Autoimmunity in endometriosis: relevance to infertility

PROBLEM: Endometriosis is a complicated multi-factorial disease. Genetic and immunologic factors play a key role in its pathophysiology. We were the first to describe endometrial and ovarian autoimmunity in women with endometriosis in 1981. METHODS OF STUDY: ELISA and Western blot analysis. It is accepted that women with endometriosis have autoimmunity to endometrial, ovarian and nuclear antigens. We have now established that: 1. The endometrial autoantigens to which the endometriosis patients have autoimmune reactions are endometrial transferrin and alpha 2-HS glycoprotein. 2. Levels of antibodies to both these proteins are specifically elevated in women with endometriosis, thus making them important candidates for developing an endometrial antibody assay for a non-invasive diagnosis of endometriosis. 3. Levels of transferrin and alpha 2-HS glycoprotein are significantly elevated in the peritoneal fluid of women with endometriosis. 4. Antibodies to transferrin and alpha 2-HS glycoprotein also inhibit in vitro sperm motility. CONCLUSION: These data strongly suggest the possibility of endometrial autoantibodies playing an important role in the infertility often associated with endometriosis.     

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.     

Autoantibodies in endometriosis sera recognize a Thomsen-Friedenreich-like carbohydrate antigen

Autoantibody responses to endometrial antigens are a common feature of endometriosis. Antibody responses to a number of serum and tissue antigens such as alpha(2)-Heremans Schmidt glycoprotein (alpha(2)-HSG), transferrin, and carbonic anhydrase have been identified. The nature of the epitopes recognized on these proteins has not been determined. In this study we show that the serum antibody response to alpha(2)-HSG and carbonic anhydrase is against a common carbohydrate epitope which is also expressed on bovine fetuin. Removal of carbohydrate moieties from these antigens resulted in loss of antibody binding. Antibody reactivity with alpha(2)-HSG, fetuin and other antigens was removed by binding with the lectin jacalin. Jacalin specifically binds the Thomsen-Friedenreich antigen (Galbeta1-3GalNAc). Demonstrating that the autoantibodies also reacted with other Thomsen-Friedenreich antigen-bearing proteins, serum IgA1 and haemopexin confirmed an association with this epitope. These antigens have not been previously described as autoantigens in endometriosis and are of interest since they raise the possibility that this autoimmune response may either play a direct role in the disease process or reflect an abnormality of glycosylation in endometriosis. These results may also prove useful in the development of a serum diagnostic test for endometriosis.     

Levels of transferrin and alpha 2-HS glycoprotein in women with and without endometriosis.

The study objective was to test the hypothesis that elevated levels of transferrin and alpha 2-HS glycoprotein occur in the peritoneal environment of patients with endometriosis that may lead to the observed autoimmunity to these proteins. We set up a double sandwich enzyme-linked immunosorbent assay (ELISA) for measuring levels of transferrin and alpha 2-HS glycoprotein in the serum and peritoneal fluid samples from women with (n = 24-60) and without endometriosis (n = 35-49). Serum and peritoneal fluid levels of alpha 2-HS glycoprotein and peritoneal fluid levels of transferrin were significantly elevated in patients with endometriosis, in contrast to the controls. Serum levels of transferrin in patients, however, were significantly less in the patients than in controls. We conclude that transferrin and alpha 2-HS glycoprotein are present at high concentrations in the peritoneal fluids of patients with endometriosis. This may play a significant role in the autoimmune pathophysiology of endometriosis.     

Detection of Antiendometrial Antibodies in Sera of Patients With Endometriosis by Dual-Colored,Double-Labeling Immunohistochemical Method and Western Blot

