Int J Colorectal Dis. 2008 Apr;23(4):447-8.

Acute abdomen caused by endometrial stromal sarcoma arising in extragonadal foci of endometriosis of the terminal ileum.

Budäus LH, Menzel T, Hartmann V, Caselitz J, Doerner A.

Med Hypotheses. 2008;70(3):671-7. Epub 2007 Aug 31.

A disorder of sympathomimetic amines leading to increased vascular permeability may be the etiologic factor in various treatment refractory health problems in women.

Check JH, Katsoff D, Kaplan H, Liss J, Boimel P.

The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Cooper Hospital/University Medical Center, Department of Obstetrics and Gynecology, Camden, NJ, United States.

There is an evidence that increased capillary permeability in the standing position is related to a deficit in the sympathetic nervous system. The leakage of this fluid leads to various clinical conditions which frequently puzzle the consulting physician because despite the frequency of this condition intelligent physicians and patients are unaware of the cause of their condition. One of the most common manifestations is the inability to lose weight despite proper dieting. A randomized study comparing the efficacy of a diuretic, a converting enzyme inhibitor, spironolactone and a sympathomimetic amine on weight loss in diet refractory women found that only the latter in the form of dextroamphetamine sulfate demonstrated significant weight reduction over a six month time span. In fact, the dextroamphetamine sulfate proved effective when given in the next 6 months to the three groups failing to respond for the first 6 months. The diagnosis of a deficit in sympathomimetic amines is established by demonstrating an abnormal clearance of a water load in the erect position and exclusion of other conditions that are associated with an abnormal free water clearance, e.g., hypothyroidism, renal or liver disease or congestive heart failure. The original definition of an abnormal water load test was excretion of <55% of a 1500 ml water load in 6h but we found that <75% defines a greater population who suffer from this problem. There are several conditions that have proven refractory to conventional theory that respond quickly and effectively to sympathomimetic amines. There have been many anecdotal reports of relieving interactable pain syndromes quickly and efficiently with sympathomimetic amine theory, despite failure with a multitude of other therapies. These include interstitial cystitis and pelvic pain that was attributed to endometriosis, gastrointestinal pain including esophagitis and gastroparesis, headaches, joint pain, fibromyalgia, and carpal tunnel syndrome. It is not clear if the improvement in pain is related to a decrease in fluid retention or a direct effect of the sympathomimetic amines on the sympathetic nervous system. Sympathomimetic amine theory has helped other conditions besides pain, e.g., chronic fatigue, vasomotor symptoms in young women not associated with decreased ovarian egg reserve, and chronic urticaria resistant to all other therapies. Thus, these studies strongly suggest that physicians be aware of this condition involving a deficit in the sympathetic nervous system when faced with various enigmatic complaints especially if standard therapy has not proven effective.

Fertil Steril. 2008 Jul;90(1):148-55. Epub 2007 Sep 4.

Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum.

Machado DE, Abrao MS, Berardo PT, Takiya CM, Nasciutti LE.

Department of Histology and Embryology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

OBJECTIVE: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium and in three different sites of endometriosis: the ovary, bladder, and rectum. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Thirty women with endometriosis (10 ovarian, 10 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). INTERVENTION(S): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. MAIN OUTCOME MEASURE(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. RESULT(S): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. CONCLUSION(S): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum.

Fertil Steril. 2008 May;89(5 Suppl):1537-45. Epub 2007 Sep 4.

Effects of anti-TNF-mAb treatment on pregnancy in baboons with induced endometriosis.

Falconer H, Mwenda JM, Chai DC, Song XY, Cornillie FJ, Bergqvist A, Fried G, D’Hooghe TM.

Division for Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.

OBJECTIVE: Hormonal suppressive therapy is not effective for endometriosis-associated subfertility and can even prevent conception. Medical inhibition of TNFalpha, which has been shown to improve conception, is effective in the prevention and treatment of endometriosis in baboons. DESIGN: Prospective, placebo-controlled fertility trial. SETTING: Animal research and laboratory facility. ANIMAL(S): Sixteen adult female baboons with induced endometriosis. INTERVENTION(S): All animals received a single IV dose of the anti-TNFalpha monoclonal antibody c5N (n = 9) or placebo (n = 7) at four different time points. The animals were then exposed to timed mating up to nine completed cycles or until pregnancy was achieved. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), cycle fecundity rate (CFR), time to pregnancy (TTP), and cumulative pregnancy rate (CPR). RESULT(S): Inhibition of TNFalpha did not result in a significant improvement in PR (100% c5N vs. 86% placebo), CFR (18% c5N vs. 30% placebo), median TTP (5 cycles c5N vs. 2 cycles placebo), or CPR (100% c5N vs. 80% placebo). The duration of the menstrual cycle was unchanged in both groups before and after the study. Two nonpregnant baboons in the c5N-group died during the study. CONCLUSION(S): Medical inhibition of TNFalpha allowed for normal conception but did not improve fecundity in baboons with induced endometriosis when compared with placebo. Larger studies with clinically available TNFalpha blockers in baboons with moderate to severe endometriosis are needed to further test the potential of these agents in the prevention or treatment of endometriosis-associated subfertility.

Best Pract Res Clin Obstet Gynaecol. 2008 Apr;22(2):333-9. Epub 2007 Aug 30.

Hormonal treatments for adenomyosis.

Fedele L, Bianchi S, Frontino G.

Fondazione Policlinico, Mangiagalli e Regina Elena, Clinica Ostetrica e Ginecologica II, Università di Milano, Istituto Luigi Mangiagalli, Via della Commenda 12, 20122 Milano, Italy.

Like endometriosis and uterine myomas, adenomyosis presents the typical characteristics of oestrogen-dependent diseases. The medical treatment of adenomyosis is based on the hormonal dependency of the disease and its strongly debated similarities with endometriosis. Infact, despite the evident differences between the two conditions, the therapies that treat endometriosis effectively have also been successful for the treatment of adenomyosis. Although the two diseases have distinct epidemiological features, they have the same ‘target tissue’ for hormonal therapy, namely ectopic endometrium. Recognized approaches are systemic hormonal treatments, which are generally used for endometriosis and are capable of suppressing the oestrogenic induction of the disease, and local hormonal treatment that targets the ectopic endometrium directly. Gonadotropin-releasing hormone agonists, danazol and intrauterine levonorgestrel- or danazol-releasing devices have been used in the treatment of adenomyosis. Despite the solid rational basis for its hormonal treatment, few studies have been performed on medical therapy for adenomyosis.

Fertil Steril. 2008 May;89(5 Suppl):1530-6. Epub 2007 Aug 30.

Basal and cytokine-stimulated production of epithelial neutrophil activating peptide-78 (ENA-78) and interleukin-8 (IL-8) by cultured human endometrial epithelial and stromal cells.

Bersinger NA, Frischknecht F, Taylor RN, Mueller MD.

Department of Obstetrics and Gynecology, University of Berne, Berne, Switzerland.

