miR-23b-3p regulates human endometrial epithelial cell adhesion implying a role in implantation.

In brief: miR-23b-3p expression is increased in fertile endometrium during receptivity. This study investigates the function of miR-23b-3p on endometrial adhesion and its downstream targets. Abstract: The human endometrium undergoes dramatic remodeling throughout the menstrual cycle that is essential for successful blastocyst attachment and implantation in the mid-secretory (receptive) phase. microRNA (miR) plays a role in the preparation of endometrial receptivity. miR-23b-3p expression is increased in fertile endometrium during receptivity. Here, we aimed to investigate miR-23b-3p function during receptivity. qPCR and in situ hybridization were used to investigate the expression and localization of miR-23b-3p in human endometrium, respectively. Ishikawa cells (endometrial epithelial cell line) and endometrial organoid-derived epithelial cells were transfected with miR-23b-3p mimic, and trophoblast progenitor spheroid (blastocyst surrogate) adhesion assay was used to determine effects on blastocyst adhesion to endometrial cells. We demonstrated that miR-23b-3p was significantly upregulated in the fertile endometrium of the receptive phase compared to the non-receptive, proliferative phase. No difference was identified for the expression of miR-23b-3p between fertile and infertile mid-secretory phase endometrium. miR-23b-3p localized to the epithelium and stroma in the mid-secretory phase but was undetectable in the proliferative phase of fertile endometrium. Functionally, miR-23-3p overexpression in Ishikawa cells and fertile endometrial organoid-derived epithelial cells significantly improved their adhesive capacity to trophoblast progenitor spheroids. miR-23b-3p overexpression in infertile endometrial organoid-derived epithelial cells did not improve adhesion. Among 10 miR-predicted gene targets examined, miR-23b-3p overexpression in Ishikawa cells significantly reduced the expression of MET, secreted frizzled-related protein 4 (SFRP4) and acyl-CoA dehydrogenase short/branched chain (ACADSB) compared to control. The reduction of SFRP4 after miR23b-3p overexpression was confirmed by immunoblotting in fertile organoid-derived epithelial cells. SFRP4 expression in fertile endometrium exhibited an inverse expression pattern compared to miR-23b-3p and was higher in the proliferative phase compared to the mid-secretory phase. Overall, miR-23b-3p is likely a critical regulator of endometrial epithelial adhesion and receptivity.

A Systematic Review of the Efficacy and Availability of Targeted Treatments for Central Sensitization in Women With Endometriosis.

OBJECTIVES: Central sensitization (CS) contributes to patient variability when treating pain in endometriosis. Targeting this process may alleviate hyperalgesia and allodynia in women refractory to current treatments. Currently, there has been no review of targeted treatments for central sensitization in women with endometriosis. Therefore, this review aims to identify and summarize the findings of studies regarding the availability and efficacy of targeted treatments for CS in women with endometriosis. MATERIALS AND METHODS: A systematic review was conducted searching MEDLINE, Embase and CINAHL. Inclusion criteria: primary research articles, women with endometriosis and CS features, and description of treatments for CS, or its effects on hyperalgesia and allodynia. Exclusion criteria: review articles, letters to the editor, commentaries, editorials, protocols, or women with endometriosis infiltrating nerves. Risk of bias analysis was conducted. Data was reviewed and summarized by treatment method. RESULTS: Eight studies met inclusion criteria, demonstrating limited research in this area. Four treatment options were addressed: surgical approaches, nerve stimulation approaches, injection-based therapies, and hormonal therapies. Surgery and nerve stimulation appear the most promising treatments for CS. Injections have limited and mixed evidence of efficacy. Limited evidence suggests hormonal therapies may be ineffective. DISCUSSION: Given the lack of evidence for any treatment, all require further research to determine treatment efficacy before options will be available clinically. There is a clear need for consistency in defining and identifying CS in study populations. This review identifies areas of interest, particularly surgery and nerve stimulation, from which future research must stem.

Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion.

Introduction: Embryo implantation failure leads to infertility. As an important approach to regulate implantation, endometrial epithelial cells produce and secrete factors apically into the uterine cavity in the receptive phase to prepare the initial blastocyst adhesion and implantation. Organoids were recently developed from human endometrial epithelium with similar apical-basal polarity compared to endometrial gland making it an ideal model to study endometrial epithelial secretions. Methods: Endometrial organoids were established using endometrial biopsies from women with primary infertility and normal fertility. Fertile and infertile organoids were treated with hormones to model receptive phase of the endometrial epithelium and intra-organoid fluid (IOF) was collected to compare the apical protein secretion profile and function on trophoblast cell adhesion. Results: Our data show that infertile organoids were dysregulated in their response to estrogen and progesterone treatment. Proteomic analysis of organoid apical secretions identified 150 dysregulated proteins between fertile and infertile groups (>1.5-fold change). Trophoblast progenitor spheroids (blastocyst surrogates) treated with infertile organoid apical secretions significantly compromised their adhesion to organoid epithelial cell monolayers compared to fertile group (P < 0.0001). Discussion: This study revealed that endometrial organoid apical secretions alter trophoblast cell adhesiveness relative to fertility status of women. It paves the way to determine the molecular mechanisms by which endometrial epithelial apical released factors regulate blastocyst initial attachment and implantation.

