Hum Reprod. 2008 Mar;23(3):530-7. Epub 2007 Dec 19.
Endometriosis and human infertility: a new investigation into the role of eutopic endometrium.
Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore (UCSC), 00168 Roma, Italy. email@example.com
BACKGROUND: Endometriosis is related to infertility even in the absence of mechanical alterations of the reproductive tract. Even though the pathogenesis of this phenomenon is still unclear, an impaired endometrial receptivity has been recently suggested. The aim of the present study was to investigate if endometriotic peritoneal fluids (EPF) could interfere with endometrial stromal cell (ESC) decidualization and if tumor necrosis factor (TNF)-alpha could be involved in the EPF effect. METHODS: Eutopic ESC were isolated from patients with or without endometriosis. ESC were treated with 17beta-estradiol 10(-8) M and 6alpha-methyl-17alpha-hydroxyprogesteroneacetate 2×10(-7) M for 16 days. In vitro decidualization was morphologically and biochemically assessed. We analysed whether ESC decidualization could be affected by EPF or peritoneal fluids from control patients (CPF), with or without soluble TNF-alpha receptor 1 (sTNFR-1). RESULTS: Compared with ESC from control patients, eutopic ESC from patients with endometriosis showed an impaired decidualization. Decidualization of normal ESC was morphologically normal but biochemically abnormal in the presence of EPF, which was able to decrease the secretion of decidualization markers. sTNFR-1 was able to partially counteract this effect. CONCLUSIONS: In endometriosis, the milieu surrounding the uterine cavity may be involved in impaired eutopic ESC decidualization, partially due to increased peritoneal levels of TNF-alpha.
Mod Pathol. 2008 Feb;21(2):115-24. Epub 2007 Dec 14.
Expression of platelet-derived growth factors and their receptors in ovarian clear-cell carcinoma and its putative precursors.
Department of Basic Pathology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Recent studies have shown that platelet-derived growth factors and their receptors are frequently co-expressed in ovarian cancers. Herein, we investigated the role of the platelet-derived growth factor pathway in the development of ovarian clear-cell adenocarcinoma, a highly chemoresistant form of ovarian cancer. Immunohistochemical expression of platelet-derived growth factor receptor-alpha and receptor-beta, platelet-derived growth factor A-chain and B-chain was examined in 31 cases of clear-cell adenocarcinoma and 56 coexisting putative precursor lesions: 17 non-atypical and 19 atypical endometrioses, and 10 non-atypical and 10 atypical clear-cell adenofibroma components. Twenty-one solitary endometrioses were also examined. Vascular endothelial cells were always positive for all the markers examined, and were used as positive controls. The frequencies of positivity for platelet-derived growth factor receptor-alpha and receptor-beta, and platelet-derived growth factor A-chain increased in accordance with higher cytologic atypia in the putative precursors: 71, 47, and 59% in the 17 non-atypical endometrioses, 84, 73, and 84% in the 19 atypical endometrioses, 0% each in the 10 non-atypical clear-cell adenofibromas, 100, 90, and 90% in the 10 atypical clear-cell adenofibromas, and 97, 97, and 100% in the 31 clear-cell adenocarcinomas, respectively. Positivity for platelet-derived growth factor B-chain increased in accordance with increased atypia in clear-cell adenofibroma: 0% in non-atypical clear-cell adenofibromas, 30% in atypical clear-cell adenofibromas, and 60% in coexisting carcinomas. However, in contrast, positivity for platelet-derived growth factor B-chain decreased in accordance with increased atypia in endometriosis coexisting with clear-cell adenocarcinomas: 35% in non-atypical endometrioses, 11% in atypical endometrioses, and 5% in coexisting carcinomas. Platelet-derived growth factor receptor-alpha and receptor-beta, and their ligands A-chain and B-chain were positive in 14, 29, 19, and 62% of the solitary endometrioses, respectively. These results indicate activation of the platelet-derived growth factor pathway in ovarian clear-cell adenocarcinomas and suggest biological differences between carcinomas that arise in association with clear-cell adenofibroma vs endometriosis.
Fertil Steril. 2008 Oct;90(4):1197.e13-6. Epub 2007 Dec 20.
Malignant transformation of abdominal wall endometriosis to clear cell carcinoma: case report and review of the literature.
Department of Surgery, Institut Gustave Roussy, Villejuif, France.
OBJECTIVE: To report a case of clear cell carcinoma in abdominal wall endometriosis after cesarean section. DESIGN: Case report. SETTING: A French oncology center. PATIENT(S): A 38-year-old woman who developed a 10-cm mass in the abdominal wall muscles, 13 years after a cesarean section. INTERVENTION(S): Abdominal wall resection and chemotherapy. MAIN OUTCOME MEASURE(S): Clinical outcome. RESULT(S): The diagnosis of clear cell carcinoma in abdominal wall endometriosis was confirmed, and wide surgical excision with abdominal wall reconstruction was performed after three courses of chemotherapy. CONCLUSION(S): The malignant transformation of abdominal wall endometrioma has not been clearly elucidated, owing to its rarity. However, the eventuality should always be considered, and the prognosis improved through wide surgical excision.
Endocrinology. 2008 Mar;149(3):1260-7. Epub 2007 Dec 13.
