Identifying the presence of antibodies against endometrial antigens. A preliminary study.

Serum and peritoneal fluid from women with and without evidence of endometriosis were tested for the presence of antibodies against endometrial tissue antigens with Western blot analysis. Serum antibodies against endometrial cytosolic antigens of molecular weight 45, 52, 58, 62 and 66 kd were present in samples obtained from women both with and without endometriosis. The patients with endometriosis had serum antibodies against 34-kd endometrial cytosolic antigen, which was not present in serum from fertile women without endometriosis. The peritoneal fluid from patients with endometriosis also reacted with 34-kd endometrial antigen but not the peritoneal fluid from control fertile women. There was no difference in the antigens detected with serum antibody when endometrium from fertile women without evidence of endometriosis and from women with endometriosis was used as a source of antigen. The presence of serum antibody against 34-kd endometrial antigen is specific to endometriosis. However, this antigen is expressed by endometrium of women both with or without endometriosis. Isolation and identification of this antigen may lead to development of a noninvasive aid for the diagnosis of endometriosis.     

Familial aggregation of endometriosis in the Yale Series

Objective  To investigate the familial aggregation and the risk of endometriosis among the female relatives of women with endometriosis. We also compared the epidemiologic characteristics of women with and without family history of endometriosis. Patient(s)  A total of 485 women with endometriosis and 197 infertile women without endometriosis underwent surgical investigation between August 1996 and February 2002. Main outcome measure(s)  The relative risk of endometriosis in a first-degree relative and the association between potential risk factors was estimated by χ² and by crude adjusted odds ratios (95% CI). Results  Endometriosis was identified in 9.5% of first-degree relatives of women with endometriosis versus only 1% of controls. The odds ratio for endometriosis in a first-degree relative was 10.21 (95% CI 2.45–42.5; P < 0.001). In 3.9% of cases women with endometriosis reported that their mother had been diagnosed with endometriosis and 5.6% of cases that at least one sister had been diagnosed. Compared to the control group the odds ratio for the mother having endometriosis (7.99, 95% CI 1.06–60.1) or at least one sister having (11.55, 95% CI 1.56–85.59) were significantly elevated. Among women with endometriosis who reported a family history of endometriosis, and women with endometriosis who did not report a family history of endometriosis, there were no differences in demographic characteristics, body habitus, or menstrual parameters. Conclusion(s)  Women with endometriosis have a tenfold increased risk of endometriosis in their first-degree relatives.     

Activin-A secretion is increased in the eutopic endometrium from women with endometriosis

BACKGROUND: Activin is a well-characterised growth and differentiation factor and an important inflammatory mediator. Activin is secreted by normal endometrial glands and stroma and is expressed by endometrial leucocytes. It is also known that the eutopic endometrium from women with endometriosis is functionally different to that from women without endometriosis. In this study, we hypothesise that the endometrial secretion of activin is altered in women with endometriosis. AIMS: To determine whether the expression of inhibin/activin subunits and the secretion of activin-A is different in eutopic endometrium from women with and without endometriosis. METHODS: Endometrial biopsies were obtained from premenopausal, regularly menstruating women with and without endometriosis. Staining intensity for the different inhibin/activin subunits was compared in endometrial and endometriotic biopsies. Activin-A secretion was studied using endometrial explants and endometrial glandular and stromal monolayer cell cultures. RESULTS: The alpha- and betaA-subunits of inhibin/activin were more abundant in eutopic glandular cells from patients with minimal to mild endometriosis compared to women without endometriosis. In patients with endometriosis, the betaB-subunit was more abundant in eutopic stromal cells and endometrial leucocytes. Comparison of paired endometrial and endometriotic biopsies from the same patient did not reveal significant differences for any of the inhibin/activin subunits or activin receptors. Activin-A secretion by glandular and stromal endometrial cells was sevenfold and threefold higher, respectively, in women with endometriosis compared to women without endometriosis. CONCLUSIONS: The expression of inhibin/activin subunits in eutopic endometrium is altered in women with endometriosis, leading to higher levels of activin-A secretion by both glandular cells and stromal cells.     

