Direct Acylation of Unactivated Alkyl Halides with Aldehydes through N-Heterocyclic Carbene Organocatalysis.

Catalytic acylation of organohalides with aldehydes is an ideal strategy for the direct synthesis of ketones. However, the utilization of unactivated alkyl halides in such a transformation remains a formidable challenge. In this study, we developed a cross-coupling reaction of aldehydes with unactivated alkyl halides through N-heterocyclic carbene catalysis. With this protocol, various ketones could be rapidly synthesized from readily available starting materials under mild conditions. This organocatalytic system was successfully applied in the late-stage functionalization of pharmaceutical derivatives. Mechanistic investigations suggest a closed-shell nucleophilic substitution mechanism for this reaction.

Intrauterine interventions for women with two or more implantation failures: A systematic review and network meta-analysis.

Objective: To compare the effectiveness of different intrauterine interventions for women with two or more unexplained implantation failures. Design: A systematic review and network meta-analysis of randomized controlled trials (RCTs). Patients: Women with two or more implantation failures undergoing fresh or frozen embryo transfer (ET). Interventions: An electronic search of the following databases: Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase. Main Outcome Measures: Clinical pregnancy, live birth/ongoing pregnancy, and miscarriage. Results: We included 21 RCTs(3079 women) in the network meta-analysis. The network meta-analysis showed that compared with control treatment, platelet-rich plasma(PRP), peripheral blood mononuclear cells (PBMC), granulocyte colony-stimulating factor(G-CSF), human chorionic gonadotropin(HCG), and endometrial scratch(ES) significantly increased clinical pregnancy(OR 3.78, 95% CI 2.72 to 5.25; 2.79, 95% CI 1.75 to 4.45; 1.93, 95% CI 1.37 to 2.72; 1.80, 95% CI 1.18 to 2.72; 1.75, 95% CI 1.29 to 2.36, respectively). PRP ranked the highest in improving clinical pregnancy, followed by PBMC, G-CSF, HCG, and ES. Compared with control treatment, PRP, PBMC, and ES significantly increased live birth/ongoing pregnancy (OR 5.96, 95% CI 3.38 to 10.52; OR 2.55, 95% CI 1.27 to 5.11; OR 1.70, 95% CI 1.07 to 2.69, respectively). PRP ranked the highest in improving live birth/ongoing pregnancy, followed by PBMC, and ES. Conclusions: PRP is the most effective intrauterine intervention in improving pregnancy outcome in women with two or more implantation failures.

Carbetocin vs oxytocin for prevention of postpartum hemorrhage after vaginal delivery: A meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin. METHODS: We conducted a systemic literature search in PubMed, the Cochrane Library, and Embase without language restrictions from inception of each of database to November 18th, 2018. Randomized controlled trials with outcome measure of blood loss ≥500 ml were eligible if they compared carbetocin with oxytocin to prevent postpartum hemorrhage during the third stage of labor in women undergoing vaginal delivery. RESULTS: This meta-analysis of 5 randomized controlled trials (30,314 women) indicated that there was no significant difference between carbetocin and oxytocin in blood loss ≥500 ml in women undergoing vaginal delivery (relative risks (RRs), 0.52; 95% confidence intervals (CIs), 0.24 to 1.15; P = .11; I = 69%). Sensitivity analyses showed the same results. No significant differences were found in blood loss ≥1000 ml, use of additional uterotonic agents, blood transfusion, uterine massage, flushing, vomiting, abdominal pain, nausea, dizziness, headache, palpitation, itching, and shivering. CONCLUSIONS: This meta-analysis showed that carbetocin was as effective and safe as oxytocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery, and the choice of carbetocin for routine prophylaxis will depend on cost-effectiveness.

Cervical Pessary for Prevention of Preterm Birth: A Meta-Analysis.

To investigate the efficacy of cervical pessary placement in preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton pregnancy and a short cervix, we searched literature in relevant databases. The meta-analysis of the 3 included trials (1412 women) showed cervical pessary placement did not reduce the risk of spontaneous preterm birth <34 weeks in these women (risk ratio (RR), 0.71; 95% confidence interval (CI), 0.21-2.43, P = 0.59; I2 = 90%). The sensitivity analyses by excluding one trial at one time showed the same results. This meta-analysis also showed that cervical pessary did not prevent preterm birth <34, 30, 28 weeks and was not associated with respiratory distress syndrome, necrotising enterocolitis, intraventricular haemorrhage, neonatal sepsis, retinopathy of prematurity, fetal death, neonatal death, perinatal death, birth weight <1500 g, birth weight <2500 g, premature preterm rupture of membranes, corticosteroid treatment for fetal maturation, and admission to neonatal intensive care unit. Although this meta-analysis showed cervical pessary placement did not reduce the risk of preterm birth in women with a singleton pregnancy and a short cervix, we could not confirm or refute this conclusion, and large-scale randomised controlled trials are urgently needed.