OBJECTIVE: To analyze the constitutive production of epithelial neutrophil activating peptide 78 (ENA-78) and interleukin-8 (IL-8) by epithelial cells and the response of these cells to cytokine stimulation. DESIGN: In vitro study using eutopic endometrial tissue. SETTING: University hospital. PATIENT(S): Cycling women undergoing laparoscopy for reasons of infertility or unexplained abdominal pain. INTERVENTION(S): Isolation of epithelial and stromal cells from endometrium, immunocytochemical characterization and separate culture of these cells in presence of IL-1, tumor necrosis factor alpha (TNF-alpha), and interferon-gamma. MAIN OUTCOME MEASURE(S): Quantitation of IL-8 and ENA-78 released into the medium by ELISA. Polymerase chain reaction was used to demonstrate the presence of ENA-78 in the cell lysate. RESULT(S): High purity of the endometrial epithelial cell preparation before culture was demonstrated by the lack of immunocytochemical staining for CD10. Stromal cell preparations were CD10 positive and cytokeratin negative. Stromal cells produced ENA-78 and IL-8 under cytokine stimulation, and epithelial cells were found not only to produce these markers in the absence of cytokine stimulation, but also to increase this output in the presence of IL-1beta or of TNF-alpha plus interferon-gamma. CONCLUSION(S): This response may be an important angiogenic step in the early stages in the pathogenesis of endometriosis.

Fertil Steril. 2008 Jun;89(6):1831-5. Epub 2007 Aug 30.

Maintenance therapy involving a tapering dose of danazol or mid/low doses of oral contraceptive after gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain.

Kitawaki J, Ishihara H, Kiyomizu M, Honjo H.

Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Pelvic pain associated with endometriosis was treated by the long-term administration of a tapering dose of danazol or mid/low doses of oral contraceptives after the end of therapy involving a GnRH agonist (GnRH-a). Results demonstrated that each of these three therapies is a practical and efficient treatment regimen to maintain the relief of pelvic pain achieved by GnRH-a therapy, at least for a period of 12 months.

Fertil Steril. 2008 Jul;90(1):234-7. Epub 2007 Aug 29.

Prolonged stimulation with tumor necrosis factor-alpha induced partial methylation at PR-B promoter in immortalized epithelial-like endometriotic cells.

Wu Y, Starzinski-Powitz A, Guo SW.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

The promoter of P receptor isoform B (PR-B) has recently been shown to be hypermethylated in endometriotic tissues, but one question remains as what causes the aberrant methylation. We show that sustained stimulation of an epithelial-like endometriotic cell line with tumor necrosis factor alpha stimulation for 30 days induced partial methylation in the promoter region of PR-B with concomitant reduction of PR-B expression.

Int J Cancer. 2008 Jan 1;122(1):170-6.

Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer.

Merritt MA, Green AC, Nagle CM, Webb PM; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group.

Population Studies and Human Genetics Division, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. Copyright 2007 Wiley-Liss, Inc.

Fertil Steril. 2008 May;89(5):1073-81. Epub 2007 Aug 13.

Panel of markers can accurately predict endometriosis in a subset of patients.

Seeber B, Sammel MD, Fan X, Gerton GL, Shaunik A, Chittams J, Barnhart KT.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

OBJECTIVE: To evaluate whether a combination of putative markers of inflammation and CA-125 could serve as a multiple-marker screening test for endometriosis in a heterogeneous population of patients. DESIGN: Case-control evaluation of a diagnostic test. SETTING: University medical center. PATIENT(S): Consenting women of reproductive age undergoing laparoscopy for indications of pain, infertility, elective tubal ligation, tubal reanastomosis, or other benign indications. INTERVENTION(S): Diagnostic laparoscopy and peripheral venipuncture. MAIN OUTCOME MEASURE(S): Serum concentrations of interleukin-6, tumor necrosis factor-alpha, macrophage migration inhibitory factor, macrophage chemotactic protein-1, interferon-gamma, leptin, and CA-125 measured by using ELISA assays; surgical staging of endometriosis. RESULT(S): Concentrations of the seven markers were compared between the 63 women with surgically confirmed stage II-IV endometriosis and 78 women who were surgically confirmed to be free of endometriosis. The individual diagnostic performance of each of the markers, based on receiver operating characteristic curves, was poor. When combinations of markers were evaluated by using classification tree analysis, a three-marker panel of CA-125, macrophage chemotactic protein-1, and leptin could diagnose 51% of subjects as to the presence of endometriosis with 89% accuracy. A four-marker panel of CA-125, macrophage chemotactic protein-1, leptin, and macrophage migration inhibitory factor could diagnose 48% of subjects with 93% accuracy. The remaining subjects would have no definitive diagnosis on the basis of the algorithm and would need to undergo standard evaluation. CONCLUSION(S): This large study evaluates the combined use of putative serum markers for the diagnosis of endometriosis, rather than the use of each singly. Using the serum concentration of four markers in a two-tiered decision rule, nearly half of the subjects in this population would have been diagnosed (and could have avoided surgery) with 93% accuracy.

Fertil Steril. 2008 May;89(5 Suppl):1490-6. Epub 2007 Aug 13.

Increased frequency of human leukocyte antigen-E inhibitory receptor CD94/NKG2A-expressing peritoneal natural killer cells in patients with endometriosis.

Galandrini R, Porpora MG, Stoppacciaro A, Micucci F, Capuano C, Tassi I, Di Felice A, Benedetti-Panici P, Santoni A.

Department of Experimental Medicine, University “La Sapienza,” Rome, Italy.

OBJECTIVE: To analyze the frequency of peritoneal natural killer (NK) cells expressing the human leukocyte antigen (HLA)-E receptor CD94/NKG2A in patients with endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Stage III and stage IV endometriosis, according to the revised American Society for Reproductive Medicine classification, was laparoscopically and histologically confirmed in 11 and 9 patients, respectively; 13 subjects without endometriosis were selected for the control group. INTERVENTION(S): Collection of peripheral venous blood, peritoneal fluid, endometriotic tissue, and normal endometrium in subjects undergoing laparoscopy. MAIN OUTCOME MEASURE(S): Surface expression levels of CD94/NKG2A and CD94/NKG2C were detected by three-color cytofluorometric analysis. Semiquantitative HLA-E messenger RNA expression analysis was performed in endometriotic lesions and in eutopic endometrium. NK cell-mediated cytotoxic activity toward HLA-E positive target, DT360 cell line, was also determined. RESULT(S): In women with endometriosis, the percentage of CD94/NKG2A-positive peritoneal NK cells was significantly higher than in the control group. The CD94/NKG2A ligand, HLA-E, was detected at high levels in endometriotic tissue as messenger RNA transcript. Target cells bearing HLA-E were resistant to NK cell-mediated lysis in a CD94/NKG2A-dependent manner. CONCLUSION(S): Increased expression of CD94/NKG2A in peritoneal NK cells may mediate the resistance of endometriotic tissue to NK cell-mediated lysis, thus contributing to the progression of the disease.

Surg Endosc. 2008 Apr;22(4):995-1001. Epub 2007 Aug 19.

Combined vaginal-laparoscopic-abdominal approach for the surgical treatment of rectovaginal endometriosis with bowel resection: a comparison of this new technique with various established approaches by laparoscopy and laparotomy.

Zanetti-Dällenbach R, Bartley J, Müller C, Schneider A, Köhler C.

Department of Gynecology, Universitätsmedizin Berlin, Berlin, Germany.

