|Year : 2019 | Volume
| Issue : 4 | Page : 296-302
Comparison of intravaginal misoprostol and intramuscular carboprost for cervical priming in the first trimester of medical termination of pregnancy
Sapna Sharma, M Tiwari
Department of Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
|Date of Submission||14-Mar-2019|
|Date of Decision||18-Aug-2019|
|Date of Acceptance||25-Sep-2019|
|Date of Web Publication||16-Jul-2020|
Dr. Sapna Sharma
Department of Obstetrics and Gynaecology, JNMC, Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Suction evacuation is a widely used method for elective termination of pregnancy in the first trimester. The step of mechanical cervical dilatation during this procedure is probably the most critical step. Difficult cervical dilatation may cause incomplete evacuation, cervical laceration, and uterine perforation. Prior cervical priming with pharmacological agents like prostaglandin derivatives, although not free from side effects, makes the procedure easier with reduced overall complication rate and hence recommended in several guidelines. Aim: The aim of the study was to compare, two prostaglandin derivatives, intravaginal misoprostol (15-deoxy-16-hydroxy 16-methylprostaglandin E1) with intramuscular carboprost (15-methyl prostaglandin F2α) for cervical priming prior to suction evacuation in the first-trimester termination of pregnancy. Settings and Design: A prospective study was conducted at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra. Materials and Methods: Eighty women requesting pregnancy termination from 6th to 12th week gestation were randomized into two groups. Two hours prior to suction evacuation, the first group (n = 40) received 400 μg of intravaginal misoprostol, while the second group (n = 40) received 125 μg of intramuscular injection carboprost. The outcomes of both the groups were recorded in terms of baseline cervical dilatation, immediate complications, drug-induced side effects, and patient's acceptability by questionnaire. Results: The “mean baseline cervical dilatation” prior to suction and evacuation in the misoprostol group was 8.11 ± 0.95 mm in the carboprost group was 6.25 ± 0.06 mm which is highly significant (t = 7.02, P <0.0001). The “mean baseline cervical dilatation” was more in misoprostol (Group A) than carboprost (Group B) >8 mm, compared to 17.5% in carboprost group (P = 0.004). The side effects including nausea, vomiting, and abdominal cramps were more in carboprost group as compared to the misoprostol group. No patient had diarrhea in misoprostol group as against 32.5% in carboprost group (P < 0.0001). There were no complications like incomplete evacuation, cervical lacerations, or uterine perforation noted in either group. Conclusion: Cervical priming prior to suction evacuation results in easier dilatation reducing the incidence of complications. Intravaginal misoprostol appears to be more effective with minimal side effects, hence easily acceptable alternative as compared to intramuscular carboprost.
Keywords: Baseline cervical dilatation, cervical priming, intravaginal, misoprostol intramuscular carboprost, suction evacuation
|How to cite this article:|
Sharma S, Tiwari M. Comparison of intravaginal misoprostol and intramuscular carboprost for cervical priming in the first trimester of medical termination of pregnancy. J Datta Meghe Inst Med Sci Univ 2019;14:296-302
|How to cite this URL:|
Sharma S, Tiwari M. Comparison of intravaginal misoprostol and intramuscular carboprost for cervical priming in the first trimester of medical termination of pregnancy. J Datta Meghe Inst Med Sci Univ [serial online] 2019 [cited 2020 Sep 22];14:296-302. Available from: http://www.journaldmims.com/text.asp?2019/14/4/296/289837
| Introduction|| |
Termination of pregnancy deliberately either by medical or by surgical method before the viability of fetus is called induction of abortion. The legal definition of abortion is the interruption of pregnancy before viability. Abortion in India is legal in certain circumstances and can be performed on certain grounds legally. For this, the Medical Termination of Pregnancy (MTP) Act was framed in 1971 to ensure safe and legal abortion.
In the first trimester, surgical evacuation is considered as the standard management for terminating pregnancies currently in many parts of the world. It is considered very safe and effective with a success rate of >95%.
