Misoprostol Alone

Overview and history

Despite evidence demonstrating the safety and efficacy of the mifepristone/misoprostol regimen, political and commercial difficulties present challenges to widespread production and distribution of mifepristone. Beginning in the early 1990s, researchers revisited the possibility of using misoprostol alone as a method of terminating early pregnancies. A growing body of evidence has now shown that misoprostol can be used as a single agent to induce early abortion. [25]

Misoprostol is widely prescribed for the prevention and treatment of gastric ulcers and is currently available in over 80 countries worldwide. Misoprostol is inexpensive, stable at ambient temperatures, easy to transport, easy to administer, and does not require refrigeration, even in hot climates. Thus misoprostol has potential to significantly expand medication abortion access in developing countries. Research on the optimal dosing and administration strategy is ongoing.

 

Misoprostol-only experience worldwide

Many women, particularly in countries with restrictive abortion laws, attempt to terminate early pregnancies with misoprostol alone. [26] Reports from Latin America suggest that women frequently use misoprostol to induce abortion early in pregnancy. However, without standardized information and instructions, women utilize misoprostol in a numerous ways, with a high degree of variation in both dosage and timing. [27] Some of these regimens are not as effective as others.

Misoprostol is currently registered in more than eighty countries worldwide, as the following map indicates.

Misoprostol is widely available, inexpensive, and stable at room temperature making it a suitable abortifacient in resource poor settings, if a standard regimen can be proven safe and effective. On-going, well-designed clinical research has the potential to establish an optimal protocol, provide additional information on the regimen's safety and side effects, and significantly improve access to safe medication abortion services worldwide.

Due to its use as an abortifacient, some governments have attempted to restrict access to and use of misoprostol. Thus, the availability and cost of misoprostol may vary widely by country.

Misoprostol-only experience in the US

In the United States, misoprostol (brand name Cytotec®) has been approved by the Food and Drug Administration (FDA) only for the prevention and treatment of gastric ulcers. However, clinicians have used misoprostol off-label for obstetric and gynecological purposes, including cervical ripening, labor induction, and mid-trimester terminations, for over a decade. [28]

Misoprostol-only regimens are not widely used in the United States, where both mifepristone/misoprostol and methotrexate/misoprostol regimens are available. However, the off-label use of misoprostol as a single agent abortifacient has been documented among Latina women in the United States. [29]

Mechanism of action of misoprostol

Prostaglandins are naturally occurring fatty acids produced by many tissues in the body. Prostaglandin E¹ causes myometrial contractions by interacting with specific receptors on myometrial cells. This interaction results in a cascade of events, including a change in calcium concentration, thereby initiating muscle contraction.

Misoprostol is an analog of prostaglandin E¹. By interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents. Misoprostol is relatively metabolically resistant, and thus has prolonged action. [30]

Misoprostol-only protocol

To date, there is no standard protocol for the use of misoprostol as a single agent abortifacient. Researchers throughout Latin America and East Asia have explored vaginal and sublingual regimens, a variety of doses, and different dosing schedules. Overall, these studies have shown that misoprostol alone is an effective medical abortion regimen, but at this time the regimen requires complicated dosing schedules as well as clinician administration, observation, and/or assessment.

Although an optimal regimen has not been developed, the most commonly used misoprostol-only regimen begins with the vaginal administration of 800 µg of misoprostol. If the abortion fails to occur, this dose is repeated every 24 hours up to three doses.  Instructions for the use of misoprostol-only can be found in the educational materials and resources section of this website.

 

Efficacy

A review of recent research indicates that the efficacy of misoprostol as a sole abortifacient varies by route of administration, dose, dosing schedule, and gestational age. There is not yet a consensus regarding a specific regimen. Most of the studies occur at different gestational ages, have small samples, test different variations, and show a range of results (65% to 93%).

Misoprostol can be absorbed through both the vaginal mucosa and the buccal mucosa. Some evidence suggests that the vascularity of the buccal mucosal would allow for more rapid absorption that would avoid first pass liver metabolism. However, more research needs to be conducted in order to identify an optimal protocol. Recent studies investigating sublingual administration also appear promising.

The misoprostol-only regimen has the potential to expand access to abortion in resource poor and developing country settings, if a standard regimen can be shown to be safe and effective. However, the misoprostol-only regimen is not as effective as either the mifepristone/misoprostol or the methotrexate/misoprostol regimen. Further, the side effects associated with the misoprostol-only regimen are generally much more severe than those associated with the combined regimens.

In 10% to 35% of cases, the medication abortion is incomplete. For women who do not experience a complete abortion an aspiration intervention may be required. Reasons for aspiration intervention include prolonged or excessive bleeding, incomplete abortion (remnants of fetal tissue in the uterus), or an ongoing pregnancy. An aspiration termination may also be performed at the request of the woman or the provider.

Eligibility

Most women early in their pregnancies appear to be eligible for the misoprostol-only regimen. If the use of misoprostol-only results in an incomplete abortion, vacuum aspiration or D&C may be necessary. Women considering the misoprostol-only regimen should we willing to undergo a vacuum aspiration procedure, if indicated.

Contraindications

Few contraindications to misoprostol use are described in the medical literature. Women with an allergy to prostaglandins should not use misoprostol. Women with uterine infections, severe anemia, cardiovascular and cerebrovascular diseases, coagulopathy or current therapy with anticoagulants, and hypertension were excluded from the clinical studies and thus may not be eligible for misoprostol use. Further, if an intrauterine device (IUD) is present, the device should be removed before a mifepristone/misoprostol termination is performed.

Side Effects and Complications

Some side effects, such as abdominal cramping and bleeding, are hallmarks of the abortion process itself. Many women and clinicians report cramps and abdominal pain similar to those associated with a heavy menstrual period. Vaginal bleeding can vary significantly in both duration and severity, and many report that the bleeding resembles a heavy period or a spontaneous miscarriage. Bleeding can be heavier than a heavy period and last for weeks. The majority of studies conducted on the misoprostol-only regimen have reported that the mean duration of bleeding is approximately two weeks.

Reported side effects include nausea, vomiting, diarrhea, dizziness, headache, fever, chills, rashes, and pelvic pain. Of women who report pelvic pain after using the misoprostol-only regimen, approximately 25% report that the pain was much stronger than menstrual pain. In most cases, side effects and pelvic pain can be managed with oral analgesics.

Several case reports have associated misoprostol use with limb defects and Mobius syndrome. However, an absolute causal relationship between misoprostol use and fetal deformities has yet to be demonstrated through prospective trials. Women electing to use the misoprostol-only regimen should be informed of the possible teratogenic effects of this drug.

Complications

Few complications have been reported with misoprostol-only regimens. However, additional studies will need to be conducted to confirm the safety of the misoprostol-only regimen. In approximately 10% to 35% of cases, aspiration intervention is required. As use of misoprostol leads to cervical dilation, mechanical dilation is generally unnecessary. [31]

Acceptability

Few studies have directly assessed the acceptability of misoprostol-only regimens. Although side effects of greater severity are associated with the misoprostol regimen, the majority of patients report that the side effects are tolerable. Patient satisfaction with both the vaginal and the sublingual regimens is high and the majority of patients state that they would use the misoprostol method for a future termination and would also recommend the method to others.

Additional Uses of Misoprostol

Misoprostol is used for a wide array of conditions including the treatment and prevention of gastric ulcers. Misoprostol is also used for a variety of obstetric and gynecological health indications, including the induction of labor, cervical ripening, and midtrimester abortion. Misoprostol has also been shown to be effective in treating postpartum hemorrhage and early pregnancy failure. [32]