Cabergoline for preventing ovarian hyperstimulation syndrome

Background Ovarian hyperstimulation syndrome (OHSS) is a complication resulting from administration of human chorionic gonadotrophin (hCG) in assisted reproduction technology (ART) treatment. Most case are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Recently, the dopamine agonist cabergoline has been introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS who are undergoing ART treatment. Objectives To assess the effectiveness and safety of cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing ART treatment. Search methods Majormedical databases (CochraneMenstrualDisorders and SubfertilityGroup SpecialisedRegister of trials,CENTRAL (TheCochrane Library), MEDLINE, EMBASE and PsycINFO) were systematically searched for randomised controlled trials (RCTs) assessing the effect of cabergoline in preventing OHSS. Databases were searched up to September 2011. Registers of clinical trials, abstracts of scientific meetings and reference lists of included studies were searched. No language restrictions were applied. Selection criteria RCTs which compared cabergoline with placebo, no treatment or another intervention for preventing OHSS in high-risk women were considered for inclusion. Primary outcome measures included incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment. Data collection and analysis Two authors independently screened titles, abstracts and the full text of publications; extracted data; and assessed risk of bias. Any disagreements were resolved by consensus. Pooled results were reported as odds ratio (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. Main results Only two trials involving 230 women met the inclusion criteria. Both studies had a moderate risk of bias. Oral cabergoline, 0.5 mg daily, was given as an intervention and compared with a matched placebo. A statistically significant reduction in OHSS was observed in the cabergoline treated group (OR 0.40, 95% CI 0.20 to 0.77; 2 RCTs, 230 women) with a number needed to treat (NTT) of 7. There was a statistically significant difference in the incidence of moderate OHSS, favouring cabergoline (OR 0.38, 95% CI 0.19 to 0.78; 2 RCTs, 230 women) but not in severe OHSS (OR 0.77, 95% CI 0.24 to 2.45; 2 RCTs, 230 women). There was no significant difference in the clinical pregnancy rate (OR 0.94, 95% CI 0.56 to 1.59; 2 RCTs, 230 women), miscarriage rate (OR 0.31, 95% CI 0.03 to 3.07; 1 RCT, 163 women) or any other adverse effects of the treatment (OR 2.07, 95% CI 0.56 to 7.70; 1 RCT, 67 women). However, no data on multiple pregnancy rate or live birth rate were reported in either trial. Authors' conclusions Cabergoline appears to reduce the risk of OHSS in high-risk women, especially for moderate OHSS. The use of cabergoline does not affect the pregnancy outcome (clinical pregnancy rate, miscarriage rate), nor is there an increased risk of adverse events. Further research should consider the risk of administering cabergoline and the comparison between cabergoline and established treatments (such as intravenous albumin and coasting). Large, well-designed and well-executed RCTs that involve more clinical endpoints are necessary to further evaluate the role of cabergoline in OHSS prevention.