VAGINAL AND ORAL MISOPROSTOL FOLLOWING MIFEPRISTONE ADMINISTRATION IN MEDICAL TERMINATION OF PREGNANCY UP TO 49 DAYS: A COMPARATIVE STUDY

Objective: The objective of this study was to compare and evaluate the efficacy, safety, adverse effects, and patient compliance of vaginal versus oral misoprostol in medical termination of pregnancy after tablet misoprostol up to 49 days of gestation. Methods: A comparative study of 100 patients divided randomly assigned to two control groups. Results: The study showed that 200 mg mifepristone followed by 800 mcg vaginal misoprostol is more effective for medical termination in gestational age up to 49 days as compared to 200 mg mifepristone followed by 400 mcg oral misoprostol. Conclusion: While both routes of administration are safe, gastrointestinal side effects are more with oral misoprostol. The vaginal route is more acceptable to the patients enrolled in the study.


INTRODUCTION
According to the American Journal of Public Health, 2014, half of the pregnancies among American women are unintended, and 4 in 10 of these are terminated by abortion [1]. When medical historians look back on the 20 th century, the legalization of abortion will stand out as one of its public health triumphs [2]. The term medical abortion refers to early termination of pregnancy usually in the first trimester using medications and performed without primary surgical intervention. Surgical abortion is one of the oldest methods and was practiced earlier in many parts of the world [3]. According to the American College of Obstetricians and Gynecologists [4], outpatient medical abortion is an acceptable alternative to surgical abortion in appropriately selected women with pregnancies <49 days of gestational age.
The MTP Act of India, last amended in 2003, provides recommendations for termination of certain pregnancies up to 20 weeks of gestation, by a registered medical practitioner, provided all prerequisites are fulfilled. It ensures correct intervention depending on the stage of unwanted pregnancy, thereby minimizes the chances of illegal abortions, which is the reason for higher mortality and morbidity in India.
The MTP Act allows the termination of pregnancy if: 1. The continuance of pregnancy involves a risk to the life of a pregnant woman or is likely to result in grave injury to her physical or mental health. 2. There is a substantial risk that in case, the child was born, it would suffer from physical or mental abnormalities (handicap) of a very serious nature. 3. The pregnant woman has alleged that the pregnancy has been caused by rape. 4. A pregnancy occurs as a result of failure of any device or method used by any married woman or her husband for the purpose of limiting the number of children.
Three medications for early medical abortions have been widely studied and used: Mifepristone, antimetabolic methotrexate, and prostaglandin misoprostol. These agents cause abortions by increasing uterine contractility either by reversing progesterone-induced inhibition of contractions -mifepristone causes cervical collagen degradation, possibly due to increased expression of matrix metalloproteinase [5].
While surgical abortions can be performed up to 20 weeks, the advantages of medical abortion include avoidance of surgery and anesthesia, which considerably increase the acceptability of the method [6,7]. With the use of misoprostol, 80-90% of cases lead to complete abortion [8]. It has been shown that misoprostol is an effective agent for cervical ripening and labor induction, but there have been concerns about hyperstimulation associated with its use [9]. Medical termination of pregnancy using a combination of mifepristone and misoprostol is a safe, effective alternative to suction evacuation in early abortion. Various routes of administration of misoprostol and various combination regimens of mifepristone and misoprostol have been investigated [10].

MATERIALS Place
The study was conducted in the Department of Obstetrics and Gynecology, Santosh Medical College, on carefully selected pregnant women after applying specific exclusion and inclusion criteria.

Time frame
The study duration was from March 2016 to February 2017.

Type of study
This was a prospective randomized comparison study.

Sample size
The sample size was 100 pregnant women in early pregnancy up to 49 days gestational age.

Inclusion criteria
Early intrauterine pregnancy confirmed by the last menstrual period and ultrasound sonography test of ≤49 days and fulfilling prerequisites specified in the MTP Act 1971.

Exclusion criteria
The following criteria were excluded from the study:

METHODS
The study was conducted after due approval of the Ethical Committee, Santosh Medical College, Ghaziabad. Patients were randomly assigned into two groups after taking informed consents: • Group 1 was given tablet mifepristone, 200 mg on day 1 and tablet misoprostol 800 mcg vaginally on day 3. • Group 2 was given tablet mifepristone, 200 mg on day 1 and tablet misoprostol 400 mcg orally on day 3.
Patients were recalled on day 14 for follow-up. They were questioned regarding postabortal fever, duration and amount of bleeding per vaginal, passage of products of conception, foul-smelling discharge and pain abdomen, symptoms of continuation of pregnancy, and any other complications. A necessary clinical and pelvic examination was done. USG was done in all patients to determine whether abortion is complete or not.

Statistical analysis
After the collection of data, a statistical analysis was conducted. 1. Quantitative variables were compared using unpaired t-test/Mann-Whitney U-test between the two groups -oral and vaginal. 2. Qualitative variables were compared using the Chi-square test/ Fisher's exact test.
The analysis was done using the Statistical Package for the Social Sciences [SPSS] version 17.0.

Demographic characteristics
Refer Table 1 all subjects were of Indian origin from Ghaziabad, Uttar Pradesh.

Treatment outcomes
Thus, the overall success rate for complete abortion in Group 1 was 96% and Group 2 was 80%, which is statistically significant (0.028).
The total incidence of incomplete abortion was 4% in Group 1 as compared to 20% in Group 2. There was no case of continuation of ongoing pregnancy in either group.

Acceptability
There were differences in acceptability between the two groups. Refer Tables 2 and 3. Table 4 depicts the side effects.

DISCUSSION
In this study, both groups were comparable in terms of age, gravity, gestational age, and HB concentration. The overall success rate for complete abortion was 96% in Group 1 and 80% in Group 2. There were no major complications in either group. Minor complications were reported -30% subjects in Group 1 as against 62% in Group 2, which are statistically significant. Both methods were safe. Nature of complications in Group 1 versus Group 2 was nausea (16% vs. 48%) and vomiting (6% vs. 30%), while pain abdomen, diarrhea, headache, and flushing were evenly matched in both groups. Discomfort and anxiety experienced by both group members were comparable and statistically not significant. This is consistent with the study of el-Refaey et al. [11]who reported a higher incidence of gastrointestinal and thermoregulatory side effects on oral administration of misoprostol as compared to vaginal route. Duration and amount of bleeding were statistically significant. It was more in Group 2 as compared to Group 1, whereas the amount of bleeding was more in Group 1 as compared to Group 2. Group 1 subjects were significantly more satisfied than Group 2. This is in accordance with the study of Lokeland et al. [12] who reported moderate to heavy bleeding in 74.7% of subjects in their study on medical abortion, in which they administered 200 mg mifepristone followed by 800 mcg misoprostol. In addition, 92% of subjects in Group 1 said that they would choose the same method in future, if required as compared to only 74% in Group 2. It was primarily influenced by the success rates of the procedures. The overall acceptability was 90% in Group 1 as compared to 72% in Group 2. Jyothi et al. (64) in their study had a similar experience [13].

CONCLUSION
Results of this study showed that 200 mg mifepristone followed by 800 mcg vaginal misoprostol is more effective for medical termination in gestational age up to 49 days as compared to 200 mg mifepristone followed by 400 mcg oral misoprostol. It is important to mention that both routes of administration are safe. Gastrointestinal side effects are more with oral misoprostol. The vaginal route is more acceptable to the subjects enrolled. 41.6 (42) Hemoglobin day 1 11.8 (12) 11.54 (11.6)    (12) 18 (36)