The next generation of contraceptives will likely be focused on new mechanisms of action. Targets include all aspects of the female and male reproductive system from gamete development to gamete delivery, fertilization and implantation. The goal of these new methods will be the interruption of key components of the system allowing safe, effective contraception with a minimum of side effects. The challenge facing the development of these new methods is the refinement of methods that allow modification or interruption, of only the reproductive system with a minimum of effect on other body systems. Specifically, an optimal method would provide reversible interruption of reproductive capacity of the male and/or female without affecting the endocrine system. This is particularly important in the male as secondary sexually characteristics, and even behavior, are closely linked to any change in the hormonal milieu. Other challenges include the development of simple and cost effective methods. The next breakthrough in contraceptives will be the identification of a key molecular aspect of reproduction. If a key specific receptor can be identified, an antagonist can be developed. If a critical enzyme is identified, an inhibitor can be synthesized.

Areas of interest will be in disruption of ovulation with anti-progestins or blocking the action of matrix metaloproteases needed for the physical breakdown of the follicle. Folliculogenesis may be blocked by specific FSH antagonists, or interruption of folliculogenesis at the local level growth differentiation factor-9. Other possible targets are to block resumption of meiosis in the oocyte, or to block egg activation (which is necessary before an egg is capable of fertilization and to prevent polyspermic fertilization). Finally the specific steps necessary for implantation may be identified and selectively disrupted – and research on molecules involved in implantation and angiogenesis is currently being done in mouse models.

Male Pill: Future Male Related Contraception may be aided by the dramatic increase in our understanding of the molecular genetic control of male reproduction. In particular, the identification of genes in various aspects of testicular steroidogenesis, spermatogenesis and sperm maturation may provide novel targets for fertility regulation. Progestins act on the hypothalamic pituitary axis and suppress spermatogenesis and production of the hormone testosterone. It has been hypothesized that progestin implants along with long acting add back testosterone injections, oral progestagens with testosterone injections, or oral desogestrol with testosterone implants may produce azoospermia without affecting the other physiological and biological effects of testosterone (162). Future work will determine if these targets can be useful in developing novel strategies for male contraception.