Comparative study of the effect of vaginal use of primrose oil with misoprostol on cervical preparation of prim gravid women: A double-blind clinical trial
Azar Danesh Shahraki1, Sara Mirhoseini2, Minoo Movahedi3, Maryam Hajihashemy3, Fedyeh Haghollahi4
1 Department of Obstetrics and Gynecology, Shahid Beheshti Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Obstetrics and Gynecology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
3 Department of Obstetrics and Gynecology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
4 Vali-E –Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran
|Date of Submission||25-Jan-2022|
|Date of Acceptance||15-Mar-2022|
|Date of Web Publication||28-Mar-2023|
Dr. Maryam Hajihashemy
Department of Obstetrics and Gynecology, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Background: This study compares the effect of vaginal administration of evening primrose oil with misoprostol on cervical preparation in prim gravid women at ≥40 weeks gestation.
Materials and Methods: This was a double-blind randomized clinical trial conducted in Isfahan, Iran during 2019-2020 on 110 prim gravid pregnant women with a gestational age of 40 weeks and more and cephalic presentation of the fetus with the obstetrical indication for pregnancy termination. After obstetric examinations to rule out cephalo pelvic disproportion and calculation of the Bishop score by the researcher, patients were randomized to receive 25 μg misoprostol tablets (n = 55) or 1000 mg evening primrose oil Pearls (n = 55) administrated vaginally by a midwife. We compared Bishop's score before and after the intervention, time of cervical ripening, a dose of intervention for cervical ripening, need to induce labor, the interval between cervical preparation and induction of labor, duration of oxytocin use, need for cesarean section, and its cause, Apgar score at 5 and 10 minutes, neonatal birth weight.
Results: Mean baseline Bishop Score was not significant between the groups (P = 0.45); after the intervention, it was significantly higher in the primrose oil group (P < .001). Significantly fewer patients required cesarean sections in the primrose oil group (P = 0.03). The other outcomes were. not significant between the groups (P > 0.05).
Conclusion: Misoprostol and primrose oil administration appear to positively affect cervical readiness. Primrose oil resulted in significantly better Bishop Scores and fewer cesarean sections compared to misoprostol in pregnancy 40 weeks and more.
Keywords: Cervical ripening, misoprostol, primrose oil, prolonged pregnancy, vaginal
|How to cite this article:|
Danesh Shahraki A, Mirhoseini S, Movahedi M, Hajihashemy M, Haghollahi F. Comparative study of the effect of vaginal use of primrose oil with misoprostol on cervical preparation of prim gravid women: A double-blind clinical trial. Adv Biomed Res 2023;12:78
|How to cite this URL:|
Danesh Shahraki A, Mirhoseini S, Movahedi M, Hajihashemy M, Haghollahi F. Comparative study of the effect of vaginal use of primrose oil with misoprostol on cervical preparation of prim gravid women: A double-blind clinical trial. Adv Biomed Res [serial online] 2023 [cited 2023 Jun 7];12:78. Available from: https://www.advbiores.net/text.asp?2023/12/1/78/372586
| Background|| |
Pregnancies of 40 weeks or more can be dangerous for both the mother and fetus; therefore, there is a need for an appropriate method for induction of labor. Although the most common medical intervention during labor, its success rate depends on the condition of the cervix before induction or stimulation in addition to maternal (number of births, age, body mass index [BMI]) and fetal (birth weight and gestational age) factors.,
Stimulation of labor, despite an unfavorable cervix, will lead to prolongation of the labor phase, excretion of meconium, increased chances for cesarean section, and fetal asphyxia. The Bishop score is used to determine the condition of the cervix or its readiness and is classified according to dilatation and effacement, the condition of the cervix, and consistency and position of the head in the pelvic.