BACKGROUND: A new combined vaginal-laparoscopic-abdominal approach for rectovaginal endometriosis allows intraoperative digital bowel palpation to assess bowel infiltration and prevents unnecessary bowel resections. This technique was compared to various established approaches where bowel resection was indicated by clinical symptoms and imaging results only. METHODS: Patients operated for rectovaginal endometriosis with endometriotic bowel involvement between March 2002 and April 2006 at the gynecological department Charité, Berlin, Germany were included. Bowel involvement was suspected by clinical symptoms, clinical examination, and/or results of imaging techniques. The study group (SG) was operated by the combined vaginal-laparoscopic-abdominal approach (n = 30) and the control group (CG) (n = 18) by laparoscopy (n = 4), laparotomy (n = 3), laparoscopy followed by laparotomy for bowel resection (n = 8) or laparoscopy followed by vaginal bowel resection (n = 3). In all cases histopathology was performed. RESULTS: The study group and the control group were comparable regarding age, body mass index, symptoms, American Society for Reproductive Medicine (ASRM) classification, colorectal operative procedures, operating times, length of the resected bowel specimen, and concomitant surgical procedures. However, only in the CG were protective stomas required (p = 0.047). There were significantly less complications in the SG (p = 0.027). No patient experienced leakage of anastomosis. Bowel involvement by endometriosis was confirmed by histopathology in the SG in all cases whereas in the CG only in 16/18 (88.9%) cases. Hospitalization time was significantly shorter in the SG. Rehospitalizations were necessary only in the CG to repair one rectovaginal fistula and to reverse three stomas. CONCLUSIONS: With the presented technique of a combined vaginal-laparoscopic-abdominal surgical procedure for rectovaginal endometriosis, we showed that the complication rate, rehospitalization rate, and hospitalization time were significantly lower than in the patients of the CG. Furthermore, the combined vaginal-laparoscopic-abdominal technique allowed better evaluation of the invasiveness of the endometriotic lesion and avoided unnecessary bowel surgery.

Arch Gynecol Obstet. 2008 Feb;277(2):167-9. Epub 2007 Aug 14.

Caesarean scar endometriosis presenting as an acute abdomen: a case report and review of literature.

Gajjar KB, Mahendru AA, Khaled MA.

Luton and Dunstable Hospital, Lewsey Road, Luton, LU4 0FH, Bedfordshire, UK.

OBJECTIVE: To report a case of Caesarean scar endometriosis presenting as acute abdomen and a review of literature. DESIGN: Case report and literature review. PATIENT: A 27-year-old woman presented in Accident and Emergency Department with pain and lump near left edge of pfannenstiel incision scar. INTERVENTION: After initial investigations the patient underwent examination under anesthesia. MAIN OUTCOME MEASURE: Excision of a tumour-like mass adherent to the skin and the surrounding subcutaneous tissue. The mass was dissected free from the surrounding fat tissue and excised with clear margins. RESULT: Histology of the mass confirmed endometriosis in tumour and showed a 2 cm fibrotic nodule within. CONCLUSION: In light of increasing rate of caesarean section, it is important to emphasize the early diagnosis as well as optimum management of scar endometrioma. Many recommendations have been given to modify practices at caesarean section to prevent transplantation of decidual endometrial tissue in the abdominal scar but without any published randomised trials.

Fertil Steril. 2008 May;89(5):1069-72. Epub 2007 Aug 6.

Lymph node involvement and lymphovascular invasion in deep infiltrating rectosigmoid endometriosis.

Noël JC, Chapron C, Fayt I, Anaf V.

Department of Pathology, Erasme University Hospital, Free University of Brussels, Brussels, Belgium.

OBJECTIVE: To analyze the lymph node involvement by endometriotic foci in rectosigmoid endometriosis and to correlate it with clinical and histological parameters including the presence of lymphovascular invasions, which could explain this lymph node involvement. DESIGN: A prospective study of 26 consecutive cases of rectosigmoid endometriosis between January 2005 and January 2007. SETTING: A multidisciplinary study including clinical and pathological data. PATIENT(S): Twenty-six patients with symptomatic rectosigmoid endometriosis. INTERVENTION(S): Laparoscopic surgery with pathological analysis of each specimen. MAIN OUTCOME MEASURE(S): Involvement of lymph nodes by endometriotic foci was correlated with the size and the wall layers affected by endometriotic lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions demonstrated by D2-40, a specific antibody to lymphatic vessels. RESULT(S): Lymph node involvement by endometriosis was observed in 11 of the 26 patients (42.3%) and correlated with the size of the lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions, which were observed in 36.3% of cases. CONCLUSION(S): Our data confirm that lymph node involvement by endometriotic foci is a frequent event in rectosigmoid endometriosis and may result at least partially from a lymphatic spread of the disease.

Fertil Steril. 2008 Apr;89(4):912-21. Epub 2007 Aug 6.

Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation.

Appasamy M, Jauniaux E, Serhal P, Al-Qahtani A, Groome NP, Muttukrishna S.

Academic Department of Obstetrics and Gynaecology, Royal Free and University College London, University College London Campus, London, United Kingdom.

OBJECTIVE: To investigate the relationship between oxidative stress and the underlying causes of infertility, preovulatory ovarian hormones, and ovarian response to gonadotropin stimulation in patients undergoing assisted reproductive techniques. DESIGN: Prospective, cross-sectional study. SETTING: Assisted conception unit, university hospital. PATIENT(S): One hundred thirty women presenting with infertility, of the following types: male factor (n = 56), unexplained (n = 36), tubal factor (n = 16), polycystic ovary syndrome (n = 15), and endometriosis (n = 7). INTERVENTION(S): Follicular fluid (FF) and peripheral blood samples were collected at oocyte retrieval. MAIN OUTCOME MEASURE(S): Blood and FF samples were analyzed for inhibin A, inhibin B, activin A, anti-Müllerian hormone, and E(2) by using ELISA. Total antioxidant capacity (TAC) was measured in plasma and FF by using a calorimetric microplate assay. RESULT(S): There was no significant relationship between plasma or FF TAC and the underlying etiology of infertility. There was a statistically significant positive association between FF E(2) levels and TAC (r = 0.26). Higher antral follicle count, delta E(2) (day 3 E(2) minus day 2 E(2)), preovulatory serum anti-Müllerian hormone, inhibin B, and E(2) were associated with good ovarian response, whereas higher FF E(2) was associated with a statistically significant poor response. No significant direct relationship was observed between TAC and ovarian response as well as between TAC or any of the parameters measured and pregnancy outcome. CONCLUSION(S): Oxidative stress has an impact on the production of granulosa cell steroid hormones, in particular E(2), which is an important predictor of ovarian response. The positive association between FF E(2) and total antioxidant capacity suggests that E(2) may play a role in the ovarian antioxidant-oxidant balance.

Fertil Steril. 2008 May;89(5):1082-9. Epub 2007 Aug 6.

Tenascin is highly expressed in endometriosis and its expression is upregulated by estrogen.

Tan O, Ornek T, Seval Y, Sati L, Arici A.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.

OBJECTIVE: To investigate the localization of tenascin expression in the endometrium of women without endometriosis and in endometriotic implants, and to determine the in vitro regulation of tenascin by E(2) in these tissues. DESIGN: Experimental laboratory study. SETTING: University medical center. PATIENT(S): Reproductive age women with or without endometriosis. INTERVENTION(S): Proliferative (n = 14), and secretory (n = 14) endometrium from women without endometriosis and endometriosis implants (n = 14) were used for immunohistochemical analysis. Endometrial and endometriotic stromal cells were grown in culture and treated with E(2), the estrogen receptor antagonist ICI 182 780 (ICI) alone, E(2) in combination with ICI, or vehicle (control) for 24 hours, and tenascin expression was analyzed by Western blotting. MAIN OUTCOME MEASURE(S): Expression levels of tenascin in normal endometrium and endometriotic implants and its regulation by E(2). RESULT(S): Tenascin immunostaining revealed an increasing intensity in the stromal cells, starting from normal secretory endometrium, then normal proliferative endometrium, and reaching the highest expression in endometriotic implants. Estradiol induced a significant increase in tenascin protein levels in the endometriotic stromal cells in culture. CONCLUSION(S): The modulation of tenascin as an extracellular matrix protein by E(2) in endometriotic stromal cells may be one of the factors playing a role in the development of endometriosis.

