Addition of sildenafil citrate for treatment of severe intrauterine growth restriction: a double blind randomized placebo controlled trial.

Background: Severe intrauterine growth restriction complicates approximately 0.4% of the pregnancies. It increases the risk of perinatal morbidity and mortality.Subjects and methods: A double blind placebo controlled trial was conducted in Beni Suef University hospitals during 2017. It included 46 pregnant women with severe intrauterine growth restriction. Women were randomly allocated into two groups each included 23 patients. Intervention group received sildenafil citrate 20 mg orally three times a day, in addition to fish oil and zinc supplementation. Control group received tablets similar to sildenafil and the same treatment as intervention group. Primary outcomes included improvement in umbilical and middle cerebral arteries pulsatility indices and abdominal circumference.Results: Umbilical and middle cerebral arteries Doppler indices showed significant difference between groups after intake of sildenafil. Umbilical artery pulsatility index decreased significantly (p value = .001) while middle cerebral artery pulsatility index increased significantly in intervention group (p value0.001). Moreover, abdominal circumference growth velocity improved after two weeks of sildenafil intake (p value = .001).Conclusions: Sildenafil citrate may improve uteroplacental and fetal cerebral perfusion in pregnancies complicated by severe intrauterine growth restriction. It also improves abdominal circumference growth velocity. A wide scale randomized trials are needed for evaluation of neonatal and long term morbidity and mortality outcomes of pregnancies treated by sildenafil citrate.

Vascular endothelial growth factor C/A 2578 gene polymorphism and umbilical artery Doppler in preeclamptic women.

INTRODUCTION: Preeclampsia is strongly associated with placental hypoperfusion. Genetic factors have an impact on the pathogenesis of preeclampsia. The aim is to assess the association of Vascular Endothelial Growth Factor (C2578A) gene polymorphism with the occurrence and severity of preeclampsia and the umbilical artery Doppler changes among preeclamptic women. MATERIALS AND METHODS: This case-control study was conducted in clinical and Chemical pathology and Obstetrics departments in Beni- Suef University, Egypt. Two hundred and ninety pregnant women above 20 weeks gestational age until delivery were divided into 2 main groups. The patient group included 145 preeclamptic women who were further sub grouped according to the severity of preeclampsia into 82 severe and 63 mild cases. Control group included 145 normotensive pregnant women. Our primary outcome was detection of VEGF C 2578 A gene mutations by a polymerase chain reaction. A secondary outcome was Doppler changes in the pulsatility index of the umbilical artery compared with VEGF genotypes. RESULTS: Our study showed that VEGF C 2578 A genotype and alleles frequencies were not related to the occurrence of preeclampsia (p-value 0.513 and 0.549, respectively), odds ratio (95%CI) 1.154 (0.724-1.848). Mild preeclamptic cases showed no significance comparing VEGF genotypes studied and pulsatility index of the umbilical artery. However, severe cases showed p-value < 0.0001. CONCLUSION: We concluded that VEGF 2578C/A polymorphism had no association with the occurrence of preeclampsia in studied groups, whereas there was a significant relationship among severe cases between CA and CC genotypes and pulsatility index of the umbilical artery.

Doppler and biochemical assessment for the prediction of early pregnancy outcome in patients experiencing threatened spontaneous abortion.

OBJECTIVE: To evaluate the usefulness of Doppler indices of the corpus luteum and uterine artery in combination with serum progesterone and cancer antigen 125 (CA125) as prognostic tools in first-trimester threatened spontaneous abortion. METHODS: Pregnant women with threatened spontaneous abortion at a pregnancy duration 8-10 weeks were enrolled into an observational prospective clinical trial at a university hospital in Egypt during 2015. Doppler indices (uterine artery/corpus luteum resistance index and pulsatility index) and biochemical markers (CA125, progesterone) were determined and compared by pregnancy outcome (spontaneous abortion vs continuing pregnancy at 20 weeks). RESULTS: Of 100 women included, 16 had a spontaneous abortion. These women had a higher CA125 value than did women without an abortion (P<0.001), whereas the progesterone level among women with an abortion was lower (P<0.001). The Doppler indices were not significantly different between the groups, but calculation of the uterine artery resistance index as a percentage of the normal standard value at a given pregnancy duration revealed significant differences (P<0.001) between the two groups. CONCLUSION: Serum progesterone and CA125 are useful provisional predictors of spontaneous abortion, whereas the Doppler indices are not. The two biomarkers could be used as a basis to counsel anxious couples. CLINICALTRIALS.GOV: NCT02420769.

Follicular sensitivity index (FSI): a novel tool to predict clinical pregnancy rate in IVF/ICSI cycles.

