Oil-soluble contrast medium bathing attenuated endometrial inflammation and improved endometrial receptivity in women with recurrent implantation failure: a descriptive study.

BACKGROUND: The oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF). METHODS: This descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανß-3 and HOXA10 in endometrium were collected. RESULTS: Thirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27-40 years) completed the research. The median number of embryo transfer cycles was three (range 3-8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0-13.5) to 0.65 (range 0-6), P = 0.035; additionally, the H-score of expression of ανß-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%). CONCLUSIONS: These results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανß-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.

Supplementation of rumen-protected lysine during the close-up period improves vaginal discharge clearance in Holstein dairy cows.

We aimed to evaluate the effects of rumen-protected lysine (RPL) supplementation during the close-up period on uterine involution and the resumption of ovarian function in dairy cows. Fifty-two multiparous Holstein cows were categorized based on parity and expected calving date and randomly assigned to the RPL or control (CON) groups. The RPL group received 80 g of RPL daily from day 21 before the expected calving date until parturition. Blood samples were obtained twice weekly from pre-supplementation to 6 weeks postpartum. The onset of luteal activity postpartum was determined via ultrasonography twice weekly for up to 6 weeks postpartum. Uterine involution was tracked at 3 and 5 weeks postpartum through the vaginal discharge score, percentage of polymorphonuclear cells (PMN) in endometrial cytology samples, presence of intrauterine fluid, and gravid horn diameter via ultrasonography. Before supplementation, the RPL group showed amino acid imbalance, which was improved by RPL supplementation. There were no significant differences in the onset of luteal activity, percentage of PMN, intrauterine fluid, or the diameter of the uterine horn between the two groups. The vaginal discharge score in the RPL group decreased from 3 to 5 weeks postpartum, whereas that in the CON groups did not decrease. The number of cows with clinical endometritis was lower in the RPL group. Overall, RPL supplementation during the close-up period enhanced vaginal discharge clearance, potentially averting clinical endometritis, but did not affect the first ovulation in dairy cows.

Effect of prophylactic use of cefazolin in caesarean section on postoperative infection: A meta-analysis.

Caesarean section rate is increasing and postoperative wound infection is a major health-threatening complication after caesarean section (CS). The aim of this study was to evaluate the efficacy of Cefazolin at different time for post-caesarean delivery. The aim of this study was to compare the use of Cefazolin at different times on infections after CS. The time of antibiotic use in CS can be divided into two groups: before skin incision (SI) and after cord clamping (CC). In this study, 268 relevant articles were found in the database, and finally, 10 articles were analysed. This study included a total of 5256 cases of caesarean section. The data on wound infections, endometritis, urinary tract infections and fever were analysed. Perform an analysis of the data using RevMan 5.3. The results showed that cefazolin before SI reduced wound infection compared to after CC (odds ratio [OR], 0.51; 95% CI: 0.37-0.69; p < 0.0001). Cefazolin prophylactically used before SI reduce endometritis after CS compared to after CC (OR, 0.52; 95% CI: 0.35-0.77; p = 0.001). There was no significant difference in urinary tract infections after CS between cefazolin prophylactically used before SI and after CC (OR, 0.80; 95% CI: 0.50-11.28; p = 0.35). There was no significant difference in fever after CS between the prophylactic use of cefazolin before SI and after CC (OR, 0.60; 95% CI: 0.26-11.43; p = 0.225). Cefazolin before SI reduces wound infection and endometritis after CS.

Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Interferon-tau protects bovine endometrial epithelial cells against inflammatory injury by regulating the PI3K/AKT/ß-catenin/FoxO1 signaling axis.

