Basic research to establish a treatment for asthenozoospermic patients.

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Purpose : (1) To determine the incidence of reactive oxygen species (ROS) formation by spermatozoa from asthenozoospermic patients and the relationship between ROS formation and sperm motion parameters. (2) To assess the efficacy of in vitro and in vivo pentoxifylline treatment of asthenozoospermic patients whose spermatozoa generated high ROS levels.Materials and Methods : (1) ROS formation by spermatozoa from asthenozoo-spermic patients and fertile volunteers was measured by chemiluminescence. ROS formation by the sperm preparations was investigated without stimulation (steady state) or after stimulation with N-formyl-methionyleucyl-phenylalanine (f-MLP) or phorbol-12-myristate-13-acetate (PMA). (2) Spermatozoa from 15 asthenozoospermic patients, whose spermatozoa produced high levels of ROS at steady state, were treated in vitro with pentoxifylline to determine its effect on ROS generation and sperm motion parameters. (3) These same 15 patients and 18 asthenozoospermic patients whos … More e spermatozoa did not produce ROS at steady state were treated with pentoxifylline at two different dosages (300 mg and 1200 mg/day) to determine its effect on ROS generation, sperm motion parameters and sperm fertilizing ability in vivo.Results : (1) When the steady state ROS formation was detected without stimulation and that was not stimulated by f-MLP,the source of ROS could be attributed to the spermatozoa themselves. (2) Spermatozoa from 15 out of 71 asthenozoospermic patients generated ROS at steady state. These 15 patients were assigned to group A patients. (3) Pentoxifylline decreased ROS generation by spermatozoa from group A patients and preserved the decrease of curvilinear velocity and beat cross frequency for 6 hrs in vitro. (4) For group A patients orally administered pentoxifylline failed to decrease ROS generation by spermatozoa. For group A patients orally administered pentoxifylline had no effect on sperm motility, sperm motion parameters and sperm fertilizing ability at low dosage (300mg/day). It increased motility and beat cross frequency at high dosage (1200mg/day), but had no effect on sperm fertilizing ability in group A patients.Conclusions : Stimulation of sperm preparations with f-MLP can identify the source of ROS generated at steady state. Among asthenozoospermic patients, there was a group of patients (group A) whose spermatozoa produces detectable steady state levels of ROS.For this group, pentoxifylline appeared to be effective for reducing ROS formation and preserving sperm motion parameters in vitro. Orally administered pentoxifylline had no effect at low dosage, however, it increased sperm motility and some sperm motion parameters without altering sperm fertilizing ability at high dosage.Future : Currently, there is no effective treatment for patients with deficient sperm functions, such as idiopathic asthenozoospermia. To develop new treatment strategies, it is important to learn more about the nature of these deficiencies. The present results may provide clues to a therapeutic approach for the treatment of idiopathic male-factor infertility. For the confirmation of these results, a prospective and double-blind clinical trial, dealing with fecundity as the crucial outcome measure, is necessary. Less