Effectiveness of Melatonin in combination with Sildenafil in treatment of intrauterine growth restriction: a double-blind, randomized clinical trial

Background: Intrauterine Growth Restriction (IUGR) is a common obstetrical diagnosis associated with high risks of perinatal mortality and morbidity. Some studies have suggested that either sildenafil or melatonin may improve IUGR outcomes; but we found no evidence on the effects of concomitant sildenafil and melatonin therapy on IUGR fetuses. Therefore, the aim of the present study was to investigate whether simultaneous intake of melatonin and sildenafil can be more effective in alleviating IUGR outcomes. Methods: Patients with idiopathic IUGR referred to Yasuj Women s Clinic during 2019 and 2021 were enrolled in the current double-blind, randomized clinical trial. Out of 140 participants, a total of 120 pregnant women were included, 100 pregnant women with confirmed IUGR (gestational age between 26 to 32 weeks) were randomly assigned into four groups as fellows: sildenafil group (25 mg three times a day), melatonin (3 mg three times a day), sildenafil plus melatonin, and placebo. The patients received the drugs for at least 4 weeks. Doppler ultrasound was used to evaluate some outcomes on factors such as fetal weight, systolic/diastolic (S/D), PI, and RI of the umbilical, cerebral and uterine arteries. Neonatal outcomes (anthropometric characteristics of the infant, Apgar scores, meconium aspiration, and NICU admission) were also recorded. Results: S/D of the middle cerebral artery was lower in the sildenafil plus melatonin subjects than in the other groups (p 0.05). Sildenafil plus melatonin significantly increased infant weight and decreased the risks of preeclampsia and hospitalization compared to other treatments (p 0.05). Conclusion: The results confirmed that the concomitant prescription of melatonin and sildenafil increases birth weight, normalizes middle cerebral artery indices, and reduces the incidence of preeclampsia and neonatal hospitalization for IUGR. Therefore, Melatonin plus sildenafil can be a simple and economic treatment for IUGR.