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

Oppegaard KS, Nesheim BI, Istre O, Qvigstad E - BJOG (2008)

Bottom Line: Twelve percent of the women who received misoprostol were difficult to dilate compared with 32% who received placebo.Misoprostol had no effect on cervical ripening in postmenopausal women compared with placebo, and 43% of the women were difficult to dilate.Most women did not experience misoprostol-related adverse effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecology, Helse Finnmark, Klinikk Hammerfest, Hammerfest, Norway. kevin.s.oppegaard@helse-finnmark.no

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 > or = 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 > or = 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 > or = 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 before operative hysteroscopy is safe and highly acceptable, although a small proportion of women experienced severe lower abdominal pain. There is a risk of lower abdominal pain and light preoperative bleeding with this regimen, which is very cheap and easy to use.

Show MeSH

Related in: MedlinePlus

Flow diagram.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2345467&req=5

fig01: Flow diagram.

Mentions: The study was carried out from 4 September 2006 until 27 April 2007 (Figure 1). Doctors examining women at the outpatient consultation (trainees and specialists) were responsible for recruiting the women. During the 8 months the study was carried out, 82% of the total number of premenopausal women and 79% of the total number of postmenopausal women referred to operative hysteroscopy participated in the study. The rest declined the offer (11% of the premenopausal and 10% of the postmenopausal women) or were excluded based on the exclusion criteria (7% of the premenopausal and postmenopausal women). Two separate, but identical, studies were conducted in parallel, based on the women's menopausal status. Each participant received either 1000 micrograms of misoprostol or placebo, which they self-inserted vaginally at least 12 hours before operative hysteroscopy. The randomisation was performed with permuted blocks, using the randomisation plan generator, as described by Dallal.30 The randomisation procedure was third party concealed randomisation, performed by the hospital pharmacist. Placebo misoprostol tablets are difficult to make; therefore, gelatine capsules with an identical appearance were manufactured by the hospital pharmacist. The active misoprostol was ground up as a whitish powder inserted into gelatine capsules (500 microgram misoprostol per capsule), as was an inactive ingredient, lactosum monohydricum—which has an identical appearance to ground misoprostol tablets—and subsequently inserted into gelatine capsules as placebo. The hospital pharmacist prepared numbered, opaque, sealed plastic containers labelled ‘Misoprostol 0.5 mg/Placebo, 2 vaginal capsules’. The prepared capsules were inserted into containers by the hospital pharmacist, which were sealed with tamper-proof seals. Each container contained two capsules. Half of the containers contained two capsules with 500 microgram misoprostol each, while the other half contained two placebo capsules. The containers were then delivered to the outpatient clinic. As the women were recruited, the doctor at the outpatient consultation recorded the preoperative variables on a standardised case report form (on page 1), and the women were given a plastic container containing the capsules before leaving the hospital. Hence, those involved in administering the intervention and the women were blinded to the treatment received. Each study participant opened a numbered container at home, containing either misoprostol or lactosum monohydricum in capsules. The women were instructed to insert the capsules as deep as possible vaginally after voiding urine at approximately 9 p.m. the evening before the operation.


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

Oppegaard KS, Nesheim BI, Istre O, Qvigstad E - BJOG (2008)

Flow diagram.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2345467&req=5

fig01: Flow diagram.
Mentions: The study was carried out from 4 September 2006 until 27 April 2007 (Figure 1). Doctors examining women at the outpatient consultation (trainees and specialists) were responsible for recruiting the women. During the 8 months the study was carried out, 82% of the total number of premenopausal women and 79% of the total number of postmenopausal women referred to operative hysteroscopy participated in the study. The rest declined the offer (11% of the premenopausal and 10% of the postmenopausal women) or were excluded based on the exclusion criteria (7% of the premenopausal and postmenopausal women). Two separate, but identical, studies were conducted in parallel, based on the women's menopausal status. Each participant received either 1000 micrograms of misoprostol or placebo, which they self-inserted vaginally at least 12 hours before operative hysteroscopy. The randomisation was performed with permuted blocks, using the randomisation plan generator, as described by Dallal.30 The randomisation procedure was third party concealed randomisation, performed by the hospital pharmacist. Placebo misoprostol tablets are difficult to make; therefore, gelatine capsules with an identical appearance were manufactured by the hospital pharmacist. The active misoprostol was ground up as a whitish powder inserted into gelatine capsules (500 microgram misoprostol per capsule), as was an inactive ingredient, lactosum monohydricum—which has an identical appearance to ground misoprostol tablets—and subsequently inserted into gelatine capsules as placebo. The hospital pharmacist prepared numbered, opaque, sealed plastic containers labelled ‘Misoprostol 0.5 mg/Placebo, 2 vaginal capsules’. The prepared capsules were inserted into containers by the hospital pharmacist, which were sealed with tamper-proof seals. Each container contained two capsules. Half of the containers contained two capsules with 500 microgram misoprostol each, while the other half contained two placebo capsules. The containers were then delivered to the outpatient clinic. As the women were recruited, the doctor at the outpatient consultation recorded the preoperative variables on a standardised case report form (on page 1), and the women were given a plastic container containing the capsules before leaving the hospital. Hence, those involved in administering the intervention and the women were blinded to the treatment received. Each study participant opened a numbered container at home, containing either misoprostol or lactosum monohydricum in capsules. The women were instructed to insert the capsules as deep as possible vaginally after voiding urine at approximately 9 p.m. the evening before the operation.

Bottom Line: Twelve percent of the women who received misoprostol were difficult to dilate compared with 32% who received placebo.Misoprostol had no effect on cervical ripening in postmenopausal women compared with placebo, and 43% of the women were difficult to dilate.Most women did not experience misoprostol-related adverse effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecology, Helse Finnmark, Klinikk Hammerfest, Hammerfest, Norway. kevin.s.oppegaard@helse-finnmark.no

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 > or = 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 > or = 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 > or = 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 before operative hysteroscopy is safe and highly acceptable, although a small proportion of women experienced severe lower abdominal pain. There is a risk of lower abdominal pain and light preoperative bleeding with this regimen, which is very cheap and easy to use.

Show MeSH
Related in: MedlinePlus