A Bishop score of less than or equal to 4 indicates an unfavorable cervix. Cervical preparation is performed by mechanical and medical methods, and causes softening, increased effacement, and dilatation of the cervix, leading to deformation of the cervix from enzymes that break down collagen fibers and increase interstitial fluid.,
Prostaglandins play an important role in this process. If the cervix is not ready, the length of the labor will increase by about 2-3 times, which most often results in cervical preparation. Labor at40 weeks or more increases complications such as uterine atony, bleeding, infection, shock, and the need for cesarean delivery.,,
Therefore, various methods for cervical preparation are used before induction of labor to improve the probability of a successful induction. Mechanical methods include manual dilatation to release the membranes, balloon catheters, and cervical moisture-absorbing dilators (Lamisil, dilapan, and laminaria), which can cause complications such as infection and rupture of the membranes.,,
Today, the use of prostaglandins is one of the most common methods for cervical preparation before induction of labor and it indirectly stimulates myometrial contractions. Misoprostol (Cytotec) is a synthetic product of PGE1 that is available in 100 and 200 μg tablets for intravaginal, oral, or sublingual use. This product is rapidly absorbed following oral or sublingual consumption and its side effects are less than other prostaglandins; however, their absorption rates vary in different people.
Vaginal misoprostol is proposed to be an effective, cost-effective drug that has clinical benefits for cervical preparation before labor stimulation. Evening primrose oil contains prostaglandin effects. The seeds of this plant have 60%-65% linoleic acid and 7%-14% gamma-linoleic acid (GLA). Polyunsaturated fatty acids (PUFA) are natural precursors of prostaglandins, and linoleic acid is the most important PUFA.
Primrose oil contains large amounts of PUFA. In addition, GLA, an effective converter of PUFA to prostaglandins (including prostaglandin E), is found in abundance in this oil. Therefore, evening primrose oil (EPO) can be a suitable inducer for labor. Since EPO is generally well tolerated; there are no restrictions on its use during pregnancy, as it does not affect the safety of fetuses monitored by biophysical profile testing and Non-stress test.,,
However, there are different findings on the effect of primrose oil on cervical preparation.
There is a limited of studies of its benefits on prim gravid women at ≥40 weeks gestation. This study aims to compare the effect of vaginal administration of primrose oil and misoprostol on the cervical preparation of prim gravid women at ≥40 weeks gestation.
| Materials and Methods|| |
This was a double-blind randomized clinical trial (IRCT20200217046523N14), conducted from 9-June 2020 in the Shahid Beheshti, Alzahra, and Amin hospitals affiliated with Isfahan University of Medical Sciences, Isfahan, Iran.
The study population consisted of prim gravid pregnant women with a gestational age of ≥40 weeks and cephalic fetal presentation with obstetric indications of termination of pregnancy (decreased fetal motility or decreased amniotic fluid index); however, the cervix was not ready for delivery.
After confirmation of the patient's eligibility, the researcher explained the study objectives and both drugs to the patients. The patients were asked to review and sign a written informed consent for study participation. This study was conducted by the Declaration of Helsinki and its most recent amendment and was approved by the Isfahan University of Medical Sciences Ethics Committee.
The drugs were administered by the midwife staff based on the randomization numbers.
Both the researcher (residence) and patients were unaware of the treatment assignments. All of the patients were under close monitoring until delivery.
Inclusion criteria consisted of prim gravid women with gestational age ≥40 weeks who consented to participate; maternal age of 18-35 years; singleton pregnancy and Bishop score ≤4. Exclusion criteria include maternal hypertension, diabetes, cardiac disease, pulmonary disease, pelvic stenosis; corticosteroids or anti-inflammatory medication usage; medication for depression, or antipsychotic drugs. If any maternal or fetal side effects accrued and all of high-risk pregnancy or mother's unwillingness to continue cooperation in the research, the subject takes withdrawal from the study.
A total of 110 pregnant women met the inclusion criteria. After determining their bishop scores, envelopes were used to randomly divide the patients into an intervention (EPO) or control (Misoprostol) group. To prepare the cervix, each patient in the control group (n = 55) received a 25 μg Misoprostol tablet (Samisaz co. Mashhad Iran), and each patient in the intervention group (n = 55) received 1,000 mg Pearl of primrose oil (Barijessenceco, Iran) that pierced by a sterilized needle, which was administered vaginally by a midwife. Drugs were implanted vaginally in the posterior fornix. After placement, the patient was advised to stay in bed for 30 minutes, lie on his left side, and not leave the bed.
