Association of interleukin-6 and estradiol with hepatocyte growth factor in peritoneal fluid of women with endometriosis

BACKGROUND: Different cytokines and ovarian steroid hormones have been reported to regulate the growth and maintenance of endometriosis. We determined the relationship between peritoneal fluid concentrations of interleukin-6, ovarian steroids and hepatocyte growth factor in different revised American Fertility Society (AFS) staging and morphologic appearances of endometriosis. METHODS: Peritoneal fluid was collected from 30 women with endometriosis and 20 women without endometriosis during laparoscopy, and hepatocyte growth factor, interleukin(IL)-6 and ovarian steroids were measured in peritoneal fluid. The concentrations of hepatocyte growth factor and IL-6 in peritoneal fluid were measured by ELISA, and that of estradiol and progesterone by using the immulyze-enzyme amplified luminescence system. Changes in peritoneal fluid concentrations of hepatocyte growth factor, IL-6, estradiol and progesterone in different stages and morphologic appearances of endometriosis were examined to demonstrate their differences in early and advanced endometriosis. RESULTS: Peritoneal fluid levels of hepatocyte growth factor in women with stage I-II endometriosis were significantly higher than in both women with stage III-IV endometriosis and without endometriosis. A similar significant increase in stage I-II endometriosis was also observed for IL-6 and estradiol. When we divided the women according to different morphologic appearances of endometriosis, we found significantly higher concentrations of hepatocyte growth factor (HGF), IL-6, estradiol and progesterone in women containing red lesions compared with other pigments or without endometriosis. A positive correlation was observed between peritoneal fluid levels of IL-6 and hepatocyte growth factor only but not between other markers. Although estradiol levels in peritoneal fluid showed an increased tendency to elevate in the proliferative phase of endometriosis women, hepatocyte growth factor and progesterone displayed higher concentrations in the secretory phase of the menstrual cycle. After adjusting different variables in peritoneal fluid, multiple analysis of covariance indicated that hepatocyte growth factor levels in peritoneal fluid were independently involved in the red morphologic activity of endometriosis. CONCLUSIONS: Early staging and red color appearance of endometriosis are associated with the elevation in peritoneal fluid concentrations of hepatocyte growth factor, IL-6 and estradiol, demonstrating the combined effect of these cytokines and ovarian steroids in the production of hepatocyte growth factor from endometrial tissues in active endometriosis.     

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.     

Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis

OBJECTIVE: To determine the concentrations of interleukin-18 (IL-18) in peritoneal fluid and serum in patients with endometriosis in comparison with the control group. DESIGN: A prospective analytical study. SETTING: The obstetrics and gynecology department of an academic training hospital. PATIENT(S): Forty-four patients who underwent laparoscopic surgery for benign gynecologic diseases. INTERVENTION(S): Specimens of peripheral blood and peritoneal fluid were obtained before and during laparoscopic procedures, and the levels of IL-18 were analyzed. MAIN OUTCOME MEASURE(S): The concentrations of IL-18 in peritoneal fluid and serum were correlated with the presence of endometriosis, disease stage, and the phase of the menstrual cycle. RESULT(S): Interleukin-18 was detectable in 98% of the peritoneal specimens and 84% of the serum specimens of the patients tested. Peritoneal fluid IL-18 concentrations were statistically significantly lower in patients with endometriosis than in patients without endometriosis; the difference in serum IL-18 levels showed no statistically significant difference between the patients with and without endometriosis. The concentrations of IL-18 in peritoneal fluid and serum were not correlated with the stage of endometriosis or the phase of the menstrual cycle. CONCLUSION(S): Our results suggest that the decreased levels of IL-18 in peritoneal fluid in patients with endometriosis as compared with the control group may play an important role in the pathogenesis of this disease.     

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

OBJECTIVE: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis. METHODS: Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls. RESULTS: Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups. CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.     

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis

Purpose

To determine, with extended receiver operating characteristic (ROC) curve analysis, the diagnostic value of cytokines showing significantly different peritoneal concentrations between women with and without endometriosis.

Methods

Multiplex cytokine concentration measurement of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ levels in peritoneal fluid of women with minimal to mild (n = 10) and moderate to severe (n = 26) endometriosis, and 42 controls.

