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PubMed2004

Endometriosis and the development of malignant tumours of the pelvis. A review of literature.

For several decades, endometriosis has been suspected of playing a role in the aetiology of ovarian cancer. The literature concerning a possible histogenesis of ovarian cancer from benign endometriosis is reviewed in this chapter. Epidemiological evidence from large-cohort studies confirms endometriosis as an independent risk factor for ovarian cancer. Further circumstantial evidence for this link was found in the common risk factors for ovarian cancer and endometriosis. These risk factors influence retrograde menstruation and endometriosis in the same positive or negative way. Based on data in the literature, the prevalence of endometriosis in epithelial ovarian cancer has been calculated to be 4.5, 1.4, 35.9, and 19.0% for serous, mucinous, clear-cell and endometrioid ovarian carcinoma, respectively. The risk of malignant transformation in ovarian endometriosis was calculated at 2.5% but this might be an underestimate. In addition, some authors described atypical endometriosis in a spatial and chronological association with ovarian cancer. Finally, molecular studies have detected common alterations in endometriosis and ovarian cancer. These data suggest that some tumours, especially endometrioid and clear-cell carcinomas, can arise from endometriosis. Moreover, endometriosis-associated ovarian cancer represents a distinct clinical entity, with a more favourable biological behaviour, given a lower stage distribution and better survival than non-endometriosis-associated ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed2005

Expression of apoptosis-related proteins in peritoneal, ovarian and colorectal endometriosis.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Apoptosis, a physiological process by which multicellular organisms eliminate superfluous cells, is altered in tumor tissue. Here we studied the expression of the apoptosis-related proteins p53, bcl-2, bax, p21 and fas in proliferative (n=9) and secretory (n=9) endometrium, and in peritoneal (n=11), ovarian (n=20) and colorectal (n=20) endometriosis, by qualitative and semi-quantitative immunohistochemical methods using the percentage of positive cells and HSCORE analysis. In endometrium, p53, p21 and fas expression was low, whereas bax and bcl-2 expression was elevated. Using HSCORE analysis, only bcl-2 expression varied during the menstrual cycle (48.9+/-34.2% in the proliferative phase, 11.5+/-24.7% in the secretory phase, p=0.01). Using HSCORE analysis, p53 expression was higher in ovarian endometriosis than in peritoneal (p<0.0001) and colorectal endometriosis (p=0.03). P21 expression was higher in ovarian endometriosis than in peritoneal (p=0.01) and colorectal endometriosis (p=0.01). Bcl-2 expression was lower in ovarian endometriosis than in peritoneal (p=0.0002) and colorectal endometriosis (p<0.0001). Fas expression was higher in peritoneal endometriosis than in ovarian (p=0.02) and colorectal endometriosis (p=0.008). In conclusion, these results confirm the involvement of apoptosis in the pathogenesis of endometriosis. Moreover, expression of apoptosis-related proteins varies according to the location of endometriosis suggesting the involvement of different apoptotic pathways.

Apoptosis↗
PubMed2002

Peritoneal fluid-mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis.

OBJECTIVE: To determine the effect of autologous peritoneal fluid and tumor necrosis factor-alpha (TNF-alpha) on proliferation of endometrial cells from women with endometriosis. DESIGN: Endometrial cells from eutopic and ectopic endometrium were cultured in vitro with peritoneal fluids or recombinant TNF-alpha for 72 hours before DNa synthesis determination by 3H-thymidine labeling and liquid scintillation counting. SETTING: An institute for the study and treatment of endometriosis and university-based research laboratories. PATIENT(S): Thirty-five women with endometriosis and 17 controls without endometriosis. MAIN OUTCOME MEASURE(S): In vitro incorporation of 3H-thymidine in endometrial cells was examined. RESULT(S): Peritoneal fluid from women with endometriosis enhanced proliferation of autologous and heterologous endometrial cell cultures from women with endometriosis. The soluble TNF-receptor etanercept blocked the ability of peritoneal fluid from women with endometriosis to enhance proliferation of eutopic or ectopic endometrial cells. Recombinant TNF-alpha also enhanced proliferation of eutopic and ectopic endometrial cells from women with endometriosis. In contrast, autologous peritoneal fluid, heterologous peritoneal fluid from women with endometriosis, and recombinant TNF-alpha failed to enhance, and often inhibited, the proliferation of eutopic endometrial cells from controls without endometriosis. CONCLUSION(S): Endometrial cells from women with endometriosis can utilize factors in peritoneal fluids, such as TNF-alpha, to facilitate proliferation in ectopic environments. Endometrial cells from women without endometriosis do not share this ability, suggesting that this abnormality is etiologically related to development of the disease. Therapy with agents that block the effects of TNF-alpha may be warranted.