However then, there can be major morbidity in < 1% of women and minor morbidity in 10%. There are more morbidity and mortality if cervical dilatation is not properly done. Many studies have shown that the incidences of uterine perforation, blood transfusion, and pelvic infection were 0.24%, 0.97%, and 1.69%, respectively. There were immediate abortion-related complications such as heavy bleeding (0.01%–0.25%), uterine perforation (0.01%–0.4%), cervical laceration (0.01%–0.35%), and anesthesia-related complications that occurred up to 3 h after the procedure. Uterine perforation can result in hemorrhage or injury to the other abdominal organs. Delayed complications consisted of incomplete evacuation (0.03%–2.0%) and infections (0.2%–5%). Late complications – secondary infertility and ectopic pregnancies – were caused by a severe postabortion infection and adverse effects in subsequent pregnancies.
The procedure of suction and evacuation was associated with many complications such as “excessive hemorrhage, incomplete abortion, cervical tear, and uterine perforation.” The risk increases when difficulty is encountered during cervical dilatation before suction evacuation. Therefore, cervical dilatation before suction evacuation is considered as the most critical step of the procedure. Hence, as the role of an obstetrician is to perform a safe and legal abortion with minimum complications. If cervical dilatation is difficult, it can cause incomplete evacuation, cervical and uterine perforation, and many other complications.
Cervical priming before doing the procedure with pharmacological agents like prostaglandin derivatives makes the procedure easier and also reduces the overall complication rate.
Before suction and evacuation, there were various methods which were used such as laminaria tents, mifepristone, and various prostaglandin analogs.
Laminaria tent was inserted for 12 h and caused pain at the time of the insertion. Furthermore, the patient has to stay in the hospital for the procedure. Hence, it is less used nowadays.
Misoprostol is a synthetic “15-deoxy-16-hydroxy 16-methyl” analog of prostaglandin E1 which occurs naturally and has been used in several treatment regimens with varying degrees of success for preabortion cervical priming. It can be used by oral, sublingual, or intravaginal route for cervical priming. In my study, I will be giving misoprostol by intravaginal route.
Carboprost is a synthetic analog prostaglandin F2α. It acts directly on the myometrium. This agent stimulates the gravid uterus and produces contractions which are usually sufficient to induce abortion. This drug is known for its severe gastrointestinal (GI) side effects, but low-dose carboprost (125 mcg) achieves similar results with less side effects.
This study was done for comparison of the effectiveness of intravaginal misoprostol with intramuscular carboprost in preoperative cervical priming before suction evacuation in the first trimester MTP.
| Materials and Methods|| |
Place of the study
The present study was carried out at the Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College (JNMC) and Acharya Vinoba Bhave Rural Hospital, Sawangi Meghe, Wardha.
Ethical clearance was obtained from the Institutional Ethical Committee of JNMC, Sawangi (Meghe), Wardha, on 22nd Jan 2019. With ethical clearance no DMIMS(DU)/IEC/2019-20/332
Duration of the study
The study was conducted from September 2018 to August 2019 (1 year).
This was a prospective observational study.
The study comprised 80 patients allocated into two groups.
Sample size formula
The sample size was calculated according to the following formula:
Where Z α/2 is the level of significance at 5%, i.e., 95% confidence interval = 1.96,
P = success rate of t/t = 95.2% = 0.952,
d = desired error of margin = 7% = 0.07,
= 35.82 = 40 patients needed in each group.
(Ref. Child et al., 2001 “A randomized study, comparing the use of sublingual to vaginal 'misoprostol' for preoperative cervical priming prior to surgical termination of pregnancy in the first trimester”).
Selection criteria for subjects under the study
- Patients came for the first trimester MTP.
- Patients opting for medical methods for the first trimester MTP
- Patients with ischemic heart disease, bronchial asthma, and hypertension.
Patients with a history of allergic response to carboprost and misoprostol.
This study comprised 80 patients randomly allocated into two groups:
- Group A:Patients were given pretreatment with intravaginal misoprostal (400 μg) before 4–6 h of suction and evacuation
- Group B:Patients were given pretreatment with intramuscular injection carboprost (125 μg) before 1–2 h of suction and evacuation.
