RISUG® offers early contraception: An experience during Phase III clinical trials

Abstract

An early contraceptive efficacy with reasonable assurance of reversibility has been a challenge in male contraception. With nearly four decades of research in reversible inhibition of sperm under guidance (RISUG®) as an intravasal male contraceptive, including pre-clinical trials in rats, rabbits, langur monkeys, and three phases of clinical trials, the present study aims to evaluate the additional parameters of a center of Phase III clinical trials. Subjects were recruited following ICMR guidelines of inclusion and exclusion criteria. Samples were analyzed for sperm functional tests, namely, hypo-osmotic swelling, acrosomal intactness, nuclear chromatin decondensation, and sperm mitochondrial activity index. Furthermore, seminal biochemistry and serum hormones such as follicle-stimulating hormone, luteinizing hormone, testosterone, cortisol, and prolactin were assessed along with levels of anti-sperm antibodies and prostate-specific antigen (PSA). The present study, on human subjects, emphasizes the efficacy of RISUG® with early onset of contraception and indication of a greater possibility of reversal. A significant decrease in all sperm functional parameters was observed following RISUG® injection along with increased sperm abnormalities. Semen biochemistry revealed no marked alterations in the concentration of fructose and acid phosphatase, while significantly decreased levels of glycerophosphorylcholine and neutral α-glucosidase were observed. No significant changes in the circulatory levels of hormones and the levels of PSA were observed. In addition, the development of anti-sperm antibodies, an adverse effect of other vas occlusive methods, was not indicated after RISUG® administration, implying the potential of reversibility in humans as observed earlier in different animal models. RISUG® presenting deleterious effects on spermatozoa and marked alterations in epididymal markers provides early contraception with a greater possibility of reversal. Although the progress of RISUG® toward development as an ideal male contraceptive is slow, the study implies a strong future possibility.