Effect of isosorbide mononitrate for cervical ripening before surgical termination of pregnancy in the first trimester

Objective

To evaluate the efficacy of isosorbide mononitrate (IMN) for cervical ripening prior to first trimester surgical termination of pregnancy.

Methods

A prospective, double-blind, randomized, placebo-controlled trial. Women scheduled for surgical termination of a nonviable fetus before 12 weeks of gestation from October 2008 to June 2009 were enrolled and randomly assigned to receive either 20 mg vaginally of IMN (n = 24) or a placebo (n = 24) 4 hours before suction evacuation. Cervical dilation before evacuation was assessed with 10-mm Hegar dilators followed by smaller sizes that were measured until the instrument passed freely through the internal os. Cervical dilation, adverse effects, termination complications, and patient satisfaction were the main outcomes.

Results

Mean cervical dilation was not significantly different between the IMN and placebo groups (6.29 ± 0.99 mm vs 5.71 ± 1.04 mm; P = 0.05). Mean operative time did not differ between the groups (16 ± 0.07 min vs 18 ± 0.06 min; P = 0.55), nor did patient satisfaction measured by visual analogue scale (7.04 ± 1.68 vs 6.54 ± 1.22; P = 0.24).

Conclusion

IMN was comparable to placebo in terms of efficacy and patient satisfaction for cervical priming prior to first-trimester termination of pregnancy.     

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.     

Cardiotocographic abnormalities associated with misoprostol and dinoprostone cervical ripening and labor induction

Objective

To characterize the incidence and timing of cardiotocographic (CTG) abnormalities associated with misoprostol and dinoprostone vaginal inserts during labor induction.

Study design

This was a secondary analysis of data collected during the misoprostol vaginal insert (MVI) trial, a multi-site, double-masked, randomized trial of women requiring cervical ripening before induction of labor. The timing, incidence and clinical outcomes associated with CTG abnormalities were analyzed among three study groups.

Results

1308 subjects were randomized to receive dinoprostone pessary, misoprostol 50 mcg (MVI 50) or 100 mcg (MVI 100) vaginal insert. 6.8% of MVI 50-treated women had a uterine contractile abnormality (hyperstimulation, hypertonus and/or tachysystole) while the study drug was in situ, compared to 17.4% with dinoprostone insert (p < 0.001) and 17.3% with MVI 100 (p < 0.001). There was no significant difference in incidence of fetal heart rate (FHR) abnormalities that occurred with the study drug—11.2% with dinoprostone, compared to 9.9% with MVI 50 and 10.7% with MVI 100. Cardiotocographic (CTG) abnormalities while the study drug was in situ occurred later in women treated with MVI 50 (7.5 h [6.2-9.8]) compared to dinoprostone (5.5 h [4.2-6.6], p = 0.003) and MVI 100 (7.0 h [5.7-7.9], p = 0.13). Eight participants in MVI 50 group underwent cesarean section secondary to a CTG event that was initially noted with the study drug in situ, compared to eight dinoprostone-treated participants and 16 in the MVI 100 group, but these differences were not statistically significant.

Conclusion

Cardiotocographic abnormalities were less frequent and occurred after longer exposure with MVI 50 than MVI 100 or dinoprostone. Clinical outcomes were similar among the groups.     

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.     

Comparing two dinoprostone agents for cervical ripening and induction of labor: a randomized trial

OBJECTIVE: To compare dinoprostone gel and insert in achieving successful vaginal delivery in nulliparous and multiparous women. STUDY DESIGN: 220 nulliparous and 100 multiparous with a Bishop score < or =7 were randomized to receive dinoprostone either gel or insert for cervical ripening. The main outcome measures were the rate and latency of vaginal delivery. RESULTS: In nulliparous women no significant differences were found between the gel and insert groups in the rate of vaginal delivery (85.6% vs. 80.7%) delivery < or =12 (36.8% vs. 32.9%) and < or =24h (85.3% vs. 93.4%) regardless of the preinduction Bishop score. Nulliparous with Bishop score < or =4 treated with the insert had a decreased risk (p<0.05) of post partum hemorrhage (4.8%) when compared with nulliparous treated with gel (16.7%). On the contrary, in multiparous the time to delivery interval was significantly shorter in the gel treated group (9.9+/-4.9h vs. 13.1+/-5h; p<0.001) with more patients delivering vaginally < or =12h (75% vs. 37.5%, p<0.001), regardless of the preinduction Bishop score. CONCLUSION: Both dinoprostone gel and insert are efficient in achieving cervical ripening and successful labor in nulliparous and multiparous. In multiparous, however, the gel significantly reduces the time to vaginal delivery with more patients delivering vaginally < or =12h, regardless of the Bishop score.     