Ascitic Fluid↗
PubMed2002

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis.

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis.

Apoptosis↗
PubMed2002

Location, color, size, depth, and volume may predict endometriosis in lesions resected at surgery.

OBJECTIVE: To correlate the diagnosis of endometriosis in lesions excised at laparoscopy with pathologic diagnosis. DESIGN: Prospective study. SETTING: U.S. government research hospital. PATIENT(S): Women with chronic pelvic pain thought to be due to endometriosis. INTERVENTION(S): Excision of lesions suspicious for endometriosis. MAIN OUTCOME MEASURE(S): Histologic examination of lesions for color, width, depth, and location of endometriosis. Lesion colors were grouped as black, red, white, mixed color, or endometriomas. RESULT(S): Sixty-five women with a surgical diagnosis of endometriosis had minimal (n = 22), mild (n = 25), moderate (n = 9), or severe disease (n = 9) according to the revised American Fertility Society classification. Endometriosis was confirmed in all but seven patients with minimal and one with severe disease. Twelve other patients did not have endometriosis. Of 314 lesions excised, 189 (61%) were endometriotic. Black or red lesions were less often histologically confirmed to be endometriosis than were white lesions, mixed-color lesions or endometriomas. Lesions > 5 mm wide or deep were more likely to be endometriosis than were narrower or shallower implants. Endometriomas deeper than 1 cm were histologically confirmed to be endometriosis, and 50% of peritoneal windows contained endometriosis. CONCLUSION(S): White lesions, mixed-color lesions, endometriomas, and larger lesions by depth or width were more likely to be histologically confirmed endometriosis than were smaller, black, or red lesions.

Adult↗
PubMed2004

Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women with endometriosis.

BACKGROUND: Failure of apoptosis of refluxed endometrial cells within the peritoneal cavity is a possible etiologic factor for development of endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and DR5. In the present study, we addressed the possibility that the TRAIL/OPG system is involved in the pathogenesis of endometriosis. METHODS: Concentrations of OPG and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis were measured using specific enzyme-linked immunoabsorbent assay. The expression of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription-polymerase chain reaction. RESULTS: OPG concentrations in PF of women with endometriosis were significantly higher than those of women without endometriosis (P=0.006). With respect to the stages of the disease, the concentrations of OPG in women with stage III/IV endometriosis were significantly higher than in those without endometriosis and those with stage I/II endometriosis. On the other hand, the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV endometriosis compared to those in non-endometriosis and stage I/II endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic tissues studied. CONCLUSIONS: These findings suggest that the TRAIL/OPG system is involved in the pathophysiology of endometriosis, possibly affecting the apoptosis of endometriotic cells.

Adult↗
PubMedDate not supplied

Follicular hormonal environment and embryo quality in women with endometriosis.