PROBLEM : This study was undertaken to determine whether specific binding activities against endometrial proteins in sera of patients with endometriosis are detectable and, if so, to identify endometrial antigens involved in autoimmunity in endometriosis. METHOD : Sera from 33 patients with endometriosis and 20 cord sera (controls) were tested against endometria of patients and their protein extracts by dual-colored, double-labeling immunohistochemical method, and Western blotting. RESULTS : Antiendometrial binding activities were detected in sera of 2 (10.0%) control patients and 13 (48.2%) patients with endometriosis by the immunohistochemical method. Endogenous immunoglobulin G (IgG) binding to endometrial proteins had molecular weights (MW) of 26, 28, 54, 85, 107 and 116 kDa. Most sera of both control and patients showed reactivity against endometrial proteins with MW of 34, 36, 56 and 77 kDa. However, there were specific IgG autoantibodies reactive against the endometrial proteins of 71, 92, and 103 kDa in sera of 55.2% (16/29) of patients but not in the control sera. Over 80% (10/12) of patients' sera with binding activities detectable by the immunohistochemical method also tested positive by Western blot analysis. CONCLUSIONS : These data show that specific IgG antibodies reactive against endometrial antigens are detectable in sera from some patients with endometriosis.     

Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis

BACKGROUND: The aetiology of endometriosis is unknown. Ectopic dissemination of the endometrial cells gives origin to endometriotic lesions, but occurs in women with and without endometriosis. It has been suggested that increased ectopic cell survival facilitates their implantation. The objectives of this study were to evaluate endometrial apoptosis in women with endometriosis according to: (i) cyclic changes, (ii) glandular and stromal contribution, and (iii) stage of the disease. METHODS: The subjects were women undergoing diagnostic laparoscopy and endometrial biopsies for suspected endometriosis. Spontaneous apoptosis was evaluated using TdT-mediated dUTP-biotin nick end-labelling (TUNEL) assay. Apoptotic cells per 10 mm(2) (apoptotic index) in an area of 10-50 mm(2) in 5 microm endometrial tissue sections were counted and location of these cells was recorded. RESULTS: The apoptotic index in glandular epithelium was lower in endometriosis than controls (26.0 +/- 5.5 versus 51.2 +/- 9.7, P = 0.03) but not in the stroma (36.3 +/- 6.4 versus 48.4 +/- 11.3, NS). In controls, apoptosis was highest during the late secretory/menstrual and early proliferative phases and cyclic variability was apparent. In endometriosis, this cyclic variability was lost. There was a trend toward decreased apoptosis with increasing stage of the disease, but the differences lacked statistical significance. CONCLUSIONS: Spontaneous apoptosis is decreased in the endometrial glands in women with endometriosis, especially during late secretory/menstrual and early proliferative phases of the cycle. This may indicate increased viability of endometrial cells shed during menses, facilitating their ectopic survival and implantation.     

Effects of Antibodies to Transferrin and Alpha 2-HS Glycoprotein on In Vitro Sperm Motion: Implications in Infertility Associated with Endometriosis

PROBLEM: Women with endometriosis have antibodies to endometrial transferrin and alpha 2-HS glycoprotein in their serum and peritoneal fluid. The objective of this study was to determine whether antibodies to transferrin and alpha 2-HS glycoprotein adversely affect sperm motility and survival. METHOD OF STUDY: Spermatozoa obtained from normal fertile donors and washed free of seminal plasma were incubated with the medium (control), 1:2 and 1:100 dilutions of antitransferrin, 1:4, 1:8 and 1:100 dilutions of anti-alpha 2-HS glycoprotein, and a 1:2 dilution of antialbumin antiserum (negative control). Sperm motion characteristics in 10 μl aliquots were evaluated at 30 min, 1 hr, 2 hr, 4 hr, and 24 hr using computerized sperm motion analysis. A paired t-test was done to analyze the effects of the various antibodies on sperm motion characteristics. RESULTS: Antibodies to albumin failed to adversely affect sperm motility in general or the several sperm motion characteristics in particular. In contrast, antibodies to transferrin at the dilution of 1:2 adversely affected the percentage of motile and rapid spermatozoa, progressive and path velocities, straightness, linearity, track speed, and anterior-lateral head displacement (P < 0.001) at all the time intervals, whereas a 1:100 dilution of this antiserum adversely affected these parameters only at 24 hr. Elongation and beat cross-frequency were significantly affected at 4 and 24 hr by a 1:2 dilution of antitransferrin antiserum. The effects of anti-alpha 2-HS glycoprotein were more pronounced than those of antitransferrin, but they were similar. Dilutions of 1:4 and 1:8 were effective at all time intervals, whereas a 1:100 dilution was effective in reducing the track speed and the percentage of rapid cells at 24 hr (P < 0.001). CONCLUSION: Antibodies to endometrial transferrin and alpha 2-HS glycoprotein present in the peritoneal fluid, and possibly in the oviductal fluid, of patients with endometriosis may adversely affect postcoital sperm motility and sperm survival.     

