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PubMed1994

The role of cell-mediated immunity in pathogenesis of endometriosis.

It is well recognized that cell-mediated immune responses contribute to the elimination of foreign antigens and cells from the invading organism. It is also likely that the immune system can recognize and eliminate altered or misplaced autologous cells such as ectopic endometrial cells. This mechanism may be operative in most women, preventing the development of endometriosis. Recent studies in women with endometriosis demonstrate functional changes in cells of the immune system including monocytes/macrophages, natural killer cells, cytotoxic T-lymphocytes and B cells. These changes suggest decreased surveillance, recognition and destruction of the misplaced endometrial cells and possible facilitation of their implantation and development of endometriosis. Peripheral blood monocytes (PBM) and peritoneal macrophages (PM) may play a key role in this respect, and may control the function of other immune cells. We have demonstrated that in normal fertile women without endometriosis, PBM and PM suppress endometrial cell proliferation in vitro. In endometriosis, PBM stimulate and PM inhibit endometrial cell proliferation and the cytotoxic effect of PM is inversely correlated with the stage of the disease. The decrease in PM cytotoxic function is controlled by prostaglandin synthesis. In infertile women without endometriosis, the effects of PM and PBM are variable. In about one third of patients, the effects of PM and PBM suggest subclinical endometriosis; in the remaining two thirds of patients the effects of PM and PBM are similar to those of fertile controls. Interestingly, endometrial cells in women with endometriosis are more sensitive to the stimulatory effect of PBM, and more resistant to the cytotoxicity of the immune cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1996

Decreased amounts of antibodies to 22 and 18 kDa antigens in the peritoneal fluid of patients with endometriosis. LE Group d'Investigation en Gynecologie.

Accumulated evidence implicates immunological alterations in endometriosis. The purpose of this study was to look for variations in antibodies to distinct antigens in peritoneal fluid of women with and without endometriosis. Peritoneal fluid was aspirated from 17 women undergoing laparoscopy for tubal ligation and 37 patients complaining of symptoms of pain and /or infertility. Peritoneal fluid antibodies to a standard preparation of peritoneal fluid antigens were detected by Western blot analysis using peroxidase-labelled anti-human immunoglobulin G antibodies specific to the Fc region. Antibodies to distinct antigens were quantified by estimating the ratio of the relative optical density between samples and a standard amount of antibodies. Marked changes were found in the antibody detection to two antigens having apparent molecular weights of 22 and 18 kDa. The intensity of the antibody signal was significantly weaker in the peritoneal fluid from endometriosis patients (0.36 +/- 0.06 and 0.46 +/- 0.06) compared with that in women without endometriosis (0.62 +/- 0.08 and 0.75 +/- 0.06). It was also weaker in patients without endometriosis presenting with infertility (0.36 +/- 0.07 and 0.47 +/- 0.08), but only the 18 kDa antigen result was significant. After adjusting for infertility, the P values for the 18 and 22 kDa bands were 0.03 and 0.28 (not significant) respectively in the group of endometriosis patients. These changes were not related to the phase of the menstrual cycle. These data suggest an alteration in the immune response to two distinct antigens in the peritoneal fluid from women with endometriosis and infertility. Further evaluation of these two antigens and their antibodies would be of interest to help understand endometriosis and its associated infertility.

Adult↗

PubMed1995

[Diagnostic methods in endometriosis].

The overall accuracy of preoperative diagnosis is approximately 20% with a range of 4-83%. We investigated 100 women at the age between 27-61 years, operated with histologically proven endometriosis and we made an attempt to analyse some of the diagnostic methods. Abrasio probatoria was made in 17 of the operated women prior to operation. The hystological result from the abrasive material was not indicative for the presence of endometriosis. Ultrasound examination was made on 24 operated women with endometriosis, but no one diagnosed endometriosis despite the description by many authors of characteristic ultrasound picture of endometriosis. Hysterosalpingography was made in 3 women with the endometriosis but despite the specific x-ray picture for endometriosis they were not diagnosed correctly. These data support the opinion of some authors that these diagnostic methods are not specific for endometriosis.