Fertil Steril. 2008 Feb;89(2):301-10. Epub 2007 Aug 6.

Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis.

Kyama CM, Overbergh L, Mihalyi A, Meuleman C, Mwenda JM, Mathieu C, D’Hooghe TM.

Leuven University Fertility Center, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Leuven, Belgium.

OBJECTIVE: To examine messenger (m) RNA expression of aromatase, cytokines, and adhesion factors in women with and without endometriosis. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University Hospital Gasthuisberg, Leuven, Belgium. PATIENT(S): A total of 35 patients who had laparoscopic surgery during the luteal phase (n = 20) or the menstrual phase (n = 15) were selected for this study based on cycle phase and presence/absence of endometriosis. INTERVENTION(S): Tissues of endometrium and macroscopically normal peritoneum were collected during hysteroscopy and laparoscopic surgery, respectively, from 24 women with revised American Society for Reproductive Medicine stage (rASRM) stages I-II (n = 12) and III-IV (n = 12) endometriosis and 11 control patients with normal pelvic. Tissue samples were selected from a tissue bank, based on the phase of the cycle (menstrual or luteal) and the presence/absence of endometriosis. MAIN OUTCOME MEASURE(S): The mRNA levels of aromatase, vimentin, vascular cell adhesion molecule 1 (VCAM-1), alpha(V) and beta(3) integrins, interleukin (IL)-1 beta, regulated on activation normal T-cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1) were evaluated using real-time reverse transcriptase polymerase chain reaction. RESULT(S): During menstrual phase, increased endometrial mRNA levels of alpha(V) integrin, combined alpha(V)beta(3) integrins, and increased peritoneal IL-1 beta mRNA levels–but decreased peritoneal MCP-1 mRNA levels–were observed in women with endometriosis compared with control subjects. During luteal phase, endometrial mRNA levels of IL-1 beta and RANTES were increased in women with endometriosis compared with control subjects. Endometrial aromatase mRNA expression was higher in women with endometriosis than in control subjects in combined phases. Women with endometriosis had increased peritoneal mRNA expression of RANTES and VCAM-1 during menstrual compared with luteal phase. CONCLUSION(S): Aberrant mRNA expression of aromatase, cytokines, and adhesion factors in endometrium and peritoneum suggests that both tissues are involved in the pathogenesis of endometriosis.

Fertil Steril. 2008 Jan;89(1):33-41. Epub 2007 Aug 6.

Laterality and asymmetry of endometriotic lesions.

Guo SW, Wang Y, Liu X, Olive DL.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-0509, USA.

OBJECTIVE: To identify possible sources of heterogeneities in the estimation of the proportion of bilateral cases and of left-sided cases of endometriotic lesions. DESIGN: We included 20 studies that reported estimated proportions, and examined the effect of sample size and the anatomic location of lesions on the heterogeneity using a mixed-effect logit regression model. SETTING: Academic. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): The sample size of these studies ranged from 64 to 1,407, with a median of 227 and a total sample size of 7,236 cases. There is substantial heterogeneity in the estimated proportion of both bilateral and left-sided cases. The estimated proportion of bilateral cases is positively associated with the sample size of the study, whereas that of left-sided cases is negatively associated with the sample size, irrespective of the anatomic locations of endometriotic lesions. CONCLUSION(S): There is an identifiable source of heterogeneity in proportion estimates, with the sample size being an apparent source. Although the precise causes for the sample size dependency are unclear, it is possible that the invasive nature of endometriotic lesions may eventually render most cases bilateral. Moreover, there are both promoting as well as mitigating or negating factors that contributing to the asymmetry of endometriotic lesions.

Fertil Steril. 2008 Jan;89(1):251-2. Epub 2007 Jul 31.

Endometriosis is a possible risk factor for spontaneous hemoperitoneum in the third trimester of pregnancy.

Passos F, Calhaz-Jorge C, Graça LM.

Department of Obstetrics and Gynecology, Hospital de Santa Maria, Lisboa, Portugal.

Two patients with spontaneous hemoperitoneum, occurring in the third trimester of pregnancy, had in common previous surgery for moderate endometriosis and successful in vitro fertilization. Although it is not possible to establish a direct causal relationship, we must be aware of this rare but potentially serious complication as the wide use of assisted reproduction increases the number of such patients becoming pregnant.

Fertil Steril. 2008 Jul;90(1):209-13. Epub 2007 Jul 26.

Novel noninvasive detection method for endometriosis: research and development of scintigraphic survey on endometrial implants in rats.

Hascalik S, Celik O, Kekilli E, Elter K, Karakas HM, Aydin NE.

Department of Obstetrics and Gynecology, Inonu University Medical Faculty, Turgut Ozal Medical Center, Elazig Yolu 9 km, 44069 Malatya, Turkey.

In this experimental study on endometriosis, the majority of the implants were successfully detected with technetium-(99mTc) labeled red blood cell scintigraphy.

Fertil Steril. 2008 May;89(5 Suppl):1390-6. Epub 2007 Jul 26.

An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells.

Izawa M, Harada T, Taniguchi F, Ohama Y, Takenaka Y, Terakawa N.

Department of Biosignaling, Tottori University School of Medicine, Yonago, Japan.

OBJECTIVE: To examine the molecular basis of aromatase expression in stromal cell culture from endometriotic chocolate cysts. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology and Department of Biosignaling, Tottori University, Yonago Japan. PATIENT(S): Thirty women, selected randomly, who underwent laparoscopy (n = 18) or laparotomy (n = 12). INTERVENTION(S): Endometrial and endometriotic stromal cells were obtained from the uterus and chocolate cyst lining of the ovary. MAIN OUTCOME MEASURE(S): Estradiol concentrations in the culture media were measured by means of enzyme immunoassay. Aromatase expression was examined by quantitative real-time polymerase chain reaction. Promoter usage was examined using unique exon I (PII, I.1, I.3, I.4, I.5, and I.6) and exon II primers. To determine the effect of 5-aza-deoxycytidine on endometrial stromal cells, the cells were treated with the agent for 96 hours. RESULT(S): Endometriotic cells secreted a marginal level of estradiol into the culture media, but adding testosterone to the culture produced a pronounced level of estradiol. In endometrial cells, estradiol production was far less efficient than in endometriotic cells even after adding testosterone. Real-time polymerase chain reaction analyses demonstrated the up-regulation of aromatase messenger RNA (mRNA) expression in endometriotic cells. Three proximal promoters, PII, 1.3, and 1.6, drove mRNA expression. In endometrial cells where a marginal level of aromatase mRNA expression was observed, the same promoters as those in the endometriotic cells were used. To determine the role of epigenetic modification of aromatase gene expression in endometriotic cells, endometrial cells were treated with 5-aza-deoxycytidine, which markedly enhanced aromatase mRNA expression, depending on the same proximal promoters as those in endometriotic cells. CONCLUSION(S): An epigenetic disorder may play a role in the pathophysiology of endometriosis.

Fertil Steril. 2008 Jun;89(6):1632-6. Epub 2007 Jul 26.

Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women.

Stegmann BJ, Sinaii N, Liu S, Segars J, Merino M, Nieman LK, Stratton P.

Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1109, USA.

