**4. IUDs mechanism of action**

Both copper and hormonal IUDs involve multiple mechanisms that provide contraceptive protection. The major described effect is represented by the induction of a *local inflammatory reaction* in the endometrium. Therefore, the endometrial and myometrial function is disturbed by cellular and humoral immune-inflammatory reaction. Intrauterine foreign bodies are known to interfere with reproduction in all species [21]. Other mechanisms of action for *copper IUDs* are related to copper ions' effect on the *sperm motility and viability* and also to *changes of the cervical mucus* [7]. However, recent studies demonstrated no significant increase in inflammatory reaction, so the effect of copper on the sperm or oocyte remains as the main mechanism of action [22]. The mechanism of inhibiting fertilization or sperm viability impairment may be responsible for the high efficacy of copper IUDs as emergency contraception [23]. The reported failure rate for copper IUD placement for emergency contraception within 5 days of intercourse or ovulation is less than 1‰, significantly more effective than any hormonal emergency contraceptive [24, 25]. Even if copper IUDs do not usually influence the menstrual frequency or quantity, 10–13% of women have their IUD removed in the first year due to increase of menstrual flow and cramping-type abdominal pain [26].

Besides the foreign body reaction, another mechanism of the *hormonal IUD* is represented by the release of small amount of progestin hormones, respectively, levonorgestrel. The hormonal effects induce an unfriendly and even *fatal environment to sperm* inside the uterus, with inhibition of capacitation, penetration, and survival [27]. Hormonal IUDs interfere with sperm motility by *thickening cervical mucus*, thus preventing the sperm to travel up into the uterus [28], while copper IUDs rather impair the sperm viability, with various effects as head-tail disruption [29]. A *thinner endometrium* develops under the progesterone influence and egg implantation is affected. Also, menstrual blood flow is reduced, thus hormonal IUDs are frequently used to treat menorrhagia [30].

We underline that IUDs, whether hormonal or non-hormonal, do not provide protection against sexually transmitted diseases. Still, the historical association with pelvic inflammatory disease (PID) and tubal infertility is considered false [31, 32].

The indomethacin-releasing copper IUD contains a nonsteroidal anti-inflammatory agent, indomethacin, that do not interfere with copper ions [33, 34], aimed to reduce the menstrual blood flow and cramping that are frequently related by IUDs users [33] (**Table 1**).


**Table 1.** Mechanisms of action of the main types of IUDs. Modified, Schulman et al. [35].

**4. IUDs mechanism of action**

260 Family Planning

the inferior part of the vertical body stem just above the isthmus.

Both copper and hormonal IUDs involve multiple mechanisms that provide contraceptive protection. The major described effect is represented by the induction of a *local inflammatory reaction* in the

**Figure 2.** General structure with stems, arms, and strings of the IUD. Normal location after proper IUD insertion in the middle of the endometrial cavity with no extension in the myometrium, both arms spread toward the uterine horns and

**Figure 1.** Various types of IUD. Copper devices presented in the upper row, from left to right: T Safe Cu380A®, Nova T380®, Flexi-T300®, Multiload Cu375®, GyneFix®, Ocon® Cooper intrauterine ball. In the middle row—hormonal IUDs: Mirena®, Skyla®, FibroPlant® frameless levonorgestrel-releasing device. In the lower row, other IUD types are presented,

as the indomethacin-releasing cooper device AiMu® and the flexible, low copper dose VeraCept®.