The use of in-vitro fertilization (IVF) as a therapeutic tool in patients with endometriosis has provided information about the disease and, in particular, aspects of the reproductive process in humans, particularly folliculogenesis, fertilization, embryo development and implantation. Retrospective analyses of IVF and oocyte donation programmes showed impaired implantation in patients with endometriosis. Otherwise, the observation that embryo development was blocked more frequently in cases of endometriosis, suggested that impaired embryo quality may be responsible for the reduced implantation rates. Similarly, women with the disease undergoing oocyte donation had the same chance of implantation as patients without endometriosis, suggesting that the endometrial milieu is not affected in patients with endometriosis. The quality of the oocyte may, therefore, be altered in patients with endometriosis. To investigate this, we studied steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and human chorionic gonadotrophin (HCG)-induced granulosa cell cultures. We postulated that the pattern of progesterone secretion may be related to the release of cytokines by ovarian and/or immune cells. To test this, we measured interleukin (IL)-1, IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were increased in natural cycles in women with endometriosis and showed a significant decrease in stimulated cycles in IVF. Also, IL-6 concentrations were increased in the follicular fluid of women with endometriosis and released in higher amounts by granulosa-luteal cells from patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of endometriosis patients. These observations show that the follicular environment is different in cases with endometriosis and suggest that infertility in patients with endometriosis may be related to alterations within the oocyte which, in turn, result in embryos of lower quality, and with a reduced ability to implant.

Embryo Implantation↗
PubMed1996

Soluble CD23 protein in the peritoneal fluid of patients with endometriosis.

Activated B cells are known to produce soluble CD23 protein (sCD23) from their membranes. We recently showed a higher concentration of sCD23 in the serum of patients with endometriosis. As the commonest site of endometriosis is the peritoneal cavity, we sought to evaluate the concentration of sCD23 in the peritoneal fluid of 47 fertile symptomatic women with endometriosis and 35 fertile women without endometriosis. Endometriosis was diagnosed by laparoscopy and confirmed by histopathology. There was a statistically significant difference between the sCD23 concentrations in the endometriosis and control groups (P < 0.05). When endometriosis was defined based on the revised American Fertility Society (AFS) Score, patients with mild (AFS 1 and II) but not severe (AFS III and IV) endometriosis showed a higher and significant difference in the concentration of sCD23 when compared with the controls (P < 0.05). There was no significant correlation between the peritoneal fluid concentration of sCD23 and the phase of the menstrual cycle. We conclude that the concentration of sCD23 is higher in the peritoneal fluid of patients with endometriosis when compared with the controls, suggestive of B cell activation in patients with endometriosis. Furthermore, mild endometriosis is immunologically more active than severe endometriosis as defined by the current classification.

Ascitic Fluid↗
PubMed1994

Flow cytometry analysis of lymphocyte subpopulations in peritoneal fluid of women with endometriosis.

PROBLEM: We investigated the lymphocyte subpopulations in peripheral blood (PB) and peritoneal fluid (PF) of women with and without endometriosis to evaluate if the decreased natural killer (NK)-mediated cytotoxicity in women with endometriosis was due to a quantitative defect or not. METHOD: The PB and PF mononuclear cells of 59 women undergoing a diagnostic laparoscopy for pain and/or infertility were analyzed by flow cytometry. RESULTS: The number and concentration of PF mononuclear cells (MC) was increased in women with endometriosis compared to women without endometriosis. The monocyte/macrophage marker (CD14) was expressed on 70.3 and 66.9% of PFMC of women with and without endometriosis, respectively. The CD4/CD8 ratio was inverted in the PF, and this was more pronounced in women with endometriosis. In the PF of women with endometriosis, 41.3% of the lymphocytes were CD8 positive, compared to 34.3% in women without endometriosis. The percentage of NK positive lymphocytes in PF, using three different monoclonal antibodies directed against NK cell markers (CD57, CD16, and CD56) were not different between women with and without endometriosis. In women with endometriosis, 12.7, 9.5, and 28.8% of lymphocytes were CD57, CD16, and CD56 positive, respectively. CONCLUSION: PFMC consisted mainly of phagocytic and human leukocyte antigen (HLA)-restricted or HLA unrestricted cytotoxic cells capable of reacting to various antigens entering the cavity from the lower genital tractus. Furthermore, the decreased NK activity reported in PB and PF of women with endometriosis was not likely to be caused by a quantitative defect, since the percentage of NK positive lymphocytes was not different between women with and without endometriosis.

