Resveratrol For Preventing Ovarian Hyperstimulation Syndrome In Women At Risk Undergoing Egg Donation: A Randomized Controlled Study.

Ovarian Hyperstimulation Syndrome (OHSS) is the most serious and potentially life-threatening iatrogenic complication associated with ovarian stimulation protocols, being partially mediated by vascular endothelial growth factor A (VEGF). Previously, our group has reported that resveratrol, a natural polyphenol with anti-proliferative and anti-oxidant properties, exerts anti-angiogenic actions mediated by decreased VEGF in rat granulosa cells in vitro. The present study evaluated the role of resveratrol as a potential preventive strategy of OHSS in egg donors at high risk undergoing ovarian stimulation protocols. A randomized controlled study. Fifty-six egg donors at risk to develop OHSS (21 follicles greater than 12 mm and/or estradiol levels ≥ 3000 pg/ml on the day of oocyte maturation trigger) undergoing ovarian stimulation were included. The study group (n=29) received a daily dose of 2 g of resveratrol orally for nine days from the day of GnRH administration as the trigger of oocyte maturation, whereas the control group (n=27) received a daily dose of 2 g of placebo. All participants were monitored every three days with vaginal ultrasound scans and blood tests, evaluating the amount of ascitic fluid, VEGF levels, estradiol concentration and hemoconcentration. The reduction of VEGF concentration was the primary outcome. Baseline characteristics were comparable between both groups. Resveratrol treatment did not significantly reduce VEGF concentration compared to placebo at any time point (281.72 ± 133.57 vs 224.73 ± 107.28 on Day 9, P=0.08). Similarly, resveratrol did not affect either estradiol concentration (56.41 ± 29.99 vs 53.16 ± 28.44, P>0.05), hemoconcentration (40.03 ± 2.92 vs 40.48 ±2.57, P>0.05) or the amount of ascitic fluid (11.29 ± 7.3 vs 8.61 ± 6.07, P>0.05) in the pouch of Douglas. Prophylactic treatment with resveratrol did not reduce either the incidence of OHSS or the VEGF concentration in egg donors at high risk undergoing ovarian stimulation protocols. Higher doses and/or longer exposure periods may be needed to elucidate whether resveratrol can reduce the risk of OHSS as suggested by in in vitro studies.