The Bishop score was re-evaluated by the researcher after the intervention. A score of 9 indicated a response to the drug. If the first dose did not elicit any response, it was repeated 6 hours later With the same dose as before for a maximum of four times (uterine contractions were ineffective with less than three contractions in 10 minutes uninitiated with 45 seconds duration and a normal fetal heart).
Primary outcomes included bishop score after the intervention, repeated dose administration drug, and time of cervical preparation. The secondary outcomes were the need for induction of labor, the interval between cervical preparation and induction of labor, oxytocin use, need for cesarean section and its cause, 5 and 10 minute Apgar scores, and neonatal birth weight.
The results of qualitative variables were determined by the frequency (percentage). The Chi-square test was used for between-group comparisons. For quantitative variables, the one-sample Kolmogorov-Smirnov test was used to evaluate the normal distribution of the data. Based on the results of these tests, the quantitative variables were described by mean ± standard deviation (SD) and compared between the two study groups using the independent samples t-test in cases that had a normal distribution.
Data analysis was performed using SPSS v. 21 (IBM Corp., 2012, Armonk, NY, USA) using the Chi-square test and independent t-test. P values <.05 were considered to be statistically significant.
| Results|| |
A total of 110 pregnant women with a gestational age of ≥40 weeks were enrolled in this study. The patients were randomly placed in two groups of 55 patients per group – an interventional group that received vaginal primrose oil and the control group that received vaginal misoprostol. [Figure 1] shows the consort diagram for patient participation.
[Table 1] lists the patients' demographic information. The age of the mothers in the misoprostol group was 27.04 ± 1.53 years and in the primrose oil group, it was 26.96 ± 1.38 years. The ages were not significantly different (P = 0.10). Gestational age (P = 0.33), education (P = 0.84), and occupation (P = 0.35) were not significantly different between the two groups.
The mean Bishop score before intervention was not significantly different between the two groups (P = 0.45); after the intervention, the mean Bishop score was significantly higher in the primrose oil group (P = 0.03) [Table 2].
|Table 2: Evaluation of Bishop score separately in the two study groups before and after the intervention|
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There were no significant differences in the duration of cervical preparation to induction (P = 0.09), duration of oxytocin use (P = 0.12), Apgar scores at 5 minutes (P = 0.10) and 10 minutes (P = 0.47), infant weight (P = 0.23), and mother's BMI (P = 0.87) between the two groups.
Although more patients took oxytocin in the misoprostol group, this finding was not significant (P = 0.09). Also, 65.5% of patients in the misoprostol group and 45.5% in the primrose oil group underwent cesarean sections for pregnancy termination (P = 0.03).
In the misoprostol group, the presence of meconium in the amniotic fluid and fetal distress caused cesarean section, whereas arrest of labor phase in the primrose group was the cause for cesarean section. This finding was statistically significant between the two groups (P = 0.001) [Table 3].
Also, the number of doses of both drugs was not significantly different between the two groups (P = 0.09). The highest dose was three doses, which was reported in 89.1% of the misoprostol group and 74.5% of the primrose oil group.
| Discussion|| |
In the present study, the mean Bishop score before intervention was not significantly different between the two groups; after the intervention, the Mean Bishop score was significantly higher in the primrose oil group. The number of patients who underwent cesarean section was significantly lower in the primrose oil group.
There were no significant differences between the two groups in terms of duration of cervical preparation to induction, duration of oxytocin use, number of patients who used oxytocin, and Apgar scores at 5 and 10 minutes. The results of studies show the benefits of cervical preparation on labor outcomes.
Raghuraman et al. have reported that a low Bishop score has undesirable consequences; therefore, effective measures should be taken to increase the Bishop score.
In a quasi-experimental study, Nonette examined the effectiveness of EPO on cervical preparation. The results showed significantly greater changes in Bishop Score in the intervention group. The Bishop score improved for 85% of the intervention group.