Immunoglobulin content of the endometrium in women with endometriosis

A study of the immunoglobulin content of endometria from women with and without endometriosis has shown that, in women with endometriosis, both IgG and IgA are more commonly found in the interstitium of the endometrial stroma than is the case in endometria from women without this disease. It is thought that the increased stromal content of immunoglobulins in endometriosis is simply a passive reflection of elevated serum IgG and IgA levels. Both the incidence and extent of positive endometrial glandular epithelial staining for IgG and IgA are markedly increased in women with endometriosis: the excess of intraepithelial IgA is probably simply a consequence of the excess of stromal IgA, but the increased epithelial staining for IgG lends support to the concept that many women with endometriosis develop autoantibodies directed against an endometrial epithelial antigen. No relationship could be demonstrated, however, between IgG deposition in the endometrium of women with endometriosis and a history of infertility.     

Antigenic differences between the endometrium of women with and without endometriosis

Serum and peritoneal fluid from 12 women with endometriosis, 4 women with uterine leiomyomata and 6 fertile women without endometriosis (controls) and serum from 4 women with adenomyosis were tested with a passive hemagglutination assay for antibodies against endometrium from all the controls, 8 patients with endometriosis and all patients with uterine leiomyomata and from implants from 8 patients with endometriosis. Serum antibody titers in patients with endometriosis or leiomyomata were significantly higher against endometrial or implant antigens from patients with endometriosis and 2 patients with leiomyomata than those against the controls' endometrium. Peritoneal fluid endometrial antibody titers failed to reflect these antigenic differences. Controls and patients with adenomyosis had low titers of endometrial antibodies in their serum or peritoneal fluid. Antigenic differences appear to exist between the endometrium of patients with endometriosis and that of controls.     

Revisiting the association between endometriosis and bipolar disorder

ObjectiveWe sought to study the association between endometriosis and bipolar disorder.MethodsUsing the Structured Clinical Interview for DSM-IV Axis I Disorders, the prevalence of bipolar disorder was compared in 27 patients with endometriosis and 12 women with pelvic pain not related to endometriosis who were seen at a specialty gynaecology clinic for women with chronic pelvic pain.ResultsA significantly greater proportion of women in the endometriosis group were found to have bipolar disorder and a poorer quality of life than women with pelvic pain not related to endometriosis.ConclusionThere may be an association between endometriosis and bipolar disorder An optimal approach to managing endometriosis should include evaluation and treatment of psychiatric comorbidity, particularly bipolar disorder.     

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

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

Peritoneal fluid and serum levels of hepatocyte growth factor may predict the activity of endometriosis

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

Increased rate of endometriosis and spontaneous abortion in an in vitro fertilization program: no correlation with epidemiological factors.

BACKGROUND: There are conflicting data concerning endometriosis and spontaneous abortion (SAB). The aim of the present study was to evaluate if there was any association between endometriosis and SAB. Moreover, we investigated risk factors in women with endometriosis and SAB. METHODS: The medical files of 457 married women with endometriosis and 200 infertile women without endometriosis were studied retrospectively. All cases were diagnosed by laparoscopy. Data concerning demographic variables and menstrual characteristics were recorded from 226 women with endometriosis, which were divided into two groups. Group 1 included 126 cases with endometriosis and SAB, and Group 2 comprised 100 parous women with endometriosis and without SAB. Statistical comparisons between groups were made using the chi(2) test and odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The proportion of SAB was significantly higher in women with endometriosis than in infertile women without endometriosis (126/457 (27.6%) vs. 36/200 (18.0% ); OR = 1.7, 95% CI 1.1 = 2.6; p = 0.01). The frequency of nulligravid women was significantly higher in women with endometriosis than in the control group (OR = 1.9, 95% CI 1.4 - 2.81; p = 0.001). Mean age, age at onset of endometriosis, race, height, weight, body mass index, medical history of allergies, and family histories of endometriosis and cancer were similar in women with endometriosis and SAB and in parous women with endometriosis but without SAB. Moreover, the two groups were similar in age at menarche, length of cycle, duration and amount of flow, and the severity of disease. The incidence of infertility was significantly higher in women with SAB (p < 0.001). CONCLUSION: These data suggest but do not prove that the risk of SAB is increased in women with endometriosis. The epidemiological risk factors of endometriosis are not associated with an increase in the abortion rate.     

