Prophylactic tranexamic acid to reduce blood loss and related morbidities during hysterectomy: a systematic review and meta-analysis of randomized controlled trials.

To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of prophylactic tranexamic acid (TXA) versus a control (placebo or no treatment) during hysterectomy for benign conditions. Six databases were screened from inception to January 23, 2022. Eligible studies were assessed for risk of bias. Outcomes were summarized as weighted mean differences and risk ratios with 95% confidence intervals in a random-effects model. Five studies, comprising six arms and 911 patients were included in the study. Two and three studies had an overall unclear and low risk of bias, respectively. Estimated intraoperative blood loss, requirement for postoperative blood transfusion, and requirement for intraoperative topical hemostatic agents were significantly reduced in a prophylactic TXA group when compared with a control group. Moreover, postoperative hemoglobin level was significantly higher in the prophylactic TXA group than in the control group. Conversely, the frequency of self-limiting nausea and vomiting was significantly higher in the prophylactic TXA group than in the control group. There were no significant differences between the groups in terms of surgery duration, hospital stay, and diarrhea rate. All the RCTs reported no incidence of major adverse events in either group, such as mortality, thromboembolic events, visual disturbances, or seizures. There was no publication bias for any outcome, and leave-one-out sensitivity analyses demonstrated stability of the findings. Among patients who underwent hysterectomy for benign conditions, prophylactic TXA appeared largely safe and correlated with substantial reductions in estimated intraoperative blood loss and related morbidities.

Prophylactic tranexamic acid among women undergoing vaginal delivery to reduce postpartum blood loss and related morbidities: A systematic review and meta-analysis of 17 randomized controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that inspected the efficacy and safety of prophylactic TXA compared with control (placebo/no treatment) among women undergoing vaginal delivery on reducing postpartum blood loss and related morbidities. METHODS: Six databases were screened from inception until 06-December-2021. The pooled data were summarized as mean difference or risk ratio, respectively, with 95% confidence interval in a fixed- or random-effects model. RESULTS: Sixteen studies comprising 17 RCT treatment arms were included. There were 7122 patients; 3611 and 3511 patients were allocated to prophylactic TXA and control groups, respectively. Overall, the included RCTs had a low risk of bias. Prophylactic TXA correlated with a significant decrease in mean postpartum blood loss and mean change in hemoglobin/hematocrit. Moreover, prophylactic TXA was linked to decreased incidence rates of postpartum hemorrhage, need for blood transfusion, and need for additional uterotonic agents. Nevertheless, prophylactic TXA culminated in significantly higher incidence rates of nausea, vomiting, and diarrhea, all of which were well-tolerated. There was no increased risk of thromboembolic events. Leave-one-out sensitivity analysis confirmed the robustness of efficacy endpoints. There was no publication bias for the endpoint of mean postpartum blood loss. CONCLUSION: Among patients undergoing vaginal delivery, prophylactic TXA during active management of third stage of labor (AMTSL) appeared largely safe and correlated with a significant decrease in postpartum blood loss and related morbidities compared with control intervention. Prophylactic TXA should be integrated as a "formal" component of AMTSL among women undergoing vaginal delivery.

Preemptive pregabalin for postoperative analgesia during minimally invasive hysterectomy: a systematic review and meta-analysis of randomized controlled trials.

We aimed to perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that examined the analgesic benefits of preemptive pregabalin among patients undergoing minimally invasive hysterectomy. Five major databases were systematically screened from inception until August 29, 2021 Relevant studies were evaluated for risk of bias. Endpoints were analyzed using the random-effects model and pooled as the mean difference or risk ratio with a 95% confidence interval. Four studies with seven treatment arms met the inclusion criteria. The total sample size was 304 patients: 193 and 111 patients were allocated to the pregabalin and placebo groups, respectively. Overall, the included studies revealed a low risk of bias. The summary results revealed that the mean postoperative pain scores at rest were significantly lower in the pregabalin group than in the control group at 0, 2, 4, 6, 12, and 24 hours. Moreover, the mean postoperative pain scores on movement/coughing were significantly lower in the pregabalin group than in the control group at 12 and 24 hours. The rate of patients who were opioid-free postoperatively was significantly higher in the pregabalin group than in the control group. There was no significant difference between the groups in terms of the mean postoperative time to first rescue analgesic and the rates of adverse events. Compared with placebo, preemptive pregabalin was largely safe, and was correlated with superior analgesic effects in terms of lower postoperative pain scores and higher opioid-sparing effects. Additional RCTs are needed to confirm these findings.

A genomics approach to females with infertility and recurrent pregnancy loss.

Infertility affects 10% of reproductive-age women and is extremely heterogeneous in etiology. The genetic contribution to female infertility is incompletely understood, and involves chromosomal and single-gene defects. Our aim in this study is to decipher single-gene causes in infertile women in whom endocrinological, anatomical, and chromosomal causes have been excluded. Our cohort comprises women with recurrent pregnancy loss and no offspring from spontaneous pregnancies (RPL, n = 61) and those who never achieved clinical pregnancy and were referred for in vitro fertilization [primary infertility (PI), n = 14]. Whole-exome sequencing revealed candidate variants in 14, which represents 43% of those with PI and 13% of those with RPL. These include variants in previously established female infertility-related genes (TLE6, NLRP7, FSHR, and ZP1) as well as genes with only tentative links in the literature (NLRP5). Candidate variants in genes linked to primary ciliary dyskinesia (DNAH11 and CCNO) were identified in individuals with and without systemic features of the disease. We also identified variants in genes not previously linked to female infertility. These include one homozygous variant each in CCDC68, CBX3, CENPH, PABPC1L, PIF1, PLK1, and REXO4, which we propose as candidate genes for infertility based on their established biology or compatible animal models. Our study expands the contribution of single genes to the etiology of PI and RPL, improves the precision of disease classification at the molecular level, and offers the potential for future treatment and development of human genetics-inspired fertility regulators.