The copper intrauterine device (IUD) is the only long-term, non-hormonal contraceptive available. However, its numerous side effects, including excessive bleeding and cramping, result in a high rate of removal within the first 3 months. We have developed a rat IUD model to examine an alternative contraceptive, a zinc IUD. This model involves inserting IUDs made of copper or zinc into the rat uterine horns then mating with a male of proven fertility and analysing implantation rates. We found that both copper and zinc IUDs provide effective contraception, preventing 100% of pregnancies. This model also demonstrated long-term efficacy of the zinc IUD, preventing pregnancy as rats were mated repeatedly over a 3 month period. Once the zinc IUDs were removed, rats rapidly returned to fertility proving reversibility.
However, the uterus responds differently to each metal. In copper treatments, histological studies identified local endometrial inflammation and metaplasia of the uterine epithelial cells (UECs), which mediate implantation. The zinc IUD did not cause an inflammatory response or metaplasia of the UECs.
Embryos were collected from IUD-treated rats and an embryo survival assay was performed, comparing embryo development from IUD-treated vs. non-treated control horns. The zinc IUD inhibited the development of 94% of embryos with no histological change to the endometrium, suggesting a unique impact of zinc on the early embryo. Whereas 64% of embryos exposed to copper formed blastocysts, indicating this is not the stage at which its contraceptive action occurs.
This study has shown that a zinc IUD provides similar contraceptive efficacy to a copper IUD in this rodent model. However, these IUDs function via different mechanisms and could result in zinc having a reduced side-effect profile. The zinc IUD has proven to be effective long-term and reversible in this rat model, demonstrating its potential as an alternative non-hormonal contraceptive.