All indoor patients willing for the first trimester MTP were recruited according to the exclusion and inclusion criteria by taking careful clinical history, particularly about age, previous obstetric history, last menstrual period, and previous menstrual cycles. A detailed general and systemic examination was done before including patients in the study. Complete case record of a patient was prepared and blood and urine investigations were done. Ultrasonography was done to confirm the gestational age of the fetus.
Patients were selected using opaque sealed envelope in Group A who received 400 mcg of intravaginal “misoprostol” 4–6 h prior to suction and evacuation or Group B who received an intramuscular injection of 125 mcg of “carboprost” 1–2 h prior to suction and evacuation. Both these drugs were approved by the Drug Controller General of India for use in cervical priming.
A record of the side effects associated with “Misoprostol” and “Carboprost” such as nausea, vomiting, abdominal cramps, and diarrhea was made. Then, the patients were shifted to the operation theater and total intravenous anesthesia was given. Measurement of the baseline cervical dilatation before performing suction evacuation was done using Hegar's dilators. The dilators were passed through the cervix in decreasing order of their sizes, starting with “size 12.” The largest Hegar's dilator passing through the internal os without resistance was regarded as the “baseline dilatation” achieved and if, additional mechanical dilatation of cervix required were also noted. If the dilatation of the cervix was appropriate, or more for that period of gestation, no further dilatation was performed.
Then, electrical suction and evacuation was performed using the appropriate size of Karman's cannula and this was followed by check curettage. The procedure was completed by confirming the gritty feel of the endometrium against the instrument and the appearance of bubbles at the external os. Any type of injury whether it is a cervical injury or uterine injury or from superficial to deep cervical laceration or cervical tear, uterine perforation or an injury to any other intraabdominal organs was noted in the intraoperative findings.
Recording of the primary outcome was done by checking baseline cervical dilatation. All the intraoperative complications and incidences such as “nausea, vomiting, abdominal pain and diarrhoea” were noted as the secondary outcome [Graph 1], [Graph 2], [Graph 3], [Graph 4], [Graph 5], [Graph 6].[INLIE:3]
The data collection was continuously recorded in a predefined format in a spreadsheet (“MS Excel-2010, Microsoft Inc., Redmond, Washington, USA”). Statistical analysis was done using Chi-square test to correctly ascertain the clinical applicability of the present study. Statistical significance was tested using Student's t-test. If P < 0.05, the result was considered statistically significant.
The software which was used for the analysis of data was SPSS version 17 (South Wacker Drive, Chicago, Illinois). Testing of the results was done at 5% level of significance (“P < 0.05”).
Informed, written, valid consent was obtained from all the patients, and MTP form was filled prior to enrollment in the study.
| Results|| |
This study was conducted at the “Department of Obstetrics and Gynecology,” “Acharya Vinoba Bhave Rural Hospital,” Sawangi (Meghe), Wardha.
A total of 80 patients were included for the study after obtaining informed, valid, and written consent and keeping in account the exclusion criteria.
The data obtained were coded and entered into Microsoft Excel Worksheet. The data were analyzed and tabulated as below.
[Table 1] shows the distribution of patients according to the baseline characteristics, i.e., age, parity, systolic blood pressure (BP), diastolic BP, and pulse rate.
|Table 1: Distribution of patients according to the baseline characteristics|
Click here to view
The mean age in misoprostol group (Group A) was 28.22 ± 4.88 years and the mean age in the carboprost group (Group B) was 27.27 ± 5.06 years.
The significance was calculated according to the “Chi-square test,” and the value of P was 0.39 which showed that the age parameter in both the groups was statistically nonsignificant.
In misoprostol group, 15% of the females were primipara and 85% of the females were multipara, and in carboprost group, 7.5% of the females were primipara and 92.5% were multipara. The value of P was 0.28 and the difference was “statistically nonsignificant.”
The “mean systolic BP” in misoprostol group was 108.80 ± 6.62 mmHg and the mean systolic BP in carboprost group was 106.20 ± 7.69 mmHg. The value of P was 0.10, and the difference was “statistically nonsignificant.”
The “mean diastolic BP” in misoprostol group was 70.55 ± 4.68 mmHg and the mean diastolic BP in carboprost group was 67.65 ± 5.61. The value of P was 0.014 and the difference was “statistically nonsignificant.”
