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.     

Cell proliferation in endometrium of women with endometriosis

The purpose of this study was to describe the endothelial cell activity of the endometrial tissue in women with and without endometriosis, and find out the diagnostic opportunities for everyday gynecologic practice. There were 30 women with laparoscopic proved endometriosis involved in our study and 27 women with no endometriosis used as a control group. The histological findings were scored after Noyes criteria and classified according to the phase of the menstrual cycle. We found out a significant difference between the two groups, especially during the proliferate phase of the menstrual cycle.     

Implantation failures in women with infertility associated endometriosis

Abstract

Endometriosis is currently considered as one of the most common diseases associated with infertility. A controversial issue is whether endometriosis per se exerts a detrimental effect on IVF outcomes. Failure of implantation due to endometriosis-associated infertility is a contradictory and widely discussed burden nowadays. The purpose of the study is to assess the quality of embryos and implantation rate in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 26 and 40 years who underwent IVF and ICSI procedures. The patients were divided into two groups: group I (n?=?70) involved 70 patients with recurrent unilateral endometriomas, II control group (n?=?50) with tubal factor infertility. The quality of the retrieved embryos was assessed according to the generally accepted classification of Gardner, indicating the rate of implantation in each group. Embryo transfer was performed in case of high quality embryos. Assessing the ovarian reserve indicators, in the group I patients with recurrent unilateral endometriomas the serum level of AMH was significantly lower (2.1?±?1.75 vs. 3.2?±?1.4, p?<?.005), as well as the number of retrieved oocytes (8.1?±?3.9 and 10.1?±?6.8, p?<?.005). The analysis of the results demonstrated that the duration of stimulation in the group patients with recurrent unilateral endometriomas was significantly higher in comparison with the group II (12.2?±?1.8 and 10.2?±?1.6 days, p?<?.001). Nevertheless, the number of good quality embryos retrieved was comparable in both groups (2.2?±?1.5 and 2.8?±?1.8). In the group I patients with recurrent unilateral endometriomas, there was a statistically significant decrease of implantation rate (17.1% vs. 24% p?<?.005). The results of the study revealed no statistical difference in embryo quality in the study cohort. However, it is important to note that a statistically significant difference in implantation rate in the group of endometriosis-associated infertility compared was obtained 1.5 times lower than in the control group (15.8% vs. 24.0% p?<?.005). The achieved results demonstrated an adverse IVF outcome in infertile women with recurrent endometrioma compared to the control group.     

Oocyte quality in women with infertility associated endometriosis

Abstract

The mechanisms of endometriosis-related infertility remain still unknown. Endometriosis and clinical markers of oocyte quality are a very important problem of reproduction. The purpose of the study is to assess the quality of oocytes in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 29 and 40 years who underwent IVF and ICSI procedures. The patients were divided into three groups: group I involved 50 (n?=?50) patients with recurrent unilateral endometriomas, group II included 50 patients (n?=?50) unilateral endometriomas after surgical treatment and control group with 30 (n?=?30) patients with tubal factor infertility. Clinical and morphological assessment of oocyte quality was performed in all IVF/ICSI cycles. The results of the study demonstrate a statistically significant increase in the number of immature oocytes of metaphase MI and immature oocytes at the GV germinal vesicle stage in patients with infertility associated with endometriosis, compared with the control group (p<.005). There is deterioration in the quality of the obtained oocytes in patients with the presence of endometrioma more than 3?cm in diameter. The results of this study allow to conclude that endometriomas negatively affect quality of oocyte and ovarian reserve, whereas endometriomas after cystectomy, have a deleterious and sustained effect on ovarian reserve.     

Lectin binding of endometrium in women with unexplained infertility

OBJECTIVE: To investigate whether peri-implantation phase endometrium in women with unexplained infertility differs from the endometrium of normal fertile women. DESIGN: Assessment of the function of the endometrium by using endometrial biopsy specimens and lectin histochemistry. SETTING: Infertility Clinic, Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen normal fertile women (group I) and 18 women with unexplained infertility (group II). INTERVENTIONS: Endometrial biopsies were obtained from both groups at 5, 7, and 9 days after the luteinizing hormone (LH) surge. MAIN OUTCOME MEASURES: Five biotinylated lectins, concanavalin A (ConA), wheat germ agglutinin (WGA), soybean agglutinin, Peanut, and Ulex europaeus I were used as analytical probes to study endometrial glycoconjugates. Histochemical staining was performed using the avidin-biotin peroxidase method. The lectin binding by endometrial glands, surface epithelium, stromal cells, and vessels was assessed. RESULTS: In group I, ConA stained the subnuclear glandular cytoplasm, glandular lumen, stroma cells, and surface epithelium. In group II, ConA binding to glandular or surface epithelium was none or equivocal. In group I, WGA bound to glandular cytoplasm and stroma cells on days LH + 5 and LH + 7. In group II, WGA binding was absent in glands but present in stroma. CONCLUSIONS: Reproductive failure of women with unexplained infertility may be associated with defective biosynthesis and distribution of glycoconjugates that subsequently results in an unfavorable endometrial environment during the peri-implantation phase.     