Interleukin (IL)-17A stimulates IL-8 secretion, cyclooxygensase-2 expression, and cell proliferation of endometriotic stromal cells.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
IL-17A is secreted from Th17 cells, a discovery leading to revision of the mechanism underlying the role of Th1/Th2 in the immune response. Strong evidence suggests that immune responses associated with inflammation are involved in the pathogenesis of endometriosis. In the present study, we first demonstrated that the presence of Th17 cells in peritoneal fluid of endometriotic women by flow cytometric analysis and IL-17A-positive cells in endometriotic tissues by immunohistochemistry. To investigate the role of IL-17A in the development of endometriosis, we then studied the effect of IL-17A on IL-8 production, cyclooxygensase-2 expression, and cell proliferation of cultured endometriotic stromal cells (ESCs). IL-17A enhanced IL-8 secretion from ESCs in a dose-dependent manner. The IL-17A-induced secretion of IL-8 from ESCs was suppressed by anti-IL-17 receptor A antibodies or inhibitors of p38 MAPK, p42/44 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase. Addition of TNFalpha synergistically increased IL-17A-induced IL-8 secretion from ESCs. IL-17A also enhanced the expression of cyclooxygensase-2 mRNA and proliferation of ESCs. IL-17A may play a role in the development of endometriosis by stimulating inflammatory responses and proliferation of ESCs.
Eur J Obstet Gynecol Reprod Biol. 2008 Jan;136(1):67-73.
Pyruvate reduces in vitro the embryotoxic effect of peritoneal fluid from infertile women with endometriosis.
Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.
OBJECTIVES: To ascertain the embryotoxicity of peritoneal fluid from infertile women with endometriosis (PF-E), on mouse embryos in culture and to examine the effect of pyruvate in the culture medium on PF-E induced embryotoxicity. STUDY DESIGN: Blood-free peritoneal fluid samples were obtained during laparoscopic investigation for infertility from 21 infertile women with endometriosis. The severity of endometriosis ranged from minimal or mild (PF-min to mild-E; n=7), moderate (PF-mod-E; n=7), to severe (PF-sev-E; n=7). Peritoneal fluid samples were centrifuged at 600 x g for 10 min and 4 degrees C, and the supernatant was incubated at 56 degrees C for 30 min in a water bath to inactivate the complement protein. Mice were super ovulated with intraperitoneal injection (IP) of 5IU of pregnant mare serum gonadotrophin and human chorion gonadotrophin. Twenty-four hours after confirmation of mating two-cell mouse embryos were obtained. They were then cultured in modified Whitten’s medium (mWM) with peritoneal fluid from patients with endometriosis, and either in the absence or presence of excess pyruvate (0.062 mmol(-1)). Embryos were cultured for 72 h. RESULTS AND CONCLUSION: Addition of 5% PF-E significantly (p<0.001) suppressed embryo growth at 24, 48, and 72 h of culture and the degree of suppression correlated with the severity of the disease. The presence of 0.062 mmol(-1) pyruvate in the culture medium significantly (p<0.001) reduced the embryotoxicity of PF-min to mild-E and PF-mod-E at each stage of development, but was only seen at 24h of culture (p<0.001) in cultures with PF-sev-E even when the concentration of pyruvate in the medium was increased to 0.31 mmol(-1). This study confirms the embryotoxicity of PF-E in vitro, which was reduced by the presence pyruvate in the culture medium, particularly in cultures containing fluid from women with endometriosis of minimum or mild to moderate severity.
Gynecol Obstet Invest. 2008;65(3):212-6. Epub 2007 Dec 10.
In vitro fertilization in normoresponder patients with endometriomas: comparison with basal simple ovarian cysts.
Istanbul Memorial Hospital, ART and Genetics Center, Istanbul, Turkey. firstname.lastname@example.org
OBJECTIVE: To investigate whether the space-occupying effect of an endometrioma, rather than endometriosis itself, affects results in in vitro fertilization (IVF) using women with simple ovarian cysts as the control group. METHODS: 85 normoresponder patients with endometriomas of 10-50 mm who underwent IVF treatment directly without initial removal were compared with 83 normoresponder patients with simple ovarian cysts of 10-35 mm detected at the beginning of stimulation and initiated treatment without aspiration. RESULTS: Gonadotropin consumption was higher in the endometrioma group (3,013 vs. 2,451 IU; p = 0.001), although significantly fewer numbers of oocytes were retrieved (13.9 vs. 16.4; p = 0.03). However, oocyte maturation rates were similar. The transferred grade I embryos ratio was evaluated and found to be better in the cyst group (79.7 vs. 70.7%; p = 0.03). Consequently, the implantation rate was found to be significantly higher in the cyst group (28 vs. 19%; p = 0.02), although pregnancy and ongoing pregnancy rates were similar. CONCLUSION: The presence of an endometriotic cyst during the IVF cycle was demonstrated to be associated with a lower embryo quality and implantation rate, although pregnancy success was unaffected. This adverse effect is suggested to be the result of the disease itself, not the presence of a cystic mass.
Hum Reprod Update. 2008 Jan-Feb;14(1):59-72. Epub 2007 Dec 10.
Impact of endocrine disruptor chemicals in gynaecology.
Institute of Gynecology, Perinatology and Child Health, Sant’Andrea Hospital, University of Rome La Sapienza, Via di Grottarossa 1035, 00189 Rome, Italy. email@example.com
The potential hazardous effects that estrogen- and androgen-like chemicals may have both on wildlife and human health have attracted much attention from the scientific community. Endocrine disruptors (EDCs) are chemicals that have the capacity to interfere with normal signalling systems. EDCs may mimic, block or modulate the synthesis, release, transport, metabolism and binding or elimination of natural hormones. Even though potential EDCs may be present in the environment at only very low levels, they may still cause harmful effects, especially when several different compounds act on one target. EDCs include persistent pollutants, agrochemicals and widespread industrial compounds. Not all EDCs are man-made compounds; many plants produce substances (phytoestrogens) that can have different endocrine effects either adverse or beneficial in certain circumstances. Natural substances such as sex hormones from urban or farm wastes can become concentrated in industrial, agricultural and urban areas; thus, such wastes may be considered potential ‘EDCs’ for humans and/or wildlife. Much attention has focussed on changing trends in male reproductive parameters in relation to EDC exposure; however, studies on the female reproductive system have been less comprehensive. We have focussed this article on four major aspects of female reproductive health: fertility and fecundability, endometriosis, precocious puberty and breast and endometrial cancer.