OBJECTIVE: To correlate histology with endometriosis characteristics. DESIGN: Secondary data analysis. SETTING: Government research hospital. PATIENT(S): One hundred thirty-three women with chronic pelvic pain and endometriosis who underwent laparoscopic surgery between 1999 and 2004. INTERVENTION(S): Laparoscopic excision of lesions, including recording of lesion characteristics and surgical impression of the lesions. MAIN OUTCOME MEASURE(S): All biopsies were sent for histological examination for endometriosis, and surgical and histological findings were compared. RESULT(S): Three hundred fifty-seven of 544 lesions believed to be endometriosis by the surgeon had positive histology. Mixed-color lesions most commonly contained endometriosis (76%), with the percentage of positive lesions being similar between single-color groups. Among subtle (red or white) lesions, 58% (164/283) were positive for endometriosis. Thirty women had only red or white lesions, and 18 (60%) had at least one lesion positive for endometriosis. Lesions were most commonly located in the cul-de-sac (64%), utero-sacral ligaments (68%), and ovarian fossa (70%). CONCLUSION(S): Wide, deep, mixed-color lesions in the cul-de-sac, the ovarian fossa, or the utero-sacral ligaments had the highest frequency of endometriosis. More than half of subtle lesions had endometriosis. These results should be considered when diagnosing endometriosis.

Fertil Steril. 2008 May;89(5):1260.e9-12. Epub 2007 Jul 12.

Monozygotic triplet pregnancy following egg donation and transfer of single frozen-thawed embryo.

Faraj R, Evbuomwan I, Sturgiss S, Aird I.

Centre for Assisted Reproduction, Queen Elizabeth Hospital, Gateshead, United Kingdom.

OBJECTIVE: To describe a case of monozygotic triplet pregnancy following egg donation and the transfer of a single frozen-thawed embryo. DESIGN: Case report. SETTING: District general hospital and regional department of fetal medicine in northeast England. PATIENT(S): A 38-year-old woman with a 2-year history of primary infertility due to severe endometriosis and poor ovarian reserve who conceived after egg donation and transfer of a single frozen-thawed embryo. INTERVENTION(S): Transfer of a single frozen-thawed embryo and delivery of three identical female infants by emergency caesarean section because of preterm labor at 32 weeks’ gestation. MAIN OUTCOME MEASURE(S): Review of effect of assisted conception on monozygotic twinning rates. RESULT(S): Healthy outcome for all three infants. CONCLUSION(S): Assisted reproductive treatments may lead to disturbances in zona pellucida architecture and an increase in monozygotic twinning rates. Couples need to be informed of this and the increased risks associated with these pregnancies before they begin with treatment.

Fertil Steril. 2008 Apr;89(4):993-4. Epub 2007 Jul 10.

Association between PTPN22 and endometriosis.

Ammendola M, Bottini N, Pietropolli A, Saccucci P, Gloria-Bottini F.

Division of Gynecology and Obstetrics, Department of Surgery, Hospital University of Rome Tor Vergata, School of Medicine, Rome, Italy.

PTPN22 is currently one of the few known shared-autoimmunity genes and is therefore a candidate marker for endometriosis. Our data show that female carriers of the PTPN22( *)T variant are significantly more susceptible to endometriosis than controls.

Fertil Steril. 2008 May;89(5):1064-8. Epub 2007 Jul 10.

Decreased anti-Müllerian hormone and altered ovarian follicular cohort in infertile patients with mild/minimal endometriosis.

Lemos NA, Arbo E, Scalco R, Weiler E, Rosa V, Cunha-Filho JS.

Department of Obstetrics and Gynecology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

OBJECTIVE: To evaluate the ovarian reserve and follicular cohort of infertile patients with minimal/mild endometriosis. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients were divided into two groups: group I, minimal/mild endometriosis and group II, tubal obstruction. The following exclusion criteria were established: [1] patients with previous endocrine disorders; and [2] cases in which the cause for infertility was other than endometriosis (except for patients with tubal obstruction, in the control group). INTERVENTION(S): Serum FSH and anti-Müllerian hormone were measured on day 3. On the same day all patients were submitted to transvaginal ultrasound to evaluate the antral follicular count and the ovarian follicular cohort. MAIN OUTCOME MEASURE(S): Serum FSH, anti-Müllerian hormone, and the follicular cohort with the respective antral follicular count. RESULT(S): Serum FSH were not different between the groups. However, infertile patients with endometriosis have a decreased serum anti-Müllerian hormone (1.26 +/- 0.7 ng/mL) compared to the control group (2.02 +/- 0.72 ng/mL). The analysis of follicular cohort showed that the number of selectable follicles were similar, but the follicular diameter was different. CONCLUSION(S): Minimal/mild endometriosis is associated with a decrease in the follicular ovarian reserve. In addition, the follicular cohort of these patients is more heterogeneous in comparison to the control group.

Respiration. 2008;75(1):113-9. Epub 2007 Jun 28.

Thoracic endometriosis syndrome.

Augoulea A, Lambrinoudaki I, Christodoulakos G.

2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity and is usually confined to the pelvis. Thoracic endometriosis syndrome (TES) is a rare disorder characterized by the presence of functioning endometrial tissue in the pleura, the lung parenchyma and the airways. TES may present with hemoptysis, due to the shedding of endometrial tissue in the bronchial tree, or spontaneous pneumothorax or hemothorax if the endometrial tissue is localized peripherally. Patients are of reproductive age, often nulliparous, with long-standing symptoms. The crucial issue for establishing the diagnosis is the cyclicity of the symptoms which occur along with the menstrual cycle. TES is virtually a diagnosis of exclusion, established on clinical grounds, since neither CT nor endoscopy are specific for TES. Treatment consists of gonadotropin-releasing hormone analogues, aiming to suppress the hypophyseal-gonadal axis, so as to ensure a regression of the endometrial implants. If medical treatment fails, surgical resection of the endometriomas is suggested, although relapse rate may be high. (c) 2007 S. Karger AG, Basel.

Fertil Steril. 2008 Apr;89(4):991.e13-5. Epub 2007 Jul 2.

Successful management of a massive hemorrhage due to rupture of cystic cervical endometriosis by a loop electrosurgical excision procedure.

Iwase A, Goto M, Kurotsuchi S, Harata T, Kaseki S, Kikkawa F.

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

OBJECTIVE: To report a case of cystic cervical endometriosis that caused a massive hemorrhage due to rupture of a cyst and successful management with a loop electrosurgical excision procedure (LEEP). DESIGN: Case report. SETTING: University Hospital. PATIENT: A 37-year-old nulliparous woman. INTERVENTION(S): Medical management including surgical treatment. MAIN OUTCOME MEASURE(S): Clinical follow-up and pathologic diagnosis. RESULT(S): A hemorrhagic cystic cervical mass was excised with emergent LEEP. The mass was found to be cervical endometriosis. There was no evidence of recurrence until 1 year after excision. CONCLUSION(S): Cystic formation of cervical endometriosis–like ovarian endometrioma, which causes a massive hemorrhage due to rupture–is extremely rare, although cervical endometriosis is generally asymptomatic. Hysterectomy is considered in such cases but can be avoided via LEEP that incorporates partial excision of the uterine cervix.

Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):240-6. Epub 2007 Jun 19.

Serum cytokines as biomarkers for nonsurgical prediction of endometriosis.

Othman Eel-D, Hornung D, Salem HT, Khalifa EA, El-Metwally TH, Al-Hendy A.

Department of Obstetrics & Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0587, USA.

