shift in the zona pellucida (zona) protein, huZP2. Of 48 zonae individually analysed, 58% did not have a detectable huZP2 shift. Three patterns were observed. In seven patients, none of the unfertilized oocyte huZP2 shifted (16 out of 48); in two, all zonae exhibited a huZP2 shift (five out of 48); in eight, there was a mixture of shifted and unshifted (27 out of 48) in each case. There was no clear relationship between the presence of the huZP2 shift and maternal age, pregnancy outcome, male-factor infertility, or fertilization rate. However, in six couples diagnosed as having no detectable male-factor infertility, 73% (11 out of 15) of the zonae had unshifted huZP2, suggesting that an oocyte defect is involved in some cases of failed fertilization after ICSI. One likely cause for the absence of the huZP2 shift is a failure of cytoplasmic activation. Since oocytes were injected at metaphase II, we hypothesize that some oocytes that failed to fertilize have completed nuclear (meiotic) without cytoplasmic maturation.