Evaluation of transforming growth factor-beta 1 concentrations in serum, peritoneal and endometrioma fluid in women operated on for ovarian endometriosis as a biomarker of endometrioma.

Some studies indicate the role of TNF-α, IL-6, and IL-8 in the development of endometriosis. However, a comprehensive assessment of plasma, peritoneal, and endometrioma fluids of proinflammatory cytokine concentrations in women with ovarian endometriosis has not yet been performed. Therefore, this study aimed to analyze plasma, peritoneal, and endometrioma fluids for selected proinflammatory cytokine concentrations in women operated on for ovarian endometriosis. A retrospective study was conducted with 56 women who underwent surgery for ovarian endometriosis. Body mass, height, and waist circumference were measured, as well as BMI being calculated. Plasma, peritoneal, and endometrioma fluids' interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α) were determined by ELISA. Levels of IL-6 and TNF-α were significantly higher in endometrioma fluid compared to plasma and peritoneal fluid. In addition, levels of IL-6 and TNF-α were significantly higher in peritoneal fluid than found in plasma. Levels of IL-8 did not significantly differ between plasma and both peritoneal and endometrioma fluids, or between peritoneal and endometrioma fluids. There were also positive correlations among IL-6, IL-8, and TNF-α levels in endometrioma and peritoneal fluids (ρ = 0.29; p < 0.05; ρ = 0.51; p < 0.001; ρ = 0.52; p < 0.001, respectively). There were no associations between cytokine levels in plasma, peritoneal, and endometrioma fluids and endometriosis stage. Plasma IL-8 levels can be considered an emerging biomarker of severity of local inflammation related to endometrioma. Further studies are needed for understanding the role of IL-6 and TNF-α as the markers of local inflammation in endometrioma.

IntroductionSome studies indicate the role of selected adipokines in the development of endometriosis. However, a comprehensive assessment of plasma, peritoneal, and endometrioma fluids adipokines concentrations in women with ovarian endometriosis has not yet been performed. Therefore, this study aimed to analyze plasma, peritoneal, and endometrioma fluids selected adipokines concentrations in women operated on for ovarian endometriosis.Materials and methodsA cross-sectional cohort study involved 56 women operated on for ovarian endometriosis. Body mass, height, and waist circumference were measured, and BMI was calculated. Plasma, peritoneal, and endometrioma fluids adiponectin, leptin, omentin resistin, RBP4, and visfatin/NAMPT were determined by ELISA.ResultsThe highest plasma levels of adiponectin, leptin, omentin, and RBP4 than in the endometrioma and peritoneal fluids were found, while levels of resistin and visfatin/NAMPT were significantly higher in endometrioma fluid than in plasma and peritoneal fluid. In addition, levels of visfatin/NAMPT were significantly higher in peritoneal fluid than in plasma. There were also positive correlations between leptin, RBP4, and adiponectin levels in endometrioma and peritoneal fluids (ρ = 0.28; p < 0.05; ρ = 0.31; p < 0.05; ρ= 0.32; p < 0.05, respectively). There were no associations between adipokines levels in plasma, endometrioma, and peritoneal fluids and endometriosis stage.ConclusionOur results show that visfatin/NAMPT and resistin may be locally secreted in endometrioma related to inflammation regardless of the stage of endometriosis.

Decreased concentrations of pigment epithelium–derived factor in peritoneal fluid of patients with endometriosis

PurposeIn this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored.MethodsTen patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations.ResultsPeritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04).ConclusionIn this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments.The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.

To evaluate the release of granulocyte chemotactic protein-2 (GCP-2) into peritoneal fluid in women with endometriosis, we measured its concentration with reference to the disease stage and the phase of the menstrual cycle. Surgery was scheduled in the proliferative or secretory phase of the menstrual cycle for 64 women with endometriosis (n = 38) or cystadenomas (n = 26). GCP-2 concentrations in the peritoneal fluid were measured using an enzyme-linked immunosorbent assay. Our findings indicated elevated concentrations of GCP-2 in peritoneal fluid from women with endometriosis during the proliferative phase, which were positively correlated with the stage of endometriosis. Inflammation associated with endometriosis may be involved in the pathogenesis of the disease through increasing levels of peritoneal fluid GCP-2.

