Abstract: Nineteen RCTs with a total of 1870 participants were included. They compared misoprostol with no treatment or placebo, dinoprostone or osmotic dilators. Misoprostol was more effective for cervical dilatation than placebo or no intervention, with fewer women requiring mechanical dilatation (OR 0.08, 95% CI 0.04 to 0.16, five RCTs, 441 participants, I2=0%, moderate quality evidence). This suggests that in a population in which 80% of women undergoing hysteroscopy require mechanical dilatation without use of preoperative ripening agents, use of misoprostol will reduce the need for mechanical dilatation to between 14% and 39%. Misoprostol was associated with fewer intraoperative complications (OR 0.37, 95% CI 0.18 to 0.77, 12 RCTs, 901 participants, I2=0%, moderate quality evidence). This suggests that in a population in which 3% of women undergoing hysteroscopy experience intraoperative complications without use of preoperative ripening agents, use of misoprostol will reduce the risk of complications to 2% or less. When specific complications were considered, the misoprostol group had a lower rate of cervical laceration or tearing (OR 0.25, 95% CI 0.11 to 0.57, nine RCTS, 669 women, I2=0%, moderate quality evidence) or false track formation (OR 0.34, 95% CI 0.12 to 0.97, seven RCTs, 560 participants, I2=0%, moderate quality evidence). There was no evidence of a difference between the groups in rates of uterine perforation (0.42, 95% CI 0.13 to 1.38, seven RCTs, 455 participants, I2=0%, low quality evidence) or uterine bleeding (OR 0.51, 95% CI 0.10 to 2.49, four RCTs, 340 participants, I2=0%, low quality evidence). Some treatment side effects (mild abdominal pain, vaginal bleeding, and increased body temperature) were more common in the misoprostol group. Compared with dinoprostone, misoprostol was associated with more effective cervical dilatation, with fewer women requiring mechanical dilatation (OR 0.58; 95% CI 0.34 to 0.98; one RCT, 310 participants, low quality evidence) and with fewer intraoperative complications (OR 0.32; 95% CI 0.12 to 0.83, one RCT, 310 participants, low quality evidence). However treatment side effects were more common in the misoprostol arm. Compared to osmotic dilatation (laminaria), misoprostol was associated with less effective cervical dilatation, with more women in the misoprostol group requiring mechanical dilatation (OR 5.96, 95% CI 2.61 to 13.59, one RCT, 110 participants, low quality evidence). There was no evidence of a difference between misoprostol and osmotic dilators in intraoperative complication rates (OR 5.14, 95% CI 0.24 to 109.01, three RCTs, 354 participants, low quality evidence), with only two events reported altogether. The overall quality of the evidence ranged from low to moderate. The main limitations in the evidence were imprecision and poor reporting of study methods. There is moderate quality evidence that use of misoprostol for preoperative ripening of the cervix before operative hysteroscopy is more effective than placebo or no treatment and is associated with fewer intraoperative complications such as lacerations and false tracks. However misoprostol is associated with more side effects, including preoperative pain and vaginal bleeding. There is low quality evidence to suggest that misoprostol has fewer intraoperative complications and is more effective than dinoprostone. There is also low quality evidence to suggest that laminaria may be more effective than misoprostol, with uncertain effects for complication rates. However the possible benefits of laminaria need to be weighed against the inconvenience of its insertion and retention for one to two days.

Plain-language summary: We included 19 randomised controlled trials (1870 participants) of premenopausal and postmenopausal women undergoing hysteroscopic surgery for a variety of conditions. They compared misoprostol with placebo or no treatment, dinoprostone, and osmotic agents. Key results There is moderate quality evidence that misoprostol is safer and is more effective for cervical ripening than placebo or no treatment, and that is associated with fewer complications occurring during the operation, with lower rates of lacerations and false tracks. However misoprostol is associated with more side effects such as preoperative pain and vaginal bleeding. There is low quality evidence that misoprostol may be safer and more effective than dinoprostone, and that it may be associated with fewer complications occurring during the operation. There is also low quality evidence that laminaria may be more effective than misoprostol. However, the possible benefits of laminaria need to be weighed against the inconvenience of its insertion and retention for one to two days. Quality of the evidence The quality of the evidence ranged from low to moderate. The main limitations in the evidence were imprecision and poor reporting of study methods. The evidence is current to August 2014.