On efficacy and acceptability of early medical abortion by mifepristone with oral or vaginal misoprostol.
Unsafe abortion is a major public health problem in developing countries. Globally, 20 million unsafe abortions take place each year and account for 13% of all maternal deaths. 
The incidence of induced abortions is not definitely known, because estimates of illegal abortions are generally unreliable. This has led to the liberalisation of abortion laws and search for newer methods.
Medical abortion offers great potential for improving abortion access and safety. The drugs used were mainly mifepristone (RU 486), a potent antiprogestin in combination with prostaglandin [E.sub.1] analogue misoprostol.
It has been in use for over a decade and research is ongoing since its inception. But still in 2012, WHO and the Guttmacher Institute reported that 56% of abortions in developing countries were unsafe. 
Mifepristone 200 mg was found to be as effective as 600 mg in multicentre trials by WHO.  Studies have also shown that vaginal administration of misoprostol after pretreatment with mifepristone resulted in higher complete abortion compared to oral dose.  The present study was undertaken to compare the efficacy, acceptability, side effects and factors affecting outcome of early medical abortion with oral and vaginal misoprostol after oral mifepristone in inducing medical abortion up to 49 days. Increasing access to safe abortion services is the most effective way of preventing unsafe abortions. 
MATERIALS AND METHODS
This interventional study (non-RCT) was conducted on women requesting termination of early pregnancy [less than or equal to] 49 days in the outpatient department of family planning unit for a period of one year. Women seeking MTP with USG confirmed intrauterine pregnancy; < 35 years and who were able to come for one to three follow-ups were selected for the study. Women with suspected/ confirmed ectopic pregnancy, IUCD, hypersensitivity to drugs with medical complications and previous scar on uterus were excluded.
Based on a pilot study, the mean induction abortion interval for the Group I (Oral) was 4.01 [+ or -] 2.7 and in the Group II (Vaginal) was 3.12 [+ or -] 1.2. The following formula was used to estimate the minimum sample size.
= [[3[[sigma].sup.2][([Z.sub.1-[alpha]/2] + [Z.sub.1-[beta]]).sup.2]]/[d.sup.2]]
[[sigma].sup.2] = [[[[sigma].sub.1.sup.2] + [[sigma].sub.2.sup.2]]/2]
[[sigma].sub.1] = Standard deviation of the first simple
[[sigma].sub.2] = Standard deviation of the second simple
d = [[mu].sub.1] - [[mu].sub.2]
= Observed difference between the mean values of the two samples
Substituting the Values Standard deviation in Group I 1.2 Standard deviation in Group II 2.7 Mean difference 0.89 Effect size 0.46 Alpha error (%) 5 Power (1-beta) % 80 1 or 2 sided 2 Required minimum sample size per group 87
Ethical committee approval was obtained. After getting an informed written consent, patients satisfying inclusion criteria were allocated alternately into Group I (Oral) and Group II (Vaginal). They were counselled regarding procedure characterisation like cost, efficacy, safety, number of visits and probable need of a surgical abortion.
On Day 1, both groups received 200 mg of mifepristone. They were also observed in OP and allowed to go home. If abortion had not occurred in 48 hours, Group I was given 400 mg (2 tablets) of misoprostol orally. Group II received 800 mg (4 tablets) of misoprostol vaginally. Women were observed for 4 hours. They were asked to keep record of onset of bleeding, time of expulsion of products and any side effects noted. They were given a telephone number to contact when concerned.
All the women were reviewed on Day 14 with repeat USG and Hb estimation. They were enquired about the degree of satisfaction, whether they will use it for a second time if needed and whether they would suggest it to their friends.
Outcome was measured as complete abortion (requiring no surgical intervention), incomplete abortion (clinical and USG evidence), missed abortion and ongoing pregnancy. Success was defined as expulsion of products of conception with no need for surgical intervention. Induction abortion interval was defined as the time interval in hours from the administration of misoprostol to the passing of products of conception.
Quantitative variables were analysed by 't' test and qualitative variable by [X.sup.2] test. P < 0.05 was taken as significant.
Table I. Demographic Profile of Both Groups
Table Ia. Distribution According to Age
In the present study majority of patients come under 21-25yr age group (41.87%) followed by the 26-30yrs age group (31.52%). In <20 age group it was 5.89 % in Group I and 2.97% in Group II and in 31-38yrs age group it was 16.67% in Group I and 27.72% in Group II. Both groups are comparable with respect to age.
Table Ib. Distribution According to Parity
Multipara constituted 96.08% cases in Group I and 94.05 cases in Group II whereas primis constituted 3.92% and 5.94% in Group I & II respectively. Both groups were found to be comparable after applying the Chi-square test.
Table Ic. Distribution According to Gestational Age
Both groups are comparable with respect to gestational age.
76.3% were residing in urban area and 23.3% in rural area. 79.8% were from middle socioeconomic group. 91.6% had high school or higher level of education. 86.2% were housewives. 92.6% were married. 98% induced abortions were on social grounds 91.6% had complete abortion. Check curettage was done for 8.3% with incomplete abortion. There were no cases of missed abortion or continuing pregnancy. Complete abortion was 91.1% for Group I oral and 92% for Group II vaginal (P = 0.816) showing both routes were equally effective.
