IntraUterine System
The IntraUterine System or IUS is a hormonal contraceptive device that is placed in the uterus.  An IUS has a hormone cylinder that releases a progestin (progestogen) called levonorgestrel.  The only brand currently available is the T-frame LNG-20 IUS, marketed as Mirena Coil by Schering Health and Berlex Laboratories.
The term IUS is used in the United Kingdom to distinguish the hormonal intrauterine contraceptive from copper- or silver-based IUDs.  In the United States, no distinction is made between hormonal and copper/silver devices.  In the US, all intrauterine contraceptives are referred to with the term IUD, and the term IUS is not used.

# Clinical uses
- Contraception
- menorrhagia (heavy periods), endometriosis, chronic pelvic pain, dysmenorrhea, and anemia.  In some cases, use of an IUS may prevent a need for a hysterectomy.

# Fitting
The IUS can only be fitted by a qualified medical practitioner.  The device should be inserted according to the manufacturer's instructions using aseptic technique to avoid introduction of bacteria into the uterus.  Antibiotics should be given before insertion to women at high risk for endocarditis (inflammation of the membrane lining the heart), but should not be used routinely.
During the placement appointment, the cervix is dilated in order to sound (measure) the uterus and insert the IUS.  Cervix dilation is uncomfortable and, for some women, painful.  Doctors often advise women to take painkillers before the procedure to reduce pain and discomfort.  Insertion may be more comfortable if done midcycle, when the cervix is naturally dilated.
Once in place, the IUS is approved for birth control for up to 5 years.  The cumulative 5-year pregnancy rate is estimated to be 0.7%.

# Mechanisms of contraception
The Mirena is intended to initially release a daily dose of 20 micrograms levonorgestral (a progestin). It is not known exactly how Mirena works. It has several effects on the reproductive system, which are believed to explain its use to prevent pregnancy.
- Frequency of ovulation is reduced.
- Cervical mucus is changed to obstruct passage of sperm through the cervix.
- The presence of a foreign body in the uterus prompts the release of leukocytes and prostaglandins by the endometrium, substances that are hostile to both sperm and eggs.
- The endometrium is thinned. It has been suggested that this inhibits implantation of embryos, though no experiment has yet confirmed or disproved this theory.

# Removal
Generally IUS removal is easiest if undertaken towards the end of a women's period and involves a doctor or trained nurse using a pair of forceps to take hold of the IUS's thread and gently retract.
A "lost coil" occurs when the thread can not be felt by a women on routine checking and is not seen on speculum examination.
Various thread collector devices or simple forceps may then be used to try and grasp the device through the cervix.
In the rare cases when this is unsuccessful, an ultrasound scan may be arranged to check the position of the coil and exclude its perforation through into the abdominal cavity or its unrecognised previous expulsion. Hysteroscopy is very rarely needed.
After removal of the IUS normal fertility is regained after a few months, with a near normal 80% of women able to conceive within 12 months.

# Contraindications
The WHO Medical Eligibility Criteria for Contraceptive Use and RCOG Faculty of Family Planning & Reproductive Health Care (FFPRHC) UK Medical Eligibility Criteria for Contraceptive Use list the following as conditions where insertion of a levonorgestrel IUS is not usually recommended or should not be used because of an unacceptable health risk:
Conditions where the theoretical or proven risks usually outweigh the advantages of inserting a levonorgestrel IUS:
- Postpartum between 48 hours and 4 weeks (increased IUD expulsion rate with delayed postpartum insertion)
- Current deep vein thrombosis (DVT) or pulmonary embolus (PE)
- Benign gestational trophoblastic disease
- Past history of breast cancer and no evidence of current disease for 5 years
- Ovarian cancer
- Very high individual likelihood of exposure to gonorrhea or chlamydial STIs
- AIDS (unless clinically well on anti-retroviral therapy)
- Active liver disease: (acute viral hepatitis, severe decompensated cirrhosis, benign or malignant liver tumours)
Conditions which represent an unacceptable health risk if a levonorgestrel IUS is inserted:
- Pregnancy
- Postpartum puerperal sepsis
- Immediately post-septic abortion
- Before evaluation of unexplained vaginal bleeding suspected of being a serious condition
- Malignant gestational trophoblastic disease
- Cervical cancer (awaiting treatment)
- Active liver disease: (acute viral hepatitis, severe decompensated cirrhosis, benign or malignant liver tumours)
- Current or recent breast cancer (a hormonally sensitive tumour)
- Endometrial cancer
- Distortions of the uterine cavity by uterine fibroids or anatomical abnormalities
- Current PID
- Current purulent cervicitis, chlamydial infection, or gonorrheal STIs
- Known pelvic tuberculosis

