INTRODUCTION

Termination of pregnancy is one of the most common procedures in gynecological practice. Surgical termination has been used for first trimester termination of pregnancy. With the introduction of cervical ripening agents, complications were significantly reduced. Although complications are uncommon, surgical termination has been shown to be associated with uterine perforation, cervical injuries and significant blood loss. The overall complication rate varies between four and 10 percent. (1, 2)

A regimen of 600 µg of Mifepristone followed by 400 µg oral Misoprostol was approved for use in USA in September 2000, for elective termination of pregnancy up to 49 days gestation.(3)
Misoprostol is a synthetic 15-deoxy-16-hydroxy-16-methyl analogue of naturally occurring prostaglandin E1 that has been approved for administration by oral route for the prevention and treatment of gastro-duodenal ulcers associated with use of non-steroidal anti-inflammatory drugs. The drug is cheap, so increasing the dose will not influence the cost significantly, and it can be stored at room temperature. (2, 4, 5)

It has also become an important drug in obstetrical and gynecologic practice because of its utero-tonic and cervical-ripening actions. Misoprostol is useful for elective medical abortion, cervical ripening before surgical abortion, evacuation of the uterus in cases of embryonic or fetal death, and induction of labor. The drug may also be used to treat and even prevent postpartum hemorrhage. However, Misoprostol is not approved for any of these indications in the United States. Current product labeling includes a warning that Misoprostol is contraindicated during pregnancy because of its abortifacient properties.

However, the FDA recognizes that, in certain circumstances, off-label uses of approved products are appropriate, rational, and accepted medical practice. (6, 7)
The most common adverse effects of Misoprostol are nausea, vomiting, diarrhoea, abdominal pain, chills and fever. (7)

The effects of Misoprostol on the reproductive tract are increased, and gastrointestinal adverse effects are decreased, if the oral preparation of Misoprostol is administered vaginally. (8, 9)
When Misoprostol tablets are placed in the posterior fornix of the vagina, plasma concentrations of Misoprostol acid peak in one to two hours and then decline slowly. Vaginal application of Misoprostol results in slower increases and lower peak plasma concentrations of Misoprostol acid than when administrated orally, but overall exposure to the drug is increased. (10)

Among women who were 9 to 11 weeks pregnant and given Misoprostol before a surgical abortion, intrauterine pressure began to increase an average of 8 minutes after oral administration and 21 minutes after vaginal administration and was maximal 25 minutes after oral administration and 46 minutes after vaginal administration. Uterine contractility initially increased and then platituded one hour after oral administration, whereas uterine contractility increased continuously for four hours after vaginal administration. Maximal uterine contractility was significantly higher after vaginal administration. (8)

MATERIALS AND METHODS

Prostaglandin El analogue (Cytotec) at a dose of 400 micrograms vaginally were used in this study. Patients with missed abortion confirmed by ultrasound, with and without uterine scars, were used in the study.

50 patients were selected during a one-year period. Some were referred from private clinics and others came for routine antenatal care. On examination they were found to have missed abortion without obvious symptoms. All those patients were admitted to the gynecological ward.
Full history including gynecological and obstetrical records was taken and a full general examination was made along with any necessary laboratory investigations.

400 micrograms of Misoprostol (Cytotec) was inserted into the posterior vaginal fornix. The dose was repeated for up to 48 hours at 4 hours intervals until effective uterine contractions and cervical dilatation were obtained.

All women were followed up by an obstetrician, from admission until discharge. They were assessed for complications that might occur during the termination process.
No artificial rupture of membrane was allowed during the study.

RESULTS

The general characteristics of patients selected for this study were similar to those of our general population; 30% were nulliparous women and 70% were below the age of 30 - as shown in Table (1).

The mean time for termination was 14 hours. Two cases required only four hours while the majority (90 percent) required four to 18 hours. In 10 percent of the patients, abortion was achieved in 19-48 hours.

Side effects were minimal. There was no significant drop in hemoglobin level.
There were no recorded cases of puerperal sepsis and maternal deaths. No signs of prostaglandin toxicity (hyperactivity, fever, sweating and vomiting) were reported.
20 women (40 percent) underwent evacuation and curettage under general anesthesia.

DISCUSSION

Prostaglandins have two direct actions associated with labor, ripening of cervix and direct Oxytocin action. Successful parturition requires organized changes in the upper uterus (in response to the estrogen - progesterone ratio) and the local release of prostaglandin.

The administration of Misoprostol (cytotec) intra-vaginally proved to be highly effective for termination in 50 patients with missed abortion within a gestational age that varied from 12-28 weeks.

Cytotec is an analogue of naturally occurring Prostaglandin E1, which promotes peptic ulcer healing and symptomatic relief. It is metabolized by fatty acid oxidizing systems present in organs throughout the body and it will increase uterine tone and contractions in pregnancy, which may cause partial or complete expulsion of the products of conception (4, 5).

A lot of works have shown the combination of Misoprostol and Mifepristone to be an effective method of achieving therapeutic medical termination of pregnancy, in both first and second trimesters. (4, 11, 12)

In another study, they made a comparison between vaginal and oral Misoprostol when combined with Mifepristone in termination of second trimester pregnancy. (4)

There is one study, which shows a comparison of two regimens of intra-vaginal Misoprostol for termination of second trimester pregnancy. Doses of 400 micrograms every 3 hours or every 6 hours were successful in evacuating the uterus. (5)

The variation in rates of complete abortion among women given Misoprostol alone may be due to differences in study design, since rates are often lowest in randomized trials; or to efforts to increase vaginal absorption of Misoprostol in some studies. For example, in one study in which the success rate was high, the vagina was cleansed with sterile water or moistened with two or three drops of water (or saline) and then a tablet of Cytotec was placed in the posterior fornix of the vagina; and the women were required to remain supine for three hours after placement of the tablets.(13)

CONCLUSION

Our protocol was to use cytotec tablet intra-vaginally, 400 micrograms every four hours to avoid the side effects. It is a very effective and safe method of termination, as shown in our study.
Because of the small number of women included in this study, we recommend to apply it to a larger scale to support our results.

REFERENCES