Adolescent↗

PubMed1997

AGUS in cervical endometriosis.

OBJECTIVE: To evaluate cervical endometriosis as a source of abnormal glandular cells in cervicovaginal smears. STUDY DESIGN: Histologically documented cases of cervical endometriosis with concurrent cervicovaginal smears were reviewed. The cytologic specimens were evaluated for the presence of glandular abnormalities. RESULTS: There were eight cases of superficial endometriosis (five of which had concurrent tuboendometrioid glandular metaplasia) and two cases of deep endometriosis in this series. Five of the eight cases of superficial endometriosis had abnormal glandular cells in the smears; neither of two cases of deep endometriosis had glandular abnormalities. Four of the eight cases of superficial endometriosis had previously undergone conization for cervical intraepithelial neoplasia (CIN) (squamous intraepithelial lesion [SIL]) and were being monitored for recurrence. Of the five cases of atypical glandular cells of unknown significance (AGUS), one case had concurrent high grade CIN (SIL). Another case was originally misinterpreted as recurrent glandular dysplasia. CONCLUSION: Physicians monitoring patients after treatment for CIN need to be aware that endometriosis and tuboendometrioid metaplasia may be the source of atypical glandular cells and on occasion may be subject to misinterpretation.

Cervix Uteri↗

PubMed1998

Malignancy arising in extraovarian endometriosis during estrogen stimulation.

OBJECTIVE: Endometriosis can undergo estrogen-dependent changes similar to endometrium and may carry a risk of developing hyperplasia and carcinoma during unopposed estrogen stimulation. MATERIAL-METHOD: We reviewed the existing literature to analyze the potential of a malignancy arising from extraovarian endometriosis by estrogen stimulation. RESULTS: To our knowledge, there are 20 published cases so far, with a malign transformed endometriosis during estrogen stimulation at an extraovarian site. The most common site of malignancy arising from endometriosis was the vagina (n = 5). The most common histological finding was adenocarcinoma (n = 13). The incidence of malignant transformation in extraovarian endometriosis during unopposed estrogen replacement can not be estimated based upon these case reports. CONCLUSION: Unopposed estrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, the addition of progestins to estrogen replacement therapy should be considered in women who have undergone hysterectomy with oophorectomy because of endometriosis, especially if they are known to have residual endometriosis.

Adenocarcinoma↗

PubMed2002

Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility.

OBJECTIVE: Determine whether peritoneal macrophages from women with endometriosis-associated infertility express more inducible nitric oxide synthase (NOS2) and produce more NO than fertile controls. DESIGN: Unblinded clinical study. PATIENT(S): Nine infertile women with endometriosis and nine normal fertile women undergoing laparoscopy. INTERVENTION(S): Peritoneal fluid and macrophages were collected. Cells were also cultured with the NOS2 inducers interferon-alpha (IFN-alpha) or IFN-gamma plus lipopolysaccharide (LPS). MAIN OUTCOME MEASURE(S): Peritoneal fluid NO levels, peritoneal macrophage NOS activity, and peritoneal macrophage NOS2 protein expression. RESULT(S): NOS enzyme activity was higher in peritoneal macrophages from endometriosis patients. Immunoblots demonstrated NOS2 protein only in peritoneal macrophages from women with endometriosis. Peritoneal fluid NO concentration was similar in the two groups, but total peritoneal fluid NO content was higher in endometriosis patients. After 3 days' culture, peritoneal macrophages from women with endometriosis produced more NO in response to IFN-alpha or IFN-gamma plus LPS than controls. CONCLUSION(S): Peritoneal macrophages from women with endometriosis-associated infertility express higher levels of NOS2, have higher NOS enzyme activity, and produce more NO in response to immune stimulation in vitro. As high levels of NO adversely affect sperm, embryos, implantation, and oviductal function, reducing peritoneal fluid NO production or blocking NO effects may improve fertility in women with endometriosis.