OBJECTIVE: To test the ability of a group of serum cytokines, either individually or in combination, to serve as biomarkers for the nonsurgical diagnosis of endometriosis. STUDY DESIGN: Subjects were allocated to two groups according to their laparoscopic diagnosis. The first group consisted of patients with endometriosis and the second group was made up of infertile women with no pelvic pathology (controls). Blood samples were collected preoperatively and stored. Cytokines were measured in the serum of all participants using the Bio-Plex Protein Array System. Nonparametric statistics and the Mann-Whitney test were used to compare groups. Subjects were seen at the Gynecologic endoscopy unit. RESULTS: Three cytokines were significantly higher in the serum of subjects with endometriosis than in the control group: interleukin-6 (IL-6) [4.41 pg/ml (range: 1.47-15.01) versus 0.97 pg/ml (range: 0.29-2.98), respectively; p<0.001], monocyte chemotactic protein-1 (MCP-1) [37.91 pg/ml (range: 24.54-94.74) versus 22.13 pg/ml (range: 13.85-39.45), respectively; p<0.001], and interferon-gamma (INF-gamma) [19.01 pg/ml (range: 1.19-73.52) versus 0.30 pg/ml (range: 0.00-13.05), respectively; p<0.001]. There was no statistically significant difference between subjects with endometriosis and controls in the serum concentration of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), or granulocyte macrophage colony stimulating factor (GM-CSF). Interleukin-2 (IL-2), interleukin-8 (IL-8), and interleukin-15 (IL-15) were undetectable in the serum of both groups. None of the measured cytokines showed significant correlation with the cycle phase or stage of endometriosis. In a multivariate analysis, serum interleukin-6 provided a sensitivity of 71% and a specificity of 66% to discriminate between endometriosis patients and controls at a cutoff point of 1.9 pg/ml. Adding monocyte chemotactic protein-1 and interferon-gamma to interleukin-6 did not increase the discriminative ability over that achieved by measuring serum interleukin-6 alone. CONCLUSIONS: Serum of subjects with endometriosis contains significantly higher levels of interleukin-6, monocyte chemotactic protein-1, and interferon-gamma than control women. Serum interleukin-6 measurements discriminate between women with endometriosis and controls. Interleukin-6 provides a promising serum marker for the nonsurgical prediction of endometriosis.

Fertil Steril. 2008 Apr;89(4):934-42. Epub 2007 Jun 19.

Regression of endometrial explants in a rat model of endometriosis treated with melatonin.

Güney M, Oral B, Karahan N, Mungan T.

Department of Obstetrics and Gynecology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey.

OBJECTIVE: To determine the antioxidant, antiinflammatory, and immunomodulatory effects of melatonin on endometrial explants, the distribution of cyclooxygenase-2 (COX-2), the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and levels of malondialdehyde (MDA) in the rat endometriosis model. DESIGN: Prospective, placebo-controlled experimental study. SETTING: Experimental surgery laboratory in a university department. ANIMAL(S): Twenty-five rats with experimentally induced endometriosis. INTERVENTION(S): Endometriosis was surgically induced in 25 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Four weeks later, three rats were killed and the remaining 22 rats given second-look laparotomies to identify and measure ectopic uterine tissue in three dimensions. After the second laparotomy, 4 weeks of vehicle and melatonin treatment were administered, then all of the rats were given a third laparotomy and killed. MAIN OUTCOME MEASURE(S): The volume and weight of the implants were measured. The remaining rats were randomly divided into two groups. In control group (group 1; n = 11) no medication was given. To the rats in melatonin-treated group (group 2; n = 11), 10 mg/kg a day of melatonin was administered intraperitoneally. Four weeks later, after the second laparotomy, the endometrial explants were reevaluated morphologically, and COX-2 expression was evaluated immunohistochemically and histologically. In addition, endometrial explants were analyzed for the antioxidant enzymes SOD, CAT, and MDA, a marker of lipid peroxidation. A scoring system was used to evaluate expression of COX-2 and preservation of epithelia. RESULT(S): The pretreatment and posttreatment volumes within the control group were 135.9 +/- 31.5 and 129.4 +/- 28.7, respectively. The mean explant volume was 141.4 +/- 34.4 within the melatonin group before the treatment and 42.9 +/- 14.0 after 4 weeks of treatment. There was a statistically significant difference in spherical volumes (129.4 +/- 28.7 versus 42.9 +/- 14.0 mm(3)) of explant weights (155.8 +/- 27.1 versus 49.6 +/- 19.5 mg) and COX-2 positivity (91% versus 18.1%) between groups after the third laparotomy. In the melatonin-treated group, the endometrial explant levels of MDA statistically significantly decreased and activities of SOD and CAT significantly increased when compared with the control group. The epithelia showed statistically significantly better preservation in the control group when compared with the melatonin-treated group (2.54 +/- 0.52 versus 0.63 +/- 0.50). CONCLUSION(S): Melatonin causes regression and atrophy of the endometriotic lesions in rats.

Fertil Steril. 2008 Feb;89(2):342-7. Epub 2007 Jun 11.

Gonadotropin-releasing hormone agonist/antagonist conversion with estrogen priming in low responders with prior in vitro fertilization failure.

Fisch JD, Keskintepe L, Sher G.

Sher Institute for Reproductive Medicine, Las Vegas, Nevada 89109, USA.

OBJECTIVE: To evaluate gonadotropin-releasing hormone (GnRH) agonist/antagonist conversion with estrogen priming (AACEP) in low responders with prior IVF failure. DESIGN: Descriptive. SETTING: Private practice. PATIENT(S): Women aged <or=42 with prior IVF attempts in which all embryos were <7 cells or >20% fragmentation on day 3 (n = 137; <38: n = 63; 38-42: n = 74). In addition to unexplained poor response to stimulation (n = 52), diagnoses included elevated follicle-stimulating hormone (FSH >9.0 mIU/mL; n = 40), advanced age (>41 years; n = 26), endometriosis (III-IV; n = 12), and decreased ovarian reserve (AFC <5; n = 7). INTERVENTION(S): Patients received sequential GnRH agonist, low-dose GnRH antagonist, and estradiol valerate followed by recombinant FSH, 600 IU/day (n = 72) or 750 IU/day (n = 65). MAIN OUTCOME MEASURE(S): Pregnancy, ongoing gestation, implantation rates. RESULT(S): Although women aged <38 years and those on 600 IU/day produced more mature eggs and fertilized embryos than women aged 38 to 42 years, there were no differences in peak estradiol, endometrial lining, or embryos transferred. Outcomes were similar for all patients regardless of age or FSH dosage. Ongoing gestation rates were 27% (37 out of 137) for all patients, 25% (16 out of 63) for age <38 years, and 28% (21 out of 74) for ages 38 to 42 years. CONCLUSION(S): Women aged <or=42 years who are candidates for oocyte donation may still achieve pregnancy using their own eggs with the AACEP protocol.

Fertil Steril. 2008 Feb;89(2):311-7. Epub 2007 Jun 6.

Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis factor-alpha-induced interleukin-8 production and growth in endometriotic stromal cells.

Ohama Y, Harada T, Iwabe T, Taniguchi F, Takenaka Y, Terakawa N.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.