Detection of Antiendometrial Antibodies in Patients With Endometriosis by Cell ELISA

PROBLEM: To determine whether infertile patients with endometriosis have serum antiendometrial antibodies. METHODS: Sera from 40 infertile patients with or without endometriosis were tested by cell enzyme-linked immunosorbent assay (ELISA), in which endometrial cancer cells were used as endometrial antigens, and uterine cervix cancer cells as control antigens. As a negative control, eight healthy adult males were included. The level greater than the mean + 2 standard deviations (SD) of the male control group was judged positive. RESULTS: The mean value of antiendometrial antibody level was significantly higher in patients with endometriosis than in those without endometriosis (ANOVA, P < 0.01). The frequency of antiendometrial antibody-positive patients was also higher in the former than in the latter (χ² test, P < 0.05). However, when uterine cervix cancer cells were used as antigens, no difference was observed in the mean antibody levels or in the positive rates between the two groups. CONCLUSIONS: Endometriosis seems to be associated with autoantibody production against the endometrium-related antigen(s).     

Expression of Intercellular Adhesion Molecule-1 (ICAM-1) on Cultured Human Endometrial Stromal Cells and Its Role in the Interaction With Natural Killers

PROBLEM: Recent evidence emphasizes the role of natural killer cells (NKs) as potential effectors of peritoneal immune surveillance directed against the outgrowth of endometrial cells, refluxed with menstrual debris, in ectopic sites. This NK-mediated cytotoxicity toward autologous endometrial antigens seems to be significantly decreased in endometriosis patients. METHOD: We set up experiments to clarify which molecules are involved in NK-endome-trial cell interaction. In particular, we evaluated the surface expression and functional activity of intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein that has been identified as one of the ligands for lymphocyte function-associated antigen-1 (LFA-1), present on almost all leucocyte cell types. Immunofluorescence flow cytometry was used to assess ICAM-1 expression on resting and IL 1β-activated endometrial stromal cells in culture. Dermal fibroblasts were used as control cells. Cytotoxicity and binding assays by ⁵¹Cr release in presence and absence of a specific monoclonal antibody (mAb) against ICAM-1 were then performed in order to determine the effect of this molecule on NK-mediated cytotoxic and binding activity toward endometrial stromal cells. RESULTS: The results of this study indicated that ICAM-1 expression on endometrial stromal cells seems to be constitutively higher than on dermal fibroblasts and can be up-regulated upon exposure to IL 1β. Furthermore, a mAb against ICAM-1 strongly inhibits the binding but not the cytotoxicity of NKs toward endometrial cells. No difference in the expression of this molecule was observed throughout the cycle. CONCLUSIONS: The presence of ICAM-1 on human endometrium might relate to the action of the immunocompetent cells in human specific reproductive events.     

Interleukin 1alpha and tissue-lytic matrix metalloproteinase-1 are elevated in ectopic endometrium of patients with endometriosis

BACKGROUND: Matrix metalloproteinases (MMP) play an essential role in tissue remodelling and menstruation and appear to be regulated by cytokines such as interleukin-1alpha (IL-1alpha). In order to investigate their role in the pathogenesis of endometriosis, the aim of the present study was to compare the protein localization of matrix metalloproteinase-1 (MMP-1) and of its main stimulatory cytokine IL-1alpha in eutopic and dystopic endometrium of patients with endometriosis. METHODS: MMP-1 and IL-1alpha protein localization was analysed retrospectively in paired paraffin-embedded tissue biopsies obtained simultaneously from the endometrial cavity and from endometrial lesions of 37 patients with peritoneal or ovarian endometriosis and in cycling endometria from 37 women without endometriosis. Protein localization was demonstrated by immunohistochemistry; antibody specificity was confirmed by western blot analysis. RESULTS: MMP-1 and IL-1alpha protein staining in women suffering from endometriosis was significantly more pronounced in endometriotic lesions than in eutopic endometrium. This held true for both epithelial MMP-1 and IL-1alpha staining (P < 0.006 and P < 0.001), and for stromal MMP-1 and IL-1alpha staining (P < 0.001 and P < 0.001). Furthermore, stromal MMP-1 and IL-1alpha were significantly co-expressed in dystopic endometriotic tissue (P = 0.045). Endometrial MMP-1 and IL-1alpha protein expression pattern in eutopic endometrium from women suffering from endometriosis, however, did not differ significantly from the pattern seen in healthy women. CONCLUSIONS: The increased expression of both matrix-degrading MMP-1 and its major stimulatory cytokine IL-1alpha in endometriotic lesions and the selective co-expression in the stroma of endometriotic foci clearly suggests their involvement in the pathogenic mechanisms leading to local invasion and tissue destruction.     

