Soluble factors CD14, CD163, and MIF are associated with endometriosis-related infertility.

OBJECTIVES: Myeloid cell-derived factors contribute to the immunopathology of endometriosis. Soluble CD14 (sCD14), CD163 (sCD163), and MIF serves as in vivo markers of myeloid function. However, these soluble molecules are largely unexplored in women with endometriosis-related infertility cases. We investigated three soluble markers, namely sCD14, sCD163, and MIF, in cases of infertility associated with endometriosis and correlated its level to the stage of endometriosis. DESIGN: Eighty-seven women newly diagnosed with endometriosis or other benign gynecologic control cases linked to infertility were prospectively recruited and underwent diagnostic laparoscopy. PARTICIPANTS: Forty-four patients with endometriosis were included in this study, comprising 19 patients with early-endometriosis (stages I and II) and 25 late-endometriosis (stages III and IV) based on the revised American Society for Reproductive Medicine (rASRM) classification. The remaining 43 patients constituted a control group with infertility due to other causes. METHODS: The levels of sCD14, sCD163, and MIF in serum and peritoneal fluid were assessed using ELISA. Results Endometriosis women exhibited significantly higher serum levels of sCD163 and MIF levels compared to the control group. Both sCD163 and MIF levels displayed a positive correlation with the r-ASRM adhesion score. Moreover, the MIF level in serum had a positive correlation with the r-ASRM endometriosis score. In receiver operating characteristic (ROC) analysis, serum sCD163 and MIF could significantly discriminate endometriosis and non-endometriosis in infertility cases. Limitations Some limitations of the current study deserve to be underlined. Firstly, the sensitive ELISA method was the sole validated tool for detecting the markers in patient samples. Secondly, healthy or fertile women were not involved as the control group. Conclusions The elevated systemic levels of sCD163 and MIF correlated with the severity of endometriosis. These soluble molecules have a potential diagnostic capacity as a non-invasive biomarker. Furthermore, our data warrants future studies on the underlying mechanism of sCD163 and MIF in endometriosis-related infertility.

Lay understanding and experience of sexual intercourse among couples with infertility undergoing an assisted reproduction technology program: A qualitative study.

Aim: To explore the perception and lay understanding of sexual intercourse and sexual life experiences among infertile couples before, during, and after undergoing an assisted reproduction technology (ART) program. Method: The participants of this descriptive qualitative study were Indonesian couples with infertility who underwent an ART program. Semi-structured interviews were conducted between September and December 2022, and the participants' responses were recorded. Data were analyzed using a step-by-step analysis based on Braun's qualitative analysis. The study was reported based on the Consolidated Criteria for Reporting a Qualitative Research (COREQ) Checklist. Results: Fifty participants were included, and five themes were developed before and two themes during or after the ART program. The couples' knowledge varied as they experienced sexual intercourse at different periods, such as before, during, and after the ART program. Many participants reported that ART affected their emotions and mood, leading to decreased desire to engage in sexual intercourse. However, some used sexual intercourse as a basis for creating optimism and confidence in having offspring. Furthermore, couples perceived that the purpose of sexual intercourse is not only to have offspring but also to improve communication, promote intimacy, and express affection. In contrast, some perceived the ART program as time consuming, preventing them from engaging in sexual activities. However, not all couples considered sexual activity solely as a means of procreation. They concluded that sexual behavior is not only determined by genetics. Conclusion: Couples who underwent the ART program regardless of its effectiveness were aware that sexual interaction is not only for having children but also for preserving harmony and familial connection.

Ethanol extract of basil (Ocimum Basilicum L.) leaves inhibits endometriosis growth in a mouse model by modulating vascular endothelial growth factor (VEGF) expression.

The objective of this study was to examine the effect of administering an ethanol extract obtained from basil leaves on the expression of vascular endothelial growth factor (VEGF) and the severity of endometriosis lesions in a mouse model. A total of 28 female mice, aged 2-3 months and weighing 20-30 grams, were randomly divided into four groups: the control group (C), treatment group 1 (T1) receiving a dose of basil leaf ethanol extract (0.21 mg/g-BW), treatment group 2 (T2) receiving a higher dose (0.42 mg/g BW), and treatment group 3 (T3) receiving the highest dose (0.84 mg/g-BW). Each group underwent a 14-day treatment period, and tissue samples were collected on the 29th day. An immunohistochemical examination was conducted to assess the expression of VEGF and evaluate the severity of endometriosis lesions. The statistical analysis of VEGF expression revealed a significant difference (p=0.026; p<0.05), with the most pronounced effects observed when administering basil leaf ethanol extract at doses of 0.21 mg/g-BW and 0.42 mg/g-BW. Although not statistically significant (p=0.271; p<0.05), a reduction in the severity of endometriosis lesions was observed following the administration of basil leaf ethanol extract at doses of 0.21 mg/g-BW and 0.42 mg/g-BW. Administering basil leaf ethanol extract at doses of 0.21 mg/g-BW and 0.42 mg/g-BW effectively decreased VEGF expression and limited the severity of endometriosis lesions.

