Utero-placental perfusion Doppler indices in growth restricted fetuses: effect of sildenafil citrate.

OBJECTIVE: To assess efficacy and tolerability of sildenafil citrate on utero-placental blood flow and fetal growth in pregnancies complicated by fetal growth restriction (FGR). METHODS: From March 2015, a randomized controlled trial of 54 patients at 24 weeks or more complicated by FGR and abnormal Doppler indices were randomly allocated 1:1 into an intervention arm (receive sildenafil citrate, 50 mg) or a control arm (receive placebo). The primary outcomes were changes occurred in the Doppler parameters 2 h following drug administration. RESULTS: Baseline characteristics were similar between groups. Significant difference was observed in the Delta uterine and umbilical Doppler indices among sildenafil group as compared to placebo group (p < 0.001). Middle cerebral Doppler indices, however, decreased significantly after sildenafil, which could be the result of shifting more blood to improve the utero-placental perfusion. No difference regarding Delta cerebro-placental ratio among both groups (p = 0.979). Sildenafil was also associated with pregnancy prolongation (p = .0001), increased gestational age at delivery (p = .004), improved neonatal weight (p = .0001), and less admission to neonatal intensive care unit (p = .03). No adverse effects reported in both treatment arms. CONCLUSION: Sildenafil citrate, by its vasodilator effect, can improve utero-placental blood flow in pregnancies complicated by FGR and abnormal Doppler. CLINICAL TRIAL: gov Registry: NCT02362399.

Different analgesics prior to intrauterine device insertion: is there any evidence of efficacy?

OBJECTIVES: The aims of this study were to compare three different interventions to reduce pain related to insertion of the intrauterine device (IUD), namely, lidocaine, misoprostol and a non-steroidal anti-inflammatory drug, against a placebo, and to assess the advantages of one drug over another, if any. METHODS: This was an open-label randomised placebo-controlled trial of 200 women assigned to receive one of the following medications prior to IUD insertion: 10 ml 1% lidocaine paracervical block, 400 µg oral misoprostol, oral naproxen or placebo tablets. The primary outcome measure was the level of pain experienced at different steps of IUD insertion and 15 min after the procedure, measured by a visual analogue scale (VAS). RESULTS: Between July 2015 and March 2016, 208 women were invited to participate in the study: eight refused and the remaining 200 women were randomised equally into four treatment groups (50 participants in each group). All characteristics were similar between the groups. The mean pain scores recorded during speculum placement, tenaculum application, uterine sounding, IUD insertion and 15 min after insertion were similar among the four groups (p > .05). Adjuvant methods to facilitate insertion, insertion failure or device expulsion were similar between the groups (p > .05). Complications were reported in 17 participants (8.5%); all resolved spontaneously with no further management (p > .05). CONCLUSION: Despite finding that none of the study drugs seemed effective prior to IUD insertion, insertion did not cause severe pain. The negative findings indicate the need for future research into new strategies to decrease pain during IUD placement.

Sildenafil Citrate Therapy for Oligohydramnios: A Randomized Controlled Trial.

OBJECTIVE: To compare sildenafil plus hydration with hydration alone in improving the amniotic fluid index and neonatal outcomes in pregnancies complicated by idiopathic oligohydramnios ( amniotic fluid index less than 5 cm without underlying maternal or fetal causes and with normal fetal growth). METHODS: This was an open-label randomized trial for women carrying singleton pregnancies at 30 weeks of gestation or more with idiopathic oligohydramnios detected during routine ultrasonogram. Women received either oral sildenafil citrate (25 mg every 8 hours) plus intravenous infusion of 2 L isotonic solution or fluids only until delivery. The primary study outcome was the amniotic fluid volume at 6 weeks of follow-up or the final volume before delivery, whichever occurred first. Secondary outcomes were duration of pregnancy prolongation, mode of delivery, and select neonatal outcomes. The study was powered to detect a 45% difference between groups, so, at an α level of 0.05 and 80% power, a sample size of 167 women was required. RESULTS: From February 24, 2015, through April 2016, 196 women were screened and 184 were randomized. Follow-up was completed in 166 (90%): 82 in the sildenafil group and 84 in the hydration group. Baseline characteristics were similar between groups. The amniotic fluid volume was higher in the sildenafil group at the final assessment (11.5 compared with 5.4 cm, P=.02). The sildenafil group delivered later (38.3 compared with 36.0 weeks of gestation, P=.001), had a lower rate of cesarean delivery (28% compared with 73%), and their neonates were less likely to be admitted to the neonatal intensive care unit (11% compared with 41%, P=.001). CONCLUSION: Sildenafil citrate increases amniotic fluid volume in pregnancies complicated by oligohydramnios. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT02372487.