PURPOSE: This study aims to introduce a new tool (the Follicular Sensitivity Index; FSI) for objective assessment of follicular responsiveness to exogenous gonadotropins and to evaluate its ability to predict the clinical pregnancy rate in women with unexplained infertility or tubal factor undergoing IVF/ICSI. METHODS: FSI was calculated as preovulatory follicle count (PFC) × 100,000/[antral follicle count (AFC) × total received FSH doses]. One thousand women were included and were divided according to the FSI tertile values into three groups. The primary outcome was clinical pregnancy defined by the presence of an intrauterine gestational sac 5 weeks after embryo transfer. RESULTS: There was progressive increase in the clinical pregnancy rate from the low to the high FSI groups (0.27 ± 0.4 vs 0.4 ± 0.4 and 0.58 ± 0.4; p < 0.001). Receiver operator curves showed that FSI had a greater area under the curve than those of the AFC, PFC, and the FSH dose (0.638 vs 0.509, 0.538, and 0.589 respectively). Multivariate logistic regression analysis showed that the correlation between FSI and pregnancy was independent of potential confounding factors like age and body mass index (p < 0.001). CONCLUSION: FSI can predict the clinical pregnancy rate in women with unexplained infertility or tubal factor undergoing IVF/ICSI using GnRH agonist protocol. Higher FSI values had significantly higher oocyte yield and fertilization and clinical pregnancy rates. Wider implications of these findings include the potential use of FSI to define absolute criteria of poor/good ovarian response in IVF/ICSI cycles, guide future IVF cycle management for the same couples, and guide cycle cancelation criteria for poor ovarian response.

RETRACTED: Calcium versus oral contraceptive pills containing drospirenone for the treatment of mild to moderate premenstrual syndrome: a double blind randomized placebo controlled trial.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editorial Board for the following reason: This single-author publication which reports the conducting of a large 3-arm randomised controlled trial, with no missing data from 210 recruited patients, has been questioned as implausible. The authors have been unable to provide supporting documents to provide an explanation.

Carbetocin versus oxytocin in the management of atonic post partum haemorrhage (PPH) after vaginal delivery: a randomised controlled trial.

OBJECTIVE: The objective of this study is to compare the effectiveness and safety of carbetocin vs. oxytocin in the management of atonic post partum haemorrhage (PPH) after vaginal delivery. METHODS: A prospective randomised study was conducted in which 100 pregnant women were randomised into 2 equal groups: group 1 received Carbetocin 100 µgm (Pabal(®) Ferring, UK) and group 2 received oxytocin 5 IU (Syntocinon(®), Novartis, Switzerland). RESULTS: The amount of blood loss and the need for other uterotonics were significantly lower in the carbetocin group (811 ± 389.17 vs. 1010 ± 525.66 and 10/50 vs. 21/50). There was no significant difference between the carbetocin and oxytocin groups regarding occurrence of major PPH (6 vs. 11), the need for blood transfusion (6 vs. 9), the difference between blood haemoglobin levels before delivery and 24 h after delivery (0.6 ± 0.28 vs. 0.56 ± 0.25), respectively. There was no significant difference between the 2 study groups regarding both systolic and diastolic blood pressure measured immediately after the drug administration and at 30 and 60 min later. Regarding the drugs side effects, there was no significant difference between the 2 groups in the occurrence of nausea, vomiting, tachycardia, flushing, dizziness, headache, shivering, metallic taste, dyspnea, palpitations and itching. CONCLUSIONS: Carbetocin is a better alternative to oxytocin in management of atonic PPH with non-significant hemodynamic changes or side effects .

Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women.

OBJECTIVE: To compare effectiveness and tolerability of carbetocin versus oxytocin in prevention of postpartum hemorrhage (PPH) after vaginal delivery. METHODS: A prospective double-blinded randomized study conducted on 200 pregnant women randomized into two groups: Group 1 (100 women) received single 100 µg IM dose of carbetocin and Group 2 received of 5 IU oxytocin IM. Both groups received their drug after fetal and before placental delivery. RESULTS: There was a statistically significant difference between the two study groups regarding amount of bleeding (337.73 ± 118.77 versus 378 ± 143.2), occurrence of PPH (4 versus 16%), need for other uterotonics (23 versus 37%) and hemoglobin difference between before and after delivery (0.55 ± 0.35 versus 0.96 ± 0.62) (all being lower in carbetocin group) and measured hemoglobin 24 h after delivery (being higher in carbetocin group); however, there was no significant difference between the two study groups regarding occurrence of major PPH and the need for blood transfusion. Women in carbetocin group showed a statistically significant lower systolic and diastolic blood pressure immediately after delivery and at 30 and 60 min than women in oxytocin group. There was no significant difference between the two study groups regarding occurrence of nausea, vomiting, flushing, dizziness, headache, shivering, metallic taste, dyspnea, palpitation and itching. Women in carbetocin group experienced tachycardia more than women in oxytocin group. CONCLUSIONS: Carbitocin is a better alternative to traditional oxytocin in prevention of PPH after vaginal delivery with minimal hemodynamic changes and similar side effects.