Ascitic Fluid↗
PubMed2002

The epidemiology of endometriosis.

Advances in understanding the epidemiology of endometriosis have lagged behind other diseases because of methodologic problems related to disease definition and control selection. Nevertheless, a better picture of the epidemiology of endometriosis has emerged over the past few decades. Prevalence estimates of the disease in clinic populations vary from about a 4% occurrence of largely asymptomatic endometriosis found in women undergoing tubal ligation to 50% of teenagers with intractable dysmenorrhea. General population incidence during the 1970s in this country has been suggested to be 1.6 per 1000 white females aged 15-49, while a more current study based upon hospital discharges finds endometriosis as a first listed diagnosis in 1.3 per 1000 discharges in women aged 15-44. There is a clinical impression that blacks have lower rates of endometriosis and Orientals have higher rates than whites. A variety of personal risk factors for endometriosis have also been described. Women with endometriosis may be taller and thinner. Menstrual factors reported to increase risk include dysmenorrhea, early menarche, and shorter cycle lengths. There is support for the idea that lifestyle exposures that might raise or lower estrogen levels could affect risk, including a decreased risk associated with smoking and exercise and an increased risk associated with caffeine or alcohol use. These risk factors appear to be compatible with the central importance of retrograde menstruation influenced by outflow obstruction that might affect its amount, immune factors that might affect its ability to be cleared, or hormonal stimuli that might affect its growth. In this model, dysmenorrhea could be either a disease symptom or a manifestation of outflow obstruction. Nulliparity could be either a consequence of disease or a cause since nulliparous women would not have the benefit of cervical dilation associated with labor and delivery. Since there is evidence that family history is a risk factor for disease, a challenge is how to integrate genetic factors into the model. The genetics of endometriosis might be advanced if we could identify an "endometriosis phenotype". We propose that this may consist of early menarche, short cycles, painful periods, subfertility, and possibly tall stature that could be explained by genetic factors that predispose to poor endowment of germ cells and canalization defects of the cervix. The value of establishing an "endometriosis phenotype" is that, as candidates for genetic markers are identified, particular genotypes can be correlated with these factors even if a formal diagnosis of endometriosis has not been made. Additional well-designed case-control and cohort studies will be necessary to test theories related to pathogenesis, establish the precise relationship between reproductive morbidity and endometriosis, identify specific genetic factors, and establish long-term risks.

Adolescent↗
PubMed2003

Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility.