Endometritis is one of the most common causes of infertility in dairy cows, and is histopathologically characterized by inflammation and damage of endometrial epithelium. Interferon-tau (IFN-τ) is a novel type I interferon secreted by ruminant trophoblast cells with low cytotoxicity even at high doses. Previous studies suggested that IFN-τ plays an important role in inflammation. However, the mechanisms whereby IFN-τ may modulate the inflammatory responses in the bovine endometrium are unknown. In the present study, primary bovine endometrial epithelial cells (BEEC) isolated from fresh and healthy uterine horns were used for in vitro studies. The integrity of BEEC was assessed by immunofluorescence staining for cytokeratin 18 (CK-18, a known epithelial marker). For the experiments, BEEC were stimulated with different concentrations of lipopolysaccharide (LPS; 0-20 µg/mL) for different times (0-24 h). Cell viability and apoptosis were assessed via CCK-8 and flow cytometry. In a preliminary study, we observed that compared with the control group without LPS, 10 µg/mL of LPS stimulation for 24 h induced apoptosis. In a subsequent study, 20 or 40 ng/mL of IFN-τ alleviated LPS-induced apoptosis. Relative to the LPS group, western blotting further revealed that IFN-τ inhibited the protein abundance of TLR4 and phosphorylated (p-) p65 (p-p65) and Bax/Bcl-2 ratio, suggesting that IFN-τ can protect BEEC against inflammatory injury. Furthermore, the protein abundance of p-phosphoinositide 3-kinase (p-PI3K), p-protein kinase B (p-AKT), p-glycogen synthase kinase-3ß (p-GSK3ß), ß-catenin, and p-forkhead box O1 (p-FoxO1) was lower in the LPS group, whereas IFN-τ upregulated their abundance. The use of LY294002, a specific inhibitor of PI3K/AKT, attenuated the upregulation of p-PI3K, p-AKT p-GSK3ß, ß-catenin, and p-FoxO1 induced by IFN-τ, and also blocked the downregulation of TLR4, p-p65, and Bax/Bcl-2 ratio. This suggested that the inhibition of TLR4 signaling by IFN-τ was mediated by the PI3K/AKT pathway. Furthermore, compared with the LPS group, the ß-catenin agonist SB216763 led to greater p-FoxO1 and lower p-p65 and cell apoptosis. In contrast, knockdown of ß-catenin using small interfering RNA had the opposite effects. To explore the role of FoxO1 on the inhibition of TLR4 by IFN-τ, we employed LY294002 to inhibit the PI3K/AKT while FoxO1 was knocked down. Results revealed that the knockdown of FoxO1 blocked the upregulation of TLR4 and p-p65 induced by LY294002, and enhanced the inhibition of IFN-τ on TLR4, p-p65, and cell apoptosis. Overall, these findings confirmed that IFN-τ can protect endometrial epithelial cells against inflammatory injury via suppressing TLR4 activation through the regulation of the PI3K/AKT/ß-catenin/FoxO1 axis. These represent new insights into the molecular mechanisms underlying the anti-inflammatory function of IFN-τ in BEEC, and also provide a theoretical basis for further studies on the in vivo application of IFN-τ to help prevent negative effects of endometritis.

Isolation of lactic acid bacteria from the reproductive tract of mares as potentially beneficial strains to prevent equine endometritis.

Endometritis, the inflammation of the endometrium, is the leading cause of subfertility in mares, and therefore responsible for major economic losses in the horse industry worldwide. It is generally treated with uterine lavages combined with ecbolic agents and local or systemic antibiotics. However, since antibiotic overuse has been associated with antimicrobial resistance in mares with persistent endometritis, new prevention and treatment alternatives are needed. One such alternative could be the use of probiotic lactic acid bacteria (LAB) isolated from the host. Thanks to their species specificity, resident microbiota may restore ecological equilibrium within the host, and therefore, help prevent infections and improve physiological functions. In the present study, 257 bacterial strains were isolated from 77 healthy mares, and 88.76% (n = 228) of them were phenotypically classified as LAB. Within this group, 65.79% were able to inhibit at least one strain from each of the genera that most commonly cause equine endometritis (Streptococcus equi subsp. zooepidemicus, Escherichia coli, and Staphylococcus spp.). Five strains (RCE11, RCE20, RCE91, RCE99, and RCE167) were selected on the basis of their beneficial properties: ability to autoaggregate and adhere to equine epithelial cells, high inhibition of and co-aggregation with all the bacteria isolated from clinical cases of endometritis evaluated, and negative co-inhibition between one another. All five were finally identified as Enterococcus spp., namely E. faecium (two strains), E. hirae (two strains), and E. gallinarum (one strain). Further studies will assess their safety and biotechnological potential for the design of a multi-strain probiotic formula to prevent equine endometritis.