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

Accumulated evidence implicates immunological alterations inendometriosis. The purpose of this study was to look for variationsin antibodies to distinct antigens in peritoneal fluid of womenwith and without endometriosis. Peritoneal fluid was aspiratedfrom 17 women undergoing laparoscopy for tubal ligation and37 patients complaining of symptoms of pain and/or infertility.Peritoneal fluid antibodies to a standard preparation of peritonealfluid antigens were detected by Western blot analysis usingperoxidase-labelled anti-human immunoglobulin G antibodies specificto the Fc region. Antibodies to distinct antigens were quantifiedby estimating the ratio of the relative optical density betweensamples and a standard amount of antibodies. Marked changeswere found in the antibody detection to two antigens havingapparent molecular weights of 22 and 18 kDa. The intensity ofthe antibody signal was significantly weaker in the peritonealfluid 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 weakerin patients without endometriosis presenting with infertility(036 ± 0.07 and 0.47 ± 0.08), but only the 18kDa 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 endometriosispatients. These changes were not related to the phase of themenstrual cycle. These data suggest an alteration in the immuneresponse to two distinct antigens in the peritoneal fluid fromwomen with endometriosis and infertility. Further evaluationof these two antigens and their antibodies would be of interestto help understand endometriosis and its associated infertility.     

Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis

BACKGROUND: Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. METHODS: Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. RESULTS: No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. CONCLUSIONS: There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.     

Anti-endometrial antibodies in women measured by an enzyme-linked immunosorbent assay

An enzyme-linked immunosorbent assay (ELISA) was developed tomeasure anti-endometrial antibody concentrations in the serumof women with endometriosis. Pooled cytosolic protein extractsfrom the endometrial gland cells of 10 women were used as anantigen source. Serum samples were obtained from women withendometriosis before (n = 51) and after 6 months treatment withdanazol or nafarelin (n = 30). Control sera came from womenwith a normal pelvis at laparoscopy, performed for sterilization(n = 23) or the investigation of pain and/or infertility (n= 22), 13 women with Rokitansky syndrome, and 10 umbilical cordbloods and adult males. There were no significant differencesin serum anti-endometrial antibody concentrations before andafter treatment, or between women with endometriosis and withoutendometriosis. Concentrations were lower in male and cord bloodserum than in female's serum (P < 0.0001). We conclude thatthe ELISA is not a useful diagnostic tool for endometriosisunless more specific antigens can be isolated.     

Correlation between decreased type-II interleukin-1 receptor and increased monocyte chemotactic protein-1 expression in the endometrium of women with endometriosis