Table II Comparison of induction- abortion interval between the two groups.
Table III Mean Induction Abortion Interval
The mean induction abortion interval was 4.29 hours for oral group and 3.5 hours for vaginal groups. 78.4% in oral group had induction abortion interval [less than or equal to] 4 hours compared to 90% in vaginal group. Factors affecting induction abortion interval was studied. There was no statistically significant association with age, parity and gestational age. In both groups those with a history of previous abortion had a failure rate of 33.3% (P = 0.000 and P = 0.007 respectively in oral and vaginal groups)
Table IV. Comparison of Side Effect Profile
Statistically established differences were noted in the occurrence of nausea, vomiting and fatigue between the two groups. Among the major side effect nausea (24%), vomiting (13.7%) and fatigue (50%) were significantly more in oral group.
Table V Mean duration of Bleeding
Mean duration of bleeding was significantly less in Group II compare Group I (P = 0.000). Mean Hb drop was not clinically significant between two groups. The average duration of bleeding was 9.37 [+ or -] 2.5 days with oral group and 8.28 [+ or -] 1.8 in vaginal group which was similar other studies. [3,4]
Table VI. Distribution According to Level of Acceptance
Method satisfaction was more among oral group 92.2% compared to 85% vaginal. Acceptance is further reflected by the fact that 90% of oral group and 85% in vaginal group were willing to accept to the method again and if needed the same % would suggest it to their friends.
In our study mean age was 26.2 which is comparable to other studies. [6,7] There was no association of complete abortion rate with gestational age or parity. In a WHO Multi national study of 2219 women with gestational age <63 days parity significantly affected the percentage of complete abortion . Complete abortion was 91.1% for Group I oral and 92% for Group II vaginal (P = 0.816) showing both routes were equally effective. Similar efficacy in oral and vaginal routes were noted in studies by Peyron et al  and Nitya et al . Schaff et al in randomized trial have found the complete abortion with oral group to be 95% as against 99% in the vaginal groups.  The mean induction abortion interval was 4.29 hours for oral group and 3.5 hours for vaginal groups. 78.4% in oral group had induction abortion interval [less than or equal to] 4 hours compared to 90% in vaginal group which is comparable to the study by el Refaey et al  Shorter induction abortion interval in vaginal group may be because of the long lasting and continuously increasing uterine contractility of vaginal misoprostol.  In both groups those with a history of previous abortion had a failure rate of 33.3% (P = 0.000 and P = 0.007 respectively in oral and vaginal groups). Premila et al in a study of factors affecting outcome of early medical abortion with review of 4132 consecutive cases of have found out that those who had a previous abortion were more likely to have a failed medical abortion (OR = 2.09) . The average duration of bleeding was 9.37 [+ or -] 2.5 days with oral group and 8.28 [+ or -] 1.8 in vaginal group. This was similar to studies by el Refaey et al . W H O studies showed 11-12 days bleeding . Among the major side effect nausea (24%), vomiting (13.7%) and fatigue (50%) were significantly more in oral group. Studies by Schaff et al  and el-Refaey  also showed increased vomiting in oral group compared to vaginal. The latter study4 also note fatigue as a major side effects in both groups (67% in oral and 70% in vaginal). There were no major adverse events in this study as in others studies. [4,9]
Method satisfaction was more among oral group 92.2% compared to 85% vaginal. Acceptance is further reflected by the fact that 90% of oral group and 85% in vaginal group were willing to accept to the method again and if needed the same % would suggest it to their friends. Similar acceptability rates were seen in studies by Schaff et al  whereas Winikoff et al  evaluated acceptability of Mifepristone and Misoprostol regimen and found that it was highly acceptable and 96% would recommend it to others and 91% would choose it again.
It is evident from the present study that both oral and vaginal routes of misoprostol had similar efficacy in early pregnancy termination up to 49 days. Medical abortion can be safely propagated and can replace surgical abortion in the coming years in view of its efficacy and acceptability as shown in the present study. Moreover, women can exercise their choice of the method which will ensure the acceptability and thus decreasing unsafe abortions and related morbidity.
We are extremely thankful to Dr. C P Vijayan, Professor, Head of the Department of Obstetrics and Gynaecology for the valuable suggestions and guidance. We also thank faculty members of family planning unit and all the patients who participated in the study. We also express our sincere thanks to Dr. K Babu, Associate Professor of Statistics and Demography.
 WHO: Unsafe abortion: global and regional estimated of incidence of unsafe abortion and associated mortality in 2003, Geneva: World Health Organisation, 2007.
 Guttamacher Institute and WHO. facts on induced abortion world-wide. Fact sheet. Geneva, WHO, 2012. https://www.guttmacher.org/fact-sheet/facts-induced abortion-world-wide.