Preoperative Application of Chlorhexidine to Reduce Infection with Cesarean Delivery after Labor (PRACTICAL): A Randomized Clinical Trial.

OBJECTIVE: To evaluate whether use of both preoperative 2% chlorhexidine gluconate abdominal cloth and 4% chlorhexidine gluconate vaginal scrub is effective in reducing surgical site infections (SSIs) in patients undergoing cesarean delivery after labor. STUDY DESIGN: This is a single-center, randomized clinical trial in which patients were randomized 1:1 to receive 2% chlorhexidine gluconate cloth applied to the abdomen in addition to the application of 4% chlorhexidine gluconate vaginal scrub versus standard of care. The primary outcome was rate of SSIs, including endometritis, by 6 weeks postdelivery. The secondary outcomes were other wound complications (erythema at the operative site, skin separation, drainage, fever, hematoma, seroma) by 6 weeks postdelivery, hospital readmission for wound complications, and day of discharge after cesarean delivery. RESULTS: A total of 319 patients between September 2018 and February 2021 met eligibility criteria: 160 were randomized to the chlorhexidine gluconate abdominal cloth and vaginal scrub group and 159 were randomized to the standard of care group. The groups did not have significant differences in maternal demographic characteristics. Of the 302 (95%) individuals included in primary analysis, there was no statistically significant difference in SSI and endometritis rate by 6 weeks postdelivery (6.6% in chlorhexidine vs. 5.3% standard of care, p = 0.65). Secondary outcomes were also similar among the two groups. CONCLUSION: The combination of preoperative 2% chlorhexidine gluconate abdominal cloth and 4% chlorhexidine gluconate vaginal scrub does not appear to reduce the risk of SSI with cesarean delivery after trial of labor when compared with standard of care. KEY POINTS: · Preoperative chlorhexidine abdominal cloth/vaginal scrub does not decrease SSI in cesarean after labor.. · Preoperative chlorhexidine abdominal cloth/vaginal scrub does not decrease other wound complications in cesarean after labor.. · There was no difference in discharge day, 2-week or 6-week SSI rates..

Antibiotic Recommendations After Postpartum Uterine Exploration or Instrumentation.

Importance: Multiple postpartum scenarios require uterine exploration or instrumentation. These may introduce bacteria into the uterus, increasing the risk of endometritis. Data on the use of antibiotics in these scenarios is limited, resulting in few guidelines and divergent care. Objective: To describe postpartum scenarios requiring uterine exploration and/or instrumentation, review data on antibiotic prophylaxis, and delineate antibiotic recommendations for each scenario. Evidence Acquisition: Original articles were obtained from literature search in PubMed, MEDLINE, and OVID; pertinent articles were reviewed. Results: These recommendations are based on published evidence and professional society guidelines. Antibiotic prophylaxis following manual placenta removal should include 1-time combination of ampicillin 2 g intravenously (IV) or cefazolin 1 g IV, plus metronidazole 500 mg IV. Antibiotic prophylaxis before postpartum dilation and curettage, manual vacuum aspiration, and intrauterine balloon tamponade should include 1-time combination of ampicillin 2 g IV plus metronidazole 500 mg IV. If the patient in any of the above scenarios has received group B Streptococcus prophylaxis, then only metronidazole is recommended. Further randomized clinical trials are needed to optimize these regimens. Conclusions: Uterine exploration or instrumentation increases the risk of postpartum endometritis and requires antibiotic prophylaxis. For manual placenta removal, we recommend 1-time combination of ampicillin 2 g IV or cefazolin 1 g IV, plus metronidazole 500 mg IV. For dilation and curettage, manual vacuum aspiration, and intrauterine balloon tamponade, we recommend 1-time combination of ampicillin 2 g IV plus metronidazole 500 mg IV. For patients who already received antibiotic prophylaxis for group B Streptococcus, we recommend 1-time dose of metronidazole 500 mg IV. Relevance: Providers can utilize our guidelines to prevent postpartum endometritis in these scenarios requiring postpartum uterine exploration and/or instrumentation.

