ABSTRACT

CORRESPONDING AUTHOR:
Dr. Nupur Hooja,
#A-29, Lal Bahadur Nagar,
Girdhar Marg, Malviya Nagar,
Jaipur-302017, Rajasthan, India.
E-mail: hoojasjaipur@gmail.com

ABSTRACT: INTRODUCTION: Nearly 20% of all confirmed pregnancies end in spontaneous abortion. Misoprostol’s use in early pregnancy failure is varied and dose and route are not well established. AIM: To study the efficacy of sublingual misoprostol in causing expulsion of products of conception in early pregnancy failure. METHODS: Women with an ultrasound diagnosis of early pregnancy failure, less than 12 weeks gestation were included in the study. Tablet Misoprostol 600 mcg was given six hourly sublingually for 3 doses. All observations were noted and analyzed. RESULTS: Mean gestational age was 7.946+1.2 weeks. Mean induction abortion interval was 18.241+1.2 hours. Women with gestational age six to eight weeks had least mean induction-abortion interval time of 17.38+2. Mean dose required was 1564mcg.Efficacy of protocol was 92.85% in achieving complete abortion. CONCLUSION: The regime had 92.85% efficacy, acceptability (90%) and few side effects. Thus by using a lower dose and appropriate interval between two doses (six hours), the side effects were lessened with high efficacy.

KEYWORDS: Missed Abortion, Misoprostol, Efficacy, Early Pregnancy Failure.

INTRODUCTION: Vacuum aspiration for uterine evacuation in cases of early pregnancy failure is associated with morbidity and mortality. However, the high expense of the PGE2 OR PGF2a vaginally and its instability in room temperature were barriers to their use in developing countries. Misoprostol-a synthetic prostaglandin E₁ analogue, is cheap, stable at room temperature and effective in inducing uterine contractions¹ However, the regimes for its use in early pregnancy failure are varied.

Clinical trials had shown vaginal misoprostol to be superior to oral misoprostol.² Misoprostol given vaginally took longer to start working, had a lower peak (peak concentration after 60 mins), but a more sustained effect. Thus, smaller doses were needed when misoprostol was used vaginally. Pharmacokinetics now show that sublingual misoprostol has the shortest onset of action, the highest peak concentration and greatest bioavailability among the routes of administration.³

AIM: The aim of this study was to study the efficacy and the side effects of 600 mcg of sublingual misoprostol six hourly for three doses in causing complete expulsion of products of conception in early pregnancy failure.

METHODS: This was an observational hospital based prospective study conducted from April 2012 to May 2013. Women with an ultrasound diagnosis of early pregnancy failure, singleton pregnancy, less than 12 weeks gestation, who had not experienced uterine cramping, no active bleeding (os closed on per vaginal examination) and were in a normal frame of mind to give consent and willing for a surgical evacuation in case of failure with medication or active bleeding, were included in the 

The USG criteria used for diagnosis of early pregnancy failure (missed abortion) were-embryo greater than 7 mm with no embryonic cardiac activity or irregular gestational sac with mean sac diameter greater than 16 mm or a gestational sac more than 15 mm with no visible fetal pole.

 Sample size was calculated at 80% study power and alpha error of 0.05 assuming standard deviation for duration of induction to abortion interval of 5 hours and minimum difference to be detected of 2 hours. Thus sample size came to be 50 patients which were enhanced 55 assuming 10% dropout rates.

After counseling and informed written consent, the women were given sublingual tablet Misoprostol 600 mcg every 6 hourly for 3 doses. The dose was decreased to lessen the side effects. Evaluation was done 6 hours after 3^rd dose of misoprostol, i.e.at 24 hours. If the uterus was not felt empty on per vaginal examination or ultrasonography shows products of conception, then dilatation and evacuation was done and was considered a true drug failure.

RESULTS: The mean age of women in the study was 23.79+5.1 years. 73% women came with complaints of bleeding per vaginum. 23 % women had come for routine checkup and USG had shown missed abortion. 76.78% of the women had fetal pole absent or irregular gestational sac in the ultra sonographic findings. The other finding was a blighted ovum seen in 23.21%.

Mean gestational age was 7.946+1.2 weeks. 48% women had an induction abortion interval of 12 to 18 hours. 39.28% aborted in 18 to 24 hrs. Only 5.36% aborted in 6 to 12 hours. Mean Induction abortion interval was 18.241+1.2 hours. Duration of induction to abortion interval of more than 24 hours was seen in 7.14% and was considered true drug failure and these women were surgically evacuated. Efficacy of protocol was 92.85% in achieving complete abortion Table 1.

            Mean induction abortion interval was studied in different gestational ages. Women with less than six weeks gestational age had highest mean induction-abortion interval 22+ 2hrs, while those with gestational age six to eight weeks had least mean induction-abortion interval time of 17.38+2.86 hrs. Table 2.

            Majority of women with missed abortion required three doses. Women who required one dose were 1.79%.Mean dose required was 1564mcgTable 3.

            Abdominal pain was reported by almost all cases but analgesia was required only by 32.14%. Other adverse effects requiring treatment were fever/chills and vomiting in 10.71%, diarrhea (more than 4 episodes) in 8.93%, headache and mild allergy in 5.36%.Most of women did not find these adverse effects difficult to tolerate. Table 4.

50% women were found to be highly satisfied, 15.45% women were not satisfied because of either failure of treatment or side effect of Misoprostol. The overall acceptability of medical management was good. Most women said they would choose the medical method if they were allowed to choose again and would recommend the method to others.

 Two women were dropped from the study due to excessive bleeding per vaginum and were taken for surgical evacuation. One woman got severe urticaria and Misoprostol was stopped and was taken for surgical evacuation. One woman did not take second dose of sublingual Misoprostol timely so was dropped from the study.

 On follow-up visit, most of cases had no complaints. Few women came with bleeding per vaginum, 3.57% which was mild in amount and no treatment was required. No women required evacuation on follow-up visit.

DISCUSSION: Mean induction abortion interval was 18.241+1.2 hours. Efficacy of protocol was 92.85% in achieving complete abortion. Ayres-de-Campos D et al⁴ used Misoprostol 600 mcg vaginally and repeated 4 hourly. Complete medical evacuation occurred in 56.8% with higher side effects due to short interval between doses.13.5% nausea, 5.4% vomiting, 6.8% diarrhea and 5.4% transient hyperthermia. Ngoc NT et al⁵ (2004) used 800mcg vaginal Misoprostol only single dose and mean induction abortion interval was high-21hrs.

            Barcelo F et al⁶ had a success of 87.8% with 600 mcg sublingual misoprostol every 24 h for two days but had a very long induction evacuation interval. Kushwah D. S. et al⁷ in their study also reported complete abortion rate to be 92% in 600mcg misoprostol sublingual group and the side effect were hot flashes 24%, diarrhea and nausea 2% in 10% with sublingual misoprostol and 92% women were satisfied with their study. Tang OS, Lau WN et al⁸ used 600 mcg of misoprostol three hourly up to three doses sublingually with success rates of 87.5%.their interval was shorter and they noticed a higher incidence of diarrhea (70%) and fatigue was experienced.

CONCLUSION: The advantage of evacuation by Misoprostol is that it includes no surgery and hence no anesthesia. Misoprostol tablet has advantage of low cost, long shelf life, lack of need for refrigeration and it’s easy availability. Thus, it may be advocated to be used in outpatient setting in the treatment of early pregnancy failure even at the primary care level. However, the dose schedule should be adhered to.  According to the route, these should be altered.

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