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.

Are we 'gritty' enough? The importance of 'grit' in O&G training: Association of passion and perseverance with burnout, thriving and career progression.

BACKGROUND: Objective assessment of grit and its association with burnout in obstetrics and gynaecology (O&G) training is underexplored. AIM: This study utilises the Short Grit Scale and the Oldenburg Burnout Inventory to investigate the association of grit with burnout, thriving and career progression among O&G trainees and Fellows in Australia/New Zealand. MATERIALS AND METHODS: A cross-sectional survey of the RANZCOG (Royal Australian and New Zealand College of Obstetricians and Gynaecologists) members was conducted. Participants were categorised by seniority level (core trainees, advanced trainees and Fellows). Mean grit and burnout scores were compared with one-way analyses of variance. Correlation between grit and burnout was estimated using Pearson's correlation coefficient. Logistic regression models were used to determine factors associated with high vs low burnout. Grit was categorised as low/medium/high for regression models. RESULTS: A total of 751 (26%) participants completed the survey. Fellows reported higher mean grit than core (P = 0.02) and advanced trainees (P = 0.03), and lower mean burnout than core trainees (P < 0.001). Moderate negative correlation was demonstrated between grit and burnout scores (r = -0.34). In the multivariable model, only seniority (adjusted adds ratio (OR): 0.40 for Fellows vs core trainees, P = 0.008) and grit levels (adjusted OR:4.52 for low versus high, P < 0.001; 2.32 for low vs medium, P = 0.001) were significantly associated with burnout. CONCLUSION: This study demonstrates the protective role of grit in combating burnout among RANZCOG trainees and Fellows. While further well-designed studies are warranted, findings from our study are expected to help the College in developing targeted interventions and subsequently minimise burnout-related adverse outcomes in high-risk groups.

Evaluation of safety and foeto-maternal outcome following non-obstetric surgery in pregnancy: a retrospective single-site Australian study.

BACKGROUND: Existing data on safety of non-obstetric surgery during pregnancy appear limited and conflicting. This study aimed to assess perinatal outcomes and complications in pregnant women undergoing non-obstetric surgeries. METHODS: A single-site Australian study was performed utilizing a 10-year data (2009-2018) collected retrospectively. Descriptive statistics were used to summarize the characteristics of the study population. Statistical analyses between groups were conducted by independent t-test or Mann-Whitney (for means between groups) and by chi-squared/Fisher's exact test (for categorical variables). RESULTS: A total of 108 pregnant women underwent non-obstetric surgery, with an increasing trend in annual numbers since 2014. The majority of women (91%) underwent surgeries as an emergency procedure, and under general anaesthesia (69.8%). Procedures during the first trimester comprised 45%, making it the most common trimester for non-obstetric surgeries. The most common cause for surgery arose in the gastrointestinal/digestive tract (39%). Overall perinatal complication rate was 19% with the rate of miscarriage/foetal loss, preterm birth and intrauterine growth restriction/small for gestational age being 4.7%, 10.4% and 3.8%, respectively. A total of 46 patients underwent intra-abdominal surgery. The most common surgery in the laparoscopy group was appendicectomy (56%), whereas adnexal pathology (54%) contributed to the majority of laparotomies. Subgroup comparison showed no significant difference in perinatal outcomes except for caesarean delivery rate (24% versus 67% for laparoscopy versus open, respectively (P = 0.04)). CONCLUSION: With an overall perinatal complication rate of 19%, the rate of adverse perinatal outcomes following non-obstetric surgery during pregnancy in our study was low and comparable to those of the general population.

A refined method for estimating the size of the potential blood donor pool in Australia.

BACKGROUND: To be eligible to donate blood, potential donors must meet certain eligibility criteria to ensure safety to the donor and to the blood supply. In Australia, there is no reliable estimate of the size of the donor-eligible population. This study uses a refinement to a published method to determine the population prevalence of donor-exclusion factors and subsequently estimates the size of the potential donor pool in Australia. STUDY DESIGN AND METHODS: A total of 70 donor-exclusion factors (in addition to age) were identified. The donor-eligible population was estimated by subtracting the prevalence of the exclusion factors from the total population. Prevalence of the donor-exclusion factors was adjusted for age, deferral period, and overlap of multiple conditions. Overlap was adjusted by extending a published random-probability model according to known association of epidemiologic data on overlapping conditions. RESULTS: The most prevalent (deferral period-adjusted) donor-exclusion factor among the 16- to 80-year-old Australian population was variant Creutzfeldt-Jakob disease-related travel risk (6.8%) followed by upper respiratory tract infections (6.4%). After exclusion of all factors, and accounting for overlapping factors, 62% of 16- to 80-year-olds or 47.3% of the total population were donor eligible in Australia. CONCLUSION: We developed a refined method for estimating the size of the donor-eligible population. Applying this method to Australia, we estimate that approximately 10.7 million people (62% of the 16- to 80-year-olds) were eligible to donate blood in Australia in 2012.

Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors.

BACKGROUND: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. STUDY DESIGN AND METHODS: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. RESULTS: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. CONCLUSION: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.

Trends in transfusion-transmissible infections among Australian blood donors from 2005 to 2010.

BACKGROUND: Routine monitoring of trends in transfusion-transmissible infections (TTIs) is essential to maintaining and improving transfusion safety. Although periodic studies have been published there is no comprehensive trend analysis for TTIs in Australian donors. This study determined recent trends in TTIs for which testing is conducted in Australia and described key attributes of infected blood donors. STUDY DESIGN AND METHODS: This is a retrospective analysis using data on donation testing for TTIs (2005-2010) from the national blood service donor database and data on postdonation interviews with TTI-positive donors (2008-2010) from a risk factor database incorporating responses to standardized interview questions. The study measured the prevalence and incidence of TTIs in Australia and assessed their time trends. Multivariate analysis of time trends was conducted using Poisson regression models. RESULTS: Overall, the prevalence and incidence of TTIs in 2005 to 2010 remained low and steady. The prevalence of hepatitis C virus decreased (rate ratio [RR], 0.93; 95% confidence interval [CI], 0.89-0.97) and the prevalence of active syphilis increased (RR, 1.51; 95% CI, 1.15-1.99) significantly during the study period. Prevalence of TTIs among Australian blood donors was substantially lower than that in the general population and no unique risk factors were identified in test-positive blood donors when compared with the general population. CONCLUSION: Both the prevalence and the incidence of TTIs in Australian blood donors remained low, with a steady or declining trend for most infections except active syphilis. The lower prevalence of TTIs in blood donors compared with the general population reflects the effectiveness of donor education and donor selection measures in Australia.