Endeometriosis: The influence of peritoneal fluid from patients with minimal stage or treated endometriosis on sperm motility parameters using computer-assisted semen analysis

The aim of this study was to determine the influence of peritonealfluid from patients with minimal stage or treated endometriosison sperm motility parameters. Peritoneal fluid aspirated atdiagnostic laparoscopy for unexplained infertility from womenduring the luteal phase of the menstrual cycle (days 20–23)was incubated for 5 h with fresh semen samples obtained frommen of recently proven fertility. Spermatozoa were preparedby a swim-up technique from unprocessed semen. Using computer-assistedsemen analysis (Hamilton-Thorn Research, MA, USA), sperm motilityand motion parameters were observed at 0, 120, 180 and 300 min.Compared with spermatozoa incubated in Earle's balanced saltsolution/human serum albumin, the percentage motility, percentageprogressive motility and progressive velocity of spermatozoaincubated in peritoneal fluid from patients without visibleendometriosis were significantly higher (P< 0.05). Maximaleffect was observed at 3 h and maintained until 5 h. We concludethat in an in-vitro study, in contrast to peritoneal fluid frompatients with minimal stage endometriosis, peritoneal fluidfrom patients with unexplained infertility and no visible endometriosiscan improve sperm motility when compared with culture medium.     

Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients

BACKGROUND: Leptin influences the proinflammatory immune responses and has angiogenic activity in vitro and in vivo. The objective of this study was to evaluate the peritoneal fluid levels of leptin in patients with endometriosis and idiopathic infertility and compare them with a control group of tubal ligation/reanastomosis patients. METHODS: In this observational, prospective controlled study, peritoneal fluid from 108 women was obtained while they underwent laparoscopy for pelvic pain, infertility, tubal ligation or sterilization reversal. We measured the concentration of leptin in the peritoneal fluid and compared the levels among women who were divided into groups according to their post-surgical diagnosis. Sixty patients were diagnosed with endometriosis, 10 with idiopathic infertility and 38 had undergone tubal ligation or reanastomosis (control group). RESULTS: Peritoneal fluid leptin was significantly higher in endometriosis 14.62+/-9.79 (mean+/-SD) ng/ml compared to idiopathic infertility [0.92+/-1.57 ng/ml (P=0.0007)] and to controls [0.78+/-1.94 ng/ml (P<0.0001)]. Leptin levels were positively correlated with the stage of endometriosis (r=0.45; P=0.03), and with pelvic pain in endometriosis patients (r=0.49; P=0.001). Peritoneal fluid leptin levels in patients with idiopathic infertility were comparable to controls. CONCLUSIONS: Higher levels of leptin were observed in peritoneal fluid of patients with endometriosis compared to those without the disease. These data suggest that the proinflammatory and neoangiogenic action of leptin may contribute to the pathogenesis of endometriosis. Moreover, leptin may play a role in endometriosis-associated pain.     

Endocrinology and paracrinology: Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells

lnterleukin-8 (IL-8) is a chemoattractant and activating factorfor human neutrophils and a potent angiogenic agent. The peritonealfluid of women with endometriosis has been shown to have increasedneutrophil chemotactic activity. We postulate that IL-8 maybe an important modulator in the pathogenesis of endometriosisand adhesion formation. We first investigated IL-8 concentrationsin the peritoneal fluid of women with or without endometriosis,then assessed peritoneal mesothelial cells as a potential sourceof peritoneal fluid IL-8. Northern blot analysis and enzyme-linkedimmunosorbent assay (ELISA) were used to investigate IL-8 mRNAand protein modulation. The mean concentration of IL-8 in samplesobtained from control patients (n = 28) was 4.8 ± 0.5pg/ml; from patients with minimal-mild endometriosis (n = 24)was 27.5 ± 2.6 pg/ml; and from patients with moderate-severeendometriosis (n = 21) was 530.2 ± 65.1 pg/ml. Confluentmesothelial cells were incubated with human recombinant IL-1a(0.01–100 IU/ml) or tumour necrosis factor (TNF)-a (0.01to 100 ng/ml) for 2–24 h. IL-8 mRNA was detectable innon-treated cells, however both IL-1a and TNF-     