OBJECTIVE: To evaluate the influence of peroxisome proliferator-activated receptor-gamma (PPAR gamma) ligand (pioglitazone) on tumor necrosis factor-alpha (TNF-alpha)-induced interleukin-8 (IL-8) expression in endometriotic stromal cells (ESCs) and on proliferation of ESCs. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. PATIENT(S): Twenty-seven patients who underwent laparoscopic surgery. INTERVENTION(S): The ESCs were obtained from the chocolate cyst linings of ovaries. MAIN OUTCOME MEASURE(S): The expression of PPAR gamma gene and protein was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry. We determined the effect of pioglitazone on the production of TNF-alpha-induced IL-8 protein in culture supernatant of ESCs using ELISA. The effect of pioglitazone on TNF-alpha-induced proliferation of ESCs was evaluated by 5-bromo-2′-deoxyuridine proliferation assay. The activation of nuclear factor (NF)-kappaB in ESCs was evaluated by Western blot analyses and NF-kappaB transcription factor assays. RESULT(S): Immunocytochemistry and RT-PCR revealed the expression of PPAR gamma gene and protein in ESCs. The PPAR gamma protein was predominantly located in the cell nucleus. Measurement of IL-8 protein by ELISA showed that adding TNF-alpha (100 pg/mL) significantly increased IL-8 protein. Treating ESCs with 0.1-10 microM of pioglitazone significantly reduced the TNF-alpha-induced IL-8 production. The presence of 0.1-10 microM of pioglitazone significantly suppressed growth of ESCs. The TNF-alpha increased the expression of phosphorylation of inhibitor kappaB (I kappaB). Adding pioglitazone (10 microM) did not influence the expression of phosphorylated inhibitor kappaB (I kappaB). The TNF-alpha markedly increased the intranuclear concentration of p65, and adding pioglitazone (10 microM) significantly reduced the concentration of p65. CONCLUSION(S): The present study demonstrates for the first time that PPAR gamma is expressed in ESCs, and that pioglitazone reduced IL-8 secretion and the proliferation of ESCs. The PPAR gamma ligand may be an attractive therapeutic agent for endometriosis.

Fertil Steril. 2008 Mar;89(3):724.e5-7. Epub 2007 Jun 4.

A suprapubic dermoid cyst confused with cutaneous endometriosis: a case report.

Kim MK, Lee JR, Jee BC, Ku SY, Suh CS, Kim SH.

Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea.

OBJECTIVE: To describe a case of suprapubic dermoid cyst that had been mistaken for cutaneous endometriosis. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Seoul National University Hospital, Korea. PATIENT(S): A 22-year-old woman with a 5-year history of a slowly growing suprapubic mass, which had begun to bleed intermittently 6 months before presentation. INTERVENTION(S): Complete excision of the suprapubic mass and primary closure of the wound. MAIN OUTCOME MEASURE(S): The natural course of the suprapubic dermoid cyst and histologic findings. RESULT(S): The excised suprapubic mass was histologically diagnosed as a dermoid cyst. CONCLUSION(S): Subcutaneous dermoid cysts should be part of the differential diagnosis of suprapubic wall masses.

Fertil Steril. 2008 Jul;90(1):156-64. Epub 2007 Jun 4.

Peritoneal fluid macrophages in endometriosis: correlation between the expression of estrogen receptors and inflammation.

Montagna P, Capellino S, Villaggio B, Remorgida V, Ragni N, Cutolo M, Ferrero S.

Laboratory and Division of Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy.

OBJECTIVE: To investigate the expression of estrogen receptors (ERs) and inflammatory cytokines in macrophages obtained from peritoneal fluid (PF) of women with endometriosis. DESIGN: Comparative immunocytochemical study. SETTING: University hospital. PATIENT(S): Thirty women with endometriosis and 22 controls. INTERVENTION(S): The PF samples were collected at laparoscopy. MAIN OUTCOME MEASURE(S): The expression of ERalpha, ERbeta, differentiation markers (CD68, NCL-MACRO, HAM56), and inflammatory cytokines (interleukin [IL]-1beta, tumor necrosis factor-alpha [TNF-alpha], IL-6) in PF macrophages was determined. RESULT(S): The expression of CD68, NCL-MACRO, HAM56, TNFalpha, IL-6, and IL-1beta was significantly higher in PF macrophages obtained from women with endometriosis than in controls. The ERalpha and ERbeta had significantly higher expression in macrophages of women with endometriosis than in controls. A positive correlation was observed between the expression of ERalpha and ERbeta both in women with and without endometriosis. The ERalpha expression was positively correlated with the expression of inflammatory cytokines in women with endometriosis but not in controls; ERbeta expression was correlated to the expression of inflammatory cytokines in the both groups. CONCLUSION(S): There is a correlation between the expression of ERbeta and proinflammatory cytokines both in women with and without endometriosis. The expression of ERalpha correlates with cytokine production selectively in women with endometriosis but not in controls.

Fertil Steril. 2008 Mar;89(3):529-37. Epub 2007 Jun 4.

Alteration of focal adhesion kinase expression in eutopic endometrium of women with endometriosis.

Mu L, Zheng W, Wang L, Chen XJ, Zhang X, Yang JH.

Department of Gynecology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

OBJECTIVE: To investigate whether focal adhesion kinase (FAK) expression is altered in eutopic endometrium of women with endometriosis. DESIGN: Experimental study using human endometrial tissue. SETTING: Academic research center. PATIENT(S): Women with or without endometriosis who were undergoing surgery for benign indications. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Expression of FAK was assessed by immunohistochemistry, Western blotting analysis, and reverse-transcription polymerase chain reaction. RESULT(S): At secretory phase, the average level of endometrial FAK expression of women with endometriosis was significantly higher than that of controls, but no significant difference was found between the two groups at proliferative phase. There was a positive correlation between FAK expression in secretory endometrial tissues and disease stage and pelvic pain in women with endometriosis. Furthermore, the endometrial FAK protein expression varied with the serum E(2) at proliferative phase and with the ratio of E(2) to P at secretory phase. CONCLUSION(S): The study showed a significant increase of FAK expression in the secretory endometrial tissues of women with endometriosis, a relationship between FAK expression and disease stage, pelvic pain, and serum steroid hormones. Those results suggest that FAK may play a role in the pathogenesis of endometriosis and be regulated by steroid hormones.

Fertil Steril. 2008 Mar;89(3):677-84. Epub 2007 May 25.

Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies.

Cicinelli E, De Ziegler D, Nicoletti R, Colafiglio G, Saliani N, Resta L, Rizzi D, De Vito D.

Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Bari, Bari, Italy.

OBJECTIVE: To evaluate the type and etiopathogenic role of infectious agents detected in endometrial cultures obtained from women with chronic endometritis (CE). DESIGN: Prospective controlled study. SETTING: University hospital. PATIENT(S): 2190 women undergoing hysteroscopy for different indications. INTERVENTION(S): Vaginal and endometrial samples were collected from 438 women with a CE diagnosis at hysteroscopy and 100 women with no signs of CE (controls). MAIN OUTCOME MEASURE(S): Histology and cultures for common bacteria, Neisseria gonorrhoeae and Mycoplasma, and molecular biology testing for Chlamydia were performed. RESULT(S): We compared results of vaginal and intrauterine cultures obtained from women with and without CE. Histologic results were positive in 388 of these cases (88.6%), and at least one microorganism was found in 320 endometrial samples (73.1%). In the control group, histologic results and endometrial culture were positive in only 6% and 5% of cases, respectively. The most frequent infectious agents detected at the endometrial level were common bacteria (58% of cases). Ureaplasma urealyticum was detected in 10% and Chlamydia in only 2.7% of positive endometrial cultures. In only 143 (32.6%) cases were the same infectious agent isolated in endometrial and vaginal cultures. CONCLUSION(S): More than 70% of CE cases resulted from nongonococcal, nonchlamydial infections. Common bacteria and Mycoplasma were the most frequent etiologic agents. Vaginal cultures have low concordance with endometrial cultures.

