Dopamine agonists for preventing ovarian hyperstimulation syndrome

Background Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shiI from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. Objectives To assess the eKectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. Search methods We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the eKect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. Selection criteria We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. Data collection and analysis Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. Main results The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. Thedopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the eKect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the eKect of dopamine agonists onclinical pregnancy, multiple pregnancy,miscarriageor adverse events(very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention(OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates ofmultiple pregnancy or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSScompared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; IP = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the eKect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; lowquality evidence). We are uncertain of the eKect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. Authors' conclusions Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the eKect onadverse events andpregnancy outcomes (live birth, clinical pregnancy,miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists aKect pregnancy outcomes. When compared to other active interventions, we are uncertain of the eKects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

Automated summary

Dopamine agonists are likely effective in reducing the risk of moderate or severe OHSS, while the effects on adverse events and pregnancy outcomes remain uncertain. Co-interventions with dopamine agonists may decrease the rates of OHSS, but the impact on pregnancy outcomes is unclear. When compared to other interventions, the effects of dopamine agonists on OHSS and pregnancy outcomes are uncertain.