Animals↗

PubMed1996

Decreased amounts of antibodies to 22 and 18 kDa antigens in the peritoneal fluid of patients with endometriosis

Accumulated evidence implicates immunological alterations in endometriosis. The purpose of this study was to look for variations in antibodies to distinct antigens in peritoneal fluid of women with and without endometriosis. Peritoneal fluid was aspirated from 17 women undergoing laparoscopy for tubal ligation and 37 patients complaining of symptoms of pain and/or infertility. Peritoneal fluid antibodies to a standard preparation of peritoneal fluid antigens were detected by Western blot analysis using peroxidase-labelled anti-human immunoglobulin G antibodies specific to the Fc region. Antibodies to distinct antigens were quantified by estimating the ratio of the relative optical density between samples and a standard amount of antibodies. Marked changes were found in the antibody detection to two antigens having apparent molecular weights of 22 and 18 kDa. The intensity of the antibody signal was significantly weaker in the peritoneal fluid from endometriosis patients (0.36 ± 0.06 and 0.46 ± 0.06) compared with that in women without endometriosis (0.62 ± 0.08 and 0.75 ± 0.06). It was also weaker in patients without endometriosis presenting with infertility (0.36 ± 0.07 and 0.47 ± 0.08), but only the 18 kDa antigen result was significant. After adjusting for infertility, the P values for the 18 and 22 kDa bands were 0.03 and 0.28 (not significant) respectively in the group of endometriosis patients. These changes were not related to the phase of the menstrual cycle. These data suggest an alteration in the immune response to two distinct antigens in the peritoneal fluid from women with endometriosis and infertility. Further evaluation of these two antigens and their antibodies would be of interest to help understand endometriosis and its associated infertility. Keywords: antibodies/antigens/endometriosis/peritoneal fluid/Western blot analysis

Journal Article↗

PubMedDate not supplied

Adhesions and pain in women with first diagnosis of endometriosis: results from a cross-sectional study.

OBJECTIVE: To analyze the relationship between pain and presence, site, and type of adhesions in women with endometriosis. METHODS: This was a multicenter, observational cross-sectional study. Eligible for the study were women with endometriosis and pelvic pain, consecutively observed during the study period at the collaborating centers. A total of 574 women entered the study. RESULTS: Adhesions were observed in 81.9% of cases (470 women). The frequency was lower in women with endometriosis at stage I-II (65%) and higher in women with stage III-IV (88%); this difference was statistically significant (p < .01). The frequency of adhesions was lower in women with ovarian endometriosis (74%) and higher in those with ovarian and peritoneal endometriosis (87%) or other sites (96%) (p < .01). The presence of adhesions was associated with higher mean visual analog scale (VAS) scores and median multidimensional scale ratings in women with ovarian disease and with stage I-II disease. Women with ovarian adhesions reported higher VAS and multidimensional scale scores (p < .05) than women with peritoneal adhesions or adhesions in other sites. CONCLUSIONS: The results of this study suggest that there is no overall association between the presence of adhesions and the degree of pain in women with endometriosis. The data suggests that there may be an association between adhesions and pain in women with ovarian and Type I-II endometriosis. However, these associations were no longer significant after correction for multiple comparisons. Further research is indicated to test these associations.

Adolescent↗

PubMed1999

Tenascin is differentially expressed in endometrium and endometriosis.

Endometriosis is characterized by the presence of functional endometrial tissue outside the uterine cavity, most commonly on the ovary and peritoneum. The aetiology of endometriosis is not understood, although the adhesion of endometrial cells to the extracellular matrix (ECM) would be expected to play a central role in its pathogenesis. The expression of ECM molecules in endometrium and in endometriosis has been investigated using immunohistochemistry and western blotting techniques. The ECM components collagen IV, laminin, vitronectin, and fibronectin had a similar pattern of expression throughout the menstrual cycle in endometrium and endometriosis. Expression of tenascin was elevated in the stroma of the functionalis region of the endometrium during the proliferative stage of the menstrual cycle and in endometriosis. Tenascin expression in endometriosis was not modulated according to the stage of the menstrual cycle. It is concluded that expression of tenascin is strictly regulated in endometrium and may be important in endometrial regeneration and in the pathogenesis of endometriosis.