# Side effects and complications

## Location of device
Following insertion, the IUS may be expelled through the cervix. An expulsion rate of 4% was observed in the manufacturer's clinical trials, with most (3%) occurring in the first year of use. Expulsion is more common in younger women, women who have not had children, and when an IUS is inserted immediately after childbirth or abortion.
A rare but potentially serious complication is that of uterine perforation. This may occur either during the device's insertion, or from its later embedment into the myometrium (uterine wall) and subsequent migration through to the intra-abdominal cavity. Perforation can cause internal scarring, infection, or damage to other organs, and may require surgery. Uterine perforation has been reported at rates ranging from 1 to 2.6 per 1000 insertions.  It is believed that perforations are significantly underreported, however, and actual perforation rates are likely higher.
Both expulsion and perforation result in loss of contraceptive cover and the position of the thread of the IUS should be self-checked at least once per menstrual cycle to verify that it is still in place, or, in the absence of menstrual cycles, once per month.
The string(s) may be felt by some men during intercourse.  If this is problematic, the provider may tuck the strings behind the cervix, cut the strings shorter, or in more extreme cases cut the strings to level with the cervix. Cutting the strings even with the cervix prevents the woman from checking the device's correct placement, and may complicate removal.

## Pelvic inflammatory disease and sexually transmitted diseases
Pelvic inflammatory disease (PID) is caused by certain sexually transmitted diseases (STDs).  PID is a serious condition that may result in infertility.  In women who have STDs, an IUD will increase the risk of PID.  Therefore, IUDs are not recommended for women at high risk of STDs.
Women who have more than one sexual partner, or whose partners have more than one sexual partner, are at increased risk for STDs.  Younger women are statistically at higher risk for STDs.
An animal study suggested that progestin-only hormonal contraceptives such as Mirena might increase the risk of HIV transmission, because of the thinning of the vaginal walls caused by these methods.  However, a number of studies of human populations showed that progestin contraceptive use does not increase the risk of acquiring HIV.
However, like the Pill and other non-barrier forms of contraception, the IUS offers no protection against sexually transmitted disease.

## Postpartum and post-abortion insertion
An IUS may be inserted immediately postpartum (within 48 hours). With insertions after 48 hours, perforation of the uterus is more likely to occur when uterine involution is incomplete; involution usually completes by 4-6 weeks postpartum. Special considerations apply to women who plan to breastfeed.
Also to allow for uterine involution, insertion of an IUS is not recommended for women who have had a D&E abortion (second-trimester abortion) within the past four weeks.
To reduce the risk of infection, insertion of an IUS is not recommended for women who have had a medical abortion but have not yet had an ultrasound to confirm that the abortion was complete, or who have not yet had their first menstruation following the chemical abortion.
Expulsion is more common when an IUS is inserted immediately after childbirth or abortion.

## Hormonal side effects

### Localised
Menstrual periods become lighter, or, in about 20% of women, stop completely within one year of insertion.  Irregular bleeding is common in the first few months after insertion, with the average user reporting 16 days of bleeding or spotting in the first month of use, but this diminishes to about four days at 12 months.

### Systemic
The progestin in an IUS is intended to be released at a lower dose than that used in other progestogen-only contraceptives such as the mini-pill or Norplant (blood levels of levonorgestrel in Mirena users are half those found in Norplant users and one-tenth those found in users of levonorgestrel-only pills).
Enlarged follicles (ovarian cysts) have been diagnosed in about 12% of the subjects using a levonorgestrel IUS. Most of these follicles are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases the enlarged follicles disappear spontaneously during two to three months observation. Surgical intervention is not usually required.

