Intrauterine Devices: A Review

 

Chinmaya Keshari Sahoo¹, Amiyakanta Mishra¹, D. Venkata Ramana², Jimidi Bhaskar³

¹Department of Pharmaceutics, College of Pharmaceutical Sciences (Affiliated to BPUT), Bidyaniketan,

Marine Drive Road, Baliguali, Puri, Odisha.

²Department of Pharmaceutical Technology, Samskruti College of Pharmacy, Kondapur, Ghatkesar,

Medchal, Telangana, India.

³Department of Pharmaceutics, KLR Pharmacy College, Paloncha Bhadradri, Kothagudem, Telangana.

 

ABSTRACT:

An intra-uterine device is a special device that fits inside of the uterus. Intrauterine contraceptive device (IUD) is the most commonly used method of contraception in many countries. The IUDs are a long-acting reversible method of contraception. Despite the availability of many generations of IUDs with variable shapes and configurations, side effects and complications are frequent. Evidence-based practices have increased the number of women who are medically eligible for IUDs and have enabled more rapid access to the methods. Currently hormonal IUDs are available in the market. Each IUD is extremely effective, convenient, and safe. The newer IUDs have been tested in populations not usually included in clinical trials and provide reassuring answers to older concerns about IUD use in these women, including information about expulsion, infection, and discontinuation. On the other hand, larger surveillance studies have provided new estimates about the risks of complications such as perforation, especially in postpartum and breastfeeding women.

 

 

 

INTRODUCTION:

Intrauterine Device (IUD) is a small object that is inserted through the cervix [1] and placed in the uterus to prevent pregnancy. A small string hangs down from the IUD into the upper part of the vagina [2]. The IUD is not noticeable during intercourse [3]. IUDs can last 1-10 years. They affect the movements of eggs and sperm to prevent [4] fertilization. They also change the lining of the uterus and prevent implantation. IUDs are 99.2-99.9% effective as birth control. They do not protect against sexually transmitted infections [5], including HIV/AIDS. Insertion of an IUD takes only about 5 to 10 minutes.

 

 

It is put inside using a special applicator that keeps the IUD flat and closed until it is at the top of the uterus. An IUD prevents pregnancy by stopping sperm from reaching an egg [6] that from ovaries. It does this by not letting sperm go into the egg. An IUD also changes the lining of the uterus so an egg does not implant in the lining if it has been fertilized. Therefore, the egg has no place to grow. IUDs are the most effective form of nonpermanent birth control. They are more than 99% effective. An intrauterine device (IUD) usually is a small, flexible plastic frame. It often has copper wire or copper sleeves on it. It is inserted into a woman’s vagina through her uterus [7]. Almost all brands of IUDs have two strings, or threads, tied to them. The strings hang through the opening of the cervix into the vagina. A provider can remove the IUD by pulling gently on the strings with forceps.

 

 

Advantages of IUDs [8-10]

1.     It is highly effective in preventing pregnancy.

2.     It is inexpensive.

3.     It does not interrupt sex.

4.      It does not require partner’s involvement.

5.      It can be used for a long period of time.

6.     It can be used as an emergency method of birth control.

7.     An IUD provides long-term contraception for 3 to 5 years and is cost-effective.

 

Disadvantages of IUDs [11-13]

1.     It does not protect against sexually transmitted infections (STIs).

2.     It may increase the likelihood of ectopic pregnancy (pregnancy outside the uterus).

3.     It can cause heavier and more painful periods.

4.     Cramping and discomfort occurs during and 24-48 hours after insertion

5.      There are risks during insertion and removal

 

Table 1: Time of IUD insertion

 

Time of using an IUD [14-17]

An IUD is usually inserted during a menstrual period, when the cervix is slightly open and pregnancy is least likely. There is however a greater chance of expulsion if a device is introduced early in the cycle because the uterus can squeeze the device back out. Therefore, the best time for insertion is just after a period. However, an IUD may be inserted at any time. The best timing for IUD insertion for women in different situations is given in Table 1.

 

Types of intrauterine systems [18,19]:

The type now most widely used is

1. Copper-bearing IUDs:

These are made of plastic with copper sleeves and copper wire on the plastic, such as TCu-380A and MLCu-375

 

2. Hormone-releasing IUDs:

These are made of plastic and steadily release small amounts of progesterone or other progestin hormones, such as LNG-20 and Progestasert.

 

3. Inert or unmedicated IUDs:

These are made of plastic or stainless steel only, such as Lippes Loop and Chinese stainless steel rings.