Colorectal Dis. 2008 Jun;10(5):518-9. Epub 2007 Dec 7.
Endometriosis of the vermiform appendix as an exceptional cause of acute perforated appendicitis during pregnancy.
Department of Colorectal Surgery, University Hospital, Grenoble, France. firstname.lastname@example.org
The incidence of appendicitis presenting during pregnancy is less than 1 in 1500. Most cases of endometriosis of the appendix are discovered as a result of incidental appendectomy. True perforated appendicitis in an endometriotic area has not been reported before. The authors report the case of a 28-year-old woman in her 27th week of pregnancy who underwent an appendicectomy for inflamed, perforated appendix with transmural endometriosis and accompanying decidual reaction.
Eur J Obstet Gynecol Reprod Biol. 2008 Jul;139(1):106-10. Epub 2007 Dec 11.
The G(-2518)A polymorphism of monocyte chemotactic protein-1 (MCP-1) and its serum and peritoneal fluid levels in Korean women with endometriosis.
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 110-744, Republic of Korea.
OBJECTIVES: To investigate the associations between endometriosis and the G(-2518)A polymorphism of monocyte chemotactic protein-1 (MCP-1), and serum and peritoneal fluid MCP-1 levels in Korean women. STUDY DESIGN: The G(-2518)A polymorphism of MCP-1 was analyzed by restriction fragment length polymorphism in 105 women with and in 101 women without endometriosis. Serum and peritoneal fluid MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The genotype frequencies of the MCP-1 G (-2518)A polymorphism were GG 36.9%, AG 52.9%, and AA 10.2%. MCP-1 genotype frequencies and serum and peritoneal fluid MCP-1 levels were similar in those with or without endometriosis and were not dependent on disease stage. A significant correlation was found between serum and peritoneal fluid levels of MCP-1. However, no differences were found between MCP-1 genotypes in terms of serum and peritoneal fluid MCP-1 levels. CONCLUSIONS: Serum and peritoneal fluid MCP-1 levels and the G (-2518)A MCP-1 polymorphism were found not to be associated with endometriosis in Korean women.
Eur J Obstet Gynecol Reprod Biol. 2008 Jul;139(1):111-5. Epub 2008 Feb 20.
Endometriosis and the primary care consultation.
Faculty of Health, Birmingham City University, Perry Barr, Birmingham B42 2SU, United Kingdom. email@example.com
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.
J Clin Ultrasound. 2008 Feb;36(2):91-7.
Sonography of endometriosis in infrequent sites.
Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, South Korea.
We reviewed the sonographic features of endometriosis in infrequent sites, including the abdominal wall, appendix, perineum, and bladder. Familiarity with the clinical setting and the sonographic appearance of endometriosis in both frequent and infrequent sites can help facilitate prompt, accurate diagnosis and treatment. (c) 2007 Wiley Periodicals, Inc.
Fertil Steril. 2008 Nov;90(5):1589-98. Epub 2007 Dec 3.
Effects of hormonal treatment on nerve fibers in endometrium and myometrium in women with endometriosis.
Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, Australia. firstname.lastname@example.org
OBJECTIVE: To investigate how hormonal treatment can change nerve fiber density and to identify types of nerve fibers in endometrium and myometrium in women with endometriosis. DESIGN: Laboratory study using human tissue. SETTING: University-based laboratory. PATIENT(S): Hormonally treated and untreated women with endometriosis undergoing hysterectomy or curettage. INTERVENTION(S): Endometrial and myometrial tissues were prepared from women with hormonally treated endometriosis and women with untreated endometriosis. MAIN OUTCOME MEASURE(S): Types and density of nerve fibers in endometrium and myometrium in women with hormonally treated and untreated endometriosis were determined immunohistochemically. RESULT(S): The nerve fiber density (mean density +/- SD per square millimeter) in the functional and the basal layers of endometrium (0.2 +/- 0.7/mm(2) and 0.9 +/- 1.3/mm(2), respectively) and myometrium (1.5 +/- 0.8/mm(2)) from women with hormonally treated endometriosis was much lower than that of endometrium (functional layer: 11 +/- 5/mm(2), basal layer: 18 +/- 8/mm(2), respectively) and myometrium (3 +/- 1/mm(2)) from women with untreated endometriosis. Nerve growth factor and nerve growth factor receptor p75 expression was also significantly reduced in women with hormonally treated endometriosis compared with women with untreated endometriosis. CONCLUSION(S): Hormonal treatment significantly reduced nerve fiber density in endometrium and myometrium in women with endometriosis.
Fertil Steril. 2008 May;89(5 Suppl):1306-13. Epub 2007 Dec 3.
Effect of recombinant human TNF-binding protein-1 and GnRH antagonist on mRNA expression of inflammatory cytokines and adhesion and growth factors in endometrium and endometriosis tissues in baboons.
Leuven University Fertility Centre, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium.
