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Objective: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100–125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first‐trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first‐ trimester fasting plasma glucose levels, as compared with gestational diabetes, a well‐established risk factor for diabetes, in up to 5‐year follow‐up postpartum. Methods: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post‐delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic‐area under the curve (ROC‐AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. Results: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut‐off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. Conclusions: Increased first‐trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first‐trimester fasting plasma glucose has a more pronounced impact on progression to diabetes. Synopsis: First‐trimester fasting plasma glucose levels exceeding 86.5 mg/dL carry at least a comparable risk for type 2 diabetes progression as gestational diabetes, regardless of obesity status. [ABSTRACT FROM AUTHOR]

Introduction: The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC) and is considered a promising therapeutic target. EOC is an immunosuppressive disease, although there are limited data about the involvement of the IGF1R system in the anti-tumor immune response in the EOC microenvironment. Methods: In the current study, we hypothesized that IGF 1 receptor (IGF1R) involvement in the maturation of dendritic cells (DC) with the co-inhibition of IGF1R and PD-1 would affect the EOC microenvironment. Results: We found that DC pretreated with IGF1R inhibitor resulted in fewer EOC cells. Moreover, in vivo experiments conducted with an EOC mouse model, with anti-PD-1/IGF1R combined, resulted in lower tumor weight compared to individual treatments. Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1. The combined treatment increased CD8+ T-cell levels compared to AEW-541 alone. RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone. Discussion: These findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations. [ABSTRACT FROM AUTHOR]

Background: Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. Objective: To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. Study design: Retrospective cohort and validation study. Methods: Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48–72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. Results: The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0–8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0–3) was 9%, compared with 82% in the highest likelihood score group (score 7–8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. Conclusions: MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the extent to which childbirth may function as a retraumatization of childhood sexual abuse, and may exacerbate postpartum posttraumatic stress reactions. Methods: Data was obtained from a convenience sample of 837 women in mid-pregnancy, at 2 and 6 months following childbirth. Three groups were drawn from this sample: women who experienced childhood sexual abuse (CSA), women survivors of trauma other than CSA, and women who reported no-trauma experiences. Results: PTSD subcategories of intrusion and arousal were increased in the CSA group following childbirth, although the overall PTSD score did not increase following childbirth in any of the groups CSA survivors scored higher at all data collection time points. Conclusions: CSA is a traumatic event that has greater negative long-term effects than other traumas in the population of pregnant women. Practice implications: Identifying women who are survivors of CSA early in their pregnancy and establishing a risk assessment may significantly reduce delivery complications and consequently mitigate postpartum PTS outcomes. (Contains 11 tables.)

Purpose: Heparanase is an endo-b-glucuronidase that cleaves side chains of heparan-sulfate proteoglycans, an integral constituent of the extra cellular matrix. The abundance of heparanase in placental trophoblast cells implies its role in the processes of placentation and trophoblast invasion. This study aims to explore the involvement of heparanase in parturition and preterm deliveries (PTD). Methods: Sixteen human placentas were collected following singleton spontaneous onset term vaginal deliveries (n = 6), spontaneous onset preterm vaginal deliveries (n = 7) and term elective cesarean sections (n = 3). Placentas were excluded in case of any maternal chronic illness, pregnancy or delivery complications apart from PTD. Placental tissue samples were dissected, homogenized and proteins were extracted. Additionally, cryosections were prepared from the placental tissues. Heparanase expression was evaluated utilizing western blot analysis and immunofluorescence staining using heparanase specific antibodies. Heparanase expression was compared between the study groups qualitatively and quantitatively. Results: Western blot analysis results demonstrated higher expression of both pro-heparanase and heparanase in PTD placentas compared to term vaginal placentas. Accordingly, immunofluorescence staining shows elevated heparanase expression in PTD placentas compared to term vaginal placentas (5.1 ± 0.92 vs. 1.2 ± 0.18, p < .005). Expression level of heparanase was higher in term cesarean section placentas as compared to term vaginal deliveries placentas, but did not reach statistical significance (1.8 ± 0.39 vs. 1.2 ± 0.18, p = .06). Conclusion: This study demonstrates for the first time that preterm vaginal deliveries are associated with higher expression of heparanase in placental tissue. This may imply a direct effect of heparanase on preterm labor. Further studies should evaluate the functional role by which heparanase influence preterm delivery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between congenital uterine anomalies (CUA) and adverse perinatal outcomes stratified by type of anomaly. Methods: A retrospective cohort study of all women delivered in one university-affiliated medical center between 2010 and 2017 with CUA. Multiple pregnancies and pregnancies complicated by fetal anomalies were excluded. Maternal and short-term neonatal outcomes were evaluated and compared between women with unification defects (unicornuate, bicornuate, or uterus didelphys), and canalization defects represented by septate uterus. Univariate analysis was utilized followed by multivariate analysis to adjust for confounders. p < .05 was considered significant. Results: Among 167 pregnancies with CUA, 92 (55.1%) had bicornuate uterus, 32 (19.1%) septate uterus, 26 (15.6%) didelphys uterus, and 17 (10.1%) unicornuate uterus. Maternal demographics and obstetric characteristics were similar between women with unification and canalization defects. The entire cohort had high rates of preterm delivery (PTD), malpresentation, and cesarean delivery (CD) (25.7%, 42.5%, and 63.5%, respectively). In comparison to unification defects, pregnancies in women with canalization defects (septate uterus), had increased risk for PTD <32 weeks (12.5% vs. 2.9%, p = .02), and placental abruption (12.5% vs. 3%, p = .02), however, a lower overall rate of CD (46.9% vs. 67.4%, p = .03). Following adjustment to confounders (age, BMI, nulliparity, chronic hypertension, and smoking) none of the results remained statistically significant. There were no differences in neonatal outcomes between the groups. Conclusions: Overall, women with CUA have a high prevalence of adverse pregnancy outcomes. However, outcome does not differ by type of anomaly. [ABSTRACT FROM AUTHOR]