 

1. Copper IUDs [20, 21]:

Copper wire or copper sleeves are put on the plastic frame (polyethylene frame). Examples include Copper T, CuT380 A, Multiload 375 etc. The various types of Copper IUDs differ from each other by the amount of copper. The initial Copper IUDs were wound with 200-250 mm2 wire (CopperT 200). The modern copper containing devices contain more copper and a part of copper in the form of solid tubal sleeves rather than wire. This increases the efficacy and lifespan (Cu T-380 A).

 

·       CuT 380A –

It is a T shaped device with a polyethylene frame holding 380 mm2 of exposed surface area of copper. The IUD frame contains barium sulfate thus making it radio-opaque.

 

·       CuT-380Ag –

It is identical to 380 A except that the copper wire on the stem has a silver core to prevent fragmentation and extend the life span of the copper.

 

·       CuT 380 slimline –

It has copper sleeves flushed at the ends of horizontal arms to facilitate easier loading and insertion. The performance of CuT-380 Ag and the CuT-380 slimline is equal to that of CuT-380 A.

 

·       Multiload 375 –

It has 375 mm2 of copper wire wound around its stem. The flexible arms are designed to minimize expulsions. The multiload 375 and T cu-380 A are similar in their efficacy and performance.

 

 

·       Nova T –

It is similar to the CuT-200, containing 200 mm2 of copper. However, the Nova T has a silver core to the copper wire, flexible arms, and a large flexible loop at the bottom to prevent cervical perforation.

 

Copper T 380A:

Copper T 380A (ParaGard; Teva Pharmaceutical Industries Ltd., Sellersville, PA, USA) is one of the most commonly available and widely used in many countries. It contains 380 mm² copper surface area supplied by a sleeve of solid copper on each of the arms (together 32 cm in width) and wrapped by a copper wire along the 36 mm vertical stem. Monofilament polyethylene thread is tied through the base creating two white tail strings measuring 10.5 cm in length to facilitate detection and removal of the device. The CuT-380A IUD is designed to be used in women whose uterine cavities sound to a depth of 6–9 cm.

 

The CuT-380A IUD is placed [22] into the uterus using a two-handed technique. The IUD arms are loaded manually pointing downward into the insertion tubing after uterine sounding has verified that the woman’s uterus is in the appropriate depth (6–9 cm). The loaded IUD tubing should be advanced directly in one step to the uterine fundus, and then the arms are to be released.

 

Mechanisms of action:

The copper IUD functions as a contraceptive (inhibiting fertilization). Ova retrieved at the time of tubal sterilization performed following timed intercourse midcycle showed no normal division of the ova, which might have indicated union of the gametes. On the other hand, the inflammatory changes in the endometrium do have spermicidal [23] activity. In vitro, copper ions in concentrations typical of those found within the endometrial cavity with the CuT-380A IUD inhibit sperm motility and block activation of acrosomal enzymes in the sperm head needed for the sperm to penetrate through the zona pellucida to enable union of the gametes. These observations lead to the characterization of copper IUDs used for ongoing pregnancy prevention as “functional spermicides”. The copper slows down the movement of sperm [24] within the woman’s uterus and so prevents them from reaching the fallopian tubes and fertilizing the egg. The device also stimulates a strong reaction in the wall of the uterus, which prevents implantation of the egg (even if it is fertilized).

 

Effectiveness of IUDs:

An IUD is a highly effective, long-term, reversible contraception. Using an IUD can be as effective as female surgical sterilization in preventing pregnancy [25], but unlike sterilization it is a completely reversible contraceptive method. Among women who use the Copper T 380A IUD, less than 1% becomes pregnant (0.6 to 0.8 per 100 women) during the first year of use. Additionally, the cumulative risk of pregnancy over the ten-year service life of an IUD is less than 3%. In addition, fertility [26] returns soon after removal. The Copper T 380A can prevent a woman from becoming pregnant for up to 12 years. However, its effect is reduced after seven years of use, after which the likelihood of becoming pregnant increases.

 

Checking the IUD:

It is advised to women that they can keep track of an IUD by checking for its strings, and they can feel for the strings by putting a finger into their vagina. Some women prefer to look for the string with a mirror and flashlight. It is generally recommended that women check their IUD after each period. A shorter than normal string can be a warning sign of a misplaced IUD. Missing strings may mean that the IUD has been expelled. If the string is missing, it is advised to the woman to visit the health post or health centre in order to have a back-up method of birth control. If the woman misses a period while on an IUD, she may need to take a pregnancy test.