OBJECTIVE: To evaluate the mechanism of action of recombinant human tumor necrosis factor (TNF)-binding protein-1 by assessing differential expression of messenger RNA (mRNA) for cytokines, matrix metalloproteinases, and growth and adhesion factors in baboons. DESIGN: Analysis of gene expression in a prospective randomized study. SETTING: University Fertility Center. ANIMAL(S): In the in vivo study, 14 baboons were randomly and subcutaneously (SC) treated with either phosphate-buffered saline (PBS), GnRH antagonist, or recombinant human TNF-binding protein-1 at the time of induction. In the ex vivo study, 4 baboons were treated by menstrual endometrium that had been incubated randomly with either PBS or recombinant human TNF-binding protein-1 before intrapelvic injection. INTERVENTION(S): In the in vivo study, analysis of 11 endometrial and 10 endometriosis biopsies included either PBS (n = 5), GnRH antagonist (n = 8), or recombinant human TNF-binding protein-1 (n = 8). In the ex vivo study, 2 endometrial and 4 endometriosis biopsies were analyzed from 4 baboons. MAIN OUTCOME MEASURE(S): The mRNA expression of TNF-alpha, IL-8, IL-6, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, intercellular adhesion molecule-1, matrix metalloproteinase-1, and regulated on activation, normal T-cell expressed and secreted were investigated using real-time reverse transcriptase-polymer chain reaction (PCR). RESULT(S): TGF-beta mRNA expression was decreased in endometriotic lesions from baboons treated with recombinant human TNF-binding protein-1 when compared with the placebo group. CONCLUSION(S): Except TGF-beta, mRNA expression of inflammatory cytokines and adhesion/growth factors is not affected in endometrial and endometriosis biopsies from baboons after induction of endometriosis combined with either systemic injection of recombinant human TNF-binding or GnRH antagonist or ex vivo treatment with recombinant human TNF-binding protein-1. Further studies are needed to elucidate the mode of action on how inhibition of TNF-alpha activity prevents the development of endometriosis.
Hum Reprod. 2008 Feb;23(2):290-7. Epub 2007 Dec 2.
Inhibition of steroid sulphatase activity in endometriotic implants by 667 COUMATE: a potential new therapy.
Endocrinology and Metabolic Medicine and Sterix Ltd, Imperial College London, St. Mary’s Hospital, London W2 1NY, UK.
BACKGROUND: Local biosynthesis of estrogens is thought to be important for the maintenance and growth of endometriotic implants. In addition to the formation of estrogen via the aromatase pathway, steroid sulphatase (STS), which is responsible for the hydrolysis of estrogen sulphates, may be an important source of estrogens in endometriosis. METHODS: Eutopic and ectopic endometrial samples from 14 women with minimal or mild (MM) endometriosis and from 13 women with moderate to severe (MS) endometriosis were analysed for aromatase and STS activities. RESULTS: Aromatase and STS activity were detected in all samples. STS enzyme activity in both eutopic and ectopic endometrium was considerably higher and less variable than aromatase activity. Moreover, STS, but not aromatase, activity in endometriotic implants correlated with the severity of the disease (mean +/- SEM: 203 +/- 38 nmol/4 h/g wet weight tissue in MM disease versus 423 +/- 44 nmol/4 h/g wet weight tissue in MS endometriosis, P < 0.001). The STS inhibitor 667 COUMATE almost completely blocked STS activity (>99%) in both eutopic and ectopic tissues. CONCLUSIONS: The high levels of STS activity detected in ectopic endometrium and the correlation with severity of disease suggest that STS inhibitors could be useful for the treatment of endometriosis.
Fertil Steril. 2008 Sep;90(3):849.e5-8. Epub 2007 Dec 11.
Local lymphocytic and epithelial activation in a case of autoimmune oophoritis.
Immunology Laboratory, Faculty of Medicine & CHU, Vandoeuvre-les-Nancy, Nancy, France.
OBJECTIVE: To further define the immunological tissular modifications in premature ovarian failure (POF). METHOD: The patient was followed up for premature ovarian failure and mild endometriosis associated with serum antiovarian antibodies. A laparoscopic ovarian biopsy was decided on to analyze the tissue and support the onset of immunosuppressive therapy. Immunohistochemistry was performed using monoclonal antibodies directed against T cell membrane markers, as well as activation molecules, to define the composition of the cellular infiltrate and the consequences on ovarian tissue. RESULT(S): A dense infiltration of activated T lymphocytes was observed in close contact with follicular epithelium expressing HLA-DR and CD40. CONCLUSION(S): This observation supports the role of cellular immunity in ovarian autoimmunity with features very similar to those reported in murine models and other human autoimmune endocrine pathologies.
Fertil Steril. 2008 Sep;90(3):850.e1-3. Epub 2007 Dec 11.
Robot-assisted laparoscopic trachelectomy after supracervical hysterectomy.
Atlanta Center for Special Minimally Invasive Surgery and Reproductive Medicine, Atlanta, Georgia 30342, USA. email@example.com
OBJECTIVE: To present a case of successful robotic assisted laparoscopic trachelectomy. DESIGN: Case report. SETTING: Tertiary care facility. PATIENT(S): A 40-year-old female with history of severe endometriosis and adhesions presented with persistent pain and bleeding after abdominal supracervical hysterectomy after failed attempt for laparoscopic-assisted vaginal hysterectomy and total abdominal hysterectomy. INTERVENTION(S): Robot-assisted laparoscopic trachelectomy and treatment of associated pelvic disease. MAIN OUTCOME MEASURE(S): Successful completion of robot-assisted trachelectomy. RESULT(S): There were no intraoperative or postoperative complications and minimal blood loss. At 10 months’ follow-up the patient was doing well with resolution of her symptoms. CONCLUSION(S): Robotic surgery may bridge the gap between laparotomy and laparoscopy for trachelectomy in complicated cases.
Fertil Steril. 2008 Oct;90(4 Suppl):1496-502. Epub 2007 Dec 3.
Oral eicosapentaenoic acid supplementation as possible therapy for endometriosis.
Department of Gynecology, Jichi Medical University Sitama Medical Center, Omiya, Saitama, Japan.