Apoptosis pattern in human endometrium in women with pelvic endometriosis

OBJECTIVE: In the present study we aimed to describe apoptosis patterns in eutopic endometrium in women suffering from endometriosis in order to assess its value as a marker of early forms of endometriosis, and also to try to answer whether endometriosis is caused by changes within the eutopic endometrium or whether endometriotic lesions change the characteristics of eutopic endometrium. STUDY DESIGN: The study was performed on 125 women treated in Division of Reproduction. In 52 patients peritoneal endometriosis was diagnosed (I(0)-23; II(0)-29). Seventy-three patients in whom no endometriotic foci could be found at laparoscopy were qualified as the control group. Endometrial biopsy 7-9 days after ovulation was taken for assessment of apoptosis (TUNEL) and routine histology. RESULTS: Apoptosis indices in the eutopic endometrium of women with endometriosis were lower compared to women without endometriosis. In the endometrial glands apoptosis indices were 2.94+/-1.66 versus 5.23+/-2.06 (p<0.01) in the group of women with and without endometriosis, respectively. In the endometrial stroma apoptosis indices were estimated at 2.04+/-1.72 in women with endometriosis and 4.12+/-1.62 in the control group (p<0.01). CONCLUSIONS: The observed changes could support the hypothesis of the different properties of eutopic endometrium in endometriotic women as a causing factor of peritoneal endometriosis.     

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.     

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.     

Increased expression of endoglin in the eutopic endometrium of women with endometriosis.

OBJECTIVE: To compare the angiogenic activities of endothelial cells in the eutopic endometrium of women with and without endometriosis. DESIGN: Vessels with active angiogenesis were identified using the monoclonal antibody to endoglin. SETTING: University department of obstetrics and gynecology. PATIENT(S): Twenty women with histologically confirmed endometriosis after laparotomy or laparoscopy. Women with carcinoma in situ of uterine cervix, but no evidence of endometriosis (n = 20), served as control subjects. INTERVENTION(S): Formalin-fixed, paraffin-embedded archival tissues were sectioned and stained. MAIN OUTCOME MEASURE(S): Number of vessels stained with monoclonal antibody to endoglin. RESULT(S): For all menstrual phases, the mean number of vessels with endoglin expression was significantly greater in patients with endometriosis compared with control subjects. In each menstrual phase, a significant difference was observed only during the late secretory phase. Within the group with endometriosis, the mean numbers of vessels with endoglin expression in stages I and II were not different from the numbers in stages III and IV. CONCLUSION(S): This study shows the expression of endoglin in the eutopic endometrium of women with endometriosis is significantly increased and the increase is observed only in the late secretory phase. It is suggested from these findings that activation of angiogenesis in the eutopic endometrium might be a key factor in the pathogenesis of endometriosis.     

P27Kip1 is down-regulated in the endometrium of women with endometriosis

OBJECTIVE: To evaluate p27 protein expression in the endometrium of women with endometriosis. DESIGN: Transversal case-control study. SETTING: Endometriosis Unit, Federal University of S?o Paulo, Brazil. PATIENT(S): Thirteen patients with stage I/II endometriosis, five with stage III/IV endometriosis, and 11 control subjects. INTERVENTION(S): Endometrial biopsies were obtained from patients with proven endometriosis and women without disease at laparoscopy. P27 protein was immunolocalized in the biopsy tissues and quantified by light microscopy. MAIN OUTCOME MEASURE(S): Immunostaining scores of glandular and stromal cells in endometrial biopsies obtained from patients with confirmed endometriosis compared with those of healthy control women with normal pelvis at laparoscopy. The staining scores of stage I/II and stage III/IV patients and of both patient groups and the control group were compared. RESULT(S): The level of p27 protein expression observed in the control group, both in the stroma and in the endometrial glands, was significantly different from that observed in the endometriosis patient groups. Significant differences in p27 protein expression levels in the glandular epithelium and stroma were not observed among groups of patients with endometriosis. CONCLUSION(S): The decreased level of p27 protein in the endometrium of women with endometriosis suggests that cell cycle alterations in the endometrial mucosa may be involved in the pathogenesis of this disease.     

Occult ovulatory dysfunction in women with minimal endometriosis or unexplained infertility

Characteristics of follicular development and hormonal patterns were evaluated in 17 women with minimal endometriosis and 11 with unexplained infertility. The controls were 7 women with male factor infertility and 8 who conceived during an investigational cycle. Women with minimal endometriosis had more and smaller follicles at luteinizing hormone (LH) surge, lower preovulatory estradiol (E2), and lower E2 at LH surge. Women with unexplained infertility had lower LH surges and a trend to a shorter follicular phase. Occult ovulatory dysfunction and may contribute to infertility in women with minimal endometriosis or unexplained infertility.     

Genomic alterations in the endometrium may be a proximate cause for endometriosis

OBJECTIVE: To test the hypothesis that endometriosis may originate from genomic alterations in the endometrium by genomic analysis of endometrial tissues in patients with endometriosis and compare them with those from normal controls. METHODS: Endometrial tissue samples were taken from five women with endometriosis. For controls, we used endometrial tissue samples from four women who underwent elective abortions and one sample from placenta. Using array-based comparative genomic hybridization (CGH), we determined the normal range of variation in CGH signals using normal controls. CGH results were further confirmed by real-time quantitative PCR and loss of heterozygosity analysis. RESULTS: We identified several regions of genomic alterations in all five patients. Some of these regions were the same regions identified previously in endometriotic lesions. For select markers, the genomic alterations were confirmed by real-time PCR and LOH analyses. CONCLUSIONS: There is evidence that the endometrium in women with endometriosis has genomic alterations. This is consistent with numerous reports that the endometrium of women with endometriosis differ from those of women without. Our finding suggests that genomic alterations in the endometrium may be a proximate cause for endometriosis.