The suitable parameter in PF as well as in serum that may predict the activity of endometriosis is not well described. Therefore, we tried to examine the peritoneal fluid (PF) and serum concentrations of hepatocyte growth factor (HGF) in different revised American Society of Reproductive Medicine (r-ASRM) staging and morphologic appearances of endometriosis in an attempt to determine whether HGF can be clinically useful to predict the activity of pelvic endometriosis. Peritoneal fluid was collected from 137 women with endometriosis and 57 women without endometriosis during laparoscopy and blood sampling was collected from 37 women with endometriosis and 21 women without endometriosis before laparoscopy. The concentration of HGF in PF and serum was measured by enzyme-linked immunosorbent assay. The ability of isolated macrophages and stroma to secrete HGF in response to lipopolysaccharide (LPS) was evaluated. A significantly increased concentration of HGF in PF was found in women with endometriosis (1451.75 +/- 90.7 pg/mL) than that in non-endometriosis (1120.5 +/- 77.3 pg/mL, p < 0.01) without any remarkable difference in HGF levels between women with stage I-/II endometriosis and stage III-/IV endometriosis. When we distributed serum and PF levels of HGF according to different color appearances of endometriosis, we found a significantly higher serum and PF levels of HGF in women containing dominant red peritoneal lesions in pelvic cavity (740 +/- 109.3 pg/mL for serum; 1685 +/- 183.4 pg/mL for PF) than those having other pigmented lesions (649 +/- 79.5 pg/mL, p < 0.05 for serum; 1224 +/- 67.8 pg/mL, p < 0.05 for PF) or chocolate cysts (485 +/- 43.1 pg/mL, p < 0.05 for serum; 1118 +/- 83.1 pg/mL, p < 0.01 for PF). Exogenous stimulation with LPS significantly increased the production of HGF in the culture media by macrophages and stroma derived from women with endometriosis than that in women without endometriosis. These results suggest that women with early or advanced endometriosis as measured by r-ASRM scoring system are not associated with an increase in either serum or PF concentrations of HGF. Rather HGF levels in serum and PF were significantly increased in women harboring blood-filled red peritoneal lesions and may be clinically useful to predict the activity of pelvic endometriosis.

High soluble CD44 concentration in peritoneal fluid in endometriosis

Plasminogen in peritoneal fluid: a possible nonsteroidal indicator of ovulation

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment.

Endometriosis is a sex hormone-dependent and successively progressing gynecological disease, characterized by the presence of endometrial tissue outside the uterus. The etiology of endometriosis is known to be multifactorial, and its growth depends on immunological, hormonal, genetic and environmental factors. Angiogenesis plays a key role in implantation and growth of endometriotic lesions, as well as in adhesion formation. Physiologically angiogenesis is responsible for neoangiogenesis and recruitment of new capillaries from the already existing capillaries. It is well-documented that altered angiogenesis provokes improper follicular maturation, infertility recurrent miscarriages, ovarian hyperstimulation syndrome, and carcinogenesis. Factors stimulating angionesis include angiogenin, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The aim of the study was to analyze angiogenic factor concentration (angiogenin, VEGF, FGF) in blood serum and peritoneal fluid in patients with diagnosed endometriosis and idiopathic infertility. A total of 39 patients were recruited for the study including 19 patients (study group) diagnosed with endometriosis during the laparoscopic procedure and 20 patients (control group) with idiopathic infertility and no morphologic changes within the pelvis revealed during the laparoscopic procedure. All patients underwent laparoscopy during the follicular phase of the menstrual cycle. Vein blood sample was obtained before the procedure and during laparoscopy the entire peritoneal fluid was aspirated for further measurement of VEGF, FGF and angiogenin concentrations. Angiogenin concentration in peritoneal fluid was statistically higher in patient with idiopathic infertility in comparison to endometriosis (p<0.05). Higher angiogenin concentration was detected also in blood serum of patients with idiopathic infertility as compared to patients with endometriosis, but no statistical significance was found. VEGF and FGF concentration in blood serum and peritoneal fluid was similar in both groups (p>0.05). There were no significant differences between serum and peritoneal fluid in case of VEGF FGF and angiogenin in any of the groups. Angiogenic factors concentration (VEGF FGF agiogenin) in the peritoneal fluid and blood serum during the follicular phase of the menstrual cycle is not a diagnostic criterion for endometriosis.

Objective To determine the concentration of haptoglobin (Hp) in peritoneal fluid (PF) of women with and without endometriosis and its correlation with the phase of the menstrual cycle. The expression of Hpβe (determined by two-dimensional polyacrylamide gel electrophoresis) was correlated to total PF Hp concentration. Materials and methods PF samples were obtained from 240 women with or without endometriosis. PF Hp concentration was measured by a sandwich enzyme-linked immunosorbent assay. Hpβe expression in PF was estimated by two-dimensional polyacrylamide gel electrophoresis. Results PF Hp concentration was similar in women with and without endometriosis; it was significantly higher during the luteal phase of the menstrual cycle than in the follicular phase in control subjects, but not in women with endometriosis. There was a positive correlation between serum progesterone level and PF Hp concentration in control subjects during the luteal phase of the menstrual cycle. There was a mild positive correlation between PF Hp concentration and Hpβe expression in controls but not in women with endometriosis. PF Hp concentration was not correlated with the ASRM stage of endometriosis and the type of endometriotic lesions. Conclusions Women with and without endometriosis have similar PF Hp concentration. There is a mild positive correlation between PF Hp concentration and Hpβe expression in control subjects but not in women with endometriosis. Future investigations should aim to produce antibodies against specific epitopes of Hpβe that might allow its measurement by ELISA. (Journal of Endometriosis 2010; 2: 26–32)