 World Health Organisation Task Force on Postovulatory Methods of Fertility Regulation 1, Special Programme of Research, Development and Research Training, World Health Organisation. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortions: a randomized trial. BJOG 2000;107(4):524-30.
 el-Refaey H, Rajasekar D, Abdalla M, et al. Induction of abortion with mifepristone (RU 486) and or vaginal misoprostol. N Engl J Med 1995;332(15):983-7.
 Berer M. Medical abortion: issues of choice and acceptability. Reproductive Health Matters 2005;13(26):25-34.
 Nithya J, Reddi RP. Comparison of oral and vaginal misoprostol after oral mifepristone in earl medical abortion. Int J Reprod Contracept Obstet Gynecol 2017;6(3):1007-11.
 Mittal S, Agrwal S, Kumar S, et al. Comparison of oral versus vaginal misoprostol & continued use of misoprostol after mifepristone for early medical abortion. Indian J Med Res 2005;122(2):132-6.
 Peyron R, Aubeny E, Targosz V, et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Eng J Med 1993;328(21):1509-13.
 Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Contracep 2001;64(2):81-5.
 Dannielson KG, Marons L, Rodriguez A, et al. Comparison between oral and vaginal administration of misoprostol on uterine contractility. Obstet Gynecol 1999;93(2):275-80.
 Ashok PW, Templeton A, Wagaarachchi PT, et al. Factors affecting the outcome of early medical abortion: a review of 4132 consecutive cases. BJOG 2002;109(11):1281-9.
 Wnnikoff B, Ellertson C, Elul B, et al. Acceptability and feadibility of early pregnancy termination by mifepristone-misoprostol. Results of a large multicenter trial in the United States. Mifepristone Clinical Trials Group. Arch Fam Med 1998;7(4):360-6.
Asha Gopi Nath (1), Ajay Kumar (2)
(1) Associate Professor, Department of Obstetrics and Gynaecology, Government Medical College, Kottayam.
(2) Associate Professor, Department of Obstetrics and Gynaecology, Government Medical College, Kottayam.
Financial or Other, Competing Interest: None. Submission 11-07-2017, Peer Review 07-08-2017, Acceptance 12-08-2017, Published 17-08-2017.
Corresponding Author: Dr. Asha Gopi Nath, Neelambari, Udayanapuram P.O, Vaikom, Kottayam-686143.
Table 1a. Distribution according to Age Group I Group II Total Age in Years No. % No. % No. % < 20 6 5.89 3 2.97 9 4.43 21-25 49 48.04 36 35.64 85 41.87 26-30 30 29.41 34 33.66 64 31.52 31-35 17 16.67 28 27.72 45 22.16 [chi square] = 0.1154; p > 0.05 Table 1b. Distribution according to Parity Group I Group II Total Parity No. % No. % No. % Primi 4 3.92 6 5.94 10 4.93 Para 1 70 68.63 59 58.41 129 63.55 Para 2 28 27.45 36 35.64 64 31.53 Total 102 100 101 100 203 100 [chi square] = 0.311; p > 0.05 Table 1c. Distribution according to Gestational Age Group I Group II Total Gestational Age in Days No. % No. % No. % 35-42 65 63.72 55 54.45 120 59.12 43-49 37 36.27 46 45.54 83 40.88 Total 102 100 101 100 203 100 [chi square] = 18; p > 0.05 Table II. Comparison of Induction-Abortion Interval between the Two Groups Group I Group II Total Induction Abortion Interval No. % No. % No. % [less than or equal to] 4 80 78.43 91 90.09 171 84.24 hrs. > 4 hrs. 22 21.57 10 9.90 32 15.76 Table III. Mean Induction Abortion Interval Induction Abortion Interval Mean SD 't' Value P Value Group I 4.29 2.5 2.52 0.01 S Group II 3.5 1.6 Table IV. Comparison of Side Effects Profile Group I Group II Total Age in Years No. % No. % No. % Nausea 25 24.51 8 7.92 33 16.26 Vomiting 14 13.73 5 4.95 19 9.36 Diarrhoea 6 5.88 3 2.97 9 4.43 Abdominal Pain 88 83.27 83 82.18 171 84.24 Fatigue 51 50 34 33.66 85 41.87 Age in Years [chi square] P Value Nausea 7.41 < 0.05 S Vomiting 3.8 < 0.05 S Diarrhoea 0.34 > 0.05 NS Abdominal Pain 0.64 > 0.05 NS Fatigue 5.56 < 0.05 S Table V. Mean duration of Bleeding Duration of Bleeding in Days Mean SD 't' Value P Value Group I 9.38 2.5 3.49 < 0.000 S Group II 8.2 1.87 Table VI. Distribution according to Level of Acceptance Group I Group II Acceptance [chi square] P Value No. % No. % Satisfied 94 92.2 86 85.1 2.4 > 0.05 Will use the 92 90.2 86 85.1 1.2 same method Will suggest to 92 90.2 86 85.1 1.2 friends
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|Title Annotation:||Original Research Article|
|Author:||Nath, Asha Gopi; Kumar, Ajay|
|Publication:||Journal of Evolution of Medical and Dental Sciences|
|Date:||Aug 17, 2017|
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