Results

Only IL-6 and IL-10 concentrations were significantly higher in endometriosis patients than in controls. Specifically, significantly higher IL-6 and IL-10 levels were found in moderate to severe but not in minimal to mild endometriosis as compared to controls. For evaluation of diagnostic significance, ROC analysis determined discriminating parameters for IL-6, while those calculated for IL-10 were useless. Importantly, ROC analysis for IL-6 levels limited to women with moderate to severe endometriosis showed the highest area under the curve with the sample size sufficient to achieve 90 % power of the test. Finally, extended ROC including cost of analysis for this group of patients determined the optimal cut-off leading to high specificity and positive likelihood ratio resulting in 79 % effectiveness of the test.

Conclusions

While our outcomes show moderate usefulness of peritoneal IL-6 levels in discrimination of moderate to severe endometriosis, further studies might be needed to determine the usefulness of peritoneal IL-6 levels in detection of early stages of endometriosis, as such a finding would be more relevant in clinical decision making.     

子宫内膜异位症患者辅助性T细胞亚群免疫状态的研究

目的　探讨辅助性T细胞 (Th)亚群在子宫内膜异位症 (内异症 )发病中的作用。方法　采用酶联免疫吸附法检测 30例内异症患者 (内异症组 )及 2 0例非内异症患者 (对照 1组 )血清及腹腔液中白细胞介素 (IL) 2、6的水平 ;用免疫组化技术分别检测IL 2、IL 6在内异症组患者异位内膜组织和 10例子宫肌瘤患者 (对照 2组 )的正常子宫内膜组织中的表达。结果　内异症组患者血清及腹腔液中位数IL 6水平分别为 5 3、2 1ng/L ,对照 1组患者血清及腹腔液中位数IL 6水平分别为 2 5、0 9ng/L ,两组妇女血清和腹腔液中IL 6水平分别比较 ,差异均有统计学意义 (P <0 0 5 ) ;内异症组Ⅲ～Ⅳ期患者血清及腹腔液中位数IL 6水平分别为 13 6、4 1ng/L ,Ⅰ～Ⅱ期患者血清及腹腔液中位数IL 6水平分别为 3 7、1 6ng/L ,Ⅲ～Ⅳ期患者与Ⅰ～Ⅱ期患者血清及腹腔液中位数IL 6水平比较 ,差异均有统计学意义 (P <0 0 5 ) ;内异症组IL 2 /IL 6比值在血清及腹腔液中分别为 0 7、1 1,均分别低于对照组的 0 8、6 2 ,差异也有统计学意义 (P <0 0 5 )。内异症组患者腹腔液与血清IL 6水平呈正相关 (r =0 74 5 ,P <0 0 1) ,血清及腹腔液中IL 6水平与IL 2 /IL 6比值均呈负相关 (r =- 0 4 0 6 ,P <0 0 5 ;r =- 0 4 80 ,P <0 0 5 )     

Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis

OBJECTIVE(S): To determine [1] vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels in peritoneal fluid from women with endometriosis and compare them with those from oral contraceptive (OC) users and normal cycling women and [2] any correlation between VEGF and IL-6 concentrations. DESIGN: Controlled clinical study. SETTING: University medical center. PATIENT(S): Patients undergoing laparoscopy for infertility or other benign gynecologic conditions. INTERVENTION(S): Peritoneal fluid samples were collected. MAIN OUTCOME MEASURE(S): Levels of VEGF and IL-6 in peritoneal fluid were determined. RESULT(S): Compared with normal controls or women with less severe endometriosis (implant scores of 5 or less), women with more advanced endometriosis (implant scores of 6 or more) have elevated VEGF and IL-6 levels in peritoneal fluid. Compared with normal controls, markedly suppressed IL-6 but similar VEGF levels were found in peritoneal fluid from OC users. Neither VEGF nor IL-6 varied cyclically in normal women or those with endometriosis. There was no correlation between levels of VEGF and IL-6 in peritoneal fluid. There was no correlation between implant scores and VEGF or IL-6 levels. CONCLUSION: The inflammation associated with endometriosis, through increased levels of peritoneal fluid VEGF, may promote angiogenesis for the progressive growth of endometriosis. Effective treatment of endometriosis by combination estrogen-progestin pills may involve the suppression of such inflammatory responses.     