新生儿硬肿症并肺出血36例临床分析

目的 评价孕酮受体基因内含子G插入306碱基对多态性（PROGINS）在子宫内膜异位症发病中的意义。方法 2005-06—2006-06中国医科大学附属二院和解放军463医院将66例手术及组织学证实诊断的子宫内膜异位症患者和非子宫内膜异位症对照组56例，通过人末梢血提取白细胞DNA，PCR检测基因型分布频率及等位基因（野生型T1和突变型T2）频率．结果 两组比较突变型T2基因型分布频率分别为子宫内膜异位症组0．14，对照组0．04，OR：4．54（95％C1：1.50—13.78），P=0.004。子宫内膜异位症组有2例纯突变型T2（3．0％）：结论 PROG1NS可能与子宫内膜异位症发病有关。     

TWEAK在子宫内膜异位症在位和异位内膜上的表达

目的:探讨肿瘤坏死因子样凋亡的微弱诱导剂(TWEAK)在子宫内膜异位症(EMs)发病的关系。方法:采用实时定量逆转录-聚合酶链反应(Real-time RT-PCR)和免疫组化、Western Blot方法检测EMs患者在位内膜、异位病灶中TWEAK mRNA和蛋白的表达,并与正常对照子宫内膜比较。结果:TWEAK蛋白表达于子宫内膜的腺上皮细胞和间质细胞的胞浆内。与正常对照组内膜和在位组内膜相比,TWEAK mRNA和蛋白在异位内膜上表达量下调(P<0.05),且无论是EMs在位内膜还是对照组内膜,其增生期TWEAK mRNA表达明显低于分泌期(P<0.05)。结论:TWEAK在子宫内膜中表达,表达量在分泌期明显升高。EMs患者异位子宫内膜TWEAK表达降低,可能导致子宫内膜细胞的凋亡水平下降,参与EMs的发生发展过程。     

Ureteral endometriosis: the role of magnetic resonance imaging

In six women out of 792 who underwent magnetic resonance imaging (MRI) for management of deep infiltrating endometriosis (DIE), ureteral involvement was suspected. Ureteral endometriosis was identified as a hypointense nodule on T2- weighted images and hyperintense foci on T1-weighted images. Magnetic resonance urography detected obstruction and hydronephrosis in half the women. Detection with MRI of periureteral involvement (extrinsic endometriosis) in four women rather than ureteral wall lesions (intrinsic endometriosis) in two women is an original finding from this series. Magnetic resonance imaging features were correlated and matched with intraoperative and pathologic findings. Magnetic resonance imaging is a useful preoperative tool for the diagnosis and assessment of ureteral endometriosis in rare cases when such lesions have been suspected.     

Low serum and peritoneal fluid concentration of interferon-gamma-induced protein-10 (CXCL10) in women with endometriosis

OBJECTIVE: To evaluate serum and peritoneal fluid concentrations of interferon-gamma-inducible protein-10 (CXCL10), a chemokine involved in local immune function, in women with endometriosis. DESIGN: Prospective study. SETTING: Division of Obstetrics and Gynecology, University of Siena. PATIENT(S): A total of 147 women were divided in two groups: women with (n = 77) and without (n = 70) endometriosis. INTERVENTION(S): Serum and peritoneal fluid were collected from all patients undergoing laparoscopy. MAIN OUTCOME MEASURE(S): CXCL10 concentrations were measured by a specific ELISA. RESULT(S): Serum CXCL10 concentrations in women with endometriosis were significantly lower than in those without endometriosis. No statistically significant difference between women with early endometriosis and those with advanced endometriosis was found. CXCL10 concentrations in peritoneal fluid of women with advanced endometriosis were significantly lower than in that of women with an early stage of, or without, endometriosis. CONCLUSION(S): The decreased concentrations of CXCL10 in serum and peritoneal fluid of women with endometriosis indicate an impaired immune activity in women with endometriosis.     

Rapid peptidomic profiling of peritoneal fluid by MALDI-TOF mass spectrometry for the identification of biomarkers of endometriosis

Peptidomic profiling of peritoneal fluid by Matrix Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF-MS) may represent a promising, suitable, rapid method for early diagnosis and staging of endometriosis. In a case-control study, peritoneal fluid was collected from 23 patients affected by endometriosis (eight minimal/mild endometriosis and 15 moderate/severe endometriosis) and six “endometriosis free” women undergoing laparoscopy. MALDI-TOF mass spectra of the peptide fraction extracted from peritoneal fluid samples lead to identify biomarkers potentially suitable for discriminating between peritoneal fluid samples from women affected by minimal/mild endometriosis and those from women affected by moderate/severe endometriosis. Peptidomic analysis of peritoneal fluid samples may define putative peptide biomarkers suitable for staging endometriosis and improve our understanding of the pathogenesis of endometriosis.     