### Nursing mothers
There is an increased risk of perforation in women who are lactating.
Progestogen-only contraceptives such as an IUS are not believed to affect milk supply or infant growth. However, a study in the Mirena application for FDA approval found a lower continuation of breastfeeding at 75 days in IUS users (44%) versus copper IUD users (79%).
Levornogestrel is found in nursing infants at 7% of the concentration found in their mothers using the Mirena IUS. A six-year study of breastfed infants whose mothers used a levonorgestrel-only method of birth control found the infants had increased risk of respiratory infections and eye infections, though a lower risk of neurological conditions, compared to infants whose mothers used a copper IUD. No longer-term studies have been performed to assess the long-term effects on infants of levornogestrel in breast milk.
There are conflicting recommendations about use of Mirena while breastfeeding.  The U.S. FDA does not recommend any hormonal method, including Mirena, as a first choice contraceptives for nursing mothers. The World Health Organization recommends against immediate postpartum insertion, citing increased expulsion rates.  It also reports concerns about potential effects on the infant's liver and brain development in the first six weeks postpartum.  However, it recommends offering Mirena as a contraceptive option beginning at six weeks postpartum even to nursing women.  Planned Parenthood offers Mirena as a contraceptive option for breastfeeding women beginning at four weeks postpartum.

### Effect on cancer rates
The U.S. Food and Drug Administration has concluded that the carcinogenic potential of Mirena is low. According to a 1999 evaluation of the studies performed on progestin-only birth control by the International Agency for Research on Cancer, there is some evidence that progestin-only birth control reduces the risk of endometrial cancer.  The IARC concluded that there is no evidence progestin-only birth control increases the risk of any cancer, though the available studies were too small to be definitively conclusive. The use of progestin alone in treatment of menopause has been associated with a doubling of risk for breast cancer versus nonuse.
Because breast cancer cells are often hormone-sensitive, Mirena and other hormonal birth control methods are not recommended for women who have, have had, or suspect they have breast cancer.

## Pregnancy
Although the pregnancy rate during IUS use may be low, it is not a 100% effective method of birth control.  If pregnancy does occur, presence of the IUD increases the risk of miscarriage, particularly during the second trimester.  It also increases the risk of premature delivery.  These increased risks end if the IUD is removed after pregnancy is discovered. No pattern of birth defects has been suggested by the 35 babies for whom birth outcomes were available at the time of FDA approval.
As many as half of pregnancies that occur in Mirena users may be ectopic. The incidence rate of ectopics is approximately 1 per 1000 users per year.

## Bone Density
No evidence has been identified to suggest Mirena affects bone mineral density (BMD). The only published study on the effect of Mirena on BMD showed that long-term users, at 7 years of use, had similar BMD at the midshaft of the ulna and at the distal radius as nonusers matched by age and BMI. In addition, BMD measurements were similar to the expected values for women in the same age group as the participants. The authors of the study said their results were predictable since it is well established that the main factor responsible for bone loss in women is hypoestrogenism and, in agreement with previous reports, they found estradiol levels in Mirena users to be normal.

# Types of IntraUterine Systems
Progestasert was the first hormonal uterine device, developed in 1976 and manufactured until 2001. It contained progesterone that was released at a rate of 65 micrograms per day. In most countries it was replaced annually, though it was approved for 18 months of use in France.  It had a failure rate of 2% per year.
Development and studies of the Mirena Coil began in the 1970s.  Schering Health distributes Mirena outside the United States, while Berlex distributes it inside the United States.  Both companies have worked with the Population Council, a non-profit organization that has worked with other contraceptive manufacturers (including Wyeth, maker of Norplant).
Mirena was first marketed commercially in Finland in 1990, but not approved by the U.S. Food and Drug Administration until 2000.  It is intended to initially release 20 micrograms of levonorgestral per day and may be used for five years.
Contrel, the Belgian company that developed the frameless GyneFix IUD, is developing a lower-dose (14 micrograms levonorgestrel per day) T-frame IUS named Femilis.  Femilis would come in a smaller size (Femilis Slim) for nulliparous women.  It would be inserted without a plunger, and it is hoped its performance would be less dependent on the experience of the health care professional.
Several trials with positive results have been done on a frameless IUS called FibroPlant-LNG (also from Contrel).  FibroPlant is anchored to the fundus of the uterus rather than being held in by a frame.  It initially releases 14 micrograms of levonorgestrel per day, and may be used for at least three years.  As of 2005, it was not commercially available.