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Purpose

The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF).

Methods

Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women.

Results

Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P?<?0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality.

Conclusion

The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.

     

Soluble serum interleukin-2 receptor,interleukin-6 and interleukin-1a in patients with endometriosis and in controls

The aim of this study was to verify to what extent danazol alters cell-mediated immunity. To this end, cell-mediated immunity was studied in 10 infertile patients with endometriosis and in 10 normal controls. Nonspecific parameters studied included serum SIL-2R, IL-6 and IL-1a levels. We also investigated the effect of treatment with Danazol on the levels of SIL-2R, IL-6 and IL-1a in women with endometriosis. Blood SIL-2R, IL-6 and IL-1a levels were measured in endometriotic women before treatment, during the last fifteen days of a 6-months course of Danazol and three months after treatment. Only one blood sample was taken from 10 women without endometriosis. SIL-2R, IL-6 and IL-1a levels were higher in women with endometriosis before treatment compared with controls. Administration of the drug significantly reduced the levels of SIL-2R (P<0.001), IL-6 (P<0.05) and IL-1a (P<0.01). Our findings suggest that endometriosis is a condition which induces a rise in interleukin levels. Danazol also appears significantly to reduce endometriosis — associated autoimmune abnormalities.     

The evaluation of IL-12 levels in peritoneal fluid and serum of women with endometriosis

We studied levels of IL-12 in peritoneal fluid and serum in patients with minimal, advanced and recurrent endometriosis compared to women without endometriotic lesions in pelvis minor. The aim of the study was to determine whether level of IL-12 detected in peritoneal fluid or serum changes with grading of severity of endometriosis. To assess IL-12 levels immunosorbent ELISA was used. There were no statistically significant differences in IL-12 levels in peritoneal fluid nor in serum in any of studied groups. There was higher concentration (without statistical significance) of IL-12 in peritoneal fluid of healthy women compared to women with endometriosis.     

Peritoneal fluid concentrations of interleukin-17 correlate with the severity of endometriosis and infertility of this disorder

This prospective study aimed to determine whether patients with endometriosis are having different level of interlukin-17 (IL-17) in peritoneal fluid when compared with patients without endometriosis. The patients with minimal/mild endometriosis had a significantly higher level of IL-17 in peritoneal fluid compared with those with moderate/severe endometriosis or without endometriosis. The concentration of IL-17 in peritoneal fluid was significantly higher when endometriosis and infertility coexist. However, the concentration of IL-17 in peritoneal fluid did not correlate with the phase of the menstrual cycle in the patients with or without endometriosis. Our study suggested that IL-17 might play an important role in the pathogenesis of early endometriosis and endometriosis-associated infertility.     

Peritoneal fluid concentrations of interleukin-4 in relation to the presence of endometriosis, its stage and the phase of the menstrual cycle

BACKGROUND: Interleukin-4 (IL-4) is a cytokine with both stimulatory and inhibitory effects on the inflammatory system such as macrophage inhibition and T-cell activation. It is known to regulate several monocyte functions, including inhibition of the synthesis of cytokines such as IL-1, IL-6 and TNF-alpha as well as potentiating IL-8. METHOD: In an attempt to clarify the association between IL-4 and endometriosis, we measured the concentration of IL-4 in the peritoneal fluid of 52 women; 24 with endometriosis and 28 with no endometriosis, controlling for the phase of the cycle and the stage of disease. RESULTS: There was no difference in the concentrations of IL-4 between women with (n=28) and without endometriosis (n=24). No difference was found between the IL-4 concentrations in women with different stages of endometriosis. Levels of IL-4 did not show a difference according to the phase of the cycle in either group. CONCLUSION: Our results indicate no association between peritoneal fluid levels of IL-4 and endometriosis and hence suggest that IL-4 is not involved in the pathogenesis of endometriosis.     

