There is a global crisis of unintended pregnancy: nearly half of all pregnancies each year are unplanned, with severe consequences for women, society and public health. A major contributor is a lack of suitable contraceptive options, with many current options causing severe side effects leading to early discontinuation of use. There are urgent calls for the development of more non-hormonal contraceptive options, with the only current non-hormonal long-acting reversible contraceptive (LARC) being the copper intrauterine device (IUD).
We have used a rat IUD model to investigate the potential of a zinc-based IUD in comparison to the current copper standard. This model demonstrated that both copper and zinc IUDs were 100% effective at preventing pregnancy, and that zinc IUDs provided long-term protection. This was a reversible effect, as once the zinc IUDs were removed the rats rapidly returned to fertility.
Embryo culture experiments revealed that the zinc IUD specifically impacted early embryo development, unlike the copper IUD. Histological analysis of the endometrium revealed damage and inflammation in uterine horns containing a copper IUD, but only minor epithelial changes in those containing a zinc IUD. Immunofluorescent analysis of leukocytic infiltration, which is associated with inflammatory and painful side effects, revealed further differences. This work indicates zinc impacts the early embryo, rather than the endometrium, which may lead to a reduced side effect profile for the zinc IUD.
This work establishes the basis for development of a zinc-based IUD, demonstrating the fundamental requirements of long-acting efficacy and reversibility. Initial findings indicate that histological and immunological signs of side-effects are reduced in this zinc IUD model. Further development of this zinc-based intrauterine contraceptive could provide women with a new non-hormonal LARC option that is desperately needed and help address the “neglected crisis of unintended pregnancy” (UNFPA 2022).