Immunopharmacology of ulipristal as an emergency contraceptive

A new progesterone antagonist, ulipristal has been made available as an emergency contraceptive. Ulipristal’s major mechanism of action as an emergency contraceptive has been ascribed to its ability to delay ovulation beyond the life span of the sperm. This paper analyzes the potential action of ulipristal (1) when unprotected intercourse and administration of ulipristal occur outside the fertility window and (2) when unprotected intercourse and administration of ulipristal occur at or within 24 hours of ovulation. When unprotected intercourse and the use of a single low dose of ulipristal occur outside of the fertility window, ulipristal behaves like a placebo. When unprotected intercourse and the use of a single low dose of ulipristal occur within the fertility window but before ovulation, ulipristal behaves like an emergency contraceptive by delaying ovulation and thereby preventing fertilization. When unprotected intercourse and the administration of ulipristal occur at or within 24 hours of ovulation, then ulipristal has an abortifacient action. It is proposed that the abortifacient mechanism of a low dose of ulipristal taken after fertilization but before implantation is due to the ability of ulipristal to block the maternal innate immune system to become immunotolerant to the paternal allogenic embryo. Progesterone’s critical immunotolerant actions involving early pregnancy factor, progesterone-induced blocking factor, and uterine natural killer cells are compromised by ulipristal.