PROBLEM: Monocyte chemotactic protein-1 (MCP-1), a potent inducer of macrophage recruitment and activation, is overexpressed in the eutopic endometrium of women with endometriosis. Eutopic endometrial cells of women with endometriosis secrete higher levels of MCP-1 than those of normal women, following stimulation with interleukin-1 (IL-1). The aim of this study was to examine whether there is any correlation between the expression of IL-1 receptor type II (IL-IRII), a specific downregulator of IL-1 activity, and that of MCP-1 in the eutopic endometrium of women with endometriosis. METHOD OF STUDY: Endometrial biopsies of 46 women with endometriosis and 22 healthy women were evaluated simultaneously for IL-1RII and MCP-1 expression by immunohistochemistry. RESULTS: Our study revealed a highly significant correlation between the decreased expression of IL-1RII and the increased expression of MCP-1 in the endometrial tissue of women with endometriosis (Spearman correlation coefficient r = -0.377, P = 0.002), particularly in the initial stages of the disease (stages I and II; r = - 0.368, P = 0.020 and r = -0.480, P = 0.002, respectively). Furthermore, this correlation was observed in the proliferative (r = -0.366, P = 0.047) and the secretory phases (r = -0.321, P = 0.049) of the menstrual cycle. CONCLUSIONS: These results suggest that the reduced capability of endometrial tissue to downregulate IL-1 proinflammatory effects may be involved in the increased expression of MCP-1 in the endometrium of women with endometriosis and the establishment of an inflammatory state. The results also indicate a sustained process of cell activation throughout the menstrual cycle.     

Nitric oxide synthesis is increased in the endometrial tissue of women with endometriosis

BACKGROUND: Previous studies have shown that peritoneal macrophages from women with endometriosis produce excess nitric oxide (NO). This study was designed to quantify the amount of NO and determine the expression of endothelial (eNOS) and inducible NO synthases (iNOS) in women with and without endometriosis. METHODS: An enzyme-linked immunosorbent assay (ELISA) was performed on endometrial tissues obtained from controls (myoma, n = 30) and on eutopic/ectopic endometrial tissues from endometriosis patients (n = 34) to evaluate eNOS and iNOS protein concentrations in these endometrial tissues. A rapid-response chemiluminescence analyser was used to measure NO directly in fresh endometrial tissues. RESULTS: Mean (+/- SEM) levels of NO were significantly increased in the endometrial tissues of women with endometriosis (13.2 +/- 7.8 versus 19.8 +/- 12.6 nmol/g tissue; P = 0.016). Apparently higher levels of NO were found in ectopic compared with eutopic endometrium (P = 0.057). Endometrial tissues of women with endometriosis appeared to contain more iNOS than those of controls (3.6 +/- 2.2 versus 8.6 +/- 12.2 pg/ microg protein; P = 0.06), but no significant difference was found in eNOS levels. CONCLUSIONS: Greater amounts of NO and NOS are present in the endometrial tissues of women with endometriosis, implying a possible role for NO in the pathogenesis of endometriosis.     

ORIGINAL ARTICLE: Serum Anti‐endometrial Antibodies in Infertile Women – Potential Risk Factor for Implantation Failure

Citation Sarapik A, Haller‐Kikkatalo K, Utt M, Teesalu K, Salumets A, Uibo R. Serum anti‐endometrial antibodies in infertile women – potential risk factor for implantation failure. Am J Reprod Immunol 2010 Problem Female infertility patients with diverse etiologies show increased production of autoantibodies. Method of study Immunoblot analysis of sera from patients with endometriosis and tubal factor infertility (TFI) and mass spectrometry identification of candidate antigens. Results The immunoblot results demonstrated the presence of IgA and IgG anti‐endometrial antibodies (AEA) to various antigens at molecular weights ranging from 10 to 200 kDa. Differences were detected in certain AEA reactions between the patients’ groups and particular AEA were associated with in vitro fertilization (IVF) implantation failure. IgA AEA to a 47‐kDa protein were more prevalent in TFI patients and were associated with unsuccessful IVF treatment. This antigen was subsequently identified as α‐enolase. Conclusion Determination of the presence and spectra of AEA in patients with endometriosis and TFI undergoing IVF may be a useful marker to predict their pregnancy outcome.     