Different routes and forms of uterotonics for treatment of retained placenta: a randomized clinical trial.

OBJECTIVES: To compare between three different uterotonics (oxytocin, carbetocin and misoprostol) given via three different routes (intraumbilical, intravenous and sublingual, respectively) in reducing the need for manual removal of placenta (MROP). METHODS: A randomized trial for cases with retained placenta 30 min following vaginal delivery. They received intraumbilical oxytocin, intravenous carbetocin or sublingual misoprostol. Main outcome measures were delivery of the placenta within 30 min following drug administration, and need for MROP. Secondary outcome measures were injection to placental delivery time, post-delivery hemoglobin, need for blood transfusion or additional uterotonics. RESULTS: The overall success rate was 66.7% (64/96), 71.3% (67/94) and 63.7% (58/91) for oxytocin, carbetocin and misoprostol groups, respectively (p > 0.05). When time needed to achieve placental delivery considered, a significant difference was observed with the shortest time for carbetocin (16.61 ± 3.76 min), then oxytocin (18.28 ± 3.34 min) and lastly misoprostol (23.00 ± 3.38 min) (p <0.001). Again, carbetocin group needed less additional uterotonics to achieve adequate uterine contractions (p <0.001). CONCLUSIONS: Although we aimed to exploit the advantage of certain drug over another, all seemed to have close efficacy but it would be important that further research should highlight availability, cost, ease of administration and storage requirements to determine which agent would best be used in this clinical scenario.

Comparison between two management protocols for postpartum hemorrhage during cesarean section in placenta previa: Balloon protocol versus non-balloon protocol.

AIM: This study was conducted to compare two management protocols for post-partum hemorrhage (PPH) during cesarean section (CS) in placenta previa (PP), Bakri balloon protocol versus non-balloon protocol. Secondary analysis among balloon treated cases was also performed to identify predictors of success, failure or complications, if any. METHODS: A prospective cohort study was conducted in two hospitals in Saudi Arabia, including cases that developed PPH during CS for PP. The primary outcome measure was success in preventing hysterectomy, while secondary outcome measures were amount of blood loss, need for blood transfusion, need for return to theater and admission to intensive care unit. RESULTS: One hundred and fifty-one cases were identified as low-lying placenta and PP, of which 114 developed PPH. Two patients were unstable and required immediate hysterectomy. The remaining 112 cases were managed by balloon (72 cases) or non-balloon protocols (40). The balloon alone was successful in achieving hemostasis in 87.5% of cases. When analyzed specifically, balloon success was associated with the absence of accreta (odds ratio 0.001, confidence interval 0.000-0.974) and short operation duration (odds ratio 1.143, confidence interval 1.018-1.282). CONCLUSION: Application of the Bakri balloon for the management of PPH after CS in cases of PP is an effective strategy that should be affordable worldwide.

Prevention of preterm birth: a randomized trial of vaginal compared with intramuscular progesterone.

OBJECTIVE: To assess efficacy and tolerability of vaginal compared with intramuscular progesterone in reducing the rate of recurrent preterm birth before 34 weeks of gestation. DESIGN: Prospective randomized study. SETTING: Obstetrics and Gynecology Department, Armed Forces Hospital Southern Region, Kingdom of Saudi Arabia. SAMPLE: Five-hundred and eighteen women with a prior history of preterm birth. METHODS: Women were randomized to receive either 90 mg of vaginal progesterone gel once daily or 250 mg of intramuscular progesterone weekly. Treatment began between 14 and 18 weeks of gestation and continued until 36 complete weeks of gestation, delivery or the occurrence of premature rupture of membranes. MAIN OUTCOME MEASURES: The primary outcome measure was delivery before 34 weeks of gestation. The secondary outcome measures were PTB between 34 and 37 weeks of gestation and neonatal outcomes including birthweight, neonatal death, and the need for admission to the neonatal intensive care unit. RESULTS: The baseline characteristics of the study participants were similar. Two-hundred and thirty-eight (94.1%) patients in the vaginal group and 226 (90.8%) patients in the intramuscular group were compliant with their medications. Vaginal progesterone was associated with a lower percentage of deliveries before 34 weeks of gestation than the intramuscular preparation (p= 0.02). This association was also observed at 28 and 32 weeks of gestation (p= 0.04). Adverse effects were reported in 14.1% of patients in the intramuscular group, but in only 7.5% of patients in the vaginal group (p= 0.017). CONCLUSIONS: Vaginal progesterone was more effective than intramuscular progesterone for the prevention of preterm birth and had fewer adverse effects.