DISORDERED ACROSOME REACTION OF SPERMATOZOA BOUND TO THE ZONA-PELLUCIDA - A NEWLY DISCOVERED SPERM DEFECT CAUSING INFERTILITY WITH REDUCED SPERM - ZONA-PELLUCIDA PENETRATION AND REDUCED FERTILIZATION IN-VITRO

It is believed that during the process of human fertilization, acrosome-intact spermatozoa bind to the surface of the zona pellucida which triggers the acrosome reaction and the enzymes released facilitate sperm penetration through the zona pellucida. We describe here reduced frequency of the acrosome reaction on the zona pellucida as a cause of infertility in 10 couples with long durations of infertility (average 6 years) and low (< 15%, n = 3) or zero (n = 7) fertilization rates in vitro. Sperm concentration, motility, velocity (Hamilton - Thorn), morphology and DNA normality were within the normal range in all the patients. Electron microscopy of spermatozoa did not reveal any specific ultrastructural defects. Ah couples were negative for antisperm antibodies by immunobead tests. Oocytes from other patients which failed to fertilize in in-vitro fertilization and normal donor spermatozoa were used as controls for sperm - zona pellucida binding and penetration experiments. Acrosome status of spermatozoa bound to the zona pellucida was assessed with a fluorescent lectin and electron microscopy. The mean number of spermatozoa bound to the zona pellucida was not significantly different between patients and controls. However, the acrosome reaction of spermatozoa bound to the zona pellucida after 2 h incubation was significantly lower (P < 0.001) in the patients (mean 5%, range 0 - 16) than in the controls (mean 68%, range 44 - 96). No zona pellucida (out of 40) was penetrated by patient spermatozoa whereas most (39/40) zonae were penetrated by control spermatozoa (average 27 spermatozoa/four zonae pellucidae). The spontaneous acrosome reaction of spermatozoa in insemination medium was not different between patients (4%) and controls (3%), the acrosome reaction induced by calcium ionophore was low (21 and 43% respectively) in six of the eight patients examined. In conclusion, these patients have spermatozoa with a disorder of the zona pellucida-induced acrosome reaction that results in failure of sperm - zona pellucida penetration and explains their infertility.