Isosorbide mononitrate vaginal gel versus misoprostol vaginal gel versus Dilapan-S for cervical ripening before first trimester curettage

OBJECTIVE: To compare the efficacy and safety of vaginal applications of three different principles of cervical priming prior to first trimester curettage, isosorbide mononitrate (ISMN), misoprostol and Dilapan-S, a hygroscopical cervical dilator. STUDY DESIGN: Pregnant women with missed abortion between 6 and 12 gestational weeks were included and randomly assigned to receive either 80 mg ISMN vaginal gel (group 1) or 200 microg of misoprostol vaginal gel (group 2) or Dilapan-S, a hygroscopical cervical dilator (group 3), for cervical ripening before curettage. Outcome parameters were cervical dilation at the time of operation and maximum dilation reached with Hegar's dilator and the degree of difficulty in mechanical dilation as well as safety and side effects of the preparations. RESULTS: Sixty-five pregnant women with missed abortion were included and assigned to the three study groups (n=22 for group 1, n=22 for group 2, n=21 for group 3). Misoprostol vaginal gel and Dilapan-S were significantly more effective than ISMN vaginal gel in cervical dilation reached with priming (p<0.005 and p<0.005) and in the degree of difficulty in cervical dilation assessed by the surgeon (p<0.001 and p<0.01). Mild discomfort was indicated by all patients after Dilapan insertion, whereas no patient complained about discomfort after misoprostol or ISMN insertion (p<0001). Three patients suffered from mild hypotension and headache after ISMN treatment, and two had increased vaginal bleeding due to uterine atony during surgery (p<0.05). CONCLUSION: A vaginal gel of ISMN is less effective for cervical ripening prior to first trimester curettage compared to misoprostol vaginal gel or Dilapan-S. The latter could be an effective and safe alternative to prostaglandin priming avoiding preoperative contractions caused by prostaglandin preparations.     

Comparison of isosorbide mononitrate (Mono Mack) and misoprostol (Cytotec) for cervical ripening in the first trimester missed abortion

Objective: The objective of this study was to compare NO-donor isosorbide mononitrate to misoprostol, both applied as vaginal tablets for cervical ripening prior to first trimester curettage in patients with missed abortion. Materials and methods: Thirty women with missed abortion were assigned after a random list to be treated either with 200 μg gemeprost (Cytotec, Pfizer, Germany) or with 40 mg isosorbide mononitrate for cervical priming at least 3 h before curettage. Vaginal bleeding or the intracervical presence of products of conception was documented. The largest number of Hegar’s dilator, which could be introduced without difficulty and the largest number of Hegar’s dilator at which cervical dilation was performed and the ease of mechanical dilation was assessed. Results: There were no significant differences in cervical ripeness before procedure nor in ease of dilation. In the misoprostol group, the cervical canal was more dilated before any procedure (median of Hegar’s dilator 6 vs. 5) and after dilation (median of Hegar’s dilator 11 vs. 10), although this difference was not significant. Vaginal bleeding occurred in two patients in each group. Products of conception were only found in the cervix of one patient of the misoprostol group. Synopsis: Vaginal application of isosorbidemononitrate in cervical priming prior to curettage abortion is as effective as vaginal application of misoprostol.     

Outpatient cervical ripening with nitric oxide donor isosorbide mononitrate prior to induction of labor.

OBJECTIVE: To examine the effectiveness and safety of outpatient vaginal administration of isosorbide mononitrate (IMN) to induce cervical ripening. METHODS: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted on 102 singleton term pregnant women with unfavorable cervices who were randomly assigned to receive outpatient intravaginal IMN or placebo before admission for induction of labor. The main outcome variable was time from hospital admission to delivery. Secondary outcomes included fetal and maternal morbidity, labor characteristics, and incidence of cesarean delivery. RESULTS: The admission-delivery interval was 13.45+/-6.63 and 20.12+/-8.19 h (P=0.0001) for the IMN and placebo groups, respectively. Of the IMN patients 62.75% needed prostaglandins for cervical ripening versus 90.2% with placebo (P=0.002). The incidence of tachysystole was significantly lower in the IMN group (P<0.05) but there were no significant differences in cesarean delivery rate, neonatal outcomes, and incidence of hyperstimulation. CONCLUSIONS: Outpatient use of IMN resulted in shorter admission to delivery interval, and was associated with less prostaglandin use and lower incidence of uterine tachysystole.     