Ty-Torredes conducted an experimental study in the Philippines and concluded that daily consumption of one capsule of EPO had a significant effect on cervical preparation and increased Bishop score, as well as a reduction in the number of cesarean sections compared with placebo.
A retrospective cohort study by Hiersch et al. indicated that women with a gestational age of 34-41 weeks had improved cervical preparation and increased Bishop scores after administration of vaginal prostaglandin E2. Bahmani et al. showed that the use of evening primrose pearl oil with misoprostol on the cervix was more effective than misoprostol alone. The results of the present study are consistent with the above studies.,
The results of studies have shown a significant increase in GLA in the blood after the use of Evening primrose oil, followed by cervical preparation. The effect of GLA dietary supplements on prostaglandin E1, prostaglandin E2, and arachidonic acid biosynthesis in animals and humans has been reported.
According to the present study results, it seems that EPO, by increasing sufficient amounts of GLA in the blood, has a good effect on cervical preparation and decreases the duration of labor. However, we did not investigate GLA levels.
Of note, in the present study, the number of patients who required oxytocin and the duration of its use was lower in the group that received EPO. However, this difference was not statistically significant. Kalati et al. used EPO for cervical preparation. The results showed that only oxytocin consumption was significantly higher in the intervention group and other outcomes such as duration of labor between the two groups were not significantly different.
The results of a study on the amount of oxytocin consumption did not agree with our study. Other study parameters such as gestational age at admission, duration of EPO use, gestational age at delivery, need to induce labor, length of different stages of labor, infant weight, Apgar scores, and hospitalization symptoms between the two groups (primrose oil and placebo) were not different.
These findings were consistent with the present study. Hemmatzadeh et al. and Mirzadeh et al., reported that primrose oil could be effective for cervical preparation, reducing the rate of cesarean sections, and decreasing the delivery time.
In our study, 14 patients in theprime rose oil group and 7 patients in the misoprostol group did not require induction of labor. So, 30 patients in the prime rose oil group and 19 patients of the misoprostol group had a normal vaginal delivery. The most common cause of cesarean section in the misoprostol group was thick meconium.
The results of a meta-analysis by Moradi et al. showed no significant difference in Bishop Scores before and after in the intervention and control groups. Based on the current meta-analysis of four studies, the effectiveness of oral consumption of evening primrose on cervical maturation was not confirmed.
Zahran et al. found no significant benefit in using EPO preparation to shorten pregnancy, improve Bishop scores, increase the incidence of spontaneous delivery, or improve other pregnancy outcomes. This lack of any significant difference between the intervention and control groups in the different studies might be due to different therapeutic doses and duration of use.
According to the present study results and those reported by similar studies,,, evening primrose oil causes sufficient amounts of GLA in the blood and has a good effect on cervical preparation and decreasing the duration of labor. However, we recommend that additional trials with different doses and methods of administration should be undertaken to obtain stronger results.
Variations in dose, method of administration, and duration of EPO use, in addition to the few numbers of studies that have a similar design and small sample size indicate a need for further studies to identify the effects of evening primrose on induction of labor and cervical ripening. In the present study, we did not investigate GLA levels, and mother and neonatal outcomes.
The main strength of this double-blind randomized controlled trial was that it compared EPO and misoprostol between two groups of post-dating pregnant women who had similar baseline characteristics.
| Conclusion|| |
Misoprostol and evening primrose oil appear to have positive effects on cervical preparation. EPO significantly improved the Bishop score and reduced cesarean section rates compared to misoprostol in late-term pregnancy among women. A more comprehensive study of EPO should be conducted that assesses the relationship between linoleic levels and cervical readiness on childbirth, and its effect on Bishop Scores in post-term pregnancy.
The Isfahan University of Medical Sciences Ethics Committee (code: IR.MUI.MED.REC.1399.530) approved this clinical trial (IRCT20200217046523N14). Informed consent was obtained from all participants.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There is no conflicts of interest.
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[Table 1], [Table 2], [Table 3]