The mean pulse rate in misoprostol group was 81.50 ± 4.56/min and the mean pulse rate in carboprost group was 83 ± 5.06/min. The value of P 0.16 and the difference was statistically nonsignificant.
Hence, the baseline characteristics in both the groups did not differ significantly.
[Table 2] shows the distribution of patients according to the indications for MTP.
|Table 2: Distribution of patients according to the indications for medical termination of pregnancy|
Click here to view
- Category I: (medical cause)
- Category II: (eugenic cause)
- Category III: (humanitarian cause)
- Category IV: (socioeconomic cause).
About 5% of the patients in “misoprostol” group and 12.5% of the patients in “carboprost” group were in Category I.
Nearly 7.5% of the patients in “misoprostol” group and 12.5% of the patients in “carboprost” group were in Category II.
About 5% of the patients in misoprostol group and 2.5% of the patients in carboprost group were in Category III.
Almost 77.5% of the patients in “misoprostol” group and 72.5% of the patients in “carboprost” group were in Category IV.
In both the groups, in all these categories, the value of P for the mean distribution of patients was 0.54 and the difference was statistically nonsignificant.
Using Chi-square test, statistically no significant difference was found in indications for MTP among the patients of two groups (P = 0.54).
[Table 3] shows the GI side effects in both the groups.
|Table 3: Distributing patients by gastrointestinal side effects within the two groups|
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Nausea was present in 15% of the patients of misoprostol group and 45% of the patients of carboprost group and the difference was statistically significant (P = 0.003).
25% of patients in misoprostol group and 75% of patients in carboprost group had vomitting. The value of P was 0.0001 and the difference was highly significant.
About 5% in misoprostol group and 40% in carboprost group had diarrhea. The value of P was 0.0001 and the difference was highly significant.
Nearly 5% in misoprostol group and 17.5% in carboprost group had pain in the abdomen. The value of P was 0.004 and the difference was highly significant.
The side effects such as nausea (15%/45%), vomiting (25%/75%), diarrhea (5%/40%), and pain in the abdomen (0%/12.5%) were more in carboprost group as compared to the misoprostol group (P < 0.05).
[Table 4] shows the distribution of patients according to the other side effects such as shivering, fever, respiratory distress, and bleeding per vaginum.
|Table 4: Distribution of patients according to the other side effects in two groups|
Click here to view
Shivering and bleeding per vaginum were more in misoprostol group, while respiratory distress was more in carboprost group. About 10% of the patients in “misoprostol” group had fever and 7.5% of the patients had fever in carboprost group.
Nearly 45% of the patients in “misoprostol” group and 20% of the patients in carboprost group had shivering.
[Table 5] shows the “mean baseline cervical dilatation” in both of the groups.
The “mean baseline cervical dilatation” prior to suction and evacuation in misoprostol group was 8.11 ± 0.95 mm and in carbpoprost group was 6.52 ± 0.06 mm which was highly significant (t = 7.02, P < 0.0001).
The “mean baseline cervical dilatation” was more in misoprostol (Group A) than carboprost (Group B).
[Table 6] shows the “baseline cervical dilatation” in millimeters in both of these groups. In the “misoprostol group,” 17 women (42.5%) had dilatation of the cervix >8 mm in comparison with 0 women or no women in the carboprost group which had cervical dilatation >8 mm at the time of evacuation (P = 0.0001) which was highly significant and showed that cervical dilatation was more in misoprostol group.
|Table 6: Comparison of baseline cervical dilatation (mm) in the two groups|
Click here to view
≥8 mm dilatation was found in 80% of the patients in “misoprostol” group and in 25% of the patients of carboprost group which revealed that dilatation was more in “misoprost group” as compared to carboprost group.
| Discussion|| |
“Suction and evacuation” is a relatively, safer method for pregnancy termination during the first trimester. However, there can be many complications while doing the procedure like cervical injury, uterine perforation, cervical lacerations, and many more. These complications are less if the cervix is preprimed.