Sublingual versus vaginal route of misoprostol for cervical ripening prior to surgical termination of first trimester abortions

BACKGROUND: Sublingual and vaginal routes of misoprostol have been found to be effective for pharmacological ripening prior to surgical termination of first trimester abortions. We conducted this study to compare the effectiveness and acceptability of sublingual versus vaginal route of misoprostol for cervical priming prior to vacuum aspiration (VA). METHODS: In this prospective clinical trial, a total of 100 women with period of gestation between 6 and 12 weeks scheduled for day surgery abortion were sequentially allocated into two groups of 50 each. All participating women received 400 microg of misoprostol 3 h prior to VA either by sublingual (self-administered at home) or by vaginal route (inserted by the doctor in hospital) after wetting the tablet with water. RESULTS: Demographic characteristics of both the groups were comparable. For all periods of gestation, sublingual misoprostol significantly improved cervical dilatation (p<0.001) and reduced the time duration of surgery (p<0.001) compared to vaginal group without increasing the side effects. Mean pain score of the sublingual group was 2.7+/-1.1 as compared to 3.2+/-1.6 of the vaginal group (p=0.57). Misoprostol tablet was found intact in the vagina of three patients and was only partially absorbed amongst five patients at the time of VA. CONCLUSION: Sublingual route is an effective and convenient alternative to vaginal administration of misoprostol for cervical dilatation. It can be conveniently self-administered at home thereby decreasing hospital stay and cost. It also has a good patient acceptability rate.     

Vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening at term: a randomized controlled study

OBJECTIVE: Our aim was to examine the effect of the nitric oxide donor isosorbide mononitrate on the uterine cervix at term and to evaluate possible adverse effects of this treatment. STUDY DESIGN: Term pregnant women were randomly selected to receive either 40 mg vaginally administered isosorbide mononitrate or placebo 4 hours before elective cesarean section. Cervical status, maternal blood pressure, maternal pulse rate, fetal heart rate, umbilical arterial Doppler indices, and various side effects were examined. RESULTS: Isosorbide mononitrate induced a significant increase in cervical distensibility. It also caused a significant change in maternal blood pressure and maternal pulse rate. In addition, the frequency of maternal headache and palpitations was significantly higher in the isosorbide mononitrate group versus the placebo group. However, the intensity of these symptoms was moderate. CONCLUSION: Vaginal administration of 40 mg of isosorbide mononitrate induces cervical ripening at term. Although the majority of women experienced side effects, no serious clinical maternal or fetal adverse effects, resulting in specific medication or emergency cesarean section, were diagnosed.     

Sublingual misoprostol for first trimester termination of pregnancy

Objectives

To compare blood loss, efficiency, and acceptability of repeated doses of sublingual misoprostol with the standard Tunisian regimen of mifepristone-misoprostol for first trimester medical abortion.

Methods

A prospective randomized trial of 252 healthy pregnant women requesting medical abortion in the first trimester (up to 56 days). Participants were randomized to receive 200 mg of oral mifepristone followed by 400 µg of oral misoprostol (group 1) or 800 µg of sublingual misoprostol repeated every 4 hours for up to a maximum of 3 doses (group 2). Primary outcome was blood loss assessed by decrease in hematocrit.

Results

Mean decrease in hematocrit at follow-up was significantly greater in group 1 than in group 2 (3.65% ± 1.18% vs 2.69% ± 1.89%, respectively; P = 0.02). There was no difference in efficiency rates between groups 1 and 2 (94.5% vs 92.1%; P = 0.7). Comparable proportions of women experiencing at least one adverse effect after misoprostol administration were reported in groups 1 and 2 (81.7% vs 79.4%; P = 0.75).

Conclusion

Compared with the most widely used regimen in Tunisia (mifepristone-misoprostol), sublingual misoprostol alone induces less blood loss (although not clinically significant); it is less expensive and offers reduced interval time to expulsion.     

