Misoprostol in gynaecology and obstetrics

How misoprostol works:

The drug, which was introduced to the German market in the 1980s, is used orally for the prevention and treatment of gastric and duodenal ulcers. Misoprostol is a synthetically produced derivative of the tissue hormone prostagladin E1. In the course of treatment, it attaches to certain glandular cells (i.e. parietal cells) of our gastric mucosa and inhibits the release of gastric acid. In doing so, acid-induced stomach ulcers can be prevented.

This effect can also be used for obstetric medicine, as the smooth muscle of the uterine wall also possesses binding receptors for misoprostol. If the prostagladin analogue docks at this site, it can trigger contractions of the uterine muscles (i.e., contractions). The cervix becomes softer and shorter, creating better opportunities for the baby to pass through.

When misoprostol is used:

For adults with osteoarthritis or rheumatoid arthritis, a combination preparation of the active ingredients diclofenac and misoprostol in tablet form is approved. While diclofenac relieves inflammation, it can also cause gastrointestinal ulcers. In this regard, misoprostol can prevent this side effect of the anti-inflammatory drug. Due to its certain effect on the uterus, the drug is also used for the following treatments when appropriate:

Behavioral miscarriage:

In the form of high-dose tablets, misoprostol can be used for medication abortion within the legally regulated abortion period. It is used in combination with the active ingredient mifepristone to prevent complications.

To this end, a study published in August 2020, in the journal The Lancet, compared the effect of combination therapy with misoprostol alone. This involved 711 women over the age of 16 in 28 UK hospitals between October 2017 and July 2019. All study participants were diagnosed with miscarriage through ultrasound scans within the first 14 weeks of pregnancy and provided medical treatment with informed consent. While the study group received mifepristone followed by misoprostol two days later, the control group received placebo first followed by misoprostol. The double-blind, multicenter, placebo-controlled, randomized trial found that surgical intervention was needed for 17% of women on combination drug. For the control group with misoprostol, it was 25% of women, making treatment with both agents more effective than giving them individually, according to the study.

Misoprostol as a contraceptive:

Also available as a tablet, the drug is more often administered as an oxytocic in clinics in Germany. According to the German Society for Gynaecology and Obstetrics (DGGG), misoprostol is effective in inducing labour. In this context, it is used as a so-called "off-label" preparation, as it has not been approved since 2010 according to the guidelines of the Scientific Medical Societies (note: these guidelines have expired and have been under review since 2013). In this case, the physician has therapeutic freedom and is free to judge in good faith which treatment to suggest, without the active ingredient having official approval in the country. However, the patient should be accurately informed about risks and alternative treatments.

Varying dosages:

According to a 2013 evaluation of the Clinic for Obstetrics and Gynecology in Aachen, 65% of participating clinics indicated that they use misoprostol to induce labor. Only 35% of the clinics primarily adhere to the single dose of 25µg recommended by the WHO and DGGG. All 738 clinics providing obstetric care in Germany were contacted and 62% of them responded.

Oral administration beneficial:

Compared with prostagladin E2, misoprostol is advantageous in that it can be used in pregnant women at risk of asthma. In addition, the drug can also be administered orally. This brings advantages as there is a risk of infection when used locally (i.e. vaginally).

The Cochrane review, published in 2014, compared 76 randomized controlled trials involving 14,412 women and found that oral misoprostol is as effective as other current methods of induction of labour. 9 studies examined, involving 1282 women, compared misoprostol as administered with intravenous oxytocin (i.e., a hormone) and showed that significantly fewer cesarean deliveries were recorded with oral administration. Another nine studies involving 1109 participants showed that the drug induced labor more efficiently than a placebo and had concurrently fewer C-sections and neonatal intensive care unit admissions.

Conclusion:

The drug misoprostol is still a relevant issue for obstetrics and gynecology. Approximately 20% of pregnant women require induction of labor, which in an annual number of approximately 780,000 births, leaves obstetricians and physicians faced with the decision of which method or agent and dosage to administer approximately 78,000 times. Therefore, the patient should seek accurate information, especially in the case of "off-label" preparations, in order to make the birth as complication-free as possible.

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