As Pine suggests, interfering with hyaluronidase, the sperm enzyme that allows penetration of the outer ovum vestments, may be particularly appropriate. From his research in the 1940s, the concept of preventing sperm penetration of the ovum by enzyme inhibition has emerged. Considerable work has since been done. A good review is L.J.D. Zaneveld's article in Research Frontiers in Fertility Regulation, vol. 2, no. 3, pp. 1-14, 1982.
Present vaginal contraceptives use non-ionic surfactant compounds such as nonoxynol-9 as their active ingredient. No new active ingredients have been introduced for some years now, but several, such as Dpropranolol, are under development. The recent surge in litigation involving vaginal spermicides may force the manufacturers to remove nonoxynol-9 from the marketplace purely for economic reasons. This would be particularly troublesome not only because new compounds are several years away from the marketplace, but because contraceptives using nonoxynol-9 have been shown to reduce significantly the risk of infections due to gonorrhea and chlamydia. This is supported by lab experiments in vitro showing that the surfactants kill gonorrhea, chlamydia and the viruses that cause herpes and AIDS.
Many inhibitors of hyaluronidase enzyme prevent sperm penetration of the ovum's culumus mass in vitro. Some also have shown promise in vivo. Phosphorylated hesperidin, a flavonoid, and PS53, a hydroquinone sulfonic acid formaldehyde polymer, have been shown to reduce fertility when vaginally administered to rabbits. Interestingly, several marketed nonsteroidal anti-inflammatory drugs have activity in vivo. The specificity of these compounds, however, has always been in question; that is, there is doubt whether the antifertility effect can be ascribed solely to hyaluronidase inhibition.
This concern aside, the development of hyaluronidase inhibitors as antifertility agents has been overshadowed by compounds that inhibit another sperm enzyme, acrosin. Acrosin putatively is responsible for allowing sperm penetration through the ovum's glycoprotein coat, the zona pellucida. A number of compounds of this genre are highly active when administered vaginally and are being considered for human trials. Immunization with a sperm-specific hyaluronidase or acrosin vaccine against these enzymes is a related area also under consideration.
The impairment of sperm function, whether by enzyme inhibition or any other method, may well hold the most promise for the introduction of truly novel compounds for the control of human fertility.
Family Health International, with support from the National Institutes of Health and the Agency for International Development, is conducting a major program on possible new spermicides, looking especially at drugs that are already approved for other uses by the U.S. Food and Drug Administration. This strategy both accelerates the approval process and reduces the cost of bringing a product to widespread use.