Endometriosis is clinically associated with pelvic pain and infertility, with implantation failure strongly suggested as an underlying cause for the observed infertility. Eutopic endometrium of women with endometriosis provides a unique experimental paradigm for investigation into molecular mechanisms of reproductive dysfunction and an opportunity to identify specific markers for this disease. We applied paralleled gene expression profiling using high-density oligonucleotide microarrays to investigate differentially regulated genes in endometrium from women with vs. without endometriosis. Fifteen endometrial biopsy samples (obtained during the window of implantation from eight subjects with and seven subjects without endometriosis) were processed for expression profiling on Affymetrix Hu95A microarrays. Data analysis was conducted with GeneChip Analysis Suite, version 4.01, and GeneSpring version 4.0.4. Nonparametric testing was applied, using a P value of 0.05, to assess statistical significance. Of the 12,686 genes analyzed, 91 genes were significantly increased more than 2-fold in their expression, and 115 genes were decreased more than 2-fold. Unsupervised clustering demonstrated down-regulation of several known cell adhesion molecules, endometrial epithelial secreted proteins, and proteins not previously known to be involved in the pathogenesis of endometriosis, as well as up-regulated genes. Selected dysregulated genes were randomly chosen and validated with RT-PCR and/or Northern/dot-blot analyses, and confirmed up-regulation of collagen alpha2 type I, 2.6-fold; bile salt export pump, 2.0-fold; and down-regulation of N-acetylglucosamine-6-O-sulfotransferase (important in synthesis of L-selectin ligands), 1.7-fold; glycodelin, 51.5-fold; integrin alpha2, 1.8-fold; and B61 (Ephrin A1), 4.5-fold. Two-way overlapping layer analysis used to compare endometrial genes in the window of implantation from women with and without endometriosis further identified three unique groups of target genes, which differ with respect to the implantation window and the presence of disease. Group 1 target genes are up-regulated during the normal window of implantation but significantly decreased in women with endometriosis: IL-15, proline-rich protein, B61, Dickkopf-1, glycodelin, N-acetylglucosamine-6-O-sulfotransferase, G0S2 protein, and purine nucleoside phosphorylase. Group 2 genes are normally down-regulated during the window of implantation but are significantly increased with endometriosis: semaphorin E, neuronal olfactomedin-related endoplasmic reticulum localized protein mRNA and Sam68-like phosphotyrosine protein alpha. Group 3 consists of a single gene, neuronal pentraxin II, normally down-regulated during the window of implantation and further decreased in endometrium from women with endometriosis. The data support dysregulation of select genes leading to an inhospitable environment for implantation, including genes involved in embryonic attachment, embryo toxicity, immune dysfunction, and apoptotic responses, as well as genes likely contributing to the pathogenesis of endometriosis, including aromatase, progesterone receptor, angiogenic factors, and others. Identification and validation of selected genes and their functions will contribute to uncovering previously unknown mechanism(s) underlying implantation failure in women with endometriosis and infertility, mechanisms underlying the pathogenesis of endometriosis and providing potential new targets for diagnostic screening and intervention.

Blotting, Northern↗
PubMed1998

Lysophosphatidyl choline, a chemotactic factor for monocytes/T-lymphocytes is elevated in endometriosis.

Inflammatory processes have been hypothesized to mediate some of the clinical sequelae associated with endometriosis. The peritoneal fluid (PF) of women with endometriosis is known to contain more inflammatory cells and their associated cytokines, chemokines, and growth factors. This work provides strong evidence for oxidative stress in the PF of women with endometriosis. 1) The low density lipoprotein (LDL) isolated from the PF of subjects with endometriosis shows a small but detectable increase in electrophoretic mobility compatible with mildly oxidized LDL compared with LDL isolated from the plasma of the same subjects and PF of controls. 2) Isolated PF-LDL of endometriosis subjects is more readily oxidized in vitro than PF-LDL of controls, or LDL isolated from plasma. 3) Vitamin E content is significantly lower in endometriosis PF compared with controls, and compared with plasma of women with endometriosis and controls. No difference is seen between plasma and PF of control subjects. 4) The ratio of phosphatidylcholine/lyso phosphatidylcholine (Ptd/lyso PtdCho) in the PF of endometriosis subjects is significantly lower compared with PF of controls. Taken together, these data provide strong evidence for a pro-oxidant environment in the peritoneal cavity of women with endometriosis. Lyso PtdCho, a product derived from phospholipase A2 action on peroxidized phosphatidylcholine and a potent chemotactic factor for monocytes and T-lymphocytes, is elevated in endometriosis. We hypothesize that the increased presence of lipid peroxidation products in the PF of endometriosis subjects may, at least partly, account for the recruitment of leukocytes, the increase in macrophage activation, the secretion of monocyte--macrophage-derived cytokines, and the endometrial growth-promoting activity associated with endometriosis.

Adolescent↗
PubMed1993

The familial risk of endometriosis.