Adult↗

PubMed2006

No association of endometriosis with galactose-1-phosphate uridyl transferase mutations in a Chinese population.

The linkage between endometriosis and galactose-1-phosphate uridyl transferase gene (GALT) mutations is controversial. In this study, the prevalence of the most common GALT mutations, Q188R and N314D, was assessed in women with endometriosis in a Chinese population. Three hundred twenty five unrelated women with endometriosis were enrolled. Samples of umbilical cord blood obtained from 310 female newborn infants were used as population controls. Genomic DNA isolated from endometriosis patients and controls were subjected to multiple polymerase chain reactions to determine the Q188R and N314D mutations. There was no significant difference in the frequencies of the Q188R and N314D mutations between endometriosis patients and controls. The endometriosis patients were further divided into subgroups of stage III and IV disease, but still no statistically significant differences were observed in the frequency of the Q188R and N314D mutations between any of these groups and the controls. These findings suggest that Q188R and N314D mutations are not likely to be associated with an increased risk of endometriosis among Chinese Women.

Asian People↗

PubMed2004

Diagnostic accuracy of transvaginal sonography for deep pelvic endometriosis.

OBJECTIVE: To determine the accuracy of transvaginal sonography (TVS) for the diagnosis of deep pelvic endometriosis. METHODS: In a prospective study, 142 women with clinical signs of endometriosis underwent TVS followed by surgical and histopathological investigations. The presence and extent of endometriosis involving the uterosacral ligaments, vagina, rectovaginal septum, intestines, bladder and ovaries shown by TVS were compared with surgical and histological findings. The sensitivity, specificity, predictive values and accuracy of TVS for predicting deep pelvic endometriosis were assessed. RESULTS: Ovarian and deep pelvic endometriosis were found by surgery and histology in respectively 83 (58.5%) and 79 (55.6%) of the 142 patients. The sensitivity, specificity, and positive and negative predictive values of TVS for the diagnosis of deep pelvic endometriosis were 78.5%, 95.2%, 95.4% and 77.9%, respectively. The sensitivity and specificity of TVS for endometriotic involvement of the uterosacral ligaments, vagina, rectovaginal septum and intestines were 70.6% and 95.9%, 29.4% and 100%, 28.6% and 99.3%, and 87.2% and 96.8%, respectively. The sensitivity and specificity of TVS for bladder involvement were 71.4% and 100%, respectively. CONCLUSION: TVS accurately diagnoses intestinal and bladder endometriosis, but is less accurate for uterosacral, vaginal and rectovaginal septum involvement.

Adult↗

PubMed1988

In vitro fertilization and embryo transfer (IVF/ET): an established and successful therapy for endometriosis.

The purpose of this report is to present a 6-year experience in the management of endometriosis with in vitro fertilization and embryo transfer (IVF/ET). We divided 136 patients who underwent 280 cycles into three groups: (1) previous history of endometriosis but normal pelvis at the time of oocyte retrieval, (2) stages I-II endometriosis (revised AFS classification), and (3) stages III-IV endometriosis. The stimulation protocols, estradiol (E2) responses, and distribution of terminal E2 patterns were similar in all groups. Group 3 had significantly fewer preovulatory and immature oocytes retrieved and fewer embryos transferred. The fertilization rate and the per cycle/per transfer pregnancy rates were similar in all groups. The miscarriage rate was higher in group 3, and the ongoing pregnancy rate per cycle was lower. Luteal phase E2 and progesterone levels were comparable in all groups. No differences were found when groups 2 and 3 were analyzed for the presence of one or two ovaries or the presence/absence of ovarian endometriosis. The overall fertilization rate, the per cycle/per transfer pregnancy rates, and the miscarriage rate were similar to those of tubal factor patients. We underscore the excellent outcome of patients with minimal or mild endometriosis in IVF/ET. We conclude that patients with moderate or severe endometriosis have a compromised reproductive potential, probably because of a reduced oocyte recovery rate and poor embryo quality.