The cost-effectiveness of outpatient (at home) cervical ripening with isosorbide mononitrate prior to induction of labour

Objectives  To assess the cost-effectiveness of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour.
Design  Economic evaluation was conducted alongside a randomised placebo controlled trial (the IMOP trial).
Setting  Large UK maternity hospital.
Population  A total of 350 nulliparous women with a singleton pregnancy, cephalic presentation ≥37 weeks gestation, requiring cervical ripening prior to induction of labour.
Interventions  Isosorbide mononitrate ( 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.
Results  Mean health service costs between the period of randomisation and discharge for mother and infant were £1254.86 in the IMN group and £1242.88 in the placebo group, generating a mean cost difference of £11.98 (bootstrap mean cost difference £12.86; 95%CI: −£106.79, £129.39) that was not statistically significant ( P  = 0.842). The incremental cost per hour prevented from hospital admission to delivery was £7.53. At the notional willingness to pay threshold of £100 per hour prevented from hospital admission to delivery, the probability that IMN is cost-effective was estimated at 0.67. This translated into a mean net monetary benefit of £98.13 for each woman given IMN.
Conclusions  Although the probability that IMN is cost-effective approaches 0.7 at seemingly low willingness to pay thresholds for an hour prevented from hospital admission to delivery, our results should be viewed in the light of the clinical findings from the IMOP trial.     

Evaluation of isosorbide mononitrate for cervical ripening prior to induction of labor for postdated pregnancy in an outpatient setting

ObjectiveTo determine the safety and effectiveness of self-administered treatment with isosorbide mononitrate (IMN) for cervical ripening in Indian women with postdated pregnancies.MethodsA randomized, placebo-controlled study was conducted with 200 women with postdated pregnancies and unfavorable cervices who self-administered vaginally either 2 40-mg tablets of IMN or 2 40-mg tablets of pyridoxine as placebo prior to admission for induction of labor. The main outcome variables were change in Bishop score, time from admission to delivery, and presence or absence of fetal and maternal morbidity.ResultsThe Bishop score was significantly improved 24 hours after initiation of the outpatient IMN treatment (P < 0.001) and the needs for further cervical ripening and oxytocin infusion were less in the study than in the control group (P < 0.001 and P = 0.008). The time from admission to delivery was also less (P < 0.001). Moreover, the IMN treatment had no major adverse maternal or fetal effects. The vast majority of women in both groups were either satisfied or very satisfied with the outpatient treatment.ConclusionThe self-administration, at home, of isosorbide mononitrate leads to a safe and effective cervical ripening prior to labor induction in women with postdated pregnancies.CTRI Registration No.: CTRI/2011/091/000121     

Intravaginal misoprostol versus Foley catheter for cervical ripening and induction of labor.

OBJECTIVE: To compare the efficacy and safety of 100 microg of intravaginal misoprostol with intracervical Foley catheter for cervical ripening and induction of labor. METHOD: One hundred women being induced in the Lagos University Teaching Hospital, Nigeria, were randomized to receive a single 100 microg dose of misoprostol intravaginally or intracervical insertion of Foley catheter. Data analyses were by the Student's t-test and chi-square test. RESULT: Misoprostol was more effective in terms of induction to delivery interval (11.84+/-5.43 versus 20.03+/-4.68 h, P<0.05), change in Bishop score, and number delivered within 24 h, in patients with a one-time successful induction. Uterine hyperactivity and rupture were more frequent in the misoprostol group. CONCLUSION: A single 100 microg dose of intravaginal misoprostol is more efficacious than intracervical insertion of Foley catheter for cervical ripening and induction of labor. Further studies using lower doses are needed to determine the safest dose.     

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.     

Using dinoprostone vaginal insert for induction of labor: A single institute experience

ObjectiveTo evaluate the factors associated with the successful induction of labor (IOL) in women treated with dinoprostone slow-released vaginal insert.Material and methodsA retrospective study was conducted between June 2017 and December 2017, enrolling 65 patients who underwent dinoprostone slow-released vaginal insert-induced labor. The correlation between the characteristics of the pregnant women and its success, as well as perinatal complications and adverse outcomes were analyzed.ResultsFifty-three of 65 (81.5%) achieved a successful vaginal delivery. Only multi-parous pregnant women were an independent predictor factor for successful induction after dinoprostone slow-released vaginal insert, since all of them succeeded after this strategy treatment (100%, n = 18), compared to 74.5% (35/47) of successful rate in the nulliparous pregnant women with a statistically significant difference (p = 0.018). There were no adverse events occurred in both mothers and their offspring.ConclusionDinoprostone slow-released vaginal insert is a good choice for multiparous pregnant women who need IOL, regardless of which reasons are indicated. For nulliparous women, more studies might be needed to evaluate the effectiveness of PGE2 for IOL.     

Periodontal disease and nitric oxide levels in low risk women with preterm labor

Objectives

The aims of the study were to evaluate the possible association between periodontal disease (PD) and preterm labor (PTL), to assess whether the presence of periodontal disease in women with PTL increases the risk of preterm birth (PTB), and to evaluate the role of nitric oxide (NO) in this possible association.

Study design

This study included 820 nulligravid women with low risk socioeconomic status: 400 cases with PTL and 420 controls with normal pregnancy, between 25 and 33 weeks + 6 days of weeks’ gestation. At enrollment, periodontal examination and detection of plasma, gingival and cervical NO levels were performed. We compared the periodontal status of the two groups; we detected the presence of PD and compared NO levels. We then followed the outcome of women with PTL and compared obstetric status and PTB rate between patients with and without PD.