Effect of Surgical Skin Antisepsis on Surgical Site Infections in Patients Undergoing Gynecological Laparoscopic Surgery: A Double-Blind Randomized Clinical Trial.

Importance: Gynecological laparoscopies are one of the most common surgical procedures worldwide. Limited evidence exists on rates of surgical site infections in patients undergoing gynecological laparoscopies and strategies to prevent these infections. Objective: To compare rates of port-site infections, organ or space infections, and any type of surgical site infections among patients who underwent gynecological laparoscopies and received 1 of 3 types of skin preparation solutions. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted between February 28, 2017, and November 26, 2018, at a tertiary university-affiliated referral center. A total of 661 patients 18 years or older who underwent an elective operative laparoscopy for treatment of nonmalignant gynecological disorders were randomly assigned in a 1:1:1 ratio to have their skin cleaned before surgery with alcohol-based chlorhexidine, alcohol-based povidone-iodine, or water-based povidone-iodine. Statistical analysis was performed from February 28, 2017, to November 26, 2018. Analyses were performed on a modified intention-to-treat basis. Interventions: A total of 221 patients were randomized to have their skin prepared preoperatively with water-based povidone-iodine, 220 were randomized to alcohol-based povidone-iodine, and 220 were randomized to alcohol-based chlorhexidine. The patients were blinded to the solution used to clean their skin. Patients were followed up 1 and 4 weeks after surgery by a physician who was blinded to the skin preparation solution used at surgery. Evidence of infection according to Centers for Disease Control and Prevention criteria were documented. Main Outcomes and Measures: The primary outcome of this study was port-site infection 30 days after surgery. Secondary outcomes were organ or space infections and any type of surgical site infections; the study also aimed to prospectively describe rates of surgical site infections in gynecological laparoscopies. Results: Of the 661 patients, 640 (96.8%; mean [SD] age, 36.2 [10.6] years) were examined after surgery by a physician at the study site and were included in the modified intention-to-treat analysis. The overall rate of port-site infection was 10.2% (65 of 640), rate of organ or space infection was 6.6% (42 of 640), and rate of any surgical site infection was 16.3% (104 of 640). The odds ratio for port-site infection for alcohol-based chlorhexidine vs water-based povidone-iodine was 1.13 (95% CI, 0.61-2.08), for alcohol-based chlorhexidine vs alcohol-based povidone-iodine was 1.34 (95% CI, 0.71-2.52), and for water-based povidone-iodine vs alcohol-based povidone-iodine was 1.19 (95% 0.62-2.27). Conclusions and Relevance: Surgical site infections were more common than expected among patients who underwent gynecological laparoscopies. No skin preparation solution provided an advantage compared with the other solutions in reducing infection rates. Trial Registration: http://anzctr.org.au Identifier: ACTRN12617000475347.

When is laparotomy needed in hysterectomy for benign uterine disease?

STUDY OBJECTIVE: We sought to study laparotomy (conversion and initial) and complication rates among patients who underwent hysterectomy initially performed laparoscopically whenever feasible. DESIGN: A retrospective cohort study (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: A continuous series of 680 patients, operated on between January 1, 2000, and December 31, 2003, was analyzed. Patients with malignancy and prolapse were excluded. INTERVENTIONS: Hysterectomy. MEASUREMENTS AND MAIN RESULTS: Overall, 7.2% of patients underwent laparotomy. In all, 27 (3.9%) patients were treated by initial laparotomy and 22 procedures were converted to laparotomy, 13 to laparoscopic-assisted vaginal hysterectomy (1.9%). Intraoperative and postoperative bladder complication rates were 0.8% and 0.4%, respectively. Ureteric complications were 0.3% and 0.4%, respectively, and bowel complications (bowel occlusion, peritonitis) were 0.4% and 0.4%, respectively. Three patients received blood transfusion. Of 19 patients who had repeated surgery for early or late postoperative complications, 13 were treated by laparoscopy and/or vaginally. CONCLUSION: Including management of complications, laparotomy was necessary in 8.1% of cases. Laparoscopic hysterectomy may be safely used in most patients.