Abortion, Spontaneous↗

PubMed1997

Effect of peritoneal fluid from patients with mild and severe endometriosis on endometrial stromal cell proliferation.

The aim of this study was to evaluate and compare the mitogenic effect of peritoneal fluid (PF) from women with mild and severe endometriosis on the endometrial stromal cell proliferation. Increasing concentrations of PF from women with and without mild or severe endometriosis were added to primary endometrial stromal cell cultures and 3H-thymidine incorporation was used to assess DNA synthesis in these cultures. PF from women with mild endometriosis induced a statistically significant dose-dependent increase in stromal cell thymidine uptake ranged from 5.8 to 14.5 fold, whereas PF from women with severe endometriosis produced an average 51% inhibition of stromal cell proliferation of compared with cells exposed to non-endometriosis PF or exposed to nutrient medium supplemented with 2.5% calf serum alone. PF samples from patients with stage I endometriosis induced a statistically dose-dependent increase in stromal cell proliferation, whereas PF from patients with stage IV endometriosis caused a significant inhibition.

Ascitic Fluid↗

PubMed1997

Endometriosis is not detrimental to embryo implantation in oocyte recipients.

PURPOSE: Our purpose was to determine the effects of endometriosis on implantation and pregnancy rates in ovum recipients. METHODS: The medical records of 239 consecutive oocyte recipient patients who were treated between January 1, 1991, and June 30, 1995, were analyzed retrospectively. Recipients with endometriosis (group 1; n = 55) were compared to recipients without endometriosis (group II; n = 184). Patients in group I had active endometriotic disease confirmed by laparoscopy and were subdivided into mild (Stages I and II; n = 18) and moderate to severe (Stages III and IV; n = 37) endometriosis. RESULTS: No difference was found in recipient age, endometrial thickness, donor age, and embryos transferred. The pregnancy rates (28 versus 29%) and implantation rates (12 and 13%) were also comparable between group I and group II, as well as between patients with mild and patients with moderate to severe endometriosis. CONCLUSIONS: The presence of endometriosis in oocyte recipients does not lower implantation or pregnancy rates. We conclude that the adverse effect of endometriosis on reproductive outcome is not related to implantation but, in fact, is most likely an effect on oocyte or embryo quality.

Adult↗

PubMed2004

Mechanism of elevated vascular endothelial growth factor levels in peritoneal fluids from patients with endometriosis.

In order to investigate the mechanism of elevated vascular endothelial growth factor (VEGF) in peritoneal fluids from patients with endometriosis, macrophages were recovered from peritoneal fluids obtained at the time of diagnostic laparoscopy from infertile women with endometriosis (EMT group, n=20) and without endometriosis (control group, n=20). Macrophages were cultured in vitro. The VEGF levels of peritoneal fluid and the supernatant of macrophages culture were determined by enzyme linked immunoassay (ELISA). Meanwhile, the eutopic (n=20) and ectopic endometrium (n=20) from endometriosis patients, and normal edometrium (n=20) from non-endometriosis patients were obtained for the analysis of VEGF expression by labeled Streptavidin Biotin (LSAB). It was found that VEGF levels in peritoneal fluid and macrophages culture supernatant were significantly higher in EMT group than in control group (P<0.01). In normal endometrium, VEGF showed a cyclic changes and similar in eutopic and ectopic endometrium from patients with endometriosis. There was no difference in the intensity of VEGF in endometrium between two groups within each menstrual phase. It is suggested that altered VEGF production by peritoneal macrophages and ectopic endometrium secretion may contribute to the elevated VEGF levels in the peritoneal fluid of patients with endometriosis.

Adult↗

PubMedDate not supplied

Primary abdominal wall clear cell carcinoma arising in a Caesarean section scar endometriosis.

