To determine the relationship between the zona pellucida (ZP)-induced acrosome reaction (AR) and fertilization rate and pregnancy rate in standard IVF and the frequency of disordered ZP-induced AR (DZPIAR) in patients with unexplained infertility. Prospective study. Academic research and teaching tertiary hospital. Patients with unexplained infertility with normal semen analysis. None. Semen analysis, the ZP-induced AR, and measurements of fertilization rate and pregnancy rate with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). A statistically significant correlation was found for the ZP-induced AR and fertilization rate with standard IVF (n = 65). Patients with DZPIAR (ZP-induced AR of <or=16%) had an average fertilization rate of 23%, in contrast to patients with ZP-induced AR of >16%, who had an average fertilization rate of 61%. The sensitivity and specificity of DZPIAR for prediction of IVF rates <30% and >or=30% were 80% and 86%, respectively. Of 260 patients screened, the frequency of DZPIAR was 29%. Ten patients with DZPIAR had an average fertilization rate of 15% and no pregnancy with initial IVF cycles, and a fertilization rate of 61% (with three live-birth pregnancies) with subsequent ICSI cycles. Another 33 patients with DZPIAR were treated with ICSI alone, with an average fertilization rate of 71% and a live-birth pregnancy rate of 17% per embryo transfer. Sixteen of the patients had live-birth pregnancies (including one set of twins) after undergoing an average of 3.2 embryo transfers. Patients with DZPIAR have a low or zero fertilization rate with standard IVF but high fertilization and pregnancy rates with ICSI. Up to 29% of patients with unexplained infertility with normal semen analysis may have this condition, which should be diagnosed and treated with ICSI rather then standard IVF.
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