OBJECTIVE: To study the occurrence of endometriosis or adenomyosis in mothers and sisters of patients with endometriosis. METHODS: A total of 563 patients with endometriosis were interviewed about endometriosis or adenomyosis in their mothers or sisters. Five hundred and twenty-eight patients (94%) gave information about their relatives. Six patients were adopted and had no knowledge about their relatives. Among 522 patients were seven pairs of sisters, of which only one was included, giving a total of 515 cases. The control group consisted of 149 women without endometriosis documented at a recently diagnostic laparoscopy performed in connection with sterilization. The controls were likewise interviewed about their relatives, and none refused to give information. If a gynecological operation in a relative was reported, medical records were obtained (68%) or a description of the medical history was given by the proband. RESULTS: Endometriosis or adenomyosis was disclosed in 3.9% of mothers of cases and in 0.7% of mothers of controls, in 4.8% of sisters of cases and in 0.6% of sisters of controls. The relative risk of endometriosis in a first-degree relative (expressed as odds ratio), was 7.2 (95% confidence interval 2.1, 24.3). Severe manifestations of endometriosis were found more often among patients with a positive family history than among those without (26% versus 12%, p < 0.01). CONCLUSION: The study demonstrates a seven fold increased risk of endometriosis in mothers and sisters of patients with endometriosis. It is assumed that daughters of patients with endometriosis have a similar risk of developing endometriosis.

Adult↗
PubMed2005

[Determination of interleukin-17 concentrations in peritoneal fluid of women with endometriosis].

OBJECTIVE: To investigate the role of interleukin-17 (IL-17) in the pathogenesis of endometriosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of IL-17 in peritoneal fluid of 36 patients with different stage endometriosis and 26 patients without endometriosis. RESULTS: The concentrations of IL-17 in peritoneal fluid of the patients with and without endometriosis were (5.7 +/- 1.9) ng/L and (5.3 +/- 1.4) ng/L, respectively, without significant difference between the two groups (P > 0.05). According to staging criteria of r-AFS, the concentrations of peritoneal IL-17 in the patients with stage I-II endometriosis (6.4 +/- 1.7) ng/L were significantly higher than those in the patients with stage III-IV endometriosis (5.1 +/- 1.8) ng/L and in the patients without endometriosis (P < 0.05). There was no difference with regard to peritoneal IL-17 concentrations between proliferative and secretory phases in the patients with or without endometriosis (P > 0.05). The levels of peritoneal IL-17 were significantly higher in the endometriosis patients with infertility (6.4 +/- 1.8) ng/L than in the endometriosis patients without infertility (5.1 +/- 1.8) ng/L (P < 0.05). CONCLUSION: IL-17 may play an important role in the pathogenesis of early endometriosis and pathophysiology of endometriosis-associated infertility.

Adult↗
PubMed2006

[Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 mRNA in endometriosis].

OBJECTIVE: To investigate mRNA expression of matrix metalloproteinase (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) in ectopic endometriosis tissue and uterine endometrium from women with and without endometriosis. METHODS: Thirty-eight women with endometriosis (Revised American Fertility Society classification, RAFSI-IV) were selected as study group. Thirty-eight specimens of ovarian endometrioma (ovarian chocolate cysts, OCC), 16 red peritoneal endometriotic lesions (RPL), and 35 matched eutopic endometrium (Eu) were collected from them simultaneously at the time of surgery. Twenty specimens of endometrium from reproductive women undergoing laparoscopic surgery without endometriosis were obtained as control group. The mRNA expressions of MMP-9 and TIMP-1 were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Expression of TIMP-1 mRNA was detected in all samples. The level from endometriosis patients and control group was similar (2.31 +/- 1.21, 2.40 +/- 0.89). However, ectopic endometrium expressed significantly fewer TIMP-1 mRNA (OCC 1.67 +/- 0.79, RPL 1.45 +/- 0.68) compared with eutopic endometrium from both endometriosis and endometriosis-free patients (P < 0.05). The positive expression rate of MMP-9 mRNA was not distinctively different among all samples. The density of MMP-9 mRNA expression in endometrium (0.49 +/- 0.28) from endometriosis patients was similar to that in ectopic endometriosis (OCC 0.46 +/- 0.22, RPL 0.33 +/- 0.12), but was significantly higher compared with endometrium (0.29 +/- 0.12) without endometriosis (P < 0.05). CONCLUSIONS: An increase of MMP-9 mRNA expression of eutopic endometrium with endometriosis might enhance the endometrial implantation ability, thus facilitate the ectopic implantation of endometrium. Ectopic lesions express significantly less TIMP-1 mRNA, indicating they have increased invasive ability, which might facilitate the development of endometriosis.