In our study, a total of 80 women who came for pregnancy termination in the “ first trimester” fulfilling the inclusion criteria were selected and divided into two groups. Group A patients were given pretreatment with intravaginal misoprostol 400 mcg before 4–6 h for suction and evacuation and Group B patients were given pretreatment with intramuscular carboprost 125 mcg before 1–2 h of suction and evacuation as a cervical priming agent, and then, the baseline cervical dilatation achieved was compared in both the groups in the operation theater by the use of Hegar's dilator in decreasing of their sizes. The Hegar's dilator which was largest in size and which crossed the internal os without resistance was considered the “baseline cervical dilatation” achieved.,,,,
A recent study done by Darwish et al. compared 75 patients each of direct suction and evacuation with prior cervical priming with 400 mcg of sublingual misoprostol 3 h prior to the procedure. They concluded that sublingual misoprostol causes adequate cervical dilatation and facilitates surgical abortion by reducing blood loss, operative time, and complication rate significantly. Furthermore, the incidence of nausea, vomiting, and abdominal pain was less in misoprostol group.
Lawrie et al. did not find any significant difference in cervical dilatation between 400 mcg oral misoprostol and 800 mcg vaginal misoprostol groups, but there was significant pain and heavier preoperative bleeding in the oral misoprostol group. In our study, the intravaginal misoprostol group had more preoperative bleeding and intramuscular injection carboprost group had more pain in the abdomen.
MacIssac et al. conducted a randomized, double-blind, placebo-controlled study comparing 400 mcg oral misoprostol, 400 mcg vaginal misoprostol, and a medium laminaria tent for dilating the cervix over 4 h before surgical abortion of 7–14-week gestation. They found that vaginal misoprostol achieved a significantly greater mean dilatation than oral misoprostol and lamineria tent.
Ngai et al. studied the optimal dose and route of administration of misoprostol for preoperative cervical priming and recommended 400 mcg misoprostol 3 h prior to the vacuum aspiration.
Singh et al. did a randomized study comparing four different dosage groups (200, 400, 600, and 800 mcg) which showed that the efficacy of misoprostol is dose dependent at a fixed time interval of 3–4 h and there are more side effects with larger dose.
Fiala et al. found that when misoprostol was used for priming prior to surgical abortion, heavy bleeding and expulsion may occur in some women before surgery is performed.
In our study, the mean baseline cervical dilatation achieved was up to 8 mm in misoprostol group, while in carboprost group, it was up to 6 mm. Furthermore, the side effects such as nausea, vomiting, abdominal cramps, and diarrhea were more in carboprost group as compared to the misoprostol group. No patient in the misoprostol group had respiratory distress. There were no complications such as incomplete evacuation, cervical lacerations, or uterine perforation noted in either of our group. Hence, due to less and tolerable side effects and better cervical dilatation, misoprostol was more acceptable by patients when compared to carboprost.
Achieving the optimal priming intervals can be a practical problem, even under the strict study settings, as the most surgical abortions are performed on day-case operating lists with women who admitted just before the surgery. The intravaginal route may allow women to take misoprostol at home before hospital admission and help to achieve optimal priming intervals before the surgical abortion.
In our study, the side effects including nausea (30%/17.5%), vomiting (27.5%/2.5%), abdominal cramps (42.5%/20%), and diarrhea (32.5%/0%) were more in carboprost group as compared to the misoprostol group. A study by Darwish et al. found the incidence of nausea and vomiting (24%), lower abdominal pain (15%), and no incidence of diarrhea in 75 women, in whom 400 μg intravaginal misoprostol was used 3 h prior. In our study, no patient had diarrhea in misoprostol group as against 32.5% in carboprost (P < 0.0001). There were no complications such as incomplete evacuation, cervical lacerations, or uterine perforation noted in either of our group. Hence, due to less and tolerable side effects and more convenient route of administration, misoprostol was more acceptable by patients when compared to carboprost.,,,,,,,,,
| Conclusion|| |
Cervical priming prior to suction and evacuation in the first trimester MTP reduces the time required for the procedure with minimal complications.
- Intravaginal tablet misoprostol has less side effects and more effective and more acceptable by patients than intramuscular injection carboprost
- Hence, the conclusion of this study is that intravaginal misoprostol is a more effective, safer, and better alternative than intramuscular injection carboprost for cervical priming in the first trimester MTP.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]