Introduction
Induction of labour is defined as the process of artificially stimulating the uterus to start labour.1 Labour induction is required in 10-20% of the women near term. Medication that ripen the cervix play important role in modern obstetrics.
Progesterone inhibits myometrial contractility, and its ongoing secretion during pregnancy ensures cervical competence. This is the rationale for attempting to use a progesterone receptor antagonist as a cervical ripening agent. Mifepristone is a synthetic steroid hormone analogue that has both antiprogesterone and antiglucocorticoid activities. It increases the sensitivity of the uterus to prostaglandins and facilitates labour.2
Prostaglandin E2 (PGE2), also known by the name dinoprostone, is a naturally occurring compound that is involved in promoting labour. PGE2 is administered vaginally as a suppository, gel or insert.
Many studies have reported the efficacy of dinoprostone gel and misoprostol in induction, but the effectiveness of oral mifepristone lacks sufficient data relatively. Only a few studies have been reported so far where in the efficacy and safety of oral mifepristone have been assessed.3, 4, 5
The aim of this study was to compare the safety and efficacy of oral mifepristone with dinoprostone gel in induction of labour in primigravidas.
Materials and Methods
This study was conducted at the Obstetrics and Gynaecology department of a rural tertiary level institute of South India. This was a hospital based prospective study conducted from August 2019 to January 2021.
Study design
The following were the inclusion criteria in the study-
Primigravida with live singleton pregnancy in cephalic presentation and induced at term.
Ultrasonographically confirmed singleton pregnancy with no contraindications to vaginal delivery.
Bishop score <6 before induction.
Women with the following conditions were excluded from the study-
Previous scarred uterus.
Known hypersensitivity to prostaglandin or mifepristone
Major cephalopelvic disproportion.
Medical problems like impaired renal, hepatic or adrenal function.
Antepartum hemorrhage.
After detailed history, clinical examination, investigations and informed consent, the women were assigned one or the two treatment groups by random computer generated sequence. Group 1 involved cervical ripening with the use of oral 200mg Mifepristone on an inpatient basis, first assessment was done 24h after administration and later progress of labour was assessed. Induction of labour in Group II was done through endocervical instillation of Dinoprostone gel 0.5mg without mifepristone ripening.
A second dose of dinoprostone was used when the Bishop score was less than 6 at first assessment, 6h after instillation of first dose. If during labour, either of the groups, progress of labour was unsatisfactory or variable fetal heart rate patterns was observed, the participants underwent caesarean section or instrumental delivery as indicated.
Augmentation of labour was done with oxytocin in both groups with amniotomy when the Bishop score was 6 or more with oxytocin, wherever required.
Objectives
To compare the safety and efficacy of oral mifepristone with dinoprostone gel in induction of labour at term
The objectives were to be achieved by comparing the following outcomes:
Statistical analysis
Qualitative baseline characteristics were compared in both groups using Fisher’s exact test; continuous variables such as the gestational age, bishop scores, induction delivery interval and other outcomes of quantitative nature were compared using a two tailed Mann- Whitney test. Statistical analysis was carried out using SPSS version 19; statistical significance was set with a P value of 0.01.
Results
Majority of the women enrolled in both the groups were from same age group (21-25); only upto 10% of patients were elderly (>30 years) in the dinoprostone group.(Table 1)
Table 1
Distribution of cases according to age
|
Age in Yrs |
Mifepristone Group |
Dinoprostone Group |
Total |
|
≤ 20 |
6 |
10 |
16 |
|
21-25 |
27 |
17 |
44 |
|
26-30 |
6 |
8 |
14 |
|
31-35 |
0 |
4 |
4 |
|
Total |
39 |
39 |
78 |
Majority of the patients were between 39-41 weeks (74.3% in group I and 66.6% in group II) which shows almost equal distribution in both the group. (Table 2)
Table 2
Distribution of patients according to gestational age
|
Gestational age |
Mifepristone group |
Dinoprostone group |
Total |
|
37-37+6 wks |
2 |
5 |
7 |
|
38-38+6 wks |
8 |
8 |
16 |
|
39-39+6 wks |
16 |
10 |
26 |
|
40-40+6 wks |
13 |
16 |
29 |
|
Total |
39 |
39 |
78 |
Mean Bishop’s score at the time of admission observed in group I were 3.08 ± 0.70 and group II were 2.77± 0.74.