Addition of isosorbide mononitrate to misoprostol for cervical ripening in post-term pregnancy: A randomized controlled trial

ObjectiveThe purpose of this paper is to compare the effect of vaginal isosorbide mononitrate added to misoprostol versus misoprostol alone in cervical ripening and labor induction in post-term pregnancy.MethodsIn this double-blind controlled trial study, 150 pregnant women in post-term pregnancy who were candidates for labor induction were selected. The participants were assigned randomly to receive either vaginal isosorbide mononitrate (IMN) (40 mg) or placebo. Misoprostol (25 mg) was added to both groups as needed. Time to full cervical ripening, time to delivery, and the amount of misoprostol used in each group were assessed.ResultsThe time interval from the administration of IMN to full cervical ripening was shown to be significantly lower in the IMN+ misoprostol groups versus the comparison group (p = .032). The adjusted analysis of this time interval after controlling for age, BMI, gravidity, and Bishop score on administration remained significantly less (p = .045),the mean difference being ?4.85 h, CI 95% ?9.58 to ?.12. Isosorbide treatment resulted in significantly less misoprostol used versus misoprostol alone (2.37 ± 1.02 versus 3.08 ± 1.29), adjusted p-value = .001, CI 95% ?1.09 to ?.32. We found no significant increase in maternal–fetal outcomes or side effects of the IMN+ misoprostol group compared with the misoprostol group.ConclusionThis study found that intravaginal IMN added to misoprostol is more effective in reducing time to full cervical ripening versus misoprostol alone in post-term pregnancy. It also reduces the need for more misoprostol.     

Second trimester abortion using isosorbide mononitrate in addition to gemeprost compared with gemeprost alone: a double-blind randomized, placebo-controlled multicenter trial

OBJECTIVE: We aimed to determine whether second-trimester abortion using isosorbide mononitrate (IMN) in addition to gemeprost is more effective and reduces side effects compared with gemeprost alone. STUDY DESIGN: Eighty women who were age 13 to 23 weeks' gestation were randomly assigned to receive per vaginam either IMN 40 mg (group 1, 40 women) or placebo (group 2, 40 women) in addition to gemeprost 1 mg up to 3 times daily 3 hours apart for 2 days. Analysis of variance, a chi 2 test, and a multivariate analysis were performed. RESULTS: Of the 72 women analyzed, 68% (group 1) and 38% (group 2) underwent abortion within day 1 (P < .05). However, group 1 was associated with more headache (18% of women) 3 hours after induction compared to group 2 (0% of women, P = .038). CONCLUSION: IMN in addition to gemeprost is effective for second-trimester abortion, but is associated with more headache compared with gemeprost alone.     

Nitric oxide donor isosorbide mononitrate for pre-induction cervical ripening at 41 weeks' gestation: A randomized controlled trial

OBJECTIVE: Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to determine whether sustained release isosorbide mononitrate (ISMN-SR) 60 mg administered vaginally is effective for pre induction cervical ripening at 41 weeks' gestation. METHODS: A double-blind randomised controlled trial was carried out at the University Obstetric Unit, Galle, Sri Lanka for a period of 9 months, commencing 1st August 2003. One hundred and fifty-six consecutive women with uncomplicated singleton pregnancies at 41 weeks' gestation with a modified Bishop Score <5 were allocated by stratified (primip/multip) block randomization to receive either ISMN-SR 60 mg (n = 78) or vitamin C 100 mg (n = 78) vaginally. Modified Bishop Score at 41 weeks + 2 days' gestation and the proportions establishing spontaneous labor or becoming favorable for induction of labor (IOL) by 41 weeks + 2 days' gestation were evaluated in each group. RESULTS: At the commencement of the study there were no differences between the mean age, parity or modified Bishop Score of the two groups. In the ISMN-SR group, there was a marked increase in the proportion establishing spontaneous labor (28% vs 7.5%, P < 0.01) and being favorable for IOL (40% vs 9% P < 0.001), 2 days after therapy. In the ISMN-SR group, there was a significantly higher increase in the mean modified Bishop Score (3.8, 95% CI 2.3-5.3 vs 1.3, 95% CI 0.3-2.2, P < 0.01) and a marked decrease in the proportion of subjects requiring further ripening of the cervix with a Foley catheter. (32% vs 79%, P < 0.001). The cesarean section rates were similar in both groups. CONCLUSION: Sustained release ISMN administered vaginally is effective for preinduction cervical ripening.     

