This week I am going to talk about the specific interactions that occur at the cellular and tissue level after a hormonal IUD is implanted. The amount of time a hormonal intrauterine device (IUD) is effective in preventing pregnancy is somewhat proportional to the amount of levonorgestrel that it contains. For example, Mirena, the original hormonal IUD, contains 52 mg of levonorgestrel and lasts 5 years, whereas Skyla, which contains 13.5 mg of levonorgestrel, lasts only 3 years. While the hormone concentration is currently the limiting factor to the lifetime of the IUD, if the concentration could be increased without leading to any additional side effects, I’m wondering how long these devices could last. After all, the copper IUD can last for up to 10-12 years. The answer, I would hypothesize, would lie in the interactions of the device with the environment (the uterus) at the cellular and at the tissue level.

As with all biomaterials, once the IUD is implanted, there will be interactions with the device that immediately occur on the cellular level. Specifically, proteins will coat the surface of the device, cells will interact with the device via integrins, and there will be an immune response. The innate immune response will cause an immediate increase in production of neutrophils and leukocytes, and the adaptive immune response, which will kick in after the first day, will cause an increase in production of macrophages. Interestingly, the cellular degradation of these neutrophils and macrophages in particular has been shown to contribute to the anti-fertility effects of IUDs. Furthermore, it has been seen that cells that attach to the surface of IUDs lead to an increase in production of prostaglandin, which also contributes to the anti-fertility effects of IUDs. In this way, the interactions of the IUD itself with the environment on the cellular level contribute to the effectiveness of the IUD in addition to the release of levonorgestrel.

On a tissue level, effects of the material on the environment (the uterus) must be considered. Fortunately, as long as IUDs are inserted correctly, there are few side effects in regards to the material’s effect on the environment. IUDs generally do not cause toxicity or tumorigenesis, and they do not directly cause infection. While there is a slight risk of pelvic inflammatory disease, the infection would be the result of pre-existing bacteria that were disrupted by the insertion of the IUD within the first week. The largest concern in regards to the material-environment interaction is the possibility of a perforated uterus, which occurs in only 0.1% of insertions. Most case studies are isolated and the cause is unknown, but it is thought that the skill of the doctor and improper technique during insertion may play a role. Due to the limited serious adverse effects of the IUD, it is generally considered a safe device. As such, I would hypothesize that a long-term IUD may be considered safe in regards to the material’s on the body.

Finally, when looking at how long the device could last irrespective of the hormonal concentration, the effects of the environment on the IUD, specifically on the polyethylene frame, are the largest considerations. The overall wear and corrosion as a result of uterine contractions and fluid flow are the largest factors that lead to the degradation of the IUD over time. One study I found by Dr. Monica Cirstoiu at the Unviersity of Bucharest used a scanning electron microscope to characterize Mirena IUDs after certain periods of time. After 3 months, only minor degradation signs on the surface were detected. However, after 36 months, signs of severe degradation could be seen. Cirstoiu hypothesized that these cracks over time could affect the function of the device.  I found this very interesting, as I wondered specifically what she meant by that. The effectiveness of the hormonal IUD lies in its continual release of consistent amounts of levonorgestrel, but I wonder if cracks in the polyethylene frame over time can affect the amount released. Copper IUDs are also made of polyethylene, but the composition of the frame is less important, as the copper wound on the surface releases ions over time. Perhaps a different material could allow hormonal IUDs to last longer.

What material could be used? I’m not really sure. However, I do know that polypropylene is a material that is very similar to polyethylene in that it is durable and lightweight. However, Polypropylene is more resistant to corrosion, fatigue, impact, and temperature, meaning it may be able to last longer as an implant in the body. Polypropylene does not stretch as much as polyethylene does though (it has a lower elastic modulus), so given the need of flexibility in an IUD, maybe a combination of the two materials could be tested.

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Sources:

http://www.microbiologyresearch.org/docserver/fulltext/jmm/54/12/JMM5412.1199.pdf?expires=1538842545&id=id&accname=guest&checksum=14FFA56BF8077D0C2CACE8740C2BDD49

https://www.researchgate.net/publication/280944267_Levonorgestrel-releasing_Intrauterine_Systems_Device_Design_Biomaterials_Mechanism_of_Action_and_Surgical_Technique

https://www.dlib.si/stream/URN:NBN:SI:DOC-XJZ8XJU9/04e5a4f0-5f4a-4907-b67e-a8adb297014d/PDF

https://www.healthline.com/health/birth-control/iud-infection#causes

http://www.hunterindustrialsupplies.com.au/blog/polyethylene-vs-polyproylene-which-is-better/

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