 

Candidates[27]:

As a nonhormonal method, the CuT-380A IUD can be used by women who have medical contraindications to progestogens (hepatic dysfunction progestin-sensitive tumors) and those who prefer to avoid use of synthetic hormones. Interestingly, conditions that were initially listed as contraindications to the use of the CuT-380A IUD when it was launched in 1988 are now ones for which the copper IUD is preferred.

 

Side-effects and managing side-effects:

IUDs cause very few side-effects. The most common are pelvic cramping and menstrual problems, including heavy and prolonged menstrual bleeding [28], and intermenstrual spotting. Although abnormal bleeding and spotting are the leading reasons for women to discontinue the method, these side-effects do not usually affect their health, and generally decrease in the first few months after insertion.

 

One potential, though uncommon, complication of IUD use is device expulsion, which occurs in 2–8% of women. Expulsion occurs most often in the first few months after insertion, and it is most common in young women, and women who have never given birth. The IUD can only be expelled outward into the vagina or cervix. It cannot travel to any other part of the body. Expulsion is not dangerous for the user; however, if the IUD is expelled, the woman is no longer protected against pregnancy because the IUD’s contraceptive effect is immediately reversible.

 

Advantages of the Copper T 380A IUD [29, 30]:

1.     IUDs are a highly effective, safe, long-acting contraceptive method.

2.     Women need to make only a single decision to use it, whereas the pill requires daily decisions, and condoms and spermicides require decisions with each act of intercourse.

3.     Although it is more expensive initially than other contraceptives, the IUD is less costly over its years of use.

4.     In addition, the IUD is a good option for those who have to take medical precautions using hormonal methods, as there are no hormonal side effects with copper-bearing or inert IUDs.

5.     It does not interact with any medicine the client may be taking, so it is ideal for those who are taking antiepileptic or antituberculosis medications.

6.     The IUD is best used by those wanting a long-acting and prompt reversible method.

7.     A new device can be inserted without any gap as many times as a woman desires during her reproductive life.

8.     The Copper T 380A IUD also helps prevent ectopic pregnancies (there is less risk of ectopic pregnancy than for women not using any family planning method).

9.     When inserted within five to seven days of unprotected intercourse, the Copper T 380A gives good protection against unintended pregnancy.

10.  Copper T 380A IUD does not affect the quantity and quality of breast milk, it can be used by lactating women.

 

Disadvantages of the Copper T 380A IUD [31-33]:

IUDs are not suitable for all women. Using them carries the following risks:

1.     Pelvic inflammatory disease (PID):

One of the main concerns about using IUDs is the possibility of developing PID. Both using an IUD and being at high risk of acquiring sexually transmitted infections (STIs) make women more likely to develop PID. The greatest risk of pelvic infection associated with the use of IUDs occurs at insertion. This increased risk of infection may be associated with a microbiological contamination of the endometrial cavity at that time.

 

2.     Human immunodeficiency virus (HIV):

Whether IUDs increase the risk of acquiring HIV is not known. The effect of IUDs on the uterine lining may create an environment favourable to HIV transmission. It is possible that the increased bleeding associated with the use of some IUDs may increase the transmission of the virus from HIV-positive women to their partners.

 

3.     Menstrual problems:

Increased menstrual pain (dysmenorrhoea) may accompany IUD use. Between 10%–15% of IUD users have their IUD removed because of symptoms or signs associated with bleeding or spotting. However, the amount of blood is usually minor and of little consequence.

 

4.     Expulsions:

An IUD may come out of the uterus, possibly without the woman knowing. This is more common when the IUD is inserted soon after childbirth, or when there are abnormal amounts of menstrual flow or severe dysmenorrhoea (painful cramps during menstruation).

 

5.     Pregnancy:

Half of intrauterine pregnancies that occur with the IUD in place end in spontaneous abortion. If the IUD is removed early in pregnancy, the spontaneous abortion rate drops to about 25%. Leaving the IUD in place during pregnancy increases the risk that the mother will have severe pelvic infection that could lead to her death. About 5% of women who become pregnant with an IUD in place will have an ectopic pregnancy.

 

MLCu:

These devices are predominately used in Europe and Asia and are available in short versions for nulliparous women. The MLCu-375 provides 5 years of contraceptive protection while the MLCu250 lasts for 3 years. The UNFPA & IPPF provide these IUDs to partner countries.

