Recent observations on drugs and human fertility

Abstract

The transmembrane migration method has permitted quantification of the effect of drugs on human sperm motility. Calcium ionophores and calcium antagonists have paradoxical effects on motility depending on the stage of sperm maturity. Drugs with membrane stabilizing properties inhibit sperm motility. Propranolol, for example, has been shown to have contraceptive activity when administered intra-vaginally. Pharmacokinetic studies have shown that the systemic availability of vaginally administered propranolol is markedly greater than after oral administration. Seminal fluid concentrations of propranolol after oral administration are similar to those in plasma, but cervicovaginal mucus concentrations are much higher, and residence times much longer. The clinical consequences of these observations await elucidation.

PIP: The transmembrane migration method determines the effect of a drug concentrated in the chamber containing seminal fluid on human sperm motility by measuring the proportion of sperms that cross the 5 micron pores of a Nucleopore membrane from an aliquot of semen into a buffer solution. Various classes of drugs have been shown by transmembrane migration to immobilize sperm by penetrating the cell membrane, which is a function of the lipid solubility of the drugs. Sperm motility may thus provide a model for the study of membrane stabilizing drugs. Calcium ions have a different effect on sperm motility, depending on the stage of sperm maturity. They increase the motility of immotile sperm collected from the epididymis, inhibit sperm motility in ejaculated semen, and induce a premature acrosome reaction in uncapacitated sperm. Caffeine increases sperm motility and antagonizes the inhibitory effect of propranolol and procaine. Propranolol acts as a vaginal contraceptive by inhibiting sperm motility; however, some of the effect may be systemic, since propranolol drains directly into the inferior vena cava. Orally administered propranolol in men does not seem to reach sperm-immobilizing levels, but in women, oral propranolol accumulates extensively in the cervico-vaginal mucus.