OBJECTIVE: To investigate the anti-inflammatory effect of n-3 eicosapentaenoic acid (EPA) compared with n-6 linoleic acid (LA) in an endometriosis rat model. We focused on the relationship between lipid metabolism and inflammatory reactions in endometriosis based on the hypothesis that a lipid intake imbalance is one of the factors responsible for the recent increase of endometriosis. DESIGN: Prospective, randomized experimental study. SETTING: Animal surgery laboratory in a university hospital. ANIMAL(S): Sprague-Dawley rats (female, 6 weeks old). INTERVENTION(S): Rats were fed a diet with EPA (n = 9) or with LA (n = 9) for 2 weeks. Two weeks after feeding, the uterus was autotransplanted to the peritoneum to construct an endometriosis model. Feeding was continued for a total of 6 weeks. Two and 4 weeks after autotransplantation, three rats of each group were killed and evaluated. MAIN OUTCOME MEASURE(S): Endometriotic lesions were morphologically evaluated and their fatty acid composition was examined. Gene expression in these tissues was evaluated by cDNA microarray analysis and quantative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULT(S): In the EPA group, the n-3:n-6 ratio in each tissue significantly increased and the thickening of the interstitium, an active site for inflammation in endometriosis, was significantly suppressed (0.30 +/- 0.09 mm [EPA group] vs. 0.77 +/- 0.23 mm [LA group]). The mRNA of metalloproteinases, interleukin-1beta, interleukin-1r, prostaglandin E synthase (Ptges), and nuclear factor (NF)-kappaB were reduced in the EPA group. CONCLUSION(S): EPA supplementation might be a valid strategy for the treatment of endometriosis.
Fertil Steril. 2008 Oct;90(4):1014-8. Epub 2007 Dec 3.
Is painful rectovaginal endometriosis an intermediate stage of rectal endometriosis?
Department of Gynecology and Obstetrics, University Hospital Rouen, Rouen, France. firstname.lastname@example.org
OBJECTIVE: To compare the history of pain complaints of women presenting rectovaginal and rectal endometriosis to show that rectovaginal locations may progress to a rectal involvement of the disease. DESIGN: Retrospective comparative study. SETTING: Department of Gynecology and Obstetrics, University Hospital Rouen, France. PATIENT(S): Thirty-two patients with rectovaginal endometriosis and 16 patients with rectal involvement. INTERVENTION(S): Standardized questionnaires recording the clinical history of painful deep endometriosis up to diagnosis. MAIN OUTCOME MEASURE(S): Length of time from onset of pain to diagnosis, types of pain, disability related to the pain, and number of physicians consulted before the diagnosis was made. RESULT(S): Women with rectal endometriosis had an earlier onset of dysmenorrhoea. The age of dysmenorrhoea and the length of time between the onset of the first pain to the first time that the endometriosis was suspected were significantly increased in women with rectal endometriosis. Pain during defecation was more frequent in patients with rectal endometriosis. Women consulted an average of three physicians before the endometriosis diagnosis was suggested. A nongynecologist physician made the diagnosis of rectovaginal and rectal endometriosis in respectively 26% and 31% of cases. CONCLUSION(S): Rectal endometriosis is associated with an earlier onset and a longer history of painful symptoms until the diagnosis was made when compared with rectovaginal endometriosis locations. These observations support the hypothesis that rectovaginal location may be an intermediate stage of rectal endometriosis.
Fertil Steril. 2008 Oct;90(4):988-93. Epub 2007 Dec 3.
Expression of cyclooxygenase-2 and vascular endothelial growth factor in ovarian endometriotic cysts and their relationship with angiogenesis.
Department of Obstetrics and Gynecology, Gulhane Military Medical Academy and Medical School, Etlik, Ankara, Turkey. email@example.com
OBJECTIVE: To investigate the expression of cyclooxygenase-2 (Cox-2) and vascular endothelial growth factor (VEGF) in ovarian endometriotic cysts and assess their relation with angiogenesis. DESIGN: Experimental clinical study. SETTING: University hospital. PATIENT(S): Fifty patients with ovarian endometriotic cysts. INTERVENTION(S): Surgical excision of 50 ovarian endometriotic cysts. MAIN OUTCOME MEASURE(S): Microvessel density and the expression of Cox-2 and VEGF were analyzed immunohistochemically. RESULT(S): Cyclooxygenase-2 immunoreactivity was mainly cytoplasmic in glandular epithelial cells in all of the ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate expression in 21 (42%), and high expression in 17 (34%). Vascular endothelial growth factor immunoreactivity was mainly cytoplasmic in stromal cells in 46 (92%) of the ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate expression in 18 (36%), and high expression in 16 (32%). No immunoreactivity was present in 4 cases (8%). Both Cox-2 (r = 0.728) and VEGF (r = 0.670) were closely, statistically significantly related with microvessel density in ovarian endometriotic cysts. Cyclooxygenase-2 and VEGF also were highly statistically significantly correlated (r = 0.777) with each other. CONCLUSION(S): We observed Cox-2 expression mostly in glandular epithelial cells of ovarian endometriotic cysts, whereas VEGF expression was observed mainly in stromal cells. Cyclooxygenase-2 and VEGF were closely correlated with each other, and both of them appear to play a role in the angiogenesis of ovarian endometriosis.
Endocrinology. 2008 Mar;149(3):1190-204. Epub 2007 Nov 29.
Inflammatory status influences aromatase and steroid receptor expression in endometriosis.
Department of Obstetrics, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9032, USA.
Aberrant up-regulation of aromatase in eutopic endometrium and implants from women with endometriosis has been reported. Aromatase induction may be mediated by increased cyclooxygenase-2 (COX-2). Recently, we demonstrated that progesterone receptor (PR)-A and PR-B serve an antiinflammatory role in the uterus by antagonizing nuclear factor kappaB activation and COX-2 expression. PR-C, which antagonizes PR-B, is up-regulated by inflammation. Although estrogen receptor alpha (ERalpha) is implicated in endometriosis, an antiinflammatory role of ERbeta has been suggested. We examined stage-specific expression of aromatase, COX-2, ER, and PR isoform expression in eutopic endometrium, implants, peritoneum, and endometrioma samples from endometriosis patients. Endometrial and peritoneal biopsies were obtained from unaffected women and those with fibroids. Aromatase expression in eutopic endometrium from endometriosis patients was significantly increased compared with controls. Aromatase expression in endometriosis implants was markedly increased compared with eutopic endometrium. Aromatase mRNA levels were increased significantly in red implants relative to black implants and endometrioma cyst capsule. Moreover, COX-2 expression was increased in implants and in eutopic endometrium of women with endometriosis as compared with control endometrium. As observed for aromatase mRNA, the highest levels of COX-2 mRNA were found in red implants. The ratio of ERbeta/ERalpha mRNA was significantly elevated in endometriomas compared with endometriosis implants and eutopic endometrium. Expression of PR-C mRNA relative to PR-A and PR-B mRNA was significantly increased in endometriomas compared with eutopic and control endometrium. PR-A protein was barely detectable in endometriomas. Thus, whereas PR-C may enhance disease progression, up-regulation of ERbeta may play an antiinflammatory and opposing role.
