Problem: Soluble immune checkpoint molecules constitute the emerging novel mediators in immune regulation. Their role in the pathogenesis of endometriosis has not been fully addressed. In this study, we aimed to investigate the relationship between the clinical manifestation of endometriosis-associated infertility and the level of four soluble immune checkpoints: sCTLA4, sHLA-G, sPD-1, and sPD-L1. Method of study: The soluble immune checkpoint concentrations in serum and peritoneal fluid from 88 patients who underwent laparoscopy were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. Results: Endometriosis cases were evident to have significantly higher levels of serum sPD-L1 and all four molecules in peritoneal fluid compared to non-endometriosis control. Contrary, no significant differences were found in the concentration of serum sCTLA-4, sHLA-G and, sPD-1 between endometriosis and control group. There were significant positive correlations between serum and peritoneal fluid concentrations of sCTLA-4, sPD-L1, and sHLA-G. Serum sPD-L1 could discriminate endometriosis-related infertility to other pathological control. At a cutoff of 14,61 pg/ mL, serum sPD-L1 had a sensitivity of 77% and specificity of 83%. Moreover, sPD-L1 level showed positive correlations with pelvic adhesion score and myeloid cell count. Conclusion: The elevated level of sPD-L1 in serum and immune checkpoint molecules in the peritoneal fluid could represent the hallmark of immune regulation in endometriosis. Serum sPD-L1 could serve as a potential noninvasive endometriosis biomarker. Also, the immune compartment related to the local immune checkpoint molecules may be implicated in biological mechanisms underlying endometriosisrelated infertility.
Background and Aim: Endometriosis affects the ovaries and causes a decrease in the oocyte quality during endometrial receptivity. During the development of ovarian follicles, paracrine communication occurs between granulosa cells and oocytes. This study was conducted to determine the effects of bone marrow mesenchymal stem cell transplantation on tumor necrosis factor-alpha (TNF-α) receptor 1 (TNFR1) expression, granulosa cell apoptosis, and folliculogenesis in endometriosis mouse models. Materials and Methods: This study involved 42 female mice, which were divided into three groups: Healthy mice (T0), endometriosis mice without transplantation (T1), and endometriosis mice with bone marrow mesenchymal stem cell transplantation (T2). The mice were injected intraperitoneally with endometrial fragments (200 μL) to become endometriosis models. On day 15, the endometriosis models received mesenchymal stem cells. Sample collection was performed on day 29. Granulosa cell apoptosis and TNFR1 expression were examined using immunohistochemical staining, and folliculogenesis was assessed using hematoxylin and eosin staining of ovary samples. The data obtained from both examinations were statistically analyzed using Statistical Package for the Social Sciences. Results: The results showed that TNFR1 expression is significantly decreased in T2 (p<0.004). The apoptosis of granulosa cells was lower in T2 (p<0.000). The primary, secondary, and graafian follicle counts in T2 were significantly increased. Conclusion: Bone marrow mesenchymal stem cell transplantation in endometriosis mouse models can reduce TNFR1 expression and granulosa cell apoptosis and improve folliculogenesis.
Background: Endometriosis is an estrogen-dependent chronic progressive gynecological dis-ease that affects around 10% of women of reproductive age. A recent study shows that brain-derived neurotrophic factor (BDNF) has the potential as a clinical marker in the diagnosis of endometriosis. We aimed to determine whether BDNF levels are correlated with pain scores associated with endometriosis. Methods: Fifty women who underwent laparoscopy surgery at Dr. Soetomo General Hos-pital and Dr. Ramelan Navy Hospital were prospectively recruited from October 2017 until August 2018. A blood sample was obtained before surgery and BDNF was measured using the Human BDNF Quantakine®️ kit. The relationship of BDNF levels in serum with the diseases's level of pain and stages was compared between cases and controls. BDNF validity as an endometriosis diagnosis biomarker was assessed using receiver operating characteristic (ROC) analysis. Results: Serum concentrations of BDNF were significantly greater in women with endo-metriosis (30.42±7.41 pg/ml), compared to controls (25.66±3.30 pg/ml). Serum concentra-tions of BDNF were moderately correlated with the patient’s reported pain scores (r=0.44, p=0.01). Receiver operating characteristic curve analysis confirmed the potential of BDNF in the diagnosis of endometriosis. Using a cut-off value of 27.06 pg/ml, the sensitivity and specificity were reported to be 66.7% and 64.3%, respectively. Conclusion: BDNF serum levels in endometriosis women are significantly higher than in women without the disorder. BDNF serum level seems to have low accuracy and predictive value as a diagnostic marker for endometriosis. However, there was a moderate relationship between BDNF serum level and the degree of pain.
The success rate of in Vitro Fertilization (IVF) with ICSI depends on married couples factors such as maternal age, causes of infertility from the married couples, embryo status, reproductive history, lifestyle, ethnicity, and type of medical examination of infertility. The success rate of IVF was different among countries, rating from 21.4% to 51.7% meaning that the couples succeeded having a child, while in Indonesia the rate was unknown. Objective:To analyze infertility causing factors in married couples who underwent IVF and the success rate of IVF in one fertility center in Surabaya, Indonesia. Method: This observational study was conducting during January to December 2017. All couples who visited the fertility center,the female ≤ 39 years old, and the couples finished medical examination in the study place were asked to participate this study. Their characteristics (female age and duration of marriage), type infertility causing factors as well as the success rate.Results: Among 154 married couples, 64.3% of the female and 44.8% of the male had one or more abnormality in their reproductive status, while 26.6% of both (the couples) had the abnormalities, and 17.5% of both (the couples) had no abnormality (unexplained infertility). The success rate of IVF, meaning the female got pregnancy, was 37.7%.There was no significant association between male factors, female factors, more over the number of abnormalities were not associate to success rate. When correspondents divided in to 2 groups, having one or more abnormalities group vs. no abnormalities group (unexplained abnormality), we found that the success rate did not differ significantly between the two groups; suggesting additional examination were needed to predict the other factors for increasing the success rate in this study place.
Objective: Exercise is a risk factor for infertility in women. However, research on the effects of different intensities of exercise on folliculogenesis has not yielded clear results. This study was conducted to analyze the effects of differences in the intensity of exercise on folliculogenesis in mice. Methods: Nineteen female BALB/c mice (age, 3–4 months; weight, 13–25 g) were randomly divided into four groups: control, mild exercise, moderate exercise, and high-intensity exercise. The mice in the exercise groups engaged in swimming, with additional loads of 3%, 6%, or 9% of body weight, respectively. There were five swimming sessions per week for 4 weeks, with a gradually increasing duration every week. At the end of the treatment, ovarian extraction was carried out and hematoxylin and eosin staining was performed to identify folliculogenesis. Results: There were significant differences in the number of total follicles between the control and moderate-exercise groups (p=0.036) and between the mild- and moderate-exercise groups (p=0.005). The mean number of primary follicles was higher in the moderate-exercise group than in the mild-exercise group (p=0.006). The mean number of secondary, tertiary, and Graafian follicles did not differ significantly among groups (p≥0.05). However, the number of total follicles and follicles in each phase tended to increase after exercise, especially moderate-intensity exercise. Conclusion: Exercise of different intensities affected the total number of follicles and primary follicles. The number of follicles of each phase tended to increase after exercise. Moderate-intensity exercise had better effects than other intensities of exercise.
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