 

Hormone-Releasing IUDs:

Hormonal IUDs (brand names Mirena, Skyla, and Liletta; referred to as intrauterine systems in) work by releasing a small amount of levonorgestrel [34], a progestin. The primary mechanism of action is making the inside of the uterus fatal to sperm. They can thin the endometrial lining and potentially impair implantation but this is not their usual function. Because they thin the endometrial lining, they reduce or even prevent menstrual bleeding, and can be used to treat menorrhagia (heavy menses), once pathologic causes of menorrhagia (such as uterine polyps) have been ruled out. The progestin released by hormonal IUDs primarily acts locally; use of Mirena [35] results in much lower systemic progestin levels than other very-low-dose progestogen only contraceptives.

 

Progestasert:

It is a T shaped IUD made of ethylene and vinyl acetate copolymer containing titanium dioxide. The vertical stem contains a reservoir of 38 mg progesterone together with barium sulfate dispersed in silicone fluid. The progesterone is released at the rate of 65 µg per day.

 

LNG-releasing IUSs [36-40]:

There are three branded LNG-releasing IUSs currently available. There are two similarly size IUSs with 52 mg LNG and one is smaller with 13.5 mg LNG. The release rates of LNG were measured at different times following the placement, which initially lead to some confusion in naming conventions. For the existing LNG-IUSs and future devices, the convention adopted is that the name will reflect the mean amount of LNG released over a 24 suggested that for women who are above the-hour period during the first year of use.

 

LNG-releasing IUSs (20 µg/24 hours) (Mirena®, Liletta/Levosert®):

Each of these IUSs is composed of a T-shaped polyethylene radiopaque frame measuring 32 mm32 mm. Encircling the stem is a hormone cylinder composed of a mixture of 52 mg levonorgestrel (LNG) and silicone (polydimethylsiloxane). Controlling the rate of release of LNG from this reservoir is a semiopaque silicone (polydimethylsiloxane) membrane. A monofilament polyethylene thread is attached to a hook at the end of the vertical stem creating two tail strings that are useful to reassure the woman of the IUD’s continued presence and to facilitate removal. LNG is released during the first year at a rate of 20 µg/d. After early equilibration, plasma levels average 150–200 pg/mL. The average levels over the first 3 years were 218 ng/L.

 

The first LNG-IUS 20 that was widely adopted (Mirena) is approved by health authorities in more than 140 countries, for 5 years, for contraception. It is approved for the treatment of heavy or prolonged menstrual bleeding and to serve as a source of progestin for postmenopausal estrogen therapy in women with an intact uterus. Extended use of the original LNG-IUS for up to 7 years has been suggested for women who are at least 25 years of age at the time of placement.

 

Currently, the newer version (Liletta/Levosert; Allergan, Inc., Irvine, CA, USA) has only been tested for a limited number of years, so approval is for only 3 years. However, clinical trials are continuing; if the efficacy is maintained, the approval will undoubtedly be expanded in duration. Because the IUD portion of these two products is virtually identical, it is expected that ultimately the clinical impacts will both be the same. However, in the US, Liletta® is approved for contraception only, but in Europe, Levosert® (Uteron Pharma, Liege, Belgium) is also approved for the treatment of heavy menstrual bleeding.

 

There are two significant differences between these two higher-dose LNG-releasing IUDs: the systems used to place the IUD into the uterine cavity and the price of the IUDs. Both of the LNG-IUSs now use single handed techniques for device placement. The loading and release of the original IUS is simpler and more straightforward than the technique used to place the newer version. The other difference is cost. The Liletta/Levosert was developed by a foundation (Medicines360) to make this top-tier option available to women in low resource areas and to provide it to other women who cannot afford the initial upfront costs. How long the price difference will persist will depend on pricing decisions made by both manufacturers. Another minor difference is that the colors of the tail string are different.

 

Mechanisms of action:

The primary mechanism of action for all progestin IUSs is always local. The most important mechanism is thickening of the cervical mucus to blocking the entry of sperm into the upper genital tracts; ovulation is suppressed in only 50% of cycles in the first year of use and in significantly fewer cycles in later years. Sperm can penetrate through the cervix mucus by only 2–3 mm in LNG-IUS users at the time of ovulation and that this impact persists throughout the life of the IUD. Progestin also slows tubal motility, which might explain the increased risk of an ectopic implantation when pregnancy occurs with LNG-IUS use. LNG induces profound endometrial changes, which clearly explains the bleeding abnormalities seen over time with the use of the LNG-IUS.

 

Efficacy:

Mirena offers low risk for sexually transmitted infections, and who had no history of ectopic pregnancy or PID were studied. It has been suggested that for women who are above the age of 25 years at the time they initiate the use of the LNG-IUS 20, the effective life of the device may be extended to 6 years.

