Calcium versus cabergoline for prevention of ovarian hyperstimulation syndrome: A systematic review and meta-analysis

Aim: To conduct the first-ever systematic review and meta-analysis evaluating calcium infusion versus cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) among high-risk women undergoing assisted reproductive technology. Methods: Six databases were screened from inception until April 1, 2024. The included randomized and nonrandomized controlled studies were assessed for quality. The endpoints included the severity of OHSS and selected pregnancy-related outcomes. Endpoints were summarized as risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. Results: Six studies were analyzed, including 1687 patients (828 in the calcium group and 859 in the cabergoline group). The quality of the studies varied and reflected low risk and high risk of bias in two and four studies, respectively, according to the revised Cochrane risk of bias tool. No significant differences were noted between both groups regarding the rates of overall (n n = 5, RR = 0.65,95% CI [0.39, 1.07], p = 0.09), mild (n n = 4, RR = 1.05,95% CI [0.59, 1.89], p = 0.86), moderate (n n = 5, RR = 0.41,95% CI [0.15, 1.08], p = 0.07), and severe (n n = 6, RR = 0.36, 95 % CI [0.11, 1.22], p = 0.1) cases of OHSS. Leave-one-out sensitivity analysis of an outlier study revealed that calcium significantly reduced the occurrence of severe OHSS compared with cabergoline (n n = 5, RR = 0.16, 95 % CI [0.09, 0.43], p < 0.001, Higgins I-2 = 0 %). No significant differences were observed between both groups regarding the rates of clinical pregnancy (n n = 4, RR = 0.97, 95 % CI [0.88, 1.07], p = 0.57), ongoing pregnancy, live birth, and spontaneous abortion (Higgins I-2 < 50 % for all). Conclusion: Both agents yielded similar pregnancy-related outcomes. However, calcium infusion could potentially be more effective than cabergoline in reducing the rate of severe OHSS. Additional high-quality and well- controlled trials are essential to draw firm conclusions.