Endocrinology. 2008 Mar;149(3):1180-9. Epub 2007 Nov 26.
Cyclooxygenase-2 regulates survival, migration, and invasion of human endometriotic cells through multiple mechanisms.
Reproductive Endocrinology and Cell Signaling Laboratory, Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.
Endometriosis is a debilitating disease characterized by the presence of functional endometrial glandular epithelium and stroma outside the uterine cavity that affects up to 20% of women of child-bearing age. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of prostaglandin E(2) (PGE(2)), is highly expressed in endometriotic tissues and results in increased concentrations of peritoneal PGE(2) in women. In this study, we determined the expression of COX-2 protein in ectopic and eutopic endometria in humans and the role of COX-2 in endometriotic cell survival, migration, and invasion in humans. Our results indicate that COX-2 protein is abundantly expressed in ectopic endometria compared with eutopic endometria. Comparatively, expression of COX-2 protein is higher in eutopic endometria from women with endometriosis compared with women without endometriosis. Inhibition of COX-2 decreases survival, migration, and invasion of endometriotic cells that are associated with decreased production of PGE(2). Cell growth inhibitory effects of COX-2 inhibition/silencing are mediated through nuclear poly (ADP-ribose) polymerase-mediated apoptosis. Cell motility and invasion inhibitory effects of COX-2 inhibition/silencing are mediated through matrix metalloproteinase-2 and -9 activities. Interestingly, effects of COX-2 inhibition is more profound in endometriotic epithelial than in stromal cells. Furthermore, inhibition of COX-2 affects invasion rather than migration of endometriotic epithelial and stromal cells. It is the first evidence showing that inhibition of COX-2 decreases endometriotic epithelial and stromal cell survival, migration, and invasion in humans. Our results support the emerging concept that COX-2/PGE(2) promotes the pathophysiology and pathogenesis of endometriosis in humans.
Biomed Pharmacother. 2008 Jul-Aug;62(6):373-7. Epub 2007 Oct 30.
Vascular endothelial growth factor and its soluble receptor in benign and malignant ovarian tumors.
Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Via Roma 67, 56126 Pisa, Italy. firstname.lastname@example.org
An imbalance between pro-angiogenic and anti-angiogenic factors is hypothesized in the pathogenesis of ovarian cystic disease. The aim of the following study was to explore the possible role of free vascular endothelial growth factor receptor 1 (sVEGFR-1), a soluble regulator of vascular endothelial growth factor (VEGF) action, in ovarian cystoadenoma, endometriomata and cystoadenocarcinoma. Forty-eight women, of whom fourteen had ovarian serous cysts, twenty-eight had stage III-IV ovarian endometriomata, and six had stage IIIB-IIIC ovarian carcinoma, were included. Sampling of serum, peritoneal and ovarian cystic fluids and of tumor tissue was performed before, during and following surgery, respectively. Levels of VEGF and sVEGFR-1 were measured in serum, peritoneal and cystic fluid. VEGF and sVEGFR-1 expression was evaluated in tumor tissue. There were no differences in serum VEGF and sVEGFR-1 levels nor in VEGF/VEGFR-1 ratio between study groups. Peritoneal fluid VEGF levels were higher in cystoadenocarcinoma patients than in endometriosis and in cystoadenoma patients, while sVEGFR-1 peritoneal fluid concentrations were significantly higher only in endometriosis-affected women. VEGF/VEGFR-1 ratio was highest in the peritoneal fluid of cancer patients with respect to the other two groups of women. Cystic fluid VEGF and VEGFR-1 concentrations were higher in endometriomata and in cystoadenocarcinomas than in cystadenomas but the VEGF/VEGFR-1 ratio was highest in cancer patients. Western blot evidenced a marked expression of VEGF and soluble VEGFR-1 in endometriosis tissue with respect to benign cyst tissue but a lower expression of both molecules, contrary to that expected, in cancer tissue. In conclusion, all in all, our data indicate that an excess of local VEGF with respect to its soluble receptor VEGFR-1 may be a key factor in the onset and maintenance of pathological neo-angiogenesis in ovarian cyst formation.
Best Pract Res Clin Obstet Gynaecol. 2008 Apr;22(2):275-306. Epub 2007 Nov 26.
Endometriosis: current and future medical therapies.
Clinica Ostetrica e Ginecologica II, University of Milan, Istituto Luigi Mangiagalli, Via Commenda, Milan, Italy. email@example.com
Endometriosis is a chronic inflammatory disease that responds to steroidal manipulation. Creation of a steady hormonal environment with inhibition of ovulation temporarily suppresses the ectopic implants and reduces the inflammatory status as well as the associated pain symptoms. Pharmacological management of endometriosis must be set within the framework of long-term therapeutic strategies. As the available drugs are not curative, treatments will need to be administered for years or until women desire a pregnancy. The various therapies studied have shown similar efficacy. Consequently, based on a more favourable profile in terms of safety, tolerability and cost, combined oral contraceptives and progestins should be considered as the first-line option, both as an alternative to surgery and as a postoperative adjuvant measure. Gonadotrophin-releasing hormone analogues, danazol and gestrinone should be used when progestins and oral contraceptives fail, are not tolerated or are contra-indicated. Future therapies for endometriosis must compare favourably with existing drugs before hypothesizing their implementation in current practice. Medical treatment is not indicated in women seeking conception because reproductive prognosis is not ameliorated.