Actins↗
PubMed1986

[Conservative treatment of endometriosis].

The patients with endometriosis have shown a significant increase in frequency in our country. In the recent years, the incidence of endometriosis in gynecological outpatients is probably 3%. In infertile patients, endometriosis has been demonstrated by laparoscopy in 20-30% of cases. The pregnancy rate of women with endometriosis has been noted to be 80-85% in the internal endometriosis and 50-60% in the external endometriosis. The risk of infertility is greater in women with external endometriosis than in women with internal endometriosis. The causes of infertility are multiple and additive. Mechanical interference with the reproductive function plays a predominant role. Pelvic adhesions involving ovaries and fallopian tubes interfere mechanically with ovulation, ovum pick-up and ovum transport. According to Brosens et al. the frequency of LUF syndrome is in excess of 79% in the patients with endometriosis. Another antifertility effect of endometriosis may involve coital avoidance due to dyspareunia, hyperprolactinemia, increased phagocytosis of spermatozoa and altered prostaglandin secretion in peritoneal fluid. Conservative treatment of endometriosis is associated with improvement infertility and the post-treatment pregnancy rate has become an acceptable indicator of the effectiveness of therapy. The choice of therapeutic approach depends on several factors including age of the patient, extent of the disease, extent and location of pelvic adhesions and other coexisting infertility factors. Several hormonal regimens have been recommended for the treatment of endometriosis. They include androgen, progestogens and pseudopregnancy, danazol-induced pseudomenopause, gestrinone and LH-RH agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed2001

Relationship between stage, site and morphological characteristics of pelvic endometriosis and pain.

BACKGROUND: The relationship between frequency and severity of pain symptoms and site, stage and morphological characteristics of endometriotic lesions was analysed in a multicentre cross-sectional observational study. METHODS: A total of 469 women (median age 31 years, range 18-45) who met the following criteria were consecutively observed in the participating centres during the study period: age 18-45 years, first laparoscopic or laparotomic diagnosis of endometriosis, pain symptoms lasting > or = 6 months, pain as the main or only complaint of the condition, absence of pelvic anomalies and no previous pelvic surgery. Dysmenorrhoea and non-menstrual pain were evaluated using a multidimensional verbal rating scale. The women were requested to grade the severity of dysmenorrhoea, non-menstrual pelvic pain and deep dyspareunia using a 10-point linear analogue scale. RESULTS: Dysmenorrhoea was present in 77% of subjects with ovarian endometriosis, 88% of those with endometriosis of the peritoneum, 92% of subjects with endometriosis of both ovary and peritoneum and in all the subjects with endometriosis of rectovaginal septum. These differences were not statistically significant after Bonferroni's correction. No marked difference emerged between the severity of dysmenorrhoea and site of endometriosis, but women with ovarian endometriosis tended to have lower scores (not significant). No clear association emerged between frequency and severity of non-menstrual pain, dyspareunia and site of endometriosis and the presence and severity of dysmenorrhoea, non-menstrual pain and dyspareunia. Dyspareunia was more frequently reported in women with only atypical endometriosis (56.8%) versus 47.7% in women with typical endometriosis, but with borderline significance (P = 0.05). Dyspareunia occurred in 68.2% of patients with both typical and atypical lesions. CONCLUSIONS: The results of this study find no clear-cut association between stage, site or morphological characteristics of pelvic endometriosis and pain.

Adolescent↗
PubMed2005

ESHRE guideline for the diagnosis and treatment of endometriosis.

The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidence-based guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for 3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the 'gold standard' investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimal-mild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderate-severe endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.

Endometriosis↗