Randomised placebo-controlled trial of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour – clinical trial with analyses of efficacy and acceptability. The IMOP Study

Objective  To determine whether isosorbide mononitrate (IMN), self-administered vaginally by women at home, improves the process of induction of labour.
Design  Randomised double blind placebo-controlled trial.
Setting  Large UK maternity hospital.
Population or Sample  Nulliparous women with a singleton pregnancy, cephalic presentation ≥37 weeks gestation, requiring cervical ripening prior to induction of labour.
Methods  IMN ( n  = 177) or placebo ( n  = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction.
Main outcome measures  Admission to delivery interval and women's experience of induction of labour.
Results  IMN did not shorten the admission to delivery interval as compared with placebo [mean difference of −1.6 hours (95% CI −5.1,1.9, P  = 0.37)], despite being more effective than placebo in inducing a change in Bishop score [mean difference of 0.65 (95% CI 0.14,1.17, P  = 0.013)]. While both groups found the overall experience of home treatment to be positive, (mean score of 3.8/10 ± 2.3/10 for the IMN group, where 1 = extremely good and 10 = not at all good) women in the placebo group found it marginally more positive than those in the IMN group (just over half a unit on a 10-point scale, P  = 0.043). There were no differences between the groups in the pain or anxiety experienced or willingness to take the treatment in a subsequent pregnancy.
Conclusions  IMN self-administered vaginally at home does not shorten admission to delivery interval despite a significant effect on cervical ripeness assessed using the Bishop score. However, women report positive views on cervical ripening at home, and the setting deserves further investigation.     

The predictive nature of uterocervical angles in the termination of second trimester pregnancy

Aim: To establish how useful and the predictive capacity of uterocervical angles (UCA) in the termination of second trimester pregnancies.

Material and methods: This prospective cohort study was conducted at a tertiary center with a total of 120 singleton pregnancies delivered between 14 and 24 gestational weeks. Before the beginning of misoprostol induction, patients were screened for both cervical length (CL) and uterocervical angles (UCA). The UCA is defined as an angle constructed by the measurement of the cervical canal and lower uterine segment. The study population was subdivided into four groups; successful and failed terminations at the end of 24?hours of induction and successful and failed terminations at the end of 48?hours of induction. We decided to further evaluate our study population based on their UCAs, and placed them into four categories; UCA ≥95°, UCA <95°, UCA ≥105°, and UCA <105°.

Results: In the 24-hour time frame group, the mean UCA was 105.50?±?15.38 degrees in the successful termination group and was 100.22?±?11.12 degrees in the failed group (p?=?.001). In the 48-hour time frame group, the mean UCA was 104.19?±?13.51° in the successful termination group and was 93.52?±?7.84° in the failed group (p?=?.007). The mean hour of induction was shortest in the UCA ≥105° group.

Conclusions: Regardless of the time frames, patients who had successful terminations had a broader angle, less amount of misoprostol use and shorter duration of induction as compared to the failed termination groups. What do the results of this study add? The uterocervical angle has never been measured in second trimester pregnancies to predict the timing of termination. Our study demonstrated the useful application of this ultrasonographic finding in the prediction of successful second trimester terminations.

Trial registration: ClinicalTrials.gov identifier: NCT03220607.     

足月妊娠促宫颈成熟方法的探讨

目的:评价目前常用的足月妊娠促宫颈成熟方法的效果,为足月妊娠促宫颈成熟和引产提供有效、安全、方便的方法。方法:选择有引产指征的足月妊娠产妇221例,随机分为水囊组(A)80例,缩宫素组(B)45例,米索前列醇组(C)46例,普贝生组(D)50例,比较4组产妇的宫颈评分、分娩结局、新生儿结局和副作用。结果:水囊组促宫颈成熟效果最好,显著高于其他各组(P<0.05),剖宫产率低于其他各组(P<0.05)。普贝生组用药至临产时间及总产程明显短于其他各组(P<0.05)。各组新生儿窒息发生率和羊水污染率无显著差异。普贝生组发生子宫过度刺激症状者较多。结论:低位水囊有显著的促宫颈成熟的作用,配伍缩宫素在足月妊娠促宫颈成熟和引产过程中有效,普贝生促宫颈成熟安全有效,可选择性地用于有一定经济条件的孕妇。     

Sublingual misoprostol plus laminaria for cervical preparation before surgical management of late first trimester missed abortions,a randomized controlled trial

Objective: Comparing the efficacy of low-dose sublingual misoprostol plus laminaria to medium-dose sublingual misoprostol alone for cervical dilation before surgical management of late first trimester missed abortions.