Interferon-Gamma (IFN-γ) and Interleukin-6 (IL-6) in Peritoneal Fluid and Macrophage-Conditioned Media of Women With Endometriosis

PROBLEM: The presence of the various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to activation of peritoneal macrophages, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interferon gamma (IFN-γ) and interleukin-6 (IL-6), and peritoneal macrophage production of IL-6, in women with and without endometriosis. METHOD: Peritoneal fluid was obtained from 62 women at the time of diagnostic or operative laparoscopic surgery for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IFN-γ and IL-6 levels in peritoneal fluid samples and macrophage conditioned media were determined by commercial ELISA. RESULTS: IL-6 was significantly higher in the macrophage conditioned media of women with endometriosis as compared with controls. IL-6 levels were fourfold higher in early stage endometriosis (P < 0.05) and eightfold higher in advanced endometriosis. There were no significant differences between groups in the peritoneal fluid levels of IL-6 or IFN-γ. CONCLUSIONS: Peritoneal macrophage IL-6 secretion is increased in women with endometriosis, and appears to correlate with disease stage. IFN-γ does not appear to be responsible for the activation of macrophages in women with endometriosis.     

Endometriosis: Endometriosis and infertility: raised iron concentration in the peritoneal fluid and its effect on the acrosome reaction

Endometriosis and infertility are commonly associated. Thisstudy investigated the role of accelerated lipid peroxidationof spermatozoa by the peritoneal fluid of patients with endometriosisas a cause for this association. It proposes that the increasediron concentration present in the fluid of these patients actsas a catalyst for the process. Peritoneal fluid from 25 patientswith endometriosis and 25 matched controls was obtained at laparoscopy.Spermatozoa were incubated in the fluid from both groups andthe subsequent acrosome reaction rates analysed. The relationshipbetween these results and iron concentration in the fluid wasexamined. A significant decrease in the acrosome reaction ratewas seen in the endometriotic group(P = 0.034). Overall, a decreasein the acrosome reaction rate was associated with an increasediron concentration in the fluid(18 of the 25 pairs). In milddisease, (six of 11 pairs), the relationship was not as markedas that in severe disease (12 of 14 pairs). These results suggestthat the peritoneal fluid in patients with endometriosis hasa detrimental action on the acrosome reaction of spermatozoain vitro.     

Endometriosis: Increased prevalence and recurrence of retrograde menstruation in baboons with spontaneous endometriosis

This study was done to test the hypothesis that the incidenceand recurrence of retrograde menstruation is higher in baboonswith spontaneous endometriosis than in those without. A totalof 399 laparoscopies was performed on 113 female baboons. Group1 consisted of 84 animals with a normal pelvis (includIng 23that later underwent Induction of endometriosis and were assignedto group 4), group 2 comprised nine baboons with spontaneousendometriosis acquired during the last 2 years of the study,group 3 had 18 baboons with long-term spontaneous disease, andgroup 4 comprised 25 animals with induced endometriosis. Retrogrademenstruation was defined by the presence of blood-stained peritonealfluid (red or dark brown) during menses. Recurrence of retrogrademenstruation was analysed during the first two laparoscopiesin 13 baboons. Peritoneal fluid was 10 thnes more frequentlyblood-stained during menses (62%) than during non-menstrualphases (6%). Retrograde menstruation was observed more frequentlyin animals with spon taneous disease (groups 2 and 3,83%) thanin animals with a normal pelvis (group 1, 51%). Recurrence ofretrograde menstruation was observed more frequently in baboonswith spontaneous endometriosis (5/5) than in those without (3/8).The results of this study demonstrate that retrograde menstruationis common in baboons, with a higher prevalence and recurrencein animals with spontaneous endometriosis than in those without.     