Int J Gynaecol Obstet. 2008 Feb;100(2):167-70. Epub 2007 Nov 26.
Ovarian suppression treatment prior to in-vitro fertilization and embryo transfer in Chinese women with stage III or IV endometriosis.
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
OBJECTIVE: To evaluate the efficacy of a 2-month treatment with a gonadotropin-releasing hormone (GnRH) agonist prior to in-vitro fertilization in Chinese women with moderate or severe endometriosis. METHODS: A study of 162 women surgically diagnosed as having moderate or severe endometriosis. Pituitary down-regulation was achieved with injections of a GnRH agonist prior to the IVF procedures either for 7 to 10 days in the mid-luteal phase (group 1 [standard protocol], 97 cycles in total), or for 2 months (group 2, 55 cycles), or 3 months (group 3, 75 cycles). RESULTS: Women pretreated with a GnRH agonist for 2 or 3 months required significantly higher doses of gonadotropin for ovarian stimulation (P<0.001), and for a longer time, than those treated with the standard long protocol (P<0.05). The number of oocytes and good embryos was lower in group 3 than in groups 1 or 2 (P<0.05). The implantation rate was significantly higher in group 2 than in group 1 (P<0.02). CONCLUSION: A 2-month treatment with a GnRH agonist prior to IVF produced a trend toward an increase in the implantation rate in a group of Chinese women with stages III and IV endometriosis.
Gynecol Obstet Invest. 2008;65(3):174-86. Epub 2007 Nov 20.
Agents blocking the nuclear factor-kappaB pathway are effective inhibitors of endometriosis in an in vivo experimental model.
Department of Gynecology, Université Catholique de Louvain, Brussels, Belgium.
BACKGROUND: In vitro studies suggest that the transcription factor nuclear factor-kappa B (NF-kappaB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement of NF-kappaB and the processes regulated by NF-kappaB in the initial development of endometriotic lesionsin vivo. METHODS: Endometriosis was induced in nude mice by intraperitoneal injection of fluorescent-labeled menstrual endometrium. Two NF-kappaB inhibitors (BAY 11-7085 and SN-50) were injected intraperitoneally on days 0, 2 and 4 after endometriosis induction, and endometriotic lesions were recovered on day 5. Number, mass, fluorimetry and surface (morphometry) of endometriotic lesions were quantified. NF-kappaB activation, intercellular adhesion molecule (ICAM)-1 expression, cell proliferation and apoptosis were evaluated by immunohistochemical analyses and the TUNEL method. RESULTS: Both NF-kappaB inhibitors induced a significant reduction in lesion development compared to control mice. NF-kappaB activation and ICAM-1 expression of endometriotic lesions were significantly reduced in treated mice, and cell proliferation was significantly reduced in BAY 11-7085-treated mice. Both inhibitors produced a significant increase in apoptosis of endometriotic lesions, as assessed by active caspase-3 immunostaining and the TUNEL method. CONCLUSION: This study demonstrates, for the first time, that the NF-kappaB pathway is implicated in the development of endometriotic lesions in vivo and that NF-kappaB inhibition reduces ICAM-1 expression and cell proliferation, but increases apoptosis of endometriotic lesions, diminishing the initial development of endometriosis in an animal model.
Fertil Steril. 2008 Oct;90(4):1008-13. Epub 2007 Nov 26.
Endorectal ultrasound accuracy in the diagnosis of rectal endometriosis infiltration depth.
Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France. firstname.lastname@example.org
OBJECTIVE: To evaluate the accuracy of endorectal ultrasound examination to ascertain the deepest rectal layer involved in rectal endometriosis. DESIGN: Retrospective study. SETTING: Department of obstetrics and gynecology at a university hospital in France. PATIENT(S): Women presenting with rectal endometriosis who had undergone rectal resection during a 22-month period. INTERVENTION(S): Endorectal ultrasonography. MAIN OUTCOME MEASURE(S): The predicted rectal infiltration depth by using endorectal examination was compared with histological findings. The level of agreement was evaluated by using the coefficients of concordance kappa and weighted kappa. RESULT(S): Sixteen women were included in the study. Rectal resection was segmental in 14 cases and was limited in 2 cases. The agreement between 2 examinations was considered good in 9 cases (56%). Endorectal ultrasound overestimated the depth of infiltration in 5 cases and underestimated it in 2 cases. The coefficients of concordance kappa (95% confidence interval) and weighted kappa (95% confidence interval) were, respectively, 0.17 (0-0.34) and 0.22 (0.04-0.4), corresponding to poor concordance between the endorectal ultrasonography and histological examination. CONCLUSION(S): Accuracy in the prediction of rectal-layer involvement in endorectal ultrasonography appears to be limited. This information should not be considered sufficient when selecting the type of rectal-resection procedure.
Fertil Steril. 2008 Jul;90(1):174-9. Epub 2007 Nov 26.
Risk factors for deep endometriosis: a comparison with pelvic and ovarian endometriosis.