子宫内膜异位症患者腹腔液白细胞介素6,8及转化生长因子β1 …

OBJECTIVE: To investigate the role of cytokines in peritoneal fluid on pathogenesis of endometriosis (EM). METHODS: Interleukin-6 (IL-6), interleukin-8(IL-8) and transforming growth factor-beta 1 (TGF-beta 1) contents in peritoneal fluid (PF) of 31 cases with EM were detected by enzyme linked immunoabsorbent assay (ELISA) and compared with the counterparts of 22 cases without EM (controls). The correlation analyses between cytokine concentrations in peritoneal fluid of EM patients and the severity of EM or dysmenorrhea score were performed. RESULTS: The peritoneal fluid from patients with EM contained significantly greater amounts of IL-6 [(1.8 +/- 0.4) ng/L] and IL-8 [(1.7 +/- 0.5) ng/L] than those in controls [(1.2 +/- 0.2) ng/L and (1.4 +/- 0.3) ng/L respectively, P < 0.05]. However, in the amounts of TGF-beta 1 there were no significant difference (P > 0.05) between the two groups. The highest PF IL-6 and IL-8 concentrations were found in stage II, III and stag I, II EM respectively. A significant correlation between PF IL-6 content and the severity of disease was noted but there were no evidences of a relationship between concentrations of IL-8 and TGF-beta 1 and the severity of EM as well as between concentrations of three cytokines and dysmenorrhea score. CONCLUSION: Unusual levels of IL-6 and IL-8 in PF of EM patients partly account for imbalance of the immunologically dynamic environment in peritoneal cavity of EM patients.     

Increased levels of human neutrophil peptides 1, 2, and 3 in peritoneal fluid of patients with endometriosis: association with neutrophils, T cells and IL-8

Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. This disease is associated with pelvic inflammation and displays some features of autoimmune disorder. Human neutrophil peptides 1, 2, and 3 (HNP 1-3) belonging to α-defensin family play a crucial role in innate immunity against infections and may exert immunoregulatory effects. They may play a role in various inflammatory reactions; however, their role in endometriosis has not been studied. Therefore, the aim of the present study was to evaluate HNP 1-3 in the peritoneal fluid of 67 patients with endometriosis and 16 healthy control women in relation to peritoneal leukocyte subpopulations (neutrophils, T cells, and macrophages) and inflammatory cytokines (IL-6 and IL-8). HNP 1-3, IL-6 and IL-8 were evaluated in the peritoneal fluid by specific enzyme-linked immunosorbent assays (ELISA), and peritoneal leukocyte subpopulations were evaluated by flow cytometry. We found that the levels of HNP 1-3 were significantly increased in the peritoneal fluid of endometriosis patients, compared with control women, and correlated with severity of the disease. Endometriosis was also associated with increased concentrations of peritoneal neutrophils. In endometriosis the levels of HNP 1-3 strongly correlated with concentrations of neutrophils, T cells and IL-8. HNP 1-3 levels were not associated with peritoneal IL-6 or macrophages. These data suggest that HNP 1-3 and neutrophils might play a role in immunopathogenesis of endometriosis and may be worth evaluating as targets for anti-endometriosis therapy.     

Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology.

OBJECTIVE: To determine if interleukin 6 (IL-6) is a normal constituent of peritoneal fluid (PF), and if various types of pelvic pathology influence its presence within the PF microenvironment. STUDY DESIGN: Peritoneal fluid from 73 women obtained at the time of laparoscopy was examined for the presence of IL-6 using an IL-6 specific sandwich enzyme-linked immunosorbent assay. Thirty-nine patients had pelvic endometriosis, 17 had nonendometriotic pelvic adhesive disease, and 17 subjects undergoing tubal sterilization without evidence of pelvic pathology served as controls. RESULTS: Immunoreactive IL-6 was observed in the PF of all 73 subjects (range 0.26 to 11.16 ng/mL). The mean concentration of IL-6 was higher in women with nonendometriotic pelvic adhesions as compared with control subjects (1.28 +/- 0.16 versus 0.80 +/- 0.06 ng/mL, P less than 0.03). There was no difference in the mean peritoneal concentrations of IL-6 between women with endometriosis (1.16 +/- 0.28 ng/mL) and controls, P = 0.38. Twenty-seven of 73 patients (37%) demonstrated elevated levels (greater than 1.0 ng/mL) of IL-6. Patients with pelvic adhesions were significantly more likely to have elevated concentrations of IL-6 than controls (10/17 [59%] versus 3/17 [18%], P less than 0.02). Alternatively, the percentage of patients with elevated IL-6 concentrations did not differ between patients with endometriosis or controls (14/39 [36%] versus 3/17 [18%], P greater than 0.10). CONCLUSIONS: These findings demonstrate that IL-6 is a normal constituent of PF and that elevated levels are found in many patients with pelvic adhesions.     