IL-1β TNF-α, and IL-2 in Peritoneal Fluid and Macrophage-Conditioned Media of Women With Endometriosis

PROBLEM : The presence of various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to the development of endometriosis, infertility, and activation of peritoneal macrophages. This study assesses levels of IL-1β, IL-2, and TNF-α in peritoneal fluid and macrophage conditioned media of women with endometriosis. METHOD : Peritoneal fluid was collected from 51 women at the time of diagnostic or operative laparoscopy for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IL-1β, IL-2, and TNF-α levels were determined by commercial ELISA kits. RESULTS : The mean concentration of IL-1β and TNF-α was significantly higher in macrophage conditioned media of patients with endometriosis (P < 0.02). However, there were no significant changes in peritoneal fluid cytokine levels. Peritoneal macrophage concentrations were also higher in patients with endometriosis. CONCLUSION : This study supports the concept that endometriosis is associated with activation of peritoneal macrophages, and a higher concentration of these cells. This activation is reflected by the increased levels of cytokines found in macrophage conditioned media. The absence of significant changes in peritoneal fluid cytokine levels would seem to indicate that the above derangements are not responsible for the development or progression of endometriosis.     

The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women with or without endometriosis

The study was undertaken to investigate a possible mechanism for reducing the phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women suffering from endometriosis. Peritoneal fluids were collected during laparoscopy from women undergoing laparoscopic sterilization or from women under investigation for cause of infertility where the laparoscopic findings were endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro with peritoneal fluid with or without lignocaine. Samples from the incubations were studied daily and the number of viable and dead spermatozoa were counted. The number of free spermatozoa, not adhered to leukocytes, was significantly increased when incubated in human peritoneal fluid supplemented with lignocaine. Thus lignocaine contributes to increasing the number of free spermatozoa and maintaining the possibility of fertilizing an oocyte. For patients with endometriosis, treatment with lignocaine might be a means of increasing the chances of conception. A clinical study is in progress to evaluate this effect in vivo and to search for alternative methods of assisting the fertilization process.      

Peritoneal natural killer cytotoxicity and CD25+CD3+ lymphocyte subpopulation are decreased in women with stage III-IV endometriosis

We examined the lymphocytes of peripheral blood (PB) and peritonealfluid (PF) of women with or without endometriosis to investigatethe alteration of cytotoxic activity of natural killer (NK)cells and activation of T cells in the peritoneal cavity ofwomen with endometriosis. A total 16 control women and 14 patientswith stage III–IV endometriosis were selected on the basisof laparoscopic examination in National Taiwan University Hospital.The lymphocyte subpopulations (B cell, NK cell and T cell),including T-cell activation markers (CD69, CD25, HLADR), inPB and PF were analysed by dual-colour flow cytometry. The NKcytotoxicity of PB and PF mononuclear cells was evaluated by⁵¹Cr release assay. There was significant decrease of NK cytotoxicityand CD25⁺CD3⁺lymphocyte subpopulation in PF of women with endometriosiscompared with those without endometriosis. However, there wasno difference in the proportion of NK cells in both PB and PFbetween women with and without endometriosis. Therefore, thedecreased NK cytotoxicity PF of women with endometriosis wasdue to the functional defect, but not quantitative defect, ofNK cells. The concomitant reduction of activated T cells inwomen with endometriosis might suggest its possible role inthe defect of NK cytotoxicity.     

Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis

To explore the role of nitric oxide (NO) and oxidative stress in the pathogenesis of adhesion formation and in endometriosis-associated infertility, we examined the peritoneal total antioxidant status (TAS) and the concentrations of products of NO metabolism in women with endometriosis (early stage, n = 12; advanced stage, n = 12) and in fertile women without endometriosis (n = 10). Peritoneal CA 125 and oestrogen and progesterone concentrations were also measured to examine their contributions to TAS and the production of NO. We failed to demonstrate any significant difference in TAS and in the products of NO metabolism in peritoneal fluids among women with early and advanced stages of endometriosis compared with fertile women without endometriosis during the early follicular phase. TAS and the concentration of the products of NO metabolism were not related to concentrations of CA 125, oestrogen or progesterone. The concentration of CA 125 in serum, but not in peritoneal fluid, was positively correlated with the severity of endometriosis. The volume of peritoneal fluid and the progesterone concentration were significantly increased in the group with advanced endometriosis. TAS and the concentration of the products of NO metabolism did not increase in peritoneal fluids from women with endometriosis during the early follicular phase. Their role in the pathophysiology of endometriosis needs to be explored further.      

The Peritoneal Leptin,MCP‐1 and TNF‐α in the Pathogenesis of Endometriosis‐Associated Infertility

Citation Tao Y, Zhang Q, Huang W, Zhu H, Zhang D, Luo W. The peritoneal leptin, MCP‐1 and TNF‐α in the pathogenesis of endometriosis‐associated infertility. Am J Reprod Immunol 2011; 65: 403–406 Problem To explore the roles of leptin, monocyte chemotactic protein (MCP)‐1, and tumour necrosis factor (TNF)‐α in the peritoneal fluid (PF) in the pathogenesis of endometriosis‐associated infertility. Method of study Leptin, MCP‐1, and TNF‐α levels in the PF from 28 infertile women with endometriosis (study group), 23 women with fallopian‐associated infertility (controls), and 24 women with myoma (controls) were determined by performing enzyme‐linked immunosorbent assay (ELISA). Result Leptin and TNF‐α levels in the PF showed no significant difference among three groups. The MCP‐1 level in patients with endometriosis was higher than those in fallopian‐associated infertility group and myoma group (P < 0.01). There was a positive correlation between leptin and MCP‐1 levels in the PF of patients with endometriosis (P < 0.05). Conclusion Peritoneal leptin and MCP‐1 play important roles in the pathogenesis of infertility in the early stage of endometriosis.     

Immunological factors in endometriosis-associated reproductive failure: studies in fertile and infertile women with and without endometriosis

Immunopathophysiological mechanisms in endometriosis-associated reproductive failure were studied in appropriate populations: infertile and fertile women with and without endometriosis. The incidence of sera positive for any of the autoantibodies tested among infertile women with endometriosis (n = 25) was similar to that observed in the three control groups [unexplained infertility patients (n = 25) and fertile women with (n = 10) and without (n = 25) endometriosis]. The mean volume of peritoneal fluid was significantly elevated in women with endometriosis (both fertile and infertile) as compared with patients without endometriosis (fertile or infertile). The concentration of peritoneal fluid leukocytes and the percentage of cells positive for macrophage markers were significantly increased and the percentage of T lymphocytes significantly decreased in infertile women with endometriosis but not in patients with unexplained infertility and fertile women with endometriosis, as compared with fertile controls without endometriosis. Macrophages from infertile patients with endometriosis had higher sperm phagocytosis than did those from infertile women without endometriosis or fertile subjects with or without endometriosis. Incidences of serum and peritoneal fluid samples embryotoxic to the in-vitro development of 2-cell mouse embryos were significantly higher in infertile patients with endometriosis than in unexplained infertility patients and fertile women with or without endometriosis. It is concluded that immunological mechanisms of endometriosis-associated infertility exist but that these peritoneal immunological factors in infertile women with endometriosis are related to their subfertility rather than to the presence of ectopic endometrial implants. This is supported by the lack of immunological abnormalities observed among fertile women with endometriosis. These immunological abnormalities are lacking in patients with unexplained infertility.      