 

Noncontraceptive uses of LNG-IUS 20 (Mirena):

This LNG-IUS 20 has a wide variety of noncontraceptive health benefits. Women using the LNG-IUS 20 claimed that they had found noncontraceptive benefits by 12 months and that the use of the LNG-IUS increased their quality of life. Some of these benefits are treatment for heavy menstrual bleeding, treatment of dysmenorrheal, provision of endometrial protection, treatment of endometrial hyperplasia, and emergency contraception (EC).

 

Newer branded LNG-IUS 20 mg/24 h (Liletta/Levosert):

Medicines360, a nonprofit women’s health pharmaceutical company founded to expand access to quality women’s health products, has been conducting the clinical trials of a new IUS with 52 µg of LNG. These trials to date have provided the data that formed the basis for the initial 3-year approval by the FDA/European Medicines Agency of Liletta/Levosert for that time period. Those trials are ongoing and are planned to continue until 7-year data are obtained.

 

Noncontraceptive benefits:

Heavy menstrual bleeding:

In Europe, the regulatory authorities granted this IUS labeling indication as treatment for heavy menstrual bleeding.

 

LNG-IUS 8 (Skyla/Jaydess®):

The LNG-IUS 8 (Bayer Healthcare Pharmaceuticals) has the same basic structure as higher-dose LNG-IUSs, but is smaller in both vertical and horizontal dimensions. The arms measure 28 mm, and the stem is 30 mm long. The T-shaped frame is made of polyethylene. The reservoir has only 13.5 mg LNG wrapped around the stem. The monofilament tail strings are identical to Mirena. The LNG-IUS 8 is introduced into the uterine cavity in tubing with a smaller outer diameter of 3.8 mm. To distinguish this lower-dose IUD on imaging from its higher-dose versions, a ring of 99.95% pure silver was placed at the top of the vertical stem close to the horizontal arms. Even with the small ring, it is safe to perform MRI as long as the machine is rated no higher than 3 T, and the examination does not exceed 15 minutes. Marketed in the US as Skyla and worldwide as Jaydess, this lower-dose, 3-year IUD with 13.5 mg LNG releases an average of 8 µg/d over the first year.

 

Efficacy:

In the teen study, no pregnancies were reported in the 12-month period. The Kaplan–Meier estimates for the failure rates over 3 years were 0.9%.

 

Discontinuation rates:

Bleeding was a rare cause of discontinuation, but pelvic pain and dysmenorrhea were more frequent reasons given for discontinuation. Bleeding patterns with the LNG-IUS 8 are substantially different from those observed in general with the LNG-IUS 20. With both IUSs, substantial unscheduled spotting and bleeding occur in the first 3–4 months of use; however, the rates diminish rapidly over time and most events represent spotting rather than bleeding. Amenorrhea rates were significantly lower among LNG-IUS 8 users; by the end of the 3 years, only 12% of women experienced amenorrhea for the last 90-day period.

 

Inert:

Inert IUDs are IUDs with no bioactive components; they are made of inert materials like stainless steel (such as the stainless steel ring, or SSR, a flexible ring of steel coils that can deform to be pushed through the cervix) or plastic (such as the Lippes Loop, which can be inserted through the cervix in a cannula and takes a trapezoidal shape within the uterus). They are less effective than copper or hormonal IUDs, with a side effect profile similar to copper IUDs. Their primary mechanism of action is inducing a local foreign body reaction, which makes the uterine environment hostile both to sperm and to implantation of an embryo. They may have higher rates of preventing pregnancy after fertilization, instead of before fertilization, compared to copper or hormonal IUDs. No inert IUDs are approved for use by the healthcare authorities in the United States, UK, or Canada. In China, where IUDs are the most common form of contraception, copper IUD production replaced inert IUD production in 1993. As the SSR has no string for removal, it can present a challenge to healthcare providers unfamiliar with IUD types not available in their region.

 

CONCLUSION:

An IUD is inserted into the uterus (womb) by a health-care provider with specialized training. An IUD prevents pregnancy by stopping sperm from reaching an egg that from ovaries have released. An IUD also changes the lining of the uterus so an egg does not implant in the lining if it has been fertilized. Therefore, the egg has no place to grow. Copper IUDs are not recommended for women with Wilson’s disease or allergies to copper. Women with a history of breast cancer cannot use the Mirena IUD. An IUD is a good option for women who want a highly effective, long-term, easily reversible method of contraception. It can be an appropriate choice for women who can't use certain hormonal methods like birth control pills.

 

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Received on 08.04.2020          Modified on 29.04.2020

Accepted on 11.05.2020  ©AandV Publications All right reserved