PURPOSE: literature reports show that there are no conclusive data about the association between endometriosis and the concentrations of hormones involved in the control of reproduction. Thus, the present study was undertaken to determine FSH, LH, estradiol (E), progesterone (P), and histamine (Hi) concentrations in serum, peritoneal fluid and follicular fluid of women with and without endometriosis. METHODS: the extent of the disease was staged according to the revised American Fertility Society classification (1997). For the collection of serum and peritoneal fluid, 28 women with endometriosis undergoing diagnostic laparoscopy were selected (18 infertile women with endometriosis I-II and ten infertile women with endometriosis III-IV). For the control group, 21 fertile women undergoing laparoscopy for tubal sterilization were selected. Follicular fluid was obtained from 39 infertile women undergoing in vitro fertilization (21 women with endometriosis and 18 women without endometriosis). RESULTS: FSH and LH levels in serum, peritoneal fluid and follicular fluid did not differ significantly between groups. On the other hand, E and P concentrations in the peritoneal fluid were significantly lower in infertile women with endometriosis (E: 154.2±15.3 for stages I-II and 89.3 ng/mL±9.8 ng/mL for stages III-IV; P: 11.2±1.5 for stages I-II and 7.6 ng/mL±0.8 for stages III-IV) in comparison with control women (E: 289.1 ng/mL±30.1; P: 32.8±4.1 ng/mL) (Kruskal-Wallis/Dunn tests; p<0.05). In serum, estradiol and progesterone concentrations followed the same pattern. In the follicular fluid, E and Hi concentrations were significantly lower in women with endometriosis (E: 97.4±11.1 pg/mL; Hi: 6.6±0.9 ng/mL) in comparison to women without endometriosis (E: 237.5±28.5 pg/mL; Hi: 13.8±1.3 ng/mL) (Student t-test; p<0.05), while progesterone levels revealed no significant difference between groups. CONCLUSIONS: our results indicate ovary dysfunction in women with endometriosis, with reduction on E, P and Hi concentrations, which may contribute to the subfertility often associated with the disease.

Leptin is proposed to participate in the reproductive system of women by acting on either ovaries or hypothalamic-pituitary axis. The objective of the present study is to investigate the leptin concentrations in peritoneal fluid and serum samples of women diagnosed with primary infertility. A prospective study was carried out in women who underwent laparoscopy within the diagnostic process of primary infertility between January 2005 and January 2007. Leptin concentrations were determined in blood samples obtained before surgery and in peritoneal fluid samples collected during laparoscopy. Peritoneal fluid was obtained from 112 subjects; 21 with unexplained infertility 28 with polycystic ovary syndrome (PCOS), 30 with bilateral tubal occlusion, and 33 with endometriosis. Subjects with PCOS have significantly higher body weights, BMI values and plasma leptin levels when compared to other study groups. Peritoneal fluid levels of leptin were significantly higher in the endometriosis group compared to other three study groups. A positive correlation was found between peritoneal fluid leptin levels and the endometriosis stage (r=0.51, P=0.01). However, plasma leptin levels were unrelated to the disease extent. It might be hypothesized that leptin may be an active factor in the pathogenesis of PCOS and endometriosis, which are two major causes of primary infertility. A mild leptin deficiency in peritoneal environment may interrupt follicular development and ultimately lead to PCOS. Leptin has angiogenic and mitogenic properties, which trigger inflammatory cytokines and eventually result in the development of endometriosis implants. Significantly, higher levels of leptin in peritoneal environments of endometriosis subjects strongly imply the important role of this common pathology.

Peritoneal fluid and serum concentration of interleukin-16 in women with endometriosis

Background:Increase in nitric oxide (NO) concentration accompanied by alteration in peritoneal immune defense reactions is involved in the pathogenesis of endometriosis. Asymmetric dimethylarginine is an endogenous competitive inhibitor of NO synthase. This study was designed to compare NO metabolite (nitrite), asymmetric dimethylarginine, and estradiol concentrations in serum and peritoneal fluid (PF) of patients with and without endometriosis.Materials and Methods:Subjects were assigned to two groups based on their laparoscopic results. The groups consisted of women with and without endometriosis (90 and 89 participants, respectively). The serum and peritoneal levels of nitrite (stable NO metabolite), asymmetric dimethylarginine, and estradiol were measured using enzyme-linked immunosorbent assay (ELISA) kits. These parameters were analyzed and compared between the groups statistically using SPSS software version 16.Results:Both nitrite and asymmetric dimethylarginine levels were significantly higher in the serum of the participants from both groups than those in the PF group (P < 0.05). However, no significant difference in the asymmetric dimethylarginine level was detected between the two groups. In addition, the PF level of nitrite increased significantly in patients with endometriosis when compared with non-endometriosis subjects (P < 0.05). The PF levels of estradiol in both groups were significantly higher than the serum levels of estradiol (P < 0.05).Conclusions:The NO metabolite level of PF implies the possible role of NO in the pathogenesis of endometriosis.