Timing of Intravenous Prophylactic Antibiotic Agents for Cesarean Delivery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Prophylactic antibiotic administration has been used to reduce infectious morbidities in cesarean deliveries. However, no consensus on the timing has been reached. We performed this review to compare maternal and neonatal infectious morbidities of antibiotic administration before skin incision and after cord clamping. Methods: PubMed, EMBASE, MEDLINE, Cochrane Library, and Web of Science databases were searched. Only randomized controlled trials (RCTs) comparing the use of antibiotic agents pre-operatively and after cord clamping were included. Characteristics and results of the included studies were extracted, and risks of bias were assessed. A fixed-effect model was applied to estimate the relative risks (RRs) for outcomes. Results: Sixteen RCTs, including 8,027 women and 7,131 newborns, met the selection criteria. Pre-operative administration of antibiotic agents was associated with a reduction in the risk of endometritis (RR, 0.52; 95% confidence interval [CI], 0.37-0.72) and wound complications (RR, 0.54; 95% CI, 0.42-0.69), compared with administration after cord clamping. No differences were observed in the rate of febrile illness (RR, 0.79; 95% CI, 0.59-1.05), urinary tract infection (RR, 0.92; 95% CI, 0.64-1.32), neonatal intensive care unit (NICU) admission (RR, 0.94; 95% CI, 0.79-1.12), and neonatal sepsis (RR, 0.83; 95% CI, 0.61-1.14). Conclusions: The present study showed that prophylactic antibiotic agent administration before skin incision can reduce the risk of endometritis and wound complications while not increasing that of NICU admission and neonatal sepsis compared with administration after cord clamping.

Effect of adjunctive prophylactic macrolides used at the caesarean section on endometritis and surgical site wound infection: A meta-analysis.

A meta-analysis investigation was executed to measure the outcome of adjunctive prophylactic macrolides (APM) used at caesarean section (CS) on endometritis and surgical site wound infection (SSWI). A comprehensive literature inspection till February 2023 was applied and 1023 interrelated investigations were reviewed. The 10 chosen investigations enclosed 22 676 females with CS were in the chosen investigations' starting point, 14 034 of them were utilising APM, and 8642 were utilising control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the effect of APM used at CS on endometritis and SSWI by the dichotomous approaches and a fixed or random model. Adjunctive prophylactic macrolides had significantly lower SSWI (OR, 0.43; 95% CI, 0.34-0.55, P < .001), and endometritis (OR, 0.34; 95% CI, 0.20-0.60, P = .005) compared with those with control in females with CS. Adjunctive prophylactic macrolides had significantly lower SSWI, and endometritis compared with those with control in females with CS. However, care must be exercised when dealing with its values because of the low number of nominated investigations for the meta-analysis.

Different methods of vaginal preparation before cesarean delivery to prevent postoperative infection: a systematic review and network meta-analysis.

