The abortifacient properties of misoprostol were first reported in Brazil, where it was used by women attemptiug abortion of unwanted pregnancies. Abortion in Brazil is legal only in cases of rape or incest, or to save a woman’s hfe. Despite all other reasons being illegal, induced abortion is widely carried out. When used illegally, misoprostol may be inefficient in achieving complete abortion, and many women may suffer from incomplete abortions which may require uterine evacuation.
Doses used for illegal abortion ranged from 200 jigm up to 16,800 pgm of misoprostol. Most women took the drug orally, some used a combination of oral and vaginal routes, and few administered it intravaginally. The most common pattern of use associated with the highest abortion rate was 4 tablets of 2 0 0 pgm of misoprostol each; administered as 2 tablets orally and 2 tablets
intravaginally, mainly around the ninth to twelfth week of amenorrhea (Coelho et al., 1994; Fonseca et ai, 1996). Women sought hospital care only if complications such as severe vaginal bleeding and uterine cramps occurred (Costa & Vessey, 1993; Faundes et ai, 1996).
Since progesterone is essential for the establishment and maintenance of pregnancy, it has been recognised that a substance that antagonises the action of progesterone i.e. an antiprogestin, would have potential as an antifertility agent. Antiprogestin not only activates the uterus, but can also cause bleeding, uterine contractions, and ripening of the cervix. It causes an increase in uterine contractility and a significant increase in myométrial sensitivity to
prostaglandins, which is probably due to the release of the inhibitory effect of progesterone. However, antiprogestin alone is not sufficiently effective for terminating early pregnancy.
Administration of the progesterone antagonist Mifepristone (RU 486), which sensitises the uterus to prostaglandins, produces vaginal bleeding and uterine contractions in both non-pregnant and pregnant women. Extensive trials have established that a single dose of mifepristone followed 36 to 48 hours later by a prostaglandin, is an effective and safe alternative to vacuum aspiration for termination of early pregnancy. In the United Kingdom, mifepristone is used in combination with a prostaglandin agent for induction of abortion at < 63 days gestation.
Misoprostol increases uterine activity in early pregnancy, and is associated with a significant increase in the amplitude and frequency of uterine contractions (Norman et al, 1991). Several studies have proved that the combination of Misoprostol administered after mifepristone is a successful, inexpensive, simple regimen for medical termination of early pregnancy, in terms of its tolerance, safety, and minimal side-effects (Bygdeman et al,
1994; Peyron et al, 1993; El-Refaey & Templeton, 1994 a, b; 1995 b). The combination of methotrexate and misoprostol has been reported as the method of choice to induce abortion in women with uterine or cervical anomalies, in which case suction curettage may be difficult or impossible (Schaff et al,
1996). Side effects associated with misoprostol include nausea, vomiting, diarrhoea, hypotension, fever, headache and abdominal pain (Lawrie et al,
1996, Haberal et al, 1996).
In a review of the literature on medical abortion in early pregnancy. Grimes (1997) reported that both mifepristone and methotrexate when used with a
prostaglandin, could safely and effectively induce early pregnancy abortion. Single, oral mifepristone doses of 200 and 600 mg had similar efficacy when used with a prostaglandin agent. Sequential and single-dose regimens had comparable efficacy. An 800 jigm dosage of misoprostol when administered vaginally as an augmenting agent, was found to be more effective than the same dose given orally (Creinin, 1996 b; Wiebe, 1996). Regimens of mifepristone or methotrexate followed by misoprostol were found to be more effective than misoprostol alone. However, the risk of haemorrhage and gastrointestinal side effects were found to be greater with medical abortion than with suction curettage.
The efficacy of misoprostol in achieving abortion, however, decreases with the duration of pregnancy; falling slightly between 49 and 56 days, and then significantly decreasing between 56 and 63 days of pregnancy (McKinley et al, 1993; Aubeny et al, 1995). The vaginal route of administration of misoprostol appears to be more effective and better tolerated than the oral route in induction of first-trimester abortion after pre-treatment with mifepristone. Gastrointestinal side effects, such as vomiting and diarrhoea, were also found to occur more frequently among women who receive misoprostol orally than among those who receive it vaginally (El-Refaey & Templeton, 1995 b; Schaff et al, 1996; Creinin et al, 1997 a, b).
Misoprostol also plays a role as a cervical priming agent in facilitating surgical abortion. Several studies have reported the success of misoprostol, whether administered orally or vaginally, in softening the cervix and facilitating cervical dilatation in women undergoing first-trimester abortion, in both nulliparous and multiparous patients (Bugalho et al, 1994 a; Ngai et al, 1995 a, b; Ngai et al, 1996 b; Schaub et al, 1996; Koopersmith & Mishell, 1996). El-Refaey et al (1994 c) reported that misoprostol is comparable to gemeprost
in its leading to increased baseline cervical dilatation, reduction in the mechanical force required to dilate the cervix, and reduction of blood loss. Misoprostol was found to induce clinical and histochemical changes in the cervix similar in nature and degree to Gemeprost.
In the early nineties, the most widely used medical method of terminating second trimester pregnancy was intravaginal administration of the prostaglandin E2 Gemeprost. This treatment was highly effective, but was
associated with gastrointestinal side effects and hyperpyrexia. Since then, many studies have investigated and proved the safety and efficacy of misoprostol, administered intravaginally or intracervicovaginally, in achieving termination of pregnancy after eleven weeks of gestation (Bugalho et al, 1993 b, 1996; Merrell & Koch, 1995; Del-Valle et ai, 1996; Wong et al 1996; Srisomboon et al, 1997 b).
El-Refaey et al (1993) demonstrated the efficacy and acceptability of misoprostol in achieving second-trimester abortion, when compared with gemeprost, among patients pre-treated with mifepristone. There were no significant differences between the two groups in terms of the induction to abortion interval or side effects. When misoprostol was compared with Dinoprostone for second-trimester induction of abortion, side effects were reported to occur more often among women receiving dinoprostone, such as pyrexia, uterine pain, vomiting, and diarrhoea. In addition, the average cost per treatment was much higher with dinoprostone (Jain & Mishell, 1994). Bugalho et al (1996) reported that vaginally administered misoprostol used in combination with methylergometrine was highly efficient in achieving complete evacuation of the uterus in second-trimester termination of pregnancy.
Misoprostol has been recommended as the prostaglandin of choice for second- trimester pregnancy termination following pre-treatment with mifepristone. The efficacy of orally administered misoprostol has also been demonstrated as a simple, inexpensive and easy procedure for second-trimester termination (Batioglu et ai, 1997). However, vaginally administered misoprostol was reported to be more effective than oral misoprostol in that respect (El-Refaey & Templeton, 1995 b). The median induction to abortion interval in women receiving misoprostol vaginally was found to be significantly shorter than among those receiving it orally. The median amount of misoprostol used vaginally was also significantly lower (Ho et al, 1997).