Results

Logistic regression analysis revealed a strong association between PD and PTL (adjusted odds ratio: 2.83, 95% confidence interval (CI) 1.86-4.23; P < 0.0001). Non parametric Mann-Whitney U-test demonstrated significant differences in gingival and cervical NO levels between women with PTL and controls (respectively, median 85.1 μmol/L, interquartile range (i.r.) 51.2-177 vs median 50.5 μmol/L, i.r. 34.5-109.65, P < 0.0001; and median 102 μmol/L, i.r. 53.05-182.7 vs median 38.9 μmol/L, i.r. 32.87-46.1, P < 0.0001). The ability of mean-gingival NO levels to predict PTL was examined by ROC curve analysis: the area under the curve was 0.817 (95% CI 0.774-0.854; P < 0.0001). The cut-off level for the greatest sensitivity and specificity for mean-gingival NO levels was 116.04 μmol/L (sensitivity 0.57, specificity 0.94). Positive and negative predictive values were, respectively, 90.65% and 69.73%. Among women with PTL, the risk of PTB increased in women with PD (adjusted relative risk: 3.85, 95% CI 2.11-6.06; P < 0.0001).

Conclusions

In this tested population, PTL is associated with PD. The presence of PD in women with PTL increases the risk of premature delivery. NO may be a new marker to explain this association.     

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.     

Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics

OBJECTIVE: Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term. STUDY DESIGN: We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes. RESULTS: Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination-only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination-only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination-only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index. CONCLUSIONS: Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant.     

Uterine rupture associated with use of misoprostol for induction of labor.

The incidence of placenta accreta has increased 10-fold in the past 50 years and now occurs with a frequency of 1 per 2,500 deliveries. Women who have had two or more cesarean deliveries with anterior or central placenta previa have nearly a 40% risk of developing placenta accreta. If the diagnosis or strong suspicion of placenta accreta is formed before delivery, the patient should be counseled about the likelihood of hysterectomy and blood transfusion. Blood products and clotting factors should be available. Cell saver technology shoudd be considered if available as well as the appropriate location and timing for delivery to allow access to adequate surgical personnel and equipment. A preoperative anesthesia assessment should be obtained.     

Oral misoprostol versus intracervical dinoprostone for induction of labor.

OBJECTIVES: To compare oral misoprostol with dinoprostone for induction of labor and their effects on the fetal heart rate patterns. METHODS: In a randomized controlled trial, 200 patients received either misoprostol 50 mug orally for every 4 h, or dinoprostone 0.5 mg intracervically for every 6 h. Cardiotocographic recordings, in 10-min windows 30, 60, and 80 min after prostaglandin administration during induction and continuously during labor, were compared between the two groups. Primary outcome for effectiveness and safety was assessed in terms of the number of vaginal deliveries within 24 h and fetal heart rate abnormalities during induction and labor respectively. RESULTS: Data from 96 patients in the misoprostol group and 95 in the dinoprostone group were analyzed. There were no significant differences in respect of the number of vaginal deliveries within 24 h (RR 1.12; 95% CI 0.88-1.42). The frequency of suspicious and pathological fetal heart rate patterns did not differ significantly but significantly more cardiotocographs in the dinoprostone group had non-reassuring baseline variability 60 min after dose administration (RR 0.33; 95% CI 0.14-0.77). Maternal and neonatal outcomes did not differ significantly. CONCLUSION: Oral misoprostol is as effective as intracervical dinoprostone for induction of labor with no difference in the frequency of fetal heart rate abnormalities.     

Mifepristone and misoprostol in the induction of labor at term.

OBJECTIVE: To assess the ability of mifepristone to prime the cervix adequately and induce labor in pregnant women at term; and when mifepristone alone proves insufficient, to determine whether oral misoprostol taken 48 h following mifepristone administration is effective in inducing labor. METHODS: In this prospective study 50 pregnant women at term with an unfavorable cervix were given 400 mg of mifepristone orally and allowed to return home. If labor did not start within 48 h, the women were admitted and induction was continued with 50 mug of misoprostol, a prostaglandin (PG) E1 analogue, taken orally every 4 h. The 50 controls, who were matched prospectively for parity and pregnancy duration, underwent labor induction according to the routine administration of 3-mg tablets of PGE2 vaginally. RESULTS: In the study group, 66% of the women entered labor spontaneously or had a sufficiently ripened cervix within 48 h of taking mifepristone. However, there was no difference in time between prostaglandin administration and delivery between the control group and the 34% of women who required misoprostol in the study group. In the study group, the cesarean section rate was significantly lower among the women whose labor was induced with mifepristone alone than among those who required misoprostol. There were no differences overall in obstetric or neonatal outcomes between the study and control groups. CONCLUSIONS: In this pilot sample, 400 mg of mifepristone was effective in inducing cervical changes and labor. Although there were no adverse effects using oral misoprostol in combination with mifepristone, labor was more difficult to induce in the women who did not respond to mifepristone alone, and these women had a higher operative delivery rate.