004. A NEW ERA IN CONTRACEPTIVE DEVELOPMENT: NON-HORMONAL OPTIONS THAT ALSO TARGET SEXUALLY TRANSMITTED INFECTIONS

Abstract

Despite huge increases in access to contraceptives globally more than 700 000 maternal deaths related to unintended pregnancies occurred between 1995 and 2000 mostly in developing countries. Over 80 million women have unintended or unwanted pregnancies annually. Remarkably, there have been no new methods of contraceptives developed in the last 50 years. The extremely high incidence of sexually transmitted infections (STIs) indicates that it is desirable to develop contraceptives that also target STIs. Two interleukin (IL) 6-type cytokines, leukemia inhibitory factor (LIF) and IL11, are obligatory for implantation in mice and are dysregulated in endometrium of some women with infertility. Both LIF and IL11 are also thought to have roles in Chlamydia-induced inflammation which can lead to a multitude of pathologies. LIF and IL11 antagonists were produced and their contraceptive efficacy tested in mice. Polyethylene glycol (PEG) was conjugated to LIF antagonist (LA) or IL11 antagonist (IL11A) to increase their serum half-life. PEGLA injected during the peri-implantation period blocked LIF action in the endometrium and totally prevented embryo implantation while having no embryo toxic effects.¹ Similarly, injection of PEGIL11A blocked decidua formation resulting in pregnancy failure.² In women, vaginally administered drugs preferentially localise to the uterus suggesting that vaginal administration of PEGLA is an appropriate delivery method for contraceptive purposes. Further, vaginally administered PEGLA may be useful as a ‘dual-role’ contraceptive to also block STIs. PEGLA administered via vaginal gel was shown to prevent implantation having minimal effects on non-uterine LIF targets. This is the first study to show the contraceptive efficacy of a PEGylated compound delivered vaginally. It further indicates that PEGLA may be useful as a dual-role contraceptive. Contraceptive trials in non-human primates are currently underway to determine the effect of PEGLA on implantation. If effective, this will offer new opportunities as pharmacological, non-hormonal dual-role contraceptives for women.

(1) White CA, Zhang JG, Salamonsen LA, Baca M, Fairlie WD, Metcalf D, Nicola NA, Robb L, Dimitriadis E (2007) Proc Natl Acad Sci USA 104: 19 357–62.
(2) Menkhorst E, Salamonsen LA, Robb L, Dimitriadis E (2009) Biol of Reprod 80: 920–927.