BACKGROUND: Endometriosis occurring in a surgical scar is well recognized and occurs mainly in patients with a history of hysterectomy or Caesarean section. Scar endometriosis, as well as endometriosis at other sites, can undergo malignant change. Endometrioid carcinoma is the most common malignant tumour arising in endometriosis. However, clear cell carcinoma can also occur but is unusual. AIM: To discuss the diagnosis and management of such a case. METHODS: We report a case of primary clear cell carcinoma in endometriosis of a Caesarean section scar and review the literature. RESULTS: The patient presented with a large right lower quadrant abdominal wall mass within a Caesarean section scar. Histological examination revealed a clear cell carcinoma. The patient had a prior history of pelvic endometriosis. According to the Irish National Cancer Registry, this is the first reported case of a primary abdominal wall clear cell carcinoma developing within a Caesarean section scar in Ireland. CONCLUSION: Any lesion occurring in a Caesarean section scar with a history of previous endometriosis cannot be underestimated and warrants careful clinical follow-up and histological evaluation as appropriate.

Adenocarcinoma, Clear Cell↗

PubMed2002

Controlled ovarian hyperstimulation and intrauterine insemination for infertility associated with endometriosis: a retrospective analysis.

OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation and intrauterine insemination for infertility associated with endometriosis. MATERIAL AND METHODS: A retrospective analysis of 260 patients with the only diagnosis of endometriosis, or male factor, or tubal factor, or unexplained infertility were performed: a total of 56 patients with different stages of endometriosis, a control group consisting of 38 patients with male factor infertility, a group of 26 patients with tubal factor infertility and a group of 140 patients with others (unexplained infertility, ovulation disorders, cervical factor). Pregnancy rate, hormone levels, endometrial thickness and number of follicles were analyzed. RESULTS: Clinical pregnancy rates per patient were similar between endometriosis, male factor, tubal factor, and others including unexplained infertility, ovulation disorders and cervical factor groups (10.7%, 5.4%, 11.5%, 17.9%, respectively; p>0.05). Clinical pregnancy rates per patient were not effected between the 2 subgroups of endometriosis as minimal to mild and moderate to severe [5.1% (2/39) versus 23.5% (4/17), p=0.19]. CONCLUSION: Endometriosis did not affect the clinical pregnancy rate per patient compared to the other infertility factors. Endometriosis of various stages have no effect on the success of controlled ovarian hyperstimulation combined with intrauterine insemination.

Adult↗

PubMed2004

A priori implantation potential does not differ in eutopic endometrium of patients with and without endometriosis.

BACKGROUND: In endometriosis, angiogenesis is a crucial step for implantation of the exfoliates. A priori potential to induce angiogenesis by vascular endothelial growth factor (VEGF) expression was compared in eutopic endometrium of patients with and without endometriosis to discriminate the pivotal pathogenic step that differs in endometriosis. METHODS: In an experimental prospective study, endometrium samples were obtained from endometriosis patients (n=10) and from healthy, ovulating women as controls (n=6) undergoing curettage and laparoscopy for benign gynaecological conditions at the Aachen University Hospital, Aachen, Germany. Endometrial fragments were transplanted to the chicken chorioallantoic membrane (CAM) and re-explanted after 0, 24, 48, 72 and 96 h of cultivation for analysis. The main outcome measure was VEGF mRNA expression and protein localisation in endometrial fragments as parameters of angiogenic induction that was quantified by the vessel index. RESULTS: VEGF mRNA expression increased significantly in endometrial fragments of endometriosis and control patients (p<0.05). Protein is expressed in the glands and endometrial stroma. The vessel index is significantly elevated compared with native CAM controls. Endometrial fragments of endometriosis and control patients showed no significant differences in VEGF expression or angiogenic induction. CONCLUSIONS: Eutopic endometrial fragments of patients with and without endometriosis do not differ in their VEGF expression or angiogenic activity in the CAM assay. Implantation is obviously decided by external regulating influences on the exfoliates.

Animals↗