Mean Bishop’s score at first post intervention assessment observed in group I were 6.4±0.91 and group II were 5.6±1.4. It was observed that there was significant improvement in the Bishop’s score after administrating Mifepristone to the patients. This improvement was even proven statistically significant with p value <0.004.(Table 3 )
Table 3
Bishop score in both the groups
Induction to delivery interval after priming cervix with mifepristone and misoprostol was definitely reduced, which is proven not much significant with p value = 0.597. (Table 4)
Table 4
Induction delivery interval of both the groups
Most of the patients delivered vaginally (89.7%) in Group I and (61.53%) in Group II. It was observed that there is 28% reduction in LSCS in Group I, and was highly significant with p value < 0.004.(Table 5)
Table 5
Mode of delivery in both the groups
|
Mode of delivery |
Mifepristone group |
Dinoprostone group |
Total |
|
Vaginal delivery |
35 |
24 |
59 |
|
LSCS |
4 |
15 |
19 |
|
Total |
39 |
39 |
78 |
Most common complication that required operative intervention was fetal heart variability more with Group II (73.3%).(Table 6)
Discussion
In this study, study population comprised of 78 patients with equal number of patients in the mifepristone and dinoprostone group. Few studies have been done where Mifepristone is used for induction of labour. Hapangama and Neilson reported that a single dose of 200mg mifepristone appears to be the lowest effective dose for cervical ripening.6In our study, Mifepristone 200mg was chosen for induction of labour.
Gupta et al. assessed the efficacy and safety of oral mifepristone for cervical priming and induction. They gave 400mg per oral dose to the study group and did no active intervention in the control group.4 Yelikar et al., studied role of oral mifepristone and found statistically significant improvement in Bishop score after 24 h of administration in comparison to control.5
In our study, the Bishop score improved dramatically in both the treatment groups, however the improvement in Bishop’s score was statistically significant in the mifepristone group.
In a study done by Sah et al, it was found that mifepristone was more effective in improving Bishop score as compared to dinoprostone as success rate was 76% in the former while 56% in the latter group.6 The induction delivery interval in mifepristone group appears to be more because the drug takes at least 24-48 hours to have its priming effect on the cervix. Mifepristone exerts its effect by increasing uterine contractility and by increasing the sensitivity of the uterus to actions of prostaglandins. While, dinoprostone directly cause uterine smooth muscle contractility explaining the difference in the time of action of the two agents.
In present study patients included in Group I had mean Bishop score 3.08± 0.70 which were induced with mifepristone and outcome observed. In another group where Dinoprostone was used as pre induction drug for cervical ripening, mean Bishop’s score observed was 2.77±0.74.
As expected after first post intervention assessment of mifepristone mean bishop’s score observed was 6.4±0.91 and statistically proven significant with p value <0.004.
Similar observations are with Wing D.A Fassett Michael J where Bishop’s score before administration of mifepristone were unfavourable and almost 20% patients went in spontaneous labour with favourable Bishop’s score.7
Shanitha Fathima et al observed the significant difference in Bishop’s score pre and post administration of mifepristone as well as dinoprostone in their study as mean pre induction score 2.32 +-0.76 and mean post induction score as 7.25 +- 1.75 at 48 hours.8
Athawale R et al also observed pre induction Bishop’s score <3 in 84% as compared to 58% in placebo group, where Bishop’s score improved 24 hours after mifepristone upto >8 in 72% as compared to placebo where Bishop’s score remain between 4-8 in 86% patients.9
In present study mode of delivery was affected much by the induction protocol used, 38.4% of Group I patients required LSCS whereas only 10.2% patients of Group II underwent LSCS.