Endometriosis: Effect of peritoneal fluid from infertile women with endometriosis on ionophore-stimulated acrosome loss

The effect of peritoneal fluid (PF) from endometriosis patientswas studied in spontaneous and stimulus-induced (Ca-ionophore;A23187) acrosome reactions. PF samples were obtained from 21infertile women with endometriosis and five normal women (controls).Sperm acrosomes were examined by staining with Pisum sativumagglutinin labelled with fluorescein isothiocyanate. The incidenceof spontaneous acrosome reaction after 1 and 6 h of incubation(6.7 ± 1.6 and 6.9 ± 1.4 respectively) was significantly(P < 0.001) lower when the incubation was performed withPF from endometriosis patients in comparison with spermatozoaincubated in PF from the control group (12.8 ± 1.1 and12.8 ± 0.8). Similarly, the incidence of A23187-inducedacrosome reaction after 1 and 6 h of incubation (19.8 ±2.7 and 20.0 ± 2.4) was significantly (P < 0.001)lower when spermatozoa were incubated with PF from endometriosispatients in comparison with spermatozoa incubated with PF fromthe control group (34.6 ± 9.8 and 34.4 ± 1.1).The incidence of A23187-inducible acrosome reaction was alsosignificantly (P < 0.001) lower when the incubation was performedwith PF from endometriosis patients (13.1 ± 2.8 and 13.1± 2.4) when compared with that from the control group(21.8 ± 2.6 and 21.6 ± 1.5). No relationship wasfound between the stage of endometriosis and the incidence ofacrosome loss. In conclusion, the PF from endometriosis patientsdecreased both spontaneous and stimulus-induced acrosome reaction.This may represent a mechanism for the detrimental effect ofthe PF from endometriosis patients on the spermatozoa-oocyteinteraction and partially explain the aetiology of infertilityin patients with endometriosis.     

CA 125 in peritoneal fluid from patients with endometriosis.

This study was performed to evaluate CA 125 in peritoneal fluid as an indicator of endometriosis. Peritoneal fluid from patients with mostly minimal and mild endometriosis (n = 43) and normal controls (n = 17) was collected at laparoscopy or laparotomy. The median concentration of CA 125 in peritoneal fluid did not differ significantly between patients and controls (79 IU/ml versus 76 IU/ml). In patients with endometriosis, a significantly increasing concentration of CA 125 in peritoneal fluid was seen from the early follicular to the late luteal phase; a similar change was not observed in the controls. In 14 patients, peritoneal fluid was sampled again after treatment with danazol and a significant reduction in median CA 125 concentration (76.5 IU/ml versus 57 IU/ml), peritoneal fluid volume (17.5 ml versus 10.5 ml) as well as reduced endometriosis scores (4 versus 2) were found. In controls, the concentration of CA 125 was about 10 times higher in peritoneal fluid than in serum. As the peritoneal levels of CA 125 did not differ significantly between patients with endometriosis and controls and as the reduction seen after danazol treatment did not correlate with the decrease of endometriotic implants, it is concluded that the monitoring of CA 125 in peritoneal fluid will not be useful in the diagnosis or control of endometriosis.     