IL-8 and IL-12p70 are associated with pelvic pain among infertile women with endometriosis.

OBJECTIVE: To evaluate interleukin (IL)-1ß, IL-6, IL-8, and IL-12p70 levels in serum and peritoneal fluid in women related to infertility and pelvic pain. METHODS: Eighty-seven women were diagnosed with endometriosis or cases related to infertility. IL-1ß, IL-6, IL-8, and IL-12p70 levels in serum and peritoneal fluid were determined by enzyme-linked immunosorbent assay (ELISA). Pain assessment was evaluated by the Visual Analog Scale (VAS) score. RESULTS: Serum IL-6 and IL-12p70 levels increased in women with endometriosis compared to the control group. Serum and peritoneal IL-8 and IL-12p70 levels correlated with VAS scores in infertile women. A positive correlation was also found between peritoneal IL-1ß and IL-6 with VAS score. A significant difference in peritoneal IL-1ß levels was associated with menstrual pelvic pain, while peritoneal IL-8 levels were related to dyspareunia, menstrual, and post-menstrual pelvic pain in infertile women. CONCLUSIONS: An association of IL-8 and IL-12p70 levels were related to pain in endometriosis, as well as a relationship between cytokine expression and VAS score. Further studies should be addressed to investigate the precise mechanism of cytokine-related pain in endometriosis.

Vitamin D inhibited endometriosis development in mice model through interleukin-17 modulation.

Background: Endometriosis is a common, benign, estrogen-dependent, and chronic gynecological disease. Immune system disturbance and inflammatory abnormalities were involved in the pathogenesis of endometriosis. Therefore, it is logical to use vitamin D, which has an immunomodulatory capacity, as supportive therapy for endometriosis. Aim: This research aimed to study the effect of different doses of vitamin D on Interleukin-17 (IL-17) expression in endometriosis mice models. Methods: Endometriosis was induced in 24 mice divided into 4 groups of 6. Group C received no treatment, while groups T1, T2, and T3 received graded doses of oral vitamin D, sequentially 8, 16, and 24 IU, for 3 weeks. IL-17 expression and the extent of endometriotic peritoneal lesions were then measured and analyzed. Statistical tests were performed to see the difference in the mean area of endometriosis lesions and IL-17 expression between the control and treatment groups, as well as the correlation between the extent of endometriosis lesions and IL-17. Results: Endometriosis lesions decreased after 16 and 24 IU of vitamin D administration (p 0.023 and 0.009). Endometriosis lesion also tends to be smaller after 8 IU of vitamin D supplementation, although insignificant (p > 0.05). IL-17 expression was significantly lower after 24 IU vitamin D administration compared to the untreated group (p = 0.004). Lower IL-17 expressions were also observed after 8 and 16 IU vitamin D administration, although insignificant (p = 0.452 and p = 0.645). IL-17 expression was moderately and positively correlated with the extent of endometriosis lesions (p = 0.012, rho = 0.505). Conclusion: By modulating the expression of IL-17 in endometriotic lesions, vitamin D inhibited the development of endometriotic lesions in the endometriosis mice model. The recommended vitamin D dose in this study was 24 IU.

Elevated peritoneal soluble endoglin and GDF-15 in infertile women with severe endometriosis and pelvic adhesion.

OBJECTIVES: Chronic inflammation and pelvic adhesion play a critical role in endometriosis-related infertility. Research studies suggest that TGF-ß superfamily members, such as soluble endoglin (sEng), growth differentiation factor 15 (GDF-15) and tumor growth factor-beta (TGF-ß1) contribute to the regulation of inflammation, angiogenesis and cell adhesion. The objective of this study is to investigate the association between the concentrations of these TGF-ß-related members and the clinical parameters of infertile women with endometriosis. MATERIALS AND METHODS: Sixty-five infertile women who underwent laparoscopy were divided into two groups in this study: those who had endometriosis (n = 33) and control subjects with benign gynecologic disorders (n = 32). The levels of TGF-ß- related members in peritoneal fluid and serum were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. RESULTS: Endometriosis cases had significantly higher levels of sEng, GDF-15 and TGF-ß1 in peritoneal fluid (p<0.0005) compared to control subjects, but not in serum. Moreover, serum GDF-15 level was significantly elevated in the late-stage endometriosis compared to the early-stage group. The levels of three TGF-ß related molecules in peritoneal fluid showed positive correlations with rASRM score. Blood neutrophil counts have correlation with the peritoneal sEng concentration. CONCLUSION: Our novel evidence on the elevated concentration of peritoneal sEng and GDF-15 in endometriosis, specifically in the late-stage, may indicate the essential role of TGF-ß-dependent signaling in endometriosis. Serum GDF-15 might serve as a candidate biomarker for endometriosis severity. Further studies are warranted to investigate the role and regulation of these molecules in endometriosis.

Effects of different intensities of exercise on folliculogenesis in mice: Which is better?

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.

Soluble immune checkpoints CTLA-4, HLA-G, PD-1, and PD-L1 are associated with endometriosis-related infertility.

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 endometriosis-related infertility.