Endometriosis in reproductive immunology

PROBLEM: Endometriosis is suggested to represent an autoimmune disorder, but what is the prevalence of autoantibodies to antigens relevant to reproduction? METHOD OF STUDY: The humoral immune response to the women with endometriosis (stage I–II: 261 women; stage III–IV: 62 women) in serum and in peritoneal fluid was investigated compared with 101 healthy women. Enzyme‐linked immunosorbent assay (ELISA) was used in all the women for the detection of seven antiphospholipid antibodies [antiphospholipid antibodies (aPLs) against cardiolipin, L ‐phosphatidyl (ph)‐serine, ph‐glycerol, ph‐inositol, ph‐ethanolamine, phosphatidic (ph)‐acid and against β2‐glycoprotein I] of class IgG, IgA, and IgM. A passive haemmagglutination method and ELISA (BioGen) was used for assessment of antizona pellucida antibodies (aZP), tray agglutination test (TAT) and indirect mixed anti‐imunoglobulin reaction test (MAR‐test) for the determination of sperm antibody levels. RESULTS: Endometriosis I–II were associated with higher serum and peritoneal fluid levels of aPLs against inositol, cardiolipin, ethanolamine, and β2‐glycoprotein I. Forty percent of patients were positive for aZPA. CONCLUSIONS: Patients with lesions of endometriosis stage I–II had more autoantibodies than those with stage III–IV, and may be immunologically more active. This result may be significant for future treatments such as in vitro fertilization and embryo transfer.     

Immunologic Aspects of Human Endometriosis

ABSTRACT: General and specific immune function were examined in women with endometriosis. Nonspecific parameters included total leukocyte and differential counts, quantitative immunoglobulin (IgG, IgA, and IgM) determinations, total hemolytic complement, C₃, C₄, mitogen-induced lymphocyte stimulation, and human leukocyte antigen (HLA) typing; no differences were observed when data were compared to age-matched controls without endometriosis. In contrast, the specific immune response T-lymphocyte-mediated cytotoxicity to autologous endometrial cells was significantly reduced (P <0.01) in women with endometriosis. When results from patients were analyzed according to clinical severity of endometriosis, even more striking immunologic alterations were delineated. In addition, lymphocyte stimulation responses to autologous endometrial antigen were lower in patients with severe or moderate disease, approaching statistical significance (P = 0.18 and 0.12, respectively). These studies suggest an immunologic basis for development of endometriosis.     

Endometriosis: absence of recurrence in patients after endometrial ablation.

BACKGROUND: The present study was undertaken to evaluate differences between patients with and without eutopic endometrium in the recurrence of ectopic endometriotic implants. METHODS: Endometrial ablation (EA) was carried out in 14 women out of 28 laparoscopically treated for endometriosis and recurrence of the disease was evaluated 24 months later. Data were compared using paired Student's t-test and chi2 test. RESULTS: Patients undergoing EA procedures did not exhibit recurrence of endometriosis while nine patients without that procedure had recurrence of the disease (P < 0.001). The endometrial cells found in the debris of the cul de sac of eight patients who did not undergo EA were both stromal and epithelial cells. No blood or blood cells were found in the cul de sac of patients undergoing EA. CONCLUSIONS: The present study supports a role of eutopic endometrium in the recurrence of endometriosis through tubal dissemination of endometrial debris and implantation of endometrial cells into the abdomen.     

Anti-Endometrial Autoantibodies in Women with a Diagnosis of Infertility

PROBLEM: The purpose of this study was to investigate the frecuency of anti-endometrial antibodies (AEA) in infertile women. METHOD OF STUDY: Sera from fertile women (n = 6), and from patients with ovulatory dysfunction (n = 11), tubal obstruction (n = 9) and unexplained infertility (n = 5) were investigated for the presence of anti-endometrial membrane antibodies. We used two human endometrial cancer cell lines and human endometrial cells from gynecological biopsies as an antigenic source for analysis. The immunoenzymatic assay (ELISA) was performed with cultured endometrial cells in monolayers. Immunoblot analysis was performed with these two cell lines. RESULTS: A good correlation between the response with each cell line and with human endometrial cells was obtained, indicating that the antigens analyzed were probably similar. Endometrial antibodies were detectable in a high percentage of women with tubal obstruction (77.8 and 66.7%, respectively) and ovulatory dysfunction (54.5 and 45.5%, respectively). Unexplained infertility showed anti-endometrial immunological response (40 and 60%, respectively). Some endometrial antigens in infertile women are the target for autoimmune response. The serum from a patient with tubal obstruction and ovulatory dysfunction showed two antigens by immunoblot, with molecular weights of 97 and 50 kDa. CONCLUSION: The presence of anti-endometrial antibodies, detected by ELISA, is associated with infertility, mainly with ovulatory dysfunction and tubal obstruction. Some endometrial antigens may be involved in these two pathologies.