Comparison of self‐administered vaginal misoprostol versus placebo for cervical ripening prior to operative hysteroscopy using a sequential trial design*

Abstract

Objective To compare the impact of 1000 micrograms of self-administered vaginal misoprostol versus self-administered vaginal placebo at home on preoperative cervical ripening in both premenopausal and postmenopausal women before operative hysteroscopy.Design Two separate but identical parallel, randomised, double-blind, placebo-controlled sequential trials, one in premenopausal women and one in postmenopausal women. The boundaries for the sequential trials were calculated on the primary outcomes of a difference of cervical dilatation ‡1 mm, with the assumption of a type 1 error of 0.05 and a power of 0.95.Setting Norwegian university teaching hospital.Sample Eighty-six women referred to outpatient operative hysteroscopy.Methods The women were randomised to either 1000 micrograms of self-administered vaginal misoprostol or self-administered vaginal placebo the evening before outpatient operative hysteroscopy.Main outcome measures Preoperative cervical dilatation (primary outcome), number of women who achieve a preoperative cervical dilatation ‡5 mm, acceptability, complications and adverse effects (secondary outcomes).Results In premenopausal women, the mean cervical dilatation was 6.4 mm (SD 2.4) in the misoprostol group and 4.8 mm (SD 2.0) in the placebo group, the mean difference in cervical dilatation being 1.6 mm (95% CI 0.5-2.7). Among the premenopausal women receiving misoprostol, 88% achieved a cervical dilatation of ‡5 mm compared with 65% in the placebo group. Twelve percent of the women who received misoprostol were difficult to dilate compared with 32% who received placebo. Dilatation was also quicker in the misoprostol group. Misoprostol had no effect on cervical ripening in postmenopausal women compared with placebo, and 43% of the women were difficult to dilate. The trials were terminated after analysis of 21 postmenopausal women and 65 premenopausal women after reaching a conclusion on the primary outcome with only 28% of the number of women needed in a fixed sample size trial. Three of 45 women who received misoprostol experienced severe lower abdominal pain, and there was an increased occurrence of light preoperative bleeding in the misoprostol group. Most women did not experience misoprostol-related adverse effects. The majority (83% of premenopausal and 76% of postmenopausal women) found self-administered vaginal misoprostol at home to be acceptable. There were two serious complications in the premenopausal misoprostol group: uterine perforation with subsequent peritonitis and heavy postoperative bleeding requiring blood transfusion, but these were not judged to be misoprostol related. Complications were otherwise comparatively minor and distributed equally between the two dosage groups.Conclusions One thousand micrograms of self-administered vaginal misoprostol 12 hours prior to operative hysteroscopy has a significant cervical ripening effect compared with placebo in premenopausal but not in postmenopausal women. Self-administered vaginal misoprostol of 1000 micrograms at home the evening be...

Clinical use of misoprostol for cervical ripening before transcervical procedures in non pregnant women: a randomized comparison of vaginal and sublingual administrations

“…Compared to other studies which compared (studied) oral and vaginal misoprostol with placebo our study compared the sublingual and vaginal routes in both pre and post menopausal women. 5,6 400 mcg of misoprostol has been studied widely for oral, vaginal and sublingual routes with good results. In the above studies the time interval varied from 4-24 hours for oral and vaginal routes.…”

“…In the above studies the time interval varied from 4-24 hours for oral and vaginal routes. 3,5,6 Lee et al used relatively shorter time interval of 6-8 hours. 12 The sublingual misoprostol was administered with an interval of 2-4 hours.…”

“…In a RCT by Oppegard et al they found that addition of estrogen with misoprostol in postmenopausal significantly increases the cervical diameter prior to the procedure. 6 Endogenous estrogen may be essential for the cervical priming induced by prostaglandin and therefore women in a hypoestrogenic state would show little response to prostaglandins and premenopausal women respond better than postmenopusal women. Similarly pregnant women with placental sulphatase deficiency do not show ripening of their cervices due to low circulating estrogen.…”

“…3,5 Sublingual route was a better alternative for pregnancy termination however in non pregnant premenopausal women it was found that all three routes were comparable. 6 Various studies in premenopausal women have shown misoprostol is a cheap alternative to laminaria tent whereas in post menopausal women it failed to show the similar benefit. 7 As far as the route is concerned both oral and vaginal has similar efficacy rate.…”

Intracervical versus vaginal misoprostol for cervical dilatation prior to operative hysteroscopy—a comparative study

“…A number of placebo-controlled studies have attested to the efficacy of misoprostol for this purpose. [1][2][3][4][5][6][7][8][9] We found that even though pre-operative cervical dilatation with vaginal misoprostol to 5 mm or 6 mm is usual, difficulty in achieving full dilatation up to 9-10 mm is frequently encountered. The vulsellum/tenaculum often slips when force is used to negotiate the bigger dilators, leading to cervical lacerations.…”