Seconda Clinica Ostetrico Ginecologica, Università di Milano, Fondazione Policlinico Mangiagalli Regina Elena, Milan, Italy. email@example.com
OBJECTIVE: To assess whether deep endometriosis has different risk factors compared with endometriosis at other sites. In epidemiological terms, this should be the case if deep endometriosis represents a different condition than ovarian and peritoneal endometriosis. DESIGN: Case-control study. SETTING: University hospitals. PATIENT(S): The first group of cases included 181 women with a diagnosis of deep endometriosis. The second group of cases included 162 women with endometriosis at other sites. The control group included women younger than 55 years of age who were admitted for acute non-gynecological, non-hormonal, non-neoplastic conditions. INTERVENTION(S): Questionnaire. MAIN OUTCOME MEASURE(S): Odds ratios. RESULT(S): The age distribution of women with cases of deep and ovarian and pelvic endometriosis was not statistically significantly different. A higher body mass index decreased the risk of both deep as well as ovarian and pelvic endometriosis: the estimated ORs for women reporting a body mass index of > or =21 vs. those reporting a body mass index of <21 were 0.6 (95% confidence interval [CI], 0.3-0.8) for deep endometriosis and 0.6 (95% CI, 0.4-0.9) for pelvic and ovarian endometriosis. Parous women were at decreased risk: in comparison with nulliparae, the odds ratio for deep endometriosis was 0.1 (95% CI, 0.1-0.2) for women reporting one or more births. The corresponding value for pelvic and ovarian endometriosis was 0.1 (95% CI, 0.1-0.2). CONCLUSION(S): This study suggests that deep as well as ovarian and pelvic endometriosis share similar risk factors.
Eur J Obstet Gynecol Reprod Biol. 2008 Jul;139(1):100-5. Epub 2007 Nov 19.
Psychological aspects of endometriosis: differences between patients with or without pain on four psychological variables.
Institute of Psychology, University of Aarhus, Denmark. firstname.lastname@example.org
OBJECTIVE: Women with endometriosis often have pain symptoms that seemingly do not relate to the stage of disease. It has been suggested that psychological factors may contribute to this disproportion. The purpose of this study was to compare patients with and without pain symptoms to see whether they differed in profile on four psychological parameters. STUDY DESIGN: Sixty-three women with laparoscopically diagnosed endometriosis of whom 20 were symptom free, completed four psychometric tests assessing coping, emotional inhibition, depression, and anxiety. RESULTS: Significant positive correlations were found between coping and depression/anxiety, and between pain severity and subjective psychosocial impairment. There were no significant differences between the two groups on depression or anxiety and no correlations between pain severity and depression/anxiety. CONCLUSION: Coping appears to be of major importance to the psychological consequences of endometriosis. This may have implications for the treatment of endometriosis. The study could not confirm previous findings of pain related to endometriosis being associated with a higher prevalence of depression and anxiety.
Chemosphere. 2008 Mar;71(2):203-10. Epub 2007 Nov 19.
Organochlorines and endometriosis: a mini-review.
Université catholique de Louvain, Faculty of Medicine, Industrial Toxicology and Occupational Medicine Unit, Brussels, Belgium. email@example.com <firstname.lastname@example.org>
Organochlorines (polychlorinated biphenyls and dioxin-like compounds) are suspected to play a role in the etiopathogenesis of endometriosis. This hypothesis, based on experimental data, has been circulating for years in the scientific community and several epidemiologic surveys have attempted to obtain confirmatory human data. The purpose of this mini-review is to provide an overview of the twelve epidemiological studies that have assessed the relationship between endometriosis and organochlorine exposure. Several studies did not observe a significant association between peritoneal endometriosis and organochlorines. The deep nodular form of endometriosis appears associated with a higher serum level of both dioxin-like compounds and polychlorobiphenyls. The type of control women, the nature of the chemicals measured, and the definition of the disease could modulate the ability to detect the possible relationship between endometriosis and organochlorine exposure.
Int J Gynaecol Obstet. 2008 Mar;100(3):252-6. Epub 2007 Nov 19.
Effect of vitamins C and E supplementation on peripheral oxidative stress markers and pregnancy rate in women with endometriosis.
Departamento de Biología Celular, Instituto Nacional de Perinatología, Mexico City, Mexico.
OBJECTIVE: To determine whether vitamins C and E supplementation lowers oxidative stress marker levels and improves pregnancy rate in women with endometriosis. METHODS: Thirty-four women with endometriosis received a bar containing vitamins C and E (343 mg and 84 mg, respectively) or placebo for 6 months. Plasma and peritoneal fluid levels of malondialdehyde (MDA) and lipid hydroperoxides (LOOHs) were measured for all women and compared between the 2 groups. Data were analyzed by the t test or 1-way analysis of variance for parametric data and the Mann-Whitney rank sum test or Kruskall-Wallis test for nonparametric data. The Fisher exact test was used to compare pregnancy rates. RESULTS: After 4 months, the study group had lower levels of MDA and LOOHs than the control group, and the difference became statistically significant in the fourth month for MDA levels and in the sixth month for LOOH levels. The postintervention pregnancy rates were 19% and 12% in the supplementation and placebo groups, respectively, but the difference was not significant. CONCLUSIONS: Vitamins C and E supplementation was associated with a decrease in the concentration of oxidative stress markers in women with endometriosis. The pregnancy rate, however, did not improve during or after the intervention.
Fertil Steril. 2008 Mar;89(3):699-700. Epub 2007 Nov 19.
Transvaginal ultrasonography combined with water-contrast in the rectum in the diagnosis of rectovaginal endometriosis infiltrating the bowel.
Department of Obstetrics and Gynaecology, San Martino Hospital, University of Genoa, Genoa, Italy.
This prospective study evaluated the efficacy of transvaginal ultrasonography combined with water-contrast in the rectum (RWC-TVS) in the diagnosis of rectal infiltration in 35 women with rectovaginal endometriosis; ultrasonographic findings were compared with surgery and histology. The sensitivity of RWC-TVS in identifying rectal infiltration reaching at least the muscular layer was 100%, the specificity was 85.7%, the positive predictive value was 91.3%, and the negative predictive value was 100%. In 4 of 5 (80.0%) nodules reaching the submucosa, the depth of infiltration was underestimated by RWC-TVS. The RWC-TVS reliably determined the largest diameter of the endometriotic nodules and was well tolerated by the patients.