Methods: Randomized, controlled trial evaluated 70 women with missed abortion, admitted for surgical termination of pregnancy. The patients were randomly assigned to receive 200?μg sublingual misoprostol with cervical laminaria (intervention group) or 400?μg sublingual misoprostol without laminaria (control group), four hours before surgical process. The study is registered at www.irct.ir (IRCT2014070711020N4).

Results: More patients in the intervention group achieved the desired cervical dilation (≥Hegar7) before surgical process than the control group (91.4% versus 17.1%, p?p?p?=?0.02). Four patients in the intervention group and none in the control group had spontaneous expulsion of pregnancy products (p?=?0.11).

Conclusions: Compared to medium-dose sublingual misoprostol alone, using a combination of cervical laminaria plus low-dose sublingual misoprostol before surgical process is associated with significantly more effective and rapid cervical dilation, lower requirement for mechanical dilation, lower abdominal pain and discomfort during the waiting period and higher patients’ satisfaction.     

A comparison of lamicel tents and gemeprost (Cervagem) pessaries prior to first trimester abortion

Summary In an open, randomized study 108 women were treated with either a Lamicel tent or a 1 mg gemeprost pessary (Cervagem) 4 h before first trimester abortion. Both treatments were effective in producing cervical dilatation, however further dilatation was significantly easier after Cervagem. Preoperative abdominal pain and gastrointestinal side-effects were significantly more frequent in the Cervagem group. The incidence of postoperative pain and blood loss were similar in the two groups. Advantages and disadvantages of the two treatments are mentioned.     

Isosorbide mononitrate induces increased cervical expression of cyclooxygenase-2, but not of cyclooxygenase-1, at term

OBJECTIVE: Prostaglandin and nitric oxide (NO) are both known to be involved in cervical ripening at term. The aim of the study was to investigate if NO has an effect on cervical expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the two main isoenzymes involved in prostaglandin synthesis, and to localize these enzymes within the cervix. STUDY DESIGN: Women with an unripe cervix scheduled for elective caesarean section at term were randomly selected to receive vaginally either the NO donor isosorbide mononitrate (IMN) or placebo 4h before surgery. At the operating theatre, cervical tissue specimens were obtained for immunoblotting and immunohistochemistry. RESULTS: Increased expression of COX-2 was found in specimens exposed to IMN compared to specimens obtained from women in the placebo group. There was no difference in the expression of COX-1. Immunohistochemistry revealed similar localization of the two enzymes in treated and untreated women. CONCLUSIONS: Vaginal administration of IMN induces increased cervical expression of COX-2, but not of COX-1. This pathway may be of importance in the process of cervical ripening at term.     

Effects of a prolonged, 72 hours,interval between mifepristone and gemeprost in second trimester termination of pregnancy: a retrospective analysis

Objective: To evaluate if the 72 hours interval between mifepristone and gemeprost has a similar efficacy compared to the 48 hours interval for second trimester termination of pregnancy

Study Design: Two-hundred and fifteen consecutive pregnant women, admitted to our hospital, for second trimester TOP, were included in this retrospective analysis. Standard protocol was followed for all patients. On the first day of the procedure oral mifepristone 200?mg was administered. After 72 (group A, n?=?78) or 48 hours (group B, n?=?113) women were admitted for administration of gemeprost 1?mg pessary as per protocol. The induction to abortion time was defined as the interval between the insertion of the first gemeprost pessary and the expulsion of the fetus.

Results: There are no significant differences in the number of pessaries in the two groups. The induction to abortion interval was longer in group A than in group B. Twenty-one women required surgical evacuation of the uterus for retained placenta or incomplete abortion without difference between groups.

Conclusion: A 48-hours interval between mifepristone and gemeprost leads to better results than a 72-hours interval, with a shorter abortion length and represents the elective method for second trimester TOP.