Background Hysteroscopy done in an outpatient setting is the 'gold standard' method for evaluating the uterine cavity. Media used to distend the uterine cavity include gas as carbon dioxide and liquid as saline that can be used at room temperature or warmed to body temperature. Both media offer advantages as well as disadvantages. Objectives The objective of this review is to compare the effectiveness, tolerability, and safety of gas (carbon dioxide) and liquid (normal saline)used for uterine distension during outpatient hysteroscopy. Search methods We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register, CENTRAL, MEDLINE, Em base and PsycINFO on 28 April 2021. We checked references of relevant trials and contacted study authors and experts in the field to identify additional studies. CINAHL records and ongoing trials from the trial registries were included in the CENTRAL search. Selection criteria We included randomised controlled trials (RCTs) comparing saline with carbon dioxide, as well as RCTs comparing saline at different temperatures, for uterine distension in outpatient hysteroscopy done for any indication. Data collection and analysis We used standard methodological procedures recommended by Cochrane. Primary review outcomes were patient tolerability and adverse events or complications related to the distending medium. Secondary outcomes were quality of the hysteroscopic view and duration of the procedure. Main results We included 12 RCTs (1946 women). The quality of evidence ranged from very low to high: the main limitations were risk of bias due to absence of blinding due to the nature of the procedure, imprecision, and inconsistency. Saline versus carbon dioxide Analysis ruled out a clinically relevant difference in pain scores during the procedure between saline and carbon dioxide, but the quality of evidence was low (standardised mean difference (SMD) -0.07, 95% confidence interval (CI) -0.17 to 0,02; 9 RCTs, N = 1705;12=86%). This translates to differences of 0.39 cm (lower) and 0.05 cm (higher) on a 10 -cm visual analogue scale (VAS). Evidence was insufficient to show differences between groups in the proportion of procedures abandoned due to intense pain (Peto odds ratio (OR) 0.48, 950/0 CI 0.09 to 2A2; 1 RCT, N = 189; very low-quality evidence). We are uncertain whether saline decreases the need for analgesia compared to carbon dioxide (Peto OR 0.34, 95% CI 0.12 to 0.99; 1 RCT, N = 189; very low -quality evidence). Saline compared to carbon dioxide is probably associated with fewer vasovagal reaction events (Peto OR 0.53, 95% CI 0.32 to 0.86; 6 RCTs, N =1076; 12= 0%; moderate -quality evidence) and fewer shoulder-tip pain events (Peto OR 0.28, 95% CI 0.14 to 0.54; 4 RCTs, N = 623; 12 = 0%, moderate -quality evidence). Evidence suggests that if 10% of women undergoing outpatient hysteroscopy experience a vasovagal reaction event with the use of carbon dioxide, this rate would be between 3% and 9% with the use of saline. Similarly, if the rate of shoulder-tip pain with carbon dioxide is 9%, it would be between 1% and 5% with saline. We are uncertain whether saline is similar to carbon dioxide in terms of endometria I bleeding (Peto OR 0.83, 95% CI 0.25 to 2.75; 2 RCTs, N = 349;12= 0%; very low -quality evidence). Infection was not reported by any study in this comparison. Saline may result in fewer procedures with an unsatisfactory hysteroscopic view than carbon dioxide (Peto OR 0.51, 95% CI 0.32 to 0.82; 5 RCTs, N = 1082;12 = 67%; low-quality evidence). The duration of the procedure was shorter with saline in three of the four studies that reported this outcome, and duration was similar in both arms in the fourth study. Warm saline versus room temperature saline Use of warm saline for uterine distension during office hysteroscopy may reduce pain scores when compared with room temperature saline (mean difference (MD) -1.14, 95% CI -1.55 to -0.73; 3 RCTs, N = 241; 12 = 77%; low -quality evidence). Evidence is insufficient to show differences between groups in either the proportion of proceduresabandoned dueto intense pain (Peto OR 0.97, 95% CI 0.06 to 15.87;1 RCT, N = 77; very low -quality evidence) or the need for analgesia (Peto OR 1.00, 95% CI 0.14 to 7.32; 1 RCT, N = 100; very low -quality evidence). Analysis ruled out a clinically relevant difference in duration of the procedure between warm and room temperature saline, but the quality of evidence is low (MD 13.17 seconds, 95% Cl -12.96 to 39.29; 2 RCTs, N = 141; 12 = 21%). No cases of infection were reported in either group (1 RCT, N = 100). No other adverse events and no information on quality of the hysteroscopic view were reported by any study in this comparison. Authors' conclusions Evidence was insufficient to show differences between different distension media used for uterine distension in outpatient hysteroscopy in terms of patient tolerability, operator satisfaction, or duration of the procedure. However, saline was superior to carbon dioxide in producing fewer adverse events (shoulder-tip pain and vasovagal reaction).