The role of monocyte chemotactic protein-1 in intraperitoneal adhesion formation

Abdomino-pelvic adhesions arise from infection, endometriosis, or peritoneal injury during surgery, and represent a significant source of morbidity in women of reproductive age. Monocyte chemotactic protein-1 (MCP-1) plays a role in the chemotaxis of mononuclear cells and fibroblasts in a murine wound repair model. To evaluate the role of MCP- 1 in intraperitoneal adhesion formation, we investigated peritoneal fluid MCP-1 levels of women undergoing laparoscopy. Patients without endometriosis were divided into two groups: normal fertile women undergoing bilateral tubal ligation without intraperitoneal adhesions (n=14) and women with pelvic adhesions (n=8). Patients with endometriosis were arranged into two groups: women with (n=17) and without (n=17) adhesions. Peritoneal fluid MCP-1 levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Peritoneal biopsy samples were immunostained for the detection of MCP-1 protein and macrophages, and were also processed for the presence of MCP-1 mRNA expression. Among women without endometriosis, the median peritoneal fluid MCP-1 level was 144 pg/ml (range 54-261) in women without adhesions and was 336 pg/ml (range 130-2494) in women with adhesions (P=0.01). There was a significant correlation between adhesion scores and MCP-1 levels (r=0.50; P=0.018). Among women with endometriosis, peritoneal fluid MCP-1 levels significantly correlated with the stage of the disease. The presence or absence of adhesions did not significantly affect the peritoneal fluid MCP-1 levels in this group of women. In summary, we have found that women with adhesions have elevated peritoneal fluid MCP-1 levels. However, we were not able to show an incremental effect of adhesions on peritoneal fluid MCP-1 levels of patients with endometriosis. Thus, we conclude that factors besides the intraperitoneal adhesions contribute to the elevated peritoneal fluid MCP-1 levels in patients with endometriosis.      

Autoantibodies and antisperm antibodies in sera and follicular fluids of infertile patients; relation to reproductive outcome after in-vitro fertilization

Immune reactions have effects at various concentrations in thereproductive process and autoantibodies may have an impact onfertility and the outcome of assisted conception. We measuredthe prevalence of and relation between antibodies to smoothmuscle, nuclear, phospholipid and sperm antigens, and concentrationsof immunoglobulins G, M and A and complement components C3 andC4, in the sera and follicular fluids of women with unexplainedinfertility (n = 30), endometriosis (n = 20), tubal infertility(n = 50) and the sera of 20 normal non-pregnant women. We assessedfertilization and successful pregnancy rates in relation toantibody status of infertile women after in vitro fertilization.All antibodies had a higher prevalence in infertile women comparedwith controls and this was significant for smooth muscle antibodyin endometriosis (P < 0.05); anticardiolipin antibody intubal infertility P < 0.05); and antisperm antibody in alltypes of infertility (P < 0.001). There was no relation betweenpresence of specific antibodies in serum or between serum andfollicular fluids. Total biochemical pregnancy rate was higherwith endometriosis (P = 0.05) but clinical pregnancy and livebirth rates did not differ between groups or in relation toantibody status. Significant differences in immunoglobulin andcomplement components occurred in women with and without successfulbiochemical pregnancy.     

Antiendometrial Autoantibodies Are Generated in Patients With Endometriosis

PROBLEM: Our aim was to investigate endometrial antigens involved in the autoimmunity of endometriosis. METHOD: We detected endometrial antigens against which autoantibodies directed with Western blotting. RESULTS: Thirteen (72.2%), 14 (77.8%), and 15 (83.3%) of 18 serum samples from endometriosis patients had antibodies reactive against endometrial antigen wtih MW of 26 kd, 34 kd, and 42 kd, respectively, while 6 (33.3%), 8 (44.4%), and 8 (44.4%) of 18 samples from normal control women reacted against these antigens, respectively. The frequencies of antibodies to the endometrial antigens were significantly (P < 0.05) higher in the endometriosis patients than in the normal control women. Antibodies in peritoneal fluid (PF) reacted against antigens with MW of 26, 34, 38, 42, and 64 kd, while those from the normal control reacted against antigens wtih MW of 38, 42, and 64 kd. Serum samples from normal fertile males did not show any reactivity against these endometrial antigens. CONCLUSIONS: Our results show that autoantibodies reactive against endometrial antigens are present in patients with endometriosis.     

Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle

Inhibin A, inhibin B, and activin A are growth factors which play local autocrine/paracrine roles in reproductive tissues. Since peritoneal fluid hormone content may reflect in part ovarian and endometrial secretory activities, the present study aimed to evaluate: (i) whether inhibin alpha-, activin betaA- and betaB-subunits, and activin receptor type II and type IIB mRNA are expressed in peritoneal tissues; (ii) expression and secretion of inhibin A and B, and activin A in cultured endometriotic cells; and (iii) concentrations of inhibin A and B, and activin A in serum and in peritoneal fluid in healthy women and in patients with endometriosis throughout the menstrual cycle. A group of women (n = 72) was recruited at laparoscopy for infertility investigation and divided into two groups: (i) control healthy women (n = 35), (ii) women with endometriosis (n = 37). Both groups were subdivided according to the follicular and luteal phase of the menstrual cycle. At the time of laparoscopy, specimens of peritoneal tissues were collected from three healthy women, while endometriotic tissue samples were collected and cultured from three women with endometriosis. Peritoneal tissues and cultured endometriotic cells expressed inhibin alpha-, activin betaA-, and betaB-subunits, and activin receptors mRNAs; in addition, inhibin-related proteins were measurable in culture medium. In healthy women, inhibin A and B, and activin A concentrations in peritoneal fluid were significantly higher than in serum (P < 0.001), at both phases of the menstrual cycle. Peritoneal inhibin A and B, and activin A concentrations were not significantly different between healthy women and patients with endometriosis, either when evaluated according to the degree of the disease and/or to the phase of the menstrual cycle. In conclusion, the findings that high concentrations are present in peritoneal fluid and that menstrual cycle-related changes occur suggest that reproductive organs may contribute to inhibin-related proteins in peritoneal fluid.      

The peritoneal environment in endometriosis

The local environment of peritoneal fluid (PF) surrounding the endometriotic implant is immunologically dynamic and links the reproductive and immune systems. Peritoneal fluid contains a variety of free floating cells, including macrophages, mesothelial cells, lymphocytes, eosinophils and mast cells. Macrophages are attracted to the peritoneal environment more abundantly than any other cell type. These scavengers promote cellular growth and viability through secretion of growth factors and cytokines. It is now becoming evident that cytokines play an important role in reproduction at various levels, including gamete function, fertilization and embryo development, implantation and postimplantation survival of the conceptus. Peritoneal fluid has been shown to affect negatively ovum capture by the fimbria, sperm survival, spermatozoon-oocyte interaction and embryonic development. We have recently identified the presence of two pro-inflammatory chemoattractant cytokines for monocyte/macrophages (MCP-1) and for granulocytes (interleukin-8, IL-8) in the PF. Concentrations of both IL-8 and MCP-1 are not only elevated in PF of women with endometriosis compared to those without endometriosis, but they are related to the severity of the disease. Over the past 70 years, at least a dozen theories have been proposed to explain the histogenesis and aetiology of endometriosis. It appears that the aetiology is multifactorial, and today a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation for peritoneal endometriosis.     

Peritoneal fluid cytokines and the relationship with endometriosis and pain

It is generally accepted that the current scoring system forendometriosis has little correlation with clinical symptomssuch as pain, and therefore we may deduce that either endometriosisdoes not cause pain, or that the current scoring system doesnot indicate the biological activity of the disease. Pain mayoccur because the presence of endometriosis produces an intraperitonealinflammatory response, and several studies have shown that thecytokine content of peritoneal fluid differs between women withand without endometriosis. We studied the relationship betweentumour necrosis factor a (TNFa), platelet-derived growth factor(PDGF), interleukin (IL)-6, IL-4 and TNF (a and P) activityin peritoneal fluid and the clinical history of pain and infertility.TNFa concentrations were increased in peritoneal fluid of womenwith endometriosis and of infertile women; PDGF concentrationswere increased in peritoneal fluid of parous women; EL-6 wasincreased in peritoneal fluid of women with adhesions; IL-4was absent from peritoneal fluid. PDGF and IL-6 concentrationswere cycle related, with the highest amounts in the menstrualand proliferative phases respectively. We failed to demonstrateany association between concentrations of cytokines in vitroand pain symptoms or severity of endometriosis.