OBJECTIVE: Precesarean vaginal antisepsis can benefit pregnant women with ruptured membranes. However, in the general population, recent trials have shown mixed results in reducing postoperative infections. This study aimed to systematically review clinical trials and summarize the most suitable vaginal preparations for cesarean delivery in preventing postoperative infection. DATA SOURCES: We searched PubMed, Web of Science, Cochrane Library, SinoMed databases, and the ClinicalTrials.gov clinical trials registry for randomized controlled trials and conference presentations (past 20 years, 2003-2022). Reference lists of previous meta-analyses were searched manually. In addition, we conducted subgroup analysis on the basis of whether the studies were conducted in developed or developing countries, whether the membranes were ruptured, and whether patients were in labor. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials comparing vaginal preparation methods for the prevention of postcesarean infection with each other or with negative controls. METHODS: Two reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. The effectiveness of prevention strategies was assessed by frequentist-based network meta-analysis models. The outcomes were endometritis, postoperative fever, and wound infection. RESULTS: A total of 23 trials including 10,026 cesarean delivery patients were included in this study. Vaginal preparation methods included 19 iodine-based disinfectants (1%, 5%, and 10% povidone-iodine; 0.4% and 0.5% iodophor) and 4 guanidine-based disinfectants (0.05% and 0.20% chlorhexidine acetate; 1% and 4% chlorhexidine gluconate). Overall, vaginal preparation significantly reduced the risks of endometritis (3.4% vs 8.1%; risk ratio, 0.41 [0.32-0.52]), postoperative fever (7.1% vs 11.4%; risk ratio, 0.58 [0.45-0.74]), and wound infection (4.1% vs 5.4%; risk ratio, 0.73 [0.59-0.90]). With regard to disinfectant type, iodine-based disinfectants (risk ratio, 0.45 [0.35-0.57]) and guanidine-based disinfectants (risk ratio, 0.22 [0.12-0.40]) significantly reduced the risk of endometritis, and iodine-based disinfectants reduced the risk of postoperative fever (risk ratio, 0.58 [0.44-0.77]) and wound infection (risk ratio, 0.75 [0.60-0.94]). With regard to disinfectant concentration, 1% povidone-iodine was most likely to simultaneously reduce the risks of endometritis, postoperative fever, and wound infection. CONCLUSION: Preoperative vaginal preparation can significantly reduce the risk of postcesarean infectious diseases (endometritis, postoperative fever, and wound infection); 1% povidone-iodine has particularly outstanding effects.

Selenomethionine protects against Escherichia coli-induced endometritis by inhibiting inflammation and necroptosis via regulating the PPAR-γ/NF-κB pathway.

Endometritis, inflammation of the endometrium, is a major cause of subfertility in women. Selenomethionine (SeMet)is known to exert anti-inflammatory activity. We aimed to verify the protective roles of SeMet on Escherichia coli (E.coli)-induced endometritis. The extent of uterus damage was assessed by detecting histopathology and inflammatory mediators. The results revealed that SeMet significantly prevented E.coli-induced endometritis by attenuating uterine histopathology and inflammatory cytokine production. E.coli-induced MPO activity and MDA content were inhibited by SeMey. E.coli-induced ZO-1 and occludin were upregulated by SeMet. E.coli-induced necroptosis was also inhibited by SeMet. Additionally, E.coli-induced NF-κB activation was alleviated by SeMet. PPAR-γ expression was upregulated by SeMet. Notably, the protective effects of SeMet on endometritis were abolished by a PPAR-γ inhibitor. In conclusion, SeMet inhibits E.coli-induced endometritis by attenuating inflammation and necroptosis, which is mediated by the PPAR-γ/NF-κB signaling pathway.

Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway.

INTRODUCTION: Endometritis is the inflammatory condition of the uterus. Citral, a component of lemongrass oil, is known to exhibit anti-inflammatory activity. AIM: The effects of citral on LPS-induced endometritis were tested and the mechanisms were investigated. METHODS: LPS-induced endometritis mice model was established and the effects of citral were detected using this model. Inflammatory cytokines were tested by ELISA. Ferroptosis was assessed by detecting GSH, ATP, MDA, and Fe2+ levels. Signaling pathway was tested by western blot analysis. RESULTS: Citral prevented LPS-induced endometritis through attenuating uterine pathological changes and inflammatory cytokine release. Meanwhile, citral prevents LPS-induced ferroptosis through attenuating MDA and Fe2+ levels, as well as increasing ATP and GSH levels. Furthermore, citral up-regulated Nrf2 and HO-1 expression and attenuated NF-κB activation. In addition, in Nrf2 knockdown mice, the inhibitory roles of citral on ferroptosis and endometritis were largely reversed. CONCLUSION: Taken together, citral inhibited LPS-induced endometritis through preventing ferroptosis, which were regulated by Nrf2 signaling pathway.

