Document Type : Original Research Article
Department of Obstetrics and Gynecology, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Background & Objective: Hysteroscopy is an impressive diagnostic and therapeutic procedure for uterine cavity abnormalities. There are several methods for cervical preparation prior to hysteroscopy, among which misoprostol (a prostaglandin E1 analog) is the most common. However, misoprostol has some side effects, including uterine cramps, vaginal hemorrhage, nausea, vomiting, and fever-like feelings, the severity of which escalates by increasing the dosage. Therefore, in this study, we aimed to compare vaginal misoprostol in two different dosages of 200 and 400 μg with a control group to prescribe the lower dosage of misoprostol in case they were equally effective.
Materials & Methods: In this randomized clinical trial study, 87 patients, who had hysteroscopy indications at Yas Hospital, were randomly assigned into three groups (i.e., 200 μg vaginal misoprostol, 400 μg vaginal misoprostol, and placebo). Afterward, the dilatation time of the cervical response and side effects associated with medication and surgery were assessed.
Results: The mean dilatation time in the 200 μg misoprostol, 400 μg misoprostol, and placebo groups were 46.7±35.8, 36.8±31.1, and 67.6±49.5 seconds, respectively. These differences were significant (P=0.038).
Conclusion: It seems that administering vaginal misoprostol is an easy, effective, and safe procedure for cervical preparation before the hysteroscopy. Considering that increasing the dosage of misoprostol did not significantly change the dilatation time, it is recommended that 200 μg misoprostol be used to reduce the side effects.
Hysteroscopy is an effective diagnostic and therapeutic procedur for uterine cavity abnormalities, such as endometrial polyps, submucosal myomas, uterine septum, and synechiae (1-5). Cervical dilatation is one of the surgeon concerns when performing a hysteroscopy. This problem is more noticeable in cervical stenosis, as well as in nulliparous and menopausal patients. In addition, more than half of the side effects related to hysteroscopy (including cervical rupture, false tract creation, and uterine perforation) occur during the entry into the cervix. The prevalence of these side effects can be reduced by proportion cervical preparation prior to hysteroscopy (6).There are several methods for preparing the cervix before hysteroscopy. They reduce the risk of hysteroscopy-associated side effects (7-10). Among them, administering misoprostol, a prostaglandin E1 analog, is the most common (11).
Misoprostol is a prostaglandin E1 analog widely consumed to prevent and treat gastric ulcers caused by long-time consumption of nonsteroidal anti-inflammatory drugs. Furthermore, it is applied to prepare the cervix for labor induction, the first trimester pregnancy termination, and for missed abortion treatment.
Misoprostol for cervical preparation before the hysteroscopy can be administered orally, sublingually, and vaginally; however, there are still some controversies over the most effective method of administering misoprostol for cervical dilatation. No studies have mentioned the definite dosage or method for administering misoprostol in patients undergoing hysteroscopy.
in addition, misoprostol has side effects, including uterine cramps, vaginal hemorrhage, nausea, vomiting, and fever-like feelings, the severity of which escalates by increasing the dosage. Hence, in this study, we aimed to compare vaginal misoprostol in two different dosages of 200 and 400 μg with a control group to prescribe the lower dosage of misoprostol in case they were equally effective.
This double-blind clinical trial study was done on 87 patients who had hysteroscopy indications at Yas Hospital from October 2017 to February 2018. Inclusion criteria included patients who were candidates for diagnostic and surgical hysteroscopy due to irregular uterine hemorrhage or intrauterine lesions seen in hysterosalpingography or ultrasound.
Exclusion criteria were being pregnant, suffering from genital infections, having a history of cervical surgery, cervical insufficiency, or GnRH agonist treatment, dealing with prominent uterovaginal prolapse that affected vaginal use of misoprostol, observing a space-occupying lesion in the endocervical canal, having contraindication for prostaglandin use (asthma, glaucoma, hypertension, severe heart disease, and renal failure), and withdrawing to take part in the study.
This study was conducted in compliance with the Helsinki Declaration and approved by the Tehran University of Medical Sciences ethics committee (IR.TUMS.MEDICINE.REC.1396.2628). All the patients signed informed agreement.
Hysteroscopy was mainly performed in the proliferative phase of the menstrual cycle. The type of anesthesia was spinal. The patients were allocated to three groups using the block randomization method. In the first group, 200 μg vaginal misoprostol (Samisaz Pharmaceutical Company) was administered; 400 μg vaginal misoprostol (Samisaz Pharmaceutical Company) was administered in the second group, and a placebo (Caspian Tamin Pharmaceutical Company vitamin B6) was administered in the third group 4-6 hours before the surgery.
before the hysteroscopy in the lithotomy position, for cervical dilatation, Hegar dilators (numbers 1 to 7) were used according to the width of the cervix. Hysteroscopy was then performed.
For double blinding, vaginal and hysteroscopic medications were inserted by different people; the surgeon and patients were not aware of the medication administered. Simultaneous laparoscopy was performed in case of rupture or suspected uterine anomaly. The primary outcome included the duration time of dilatation up to the number 7 Hegar dilator and surgery-related side effects.