T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

In the present study, interleukin (IL)-10, IL-12, IL-17, and IL-23 levels were measured in serum and peritoneal fluid of women with minimal or mild endometriosis and compared with levels in controls without endometriosis. Higher IL-23 levels were encountered in the peritoneal fluid of women with endometriosis, suggesting a possible role of this cytokine in these women's infertility.     

子宫内膜异位症患者血清与腹腔液中肿瘤坏死因子α及白细胞 …

目的 了解子宫内膜异位症（内异症）患者血清及腹腔液中肿瘤坏死因子α（ＴＮＦ－α）、白细胞介素６（ＩＬ－６）的水平以及在腹腔镜保守性手术治疗后的变化。方法 收集内异症Ｉ、Ⅱ期及Ⅲ、Ⅳ期患者各１０例（共２０例）有腹腔镜手术前后的血清和腹腔液,并以经腹腔镜检查确诊为与内异症无关病例１０例（共２０例）有腹腔镜手术前后的血清和腹腔液,并以经腹腔镜检查确诊为与内异症无关病例１０例为对照,应用放射免疫双抗体夹心     

Expression of inflammatory cytokines in serum and peritoneal fluid from patients with different stages of endometriosis

Objective: To investigate the level of inflammatory cytokines in endometriosis patients, and explore the relationship between IL-37 concentration and endometriosis stages.

Methods: Inflammatory cytokine concentrations from 27 patients with different stages of endometriosis and 52 controls without endometriosis were examined by ELISA. Then, the specificity and sensitivity of cytokines for distinguishing from controls and the different stages of endometriosis were analyzed using the ROC curve.

Results: The difference in serum concentrations of IL-37, IL-17A, IL-10, and IL-2 between the endometriosis and control groups was statistically significant (p?p?p?=?.0034), IL-10 concentrations in PF were significantly lower in the early-stages of endometriosis than in the more advanced groups (p?=?.0439), and IL-4 concentration in PF was significantly higher in more advanced endometriosis (p?=?.0228). The sensitivity and specificity of serum IL-37 for distinguishing endometriosis were 81.48% and 83.33%, respectively, and the cutoff concentration was 69.84?pg/ml. For IL-17A, the sensitivity and specificity were 96.30% and 100%, respectively, and the cutoff concentration was 57.54?pg/ml. For IL-10, the sensitivity and specificity was 92.59% and 100%, respectively, and the cutoff concentration was 3.301?pg/ml. For IL-2, the sensitivity and specificity were 74.07% and 93.75%, respectively, and the cutoff concentration was 1.813?pg/ml. For PF IL-2, the sensitivity and specificity were 29.73% and 100%, respectively, and the cutoff concentration was 1.06?pg/ml.

Conclusions: IL-37, IL-17A, IL-10, and IL-2 may play a significant role in immune response in endometriosis. IL-37 levels may be used as a diagnostic marker for endometriosis.     

Role of cytokines in endometriosis-associated infertility

Endometriosis, which is common in women of reproductive age, may affect fertility. It is also clear that mechanical disruption of the pelvic anatomy may cause infertility. However, our understanding of the association between the early stage of endometriosis and infertility remains incomplete. Bloody peritoneal fluid (PF) is frequently observed in the cul-de-sac of endometriosis patients and contains various biologically active factors. We found that the concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in PF from patients with endometriosis were significantly higher than that of patients with endometriosis. There were significantly positive correlations between the levels of TNF-alpha and IL-6. We compared the levels of these cytokines with regard to the R-AFS stages and scores, but no differences were observed. In contrast, these cytokines correlate with the number and extent of red color peritoneal endometriosis. TNF-alpha increased the expression of IL-6 messenger RNA and protein in endometriotic stromal cells derived from chocolate cyst in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse preimplantation embryo and impaired sperm function. We concluded that increased levels of IL-6 in peritoneal fluid of patients with active red endometriosis might be related to endometriosis-associated fertility.