Efficacy and safety of broad spectrum penicillin with or without beta-lactamase inhibitors vs first and second generation cephalosporins as prophylactic antibiotics during cesarean section: a systematic review and meta-analysis.

This study assessed the efficacy and safety between broad spectrum penicillin (P2) with or without beta-lactamase inhibitors (P2+) versus first and second generation cephalosporins (C1&C2) in the prevention of post-cesarean infections. Relevant randomized controlled trials (RCTs) were searched in English and Chinese databases: nine RCTs were involved. Six trials compared P2+ vs C1&C2, no differences were found between interventions for endometritis, wound infection, urinary tract infection, febrile morbidity and maternal rashes. Four trials compared P2 vs C1&C2, no differences were found between interventions for endometritis, febrile morbidity, wound infection and urinary tract infection. Postoperative hospitalization was longer for women in P2 than C1&C2. Based on these results, P2/P2+ and C1&C2 may have similar efficacy on postoperative infections after cesarean section, there is no data on infant outcomes. PROSPERO Registration Number: CRD42022345721.

Protective effect of the total flavonoids from Clinopodium chinense against LPS-induced mice endometritis by inhibiting NLRP3 inflammasome-mediated pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense (Benth.) O. Kuntze (C. chinense) is a Chinese herbal medicine used in treating gynecological hemorrhagic diseases for hundreds of years. Flavonoids are one kind of the major components in C. chinense. The flavonoids of C. chinense (TFC) have a vital role in treating endometritis but the underlying therapeutic mechanisms of TFC against endometritis have been rarely reported. AIM OF THE STUDY: To elucidate the therapeutic effect and possible mechanisms of TFC against lipopolysaccharide (LPS)-induced endometritis in vivo and LPS-induced primary mouse endometrial epithelial cells (MEECs) injury in vitro. MATERIALS AND METHODS: The holistic phytochemicals of the TFC and TFC-contained serum were screened and identified using UPLC-Q-TOF-MS. The model of endometritis was established by intrauterine injection of LPS (5 mg/mL) into female BALB/c mice, and the model mice were treated with TFC for 7 days. The value of MPO was measured by Myeloperoxidase assay kit, the pathological changes in the endometrium were evaluated using H&E staining and transmission electron microscope (TEM), the secretions of IL-18, IL-1ß and TNF-α were determined by ELISA kits, the mRNA expressions of IL-18, IL-1ß and TNF-α were determined by RT-PCR assay, and the protein levels of TLR4, IKBα, p-IKBα, p65, p-p65, caspase-1, ASC, NLRP3 and GSDMD were measured by Western blot. Subsequently, MEECs were isolated from the uterus of pregnant female mice, injured by LPS for 24 h and incubated with the TFC-contained serum. Finally, cell viability, LDH release, hoechst 33342/PI staining, immunofluorescence staining, scanning electron microscope observation, ELISA assay, RT-PCR detection and Western blot analysis were carried out to further validate the therapeutic effect and the underlying mechanisms of TFC. RESULTS: A total of 6 compounds in the plasma of mice after being intragastric administrated of TFC were identified. The results in vivo showed that TFC significantly reduced MPO value and alleviated pathological injury of the endometrium. Furthermore, TFC significantly decreased the serum IL-18, IL-1ß and TNF-α levels, and the mRNA levels of IL-18, IL-1ß and TNF-α. TFC also inhibited the expressions of TLR4, p-IKBα, p-p65, caspase-1, ASC, NLRP3 and GSDMD. Besides, compared with the model group in MEECs cells, TFC-contained serum prevented pyroptosis, decreased the levels of IL-18 and IL-1ß, and inhibited the mRNA expressions of IL-18, IL-1ß and GSDMD. TFC-contained serum also reversed the activation of NLRP3 inflammasome caused by nigericin, and restrainted the translocation of NF-κB into nuclear. CONCLUSIONS: TFC protects mice endometritis from the injury of LPS via suppressing the activation of NLRP3 inflammasome and pyroptosis, the underlying mechanisms of which were related to restraining the TLR4/NF-κB/NLRP3 pathway activation.

Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis.

Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose-response curve was produced to evaluate the effect of AMSC-EVs on spermatozoa, and an optimal concentration of 400 × 106 EVs with 10 × 106 spermatozoa/mL was identified. At this concentration, sperm mobility parameters were not negatively affected. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with EVs (n = 8; EV group). The supplementation of AMSC-EVs to semen resulted in a reduction in polymorphonuclear neutrophil (PMN) infiltration as well as intrauterine fluid accumulation (IUF; p < 0.05). There was a significant reduction in intrauterine cytokine levels (p < 0.05) for TNF-α and IL-6 and an increase in anti-inflammatory IL-10 in mares in the EV group, suggesting successful modulation of the post-insemination inflammatory response. This procedure may be useful for mares susceptible to PPBIE.

Vaginal cleansing before unscheduled cesarean delivery to reduce infection: a randomized clinical trial.

BACKGROUND: Cesarean delivery is the most performed major surgery among women, and surgical-site infections following a cesarean delivery are a significant source of postoperative morbidity. It is unclear if vaginal cleansing before a cesarean delivery decreases post-cesarean delivery infectious morbidity. OBJECTIVE: This study aimed to evaluate if preoperative vaginal cleansing with povidone-iodine among women undergoing a cesarean delivery after labor decreases postoperative infectious morbidity. STUDY DESIGN: This randomized clinical trial was conducted from August 3, 2015 to January 28, 2021, with 30 days of follow-up and the final follow-up completed on February 27, 2021. Patients met the inclusion criteria if they underwent a cesarean delivery after regular contractions with cervical dilation, rupture of membranes, or any cesarean delivery performed at >4 cm dilation. Participants were randomly assigned in a 1:1 ratio to either abdominal cleansing plus vaginal cleansing with 1% povidone-iodine or abdominal cleansing alone. The primary outcome was composite infectious morbidity including surgical-site infection, fever, endometritis, and wound complications within 30 days after the cesarean delivery. Secondary outcomes included individual components of the composite, length of hospital stay, postoperative hospitalization or outpatient treatment related to infectious morbidity, and empirical treatment for neonatal sepsis. RESULTS: A total of 608 subjects (304 vaginal cleansing group, 304 control group) were included in the intention-to-treat analysis. Patient characteristics were similar between groups. There was no significant difference in the primary composite outcome between the 2 groups (11.8% vs 11.5%; P=.90; relative risk, 1.0; 95% confidence interval, 0.7-1.6). Individual components of the composite and secondary outcomes were also not significantly different between the groups. Similar findings were observed in the as-treated analysis (11.3% vs 11.8%; P=.9; relative risk, 1.0; 95% confidence interval, 0.7-1.6). CONCLUSION: Vaginal cleansing with povidone-iodine before an unscheduled cesarean delivery occurring after labor did not reduce the postoperative infectious morbidity. These findings do not support the routine use of vaginal cleansing for women undergoing a cesarean delivery after labor.

Effectiveness of Chlorhexidine vaginal cleansing in reducing post-caesarean endometritis at two tertiary hospitals in Enugu, Nigeria: A randomized controlled trial.

Despite the use of prophylactic antibiotics during Caesarean delivery, post-Caesarean surgical site infection (SSI) and endometritis still often complicate the puerperal period. We speculated that the use of vaginal cleansing with chlorhexidine solution would serve as an adjunct to prophylactic antibiotics in reducing the menace of post-caesarean endometritis and indeed found a significant reduction.