All the statistical analyses were performed using SPSS version 24.0 (SPSS Inc., Chicago, Ill., USA). A P-value of less than 0.05 was considered as the level of statistical significance. For normally distributed data, the analysis of variance (ANOVA) was utilized, and the Kruskal-Wallis test was employed for data, which did not have a normal distribution according to the Kolmogorov-Smirnov test. The univariate analysis of variance was used to show the interaction effect of variables. For determining the intensity of the effectiveness of the three intervention methods, two-by-two comparisons were performed among the groups using the post hoc test.
In this study, 87 patients were studied. The mean of the patients’ age was 41.1±8.3 years. Among these patients, 86 people (98.9%) were married, and only one person (1.1%) was single.
There was no significant difference (P>0.05) between the three groups in terms of baseline variables, including age, body mass index (BMI), gravidity, history of normal vaginal delivery number or C-section number, marital status, and menopause. All three groups were identical in terms of these baseline variables (Table 1).
In the present study, the most prevalent hysteroscopy indication was abnormal uterine bleeding (AUB) with polyps, which included 24 patients (27.6%). This indication was the most common cause in all three study subgroups.
The mean dilatation time in the 200 μg misoprostol group was 46.7±35.8 seconds; it was 36.8±31.1 in the 400 μg misoprostol group and 67.6±49.5 in the placebo group, indicating a significant difference among these groups in the dilatation time for the preparation prior to hysteroscopy (P=0.038). Since the dilatation time was significantly different in these three groups, the post hoc test was done to find the significant component, the results of which were presented in Table 2 in detail.
Overall, 13 participants were menopausal (14.9%). The general linear model (GLM) test showed that the occurrence of menopause did not make a difference in the results, and there was no significant difference between menopause and non-menopause patients in the three groups (Table 3).
Moreover, intraoperative side effects were examined among the participants. The results demonstrated that, among the studied patients, we only had one case of intraoperative side effects, which was a false tract, and 86 patients (98.9%) did not experience any intraoperative side effects. The difference between this variable was not statistically significant in the three study groups.
Table 1. The baseline characteristics in the study groups
|200 μg Misoprostol||400 μg Misoprostol||Vitamin B6 (control)|
|Menopause||2 (6.9)||6 (20.7)||5 (17.2)||0.309|
BMI: body mass index, NVD: normal vaginal delivery, C/S: cesarean section
Table 2. The comparison of dilatation time amongst the study groups
|Comparison Groups||Dilatation time (Mean/Mean Difference ± SE)||P-value|
|200 μg Misoprostol||400 μg Misoprostol||Vitamin B6|
|Between 3 G||46.7±35.8||36.8±31.30||67.6±49.5||0.038|
|G1- G3||- 20.91±10.64||0.049|
G: group, G1: Misoprostol 200, G2: Misoprostol 400, G3: Vitamin B6
Table 3. Using the GLM analysis to assess menopause and misoprostol dosage effects on the dilatation time
GLM: general linear model
This study indicated that administering misoprostol led to a suitable dilatation (required for hysteroscopy) much better and faster than the placebo. Because about half of the hysteroscopy-related side effects happen when entering the cervical canal (including cervical rupture, false tract creation, and uterine perforation), the occurrence of these side effects can be greatly decreased by creating proper cervical dilatation (12-13).
Although, in this study, we did not compare dilatation time based on different routes of misoprostol (oral vs vaginal), previous evidence suggested that there was no remarkable diversity in cervical dilatation according to misoprostol routes; however, cervical dilatation occurs more rapidly in the vaginal type, and diarrhea is less common in the vaginal misoprostol (14).
In the current study, 200 and 400 μg misoprostol significantly shortened the dilatation time (20.19 and 30.80 seconds, respectively) compared to the placebo. This finding is consistent with the results of Song et al., Saha et al., and Hua et al., reporting an imprtant variation in the cervical preparation with misoprostol compared to the placebo (15-17).
In the present study, it was shown that the misoprostol effect was similar in both premenopausal and postmenopausal women. This finding is similar to the results of a study performed by Gkrozou et al., which mentioned that vaginal misoprostol decreased the requirement for cervical dilatation in both premenopausal and postmenopausal patients (18). However, our finding is contrary to the results of a study conducted by Oppegaard et al., which reported that misoprostol did not affect the cervical preparation in postmenopausal women (19), as well as the results of a study carried out by Mohammadian et al., which concluded that misoprostol facilitated dilatation and curettage in multiparous and premenopausal patients but was lower efficient in nulliparous and postmenopausal women (20).
The strength of this study was the observance of the principles of randomization and blinding, as well as the use of the control group. However, there were some limitations in the current study, such as the small sample size. Besides, in the present study, only vaginal misoprostol was examined; therefore, it is recommended that future studies be performed with a larger sample size and consider possible confounding variables.
It seems that administering vaginal misoprostol is an easy, effective, and safe procedure for cervical preparation before the hysteroscopy. Considering that increasing the dosage of misoprostol did not significantly change the dilatation time, it is recommended that 200 μg misoprostol be used to reduce the side effects.
The authors thank all those who helped them writing this article.
Authors declared no conflict of interests.