Application of IVF in women with endometriosis

Application of IVF at women with endometriosis after pharmacological and surgical therapy hold out hopes to possession of child. Endometriosis occurs three times more often in the patients with primary sterility than in patients with secondary sterility. The presence of a small endometriosis does not reduce the success of the IVF therapy. The women with endometriosis who undergo IVF treatment have similar prospect in compensate with women with tubal sterility. IVF improve fertility in women with mild or minimal endometriosis. But at women after IVF the presence of endometriomas is associated with increased rates of early pregnancy losses. Women with endometriosis marking often antinuclear antibodies and antiphospholipid antibodies than women without endometriosis. To evaluate the 15% of infertile women have endometriosis.     

Endometriosis and the primary care consultation

OBJECTIVES: Endometriosis is a long term, disabling condition, and a common cause of chronic pelvic pain. Symptomatic disease is usually characterised by pelvic and abdominal pain, lower back pain, and dyspareunia, all of which may be severe and debilitating. Yet the time between onset of symptoms and diagnosis is frequently a number of years, and many women report negative experience within the primary care setting. This paper explores the experience of women with endometriosis in the primary care setting. STUDY DESIGN: A qualitative research design was considered appropriate to elicit the experience of endometriosis and the impact on women's lives. Semi-structured interviews were conducted with 30 women who suffer with endometriosis. The sample was recruited via a dedicated endometriosis clinic in the English Midlands, and participants had all been diagnosed laparoscopically with endometriosis. RESULTS: Participants described diverse experiences within the primary care setting. Although some women reported a positive relationship with their general practitioner, over half had had negative experiences, which they felt had contributed to delays in them receiving a diagnosis of endometriosis. CONCLUSION: The delay in diagnosis can be reduced and perceived attitudes of general practitioners towards women presenting with endometriosis can be improved by being alert to certain symptomology, and by detailed and sensitive history taking.     

Early endometriosis invades the extracellular matrix.

OBJECTIVES: To investigate whether the aminoterminal propeptides of type III procollagen are increased in patients with early endometriosis and to demonstrate that the subtle lesion of endometriosis is an active stage of the disease. DESIGN: Aminoterminal propeptide of type III procollagen was determined in serum and peritoneal fluid (PF) of 100 consecutive patients undergoing laparoscopy. SETTING: Academisch Ziekenhuis Maastricht, The Netherlands, a tertiary care center. RESULTS: Aminoterminal propeptide PF levels were significantly higher in women with early lesions of endometriosis compared with levels in two groups of controls, i.e., fertile, cycling, women without the disease (P = 0.019) and women on oral contraceptives without the disease (P = 0.036). No difference was found in aminoterminal propeptide PF levels when comparing patients with early lesions of endometriosis and patients with unexplained infertility, the third control group. Aminoterminal propeptide PF levels of patients with endometriosis without early lesions were not different from PF levels in controls. CONCLUSION: The early lesion is an active stage of endometriosis, invading the extracellular matrix. In women with unexplained infertility active, microscopic endometriosis may be present.     

Incidence of the luteinized unruptured follicle syndrome in fertile women and in women with endometriosis

One-hundred normal fertile women with normal luteal phase and 118 women with endometriosis underwent luteal phase laparoscopy before day 22. The luteal phase was ascertained by the presence of secretory endometrium and serum progesterone levels higher than 3 ng/ml. The ovaries were carefully inspected for the presence or absence of an ovulation ostium. The percentage of ostii that was observed in fertile women (91%) was similar to that observed in women with mild endometriosis (85%). However, in women with moderate and severe endometriosis, significantly less ostii were noted, respectively 72 and 51%. It is therefore argued that the absence of an ovulation ostium (so-called luteinized unrupted follicle syndrome, LUF) is more frequent in women with moderate and severe endometriosis and may contribute to infertility in this group of women.