Melatonin supplementation during controlled ovarian stimulation for women undergoing assisted reproductive technology: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To examine the best evidence available regarding the effect of melatonin supplementation during controlled ovarian stimulation (COS) on the main assisted reproductive technology (ART) outcomes. DESIGN: Systematic review and meta-analysis of randomized clinical trials (RCT). SETTING: Not applicable. PATIENT(S): Women undergoing COS for ART. INTERVENTION(S): Melatonin supplementation during COS for women undergoing ART. MAIN OUTCOME MEASURE(S): Live birth rate, clinical pregnancy rate, number of retrieved oocytes, miscarriage rate, ovarian hyperstimulation syndrome (OHSS) rate, and number of congenital abnormalities. Comparisons were performed using risk ratio (RR) or mean difference (MD). RESULT(S): Five RCTs were considered eligible, and their data were extracted and included in a meta-analysis. No studies reported live-birth or congenital abnormalities. Our estimates were imprecise for distinguishing between no effect and benefit considering clinical pregnancy (RR, 1.21; 95% confidence interval [CI], 0.98-1.50, five studies, 680 women, low quality-evidence) and the number of oocytes retrieved (MD, 0.6; 95% CI, -0.2-2.2, five studies, 680 women, low quality-evidence). Our estimates were imprecise for distinguishing among harm, no effect, and benefit considering miscarriage (RR, 1.07; 95% CI, 0.43-2.68, two studies, 143 clinical pregnancies, low quality-evidence) and interventions to reduce the risk of OHSS (RR,1.01; 95% CI, 0.33-3.08, one study, 358 women, low quality-evidence). CONCLUSION(S): More studies investigating the role of melatonin supplementation are still needed before recommending its use in clinical practice.

Cabergoline for the prevention of ovarian hyperstimulation syndrome: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of using cabergoline for reducing the risk of ovarian hyperstimulation syndrome (OHSS). DESIGN: Systematic review and meta-analysis of randomized clinical trials (RCTs). PATIENTS: Women submitted to controlled ovarian stimulation (COS) for assisted reproduction. INTERVENTIONS: Cabergoline. SETTING: Fertility centers. MAIN OUTCOME MEASURES: Moderate-severe OHSS, live birth, clinical pregnancy, number of retrieved oocytes, miscarriage, congenital abnormalities. Comparisons were performed with the use of risk ratios (RRs) or mean differences (MDs) and their respective 95% confidence intervals (CIs). RESULT(S): Eight RCTs were considered to be eligible; data from seven studies could be extracted and included in the meta-analysis. Cabergoline reduces the risk of moderate-severe OHSS (RR 0.38, 95% CI 0.29-0.51, 7 studies, 858 women) and probably has no clinically relevant negative impact on clinical pregnancy (RR 1.02, 95% CI 0.78-1.34, 4 studies, 561 women) or on the number of retrieved oocytes (MD 1.15, 95% CI -0.76 to 3.07, 5 studies, 628 women). However, our estimates were imprecise for distinguishing between substantial harm, no effect, and substantial benefit considering live birth (RR 1.03, 95% CI 0.71-1.48, 1 study, 200 women), and miscarriage (RR 0.69, 95% CI 0.27 to 1.76, 3 studies, 194 pregnant women). No studies reported congenital abnormalities. CONCLUSION(S): Cabergoline reduces the occurrence of moderate-severe OHSS. Cabergoline is unlikely to have a clinically relevant negative impact on clinical pregnancy or on the number of retrieved oocytes. However, we are still uncertain of its impact on live birth, miscarriage, and congenital abnormalities.