Postoperative infections after non-elective cesarean section - a retrospective cohort study of prevalence and risk factors at a single center in Denmark administering prophylactic antibiotics after cord clamping.

BACKGROUND: Mothers giving birth by non-elective cesarean section have considerably higher risk of developing postoperative infection, than mothers giving birth by elective cesarean section. Meta-analyses have shown that the risk of infection is reduced when administering antibiotics at least 30 min prior to skin incision rather than after cord clamping. If given prior to incision, antibiotics are present in the neonatal bloodstream for up to 24 h after delivery, with early exposure to antibiotics potentially disturbing development of the gut microbiome. We aimed to retrospectively assess the prevalence of postoperative infection after non-elective cesarean section at a single labor ward administering antibiotics after cord clamping, additionally investigating risk factors for developing postoperative infections. METHODS: In this retrospective cohort study, we included a total of 2,725 women giving birth by non-elective cesarean section in 2010-2017 with a review of records for prenatal risk factors, labor management, and perinatal outcomes. The primary outcomes were a main composite infection of development of either endometritis, surgical-site infection, or sepsis in conjunction with a relevant antibiotic prescription. Secondary outcomes included infection of unknown focus, mastitis, urinary tract infection, and pneumonia. RESULTS: A total of 88 patients developed a main composite infection (3.2%). These infections subdivide into endometritis (n = 37/2725, 1.4%), surgical-site infection (n = 35/2725, 1.3%) and sepsis (n = 15/2725, 0.6%). We found a high body mass index (aOR = 3.38, 95%CI 1.93-5.92) and intrapartum fever (aOR = 2.26, 95%CI 1.22-4.59) to be independent risk-factors for developing postoperative infection after non-elective cesarean section. Furthermore, we found delivery by a more expedient emergency grade 2 cesarean section (aOR = 0.61 95%CI 0.37-0.998) compared to grade 3 to be a protective factor for developing postoperative infection after non-elective cesarean section. CONCLUSION: In a labor ward administering antibiotics after cord clamping at non-elective cesarean births, we find a low prevalence of main composite infections when compared to estimates from meta-analyses on the topic. We conclude that administration of prophylactic antibiotics after cord clamping appears to result in acceptable rates of postoperative infection and avoids transplacental-transmission of antibiotics to the infant.

INFEXIT: Implementing vaginal disinfection prior to cesarean section.

OBJECTIVE: To evaluate the rate of implementation after adding vaginal disinfection to the cesarean section protocol and its effect on post cesarean infections and hospital readmissions. STUDY DESIGN: This is an intervention study where two groups were compared. Women the year before (n = 1384) and one year following (n = 1246) the addition of vaginal disinfection, with povidone-iodine 1% prior to the cesarean section, to the protocol. Primary outcome was the rate of implementation. Secondary outcomes were the rates of endometritis, wound infection and postoperative fever. With the effect expressed in the number of hospital readmissions. RESULTS: The implementation rate was 85.6%. Intention-to-treat analysis showed endometritis rates of 2.0% versus 1.1% (p = 0.07). For women with preoperative ruptured membranes there was a significant decrease in endometritis, from 3.4% to 1.3% (p = 0.02). Per-protocol analysis showed endometritis rates of 2.0% to 1.0% (p = 0.05). Women with ruptured membranes, 3.4% versus 1.3% (p = 0.02), and women who were in the second stage of labor, 4.7% versus 0.0% (p = 0.01), had a significant decrease in endometritis. For wound infection and postoperative fever rates were similar. The decrease of infections had a significant effect on hospital readmissions, 27 versus 10 (p = 0.04). CONCLUSION: The implementation of this quality improvement measure shows to be adequate as the vast majority of women undergoing a cesarean received vaginal disinfection. Vaginal disinfection showed a declining trend of endometritis and postoperative fever and for women with broken membranes prior to cesarean section the decrease in endometritis was significant. These beneficial effects have led to a statistical and clinically relevant decrease in hospital readmissions and thus cost reduction.