Fertil Steril. 2008 Jan;89(1):52-9. Epub 2007 May 25.

Decreased human leukocyte antigen-DR expression in the lipid raft by peritoneal macrophages from women with endometriosis.

Yamamoto Y, Maeda N, Izumiya C, Kusume T, Oguri H, Kawashima M, Hayashi K, Nomura A, Yamashita C, Fukaya T.

Department of Obstetrics and Gynecology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi, Japan.

OBJECTIVE: To investigate the macrophage response in endometriosis by determining the expression and localization of human leukocyte antigen (HLA)-ABC and HLA-DR by the peritoneal fluid (PF) macrophages and PF concentrations of interferon (IFN)-gamma that regulate HLA expression. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): 64 Japanese endometriosis patients, and 65 women with other laparoscopic diagnoses. INTERVENTION(S): Venipuncture and laparoscopic peritoneal fluid collection. MAIN OUTCOME MEASURE(S): Expression and localization of HLA-ABC and HLA-DR in PF macrophages were determined by flow cytometry and confocal microscopy. The concentration of IFN-gamma in PF was determined by enzyme-linked immunosorbent assay. RESULT(S): In women with endometriosis, expression of HLA-ABC and HLA-DR by PF macrophages, and the IFN-gamma concentrations in PF were statistically significantly lower than in controls. Women with endometriosis showed a statistically significant positive correlation between HLA expression and IFN-gamma concentration. By confocal microscopy, HLA-ABC was distributed homogenously on the macrophage surface whereas HLA-DR expression on these cells corresponded to the lipid raft. CONCLUSION(S): In women with endometriosis, low HLA expression and particularly reduced HLA-DR in the lipid raft may be influenced by low IFN-gamma and may compromise antigen presentation, limiting the immune response to peritoneal cavity antigens such as implanted or metaplastic endometrial tissue.

Surg Endosc. 2008 Jan;22(1):171-6. Epub 2007 May 24.

Minimizing bladder injury in laparoscopically assisted vaginal hysterectomy among women with previous cesarean sections.

Chang WC, Hsu WC, Sheu BC, Huang SC, Torng PL, Chang DY.

Department of Obstetrics and Gynecology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.

BACKGROUND: This study demonstrated a method to prevent bladder injury during laparoscopically assisted vaginal hysterectomy (LAVH) to patients with vesicocervical adhesion after previous cesarean deliveries. METHODS: Between July 2004 and July 2005, 50 women with vesicocervical adhesion who had given birth by cesarean delivery underwent LAVH. To minimize the chance of bladder injury, transvaginal lateral intervention was used to enter the anterior cul-de-sac during laparoscopic intrafascial hysterectomy. The lateral windows of the vesicocervical space were opened first. Usually, the potential spaces lateral to the adhesions could be developed easily by blunt finger dissection. Once adequate lateral spaces were created, an index finger was swept medially to define the margin of the midline adhesions secondary to the cesarean delivery scar. Under direct vision and finger guidance, the dense adhesions were dissected with more confidence and safety. Subsequently, the bladder was pushed gently aside to avert unexpected tearing or injury along the intrafascial hysterectomy. Because the vesico-uterine fold had been cut open previously under laparoscopy, the anterior cul-de-sac could be entered without much resistance. RESULTS: The average age of the patients was 45 +/- 7 years, and the extirpated uterine weight was 323 +/- 170.8 g (range, 85-730 g). Intraoperatively, the mean operation time was 124.6 +/- 28.5 min (range, 80-235 min), and the average blood loss was 79.1 +/- 47.8 ml (range, 20-250 ml). The mean intramuscular meperidine requirements were 1.2 +/- 0.8 ampules (range, 0-2 ampules) (1 ampule = 50 mg), and the average hospital stay was 3.2 +/- 0.9 days (range, 2-5 days). Of these 50 patients, 24 (48%) had one, 22 (44%) had two, and 4 (8%) had three previous cesarean deliveries. No bladder injury occurred among the patients, and there was no other complication. CONCLUSION: Transvaginal lateral intervention may help to minimize bladder injuries during LAVH for patients with previous cesarean deliveries.

J Reprod Immunol. 2008 Jan;77(1):75-84. Epub 2007 May 22.

Abnormal interleukin 1 receptor types I and II gene expression in eutopic and ectopic endometrial tissues of women with endometriosis.

Lawson C, Bourcier N, Al-Akoum M, Maheux R, Naud F, Akoum A.

Hôpital Saint-François d’Assise (HSFA), Centre Hospitalier Universitaire de Québec (CHUQ), Québec, Canada.

Interleukin-1 (IL1) is believed to play a central role in the immuno-inflammatory process associated with endometriosis. IL1 triggers cell activation via its receptor type I (IL1R1), but its receptor type II (IL1R2) is known instead as a scavenger that buffers the cytokine’s effects. Our previous studies have shown increased expression of IL1R1 in active endometriotic implants compared to normal and endometriosis women-derived endometrial tissues, and a simultaneous decrease in IL1R2 expression at the protein level. In the present study, in situ hybridization demonstrated a noticeable decrease in IL1R2 mRNA hybridization score in eutopic and matched ectopic endometrial tissues of women with endometriosis compared to normal women in the stroma (P<0.001 and P<0.001, respectively) and the epithelium (P<0.01 and P<0.05, respectively), whereas IL1R1 mRNA hybridization score was higher only in the ectopic implants, with a statistically significant difference in the stroma (P<0.05). This was corroborated by RT-PCR analysis of IL1R1 and IL1R2 mRNAs in ectopic (P<0.05 and P<0.05, respectively) and matched eutopic (P=0.22 and P<0.05, respectively) endometrial tissues from women with endometriosis compared to endometrial tissues from normal women. The decrease in IL1R2 mRNA levels in eutopic endometrial tissue of endometriosis women, and the concomitant increase in IL1R1 mRNA levels in ectopic implants, reveal a profound defect in IL1R 1 and IL1R2 gene expression which may accentuate the capability of this tissue to respond to IL1 and favor its ectopic growth.

Fertil Steril. 2008 May;89(5 Suppl):1344-7. Epub 2007 May 23.

Dienogest inhibits BrdU uptake with G0/G1 arrest in cultured endometriotic stromal cells.

Fu L, Osuga Y, Morimoto C, Hirata T, Hirota Y, Yano T, Taketani Y.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.

OBJECTIVE: To investigate the effect of dienogest on the proliferation of endometriotic stromal cells. DESIGN: Comparative and laboratory study. SETTING: University of Tokyo Hospital. PATIENT(S): Endometriotic stromal cells were isolated and cultured from ovarian endometriomas of patients undergoing surgery. INTERVENTION(S): Dienogest was added to the cultured endometriotic stromal cells. MAIN OUTCOME MEASURE(S): 5-Bromo-2′-deoxyuridine (BrdU) incorporation into DNA of the endometriotic stromal cells was measured by ELISA. Cell cycle analysis of the cultured endometriotic stromal cells was performed by flow cytometry. RESULT(S): Dienogest at concentration of 10(-7) M and 10(-6) M significantly inhibited BrdU incorporation into DNA at 24 and 48 hours. Dienogest significantly increased the cells in G0/G1 phase and reduced the cells in S phase and G2/M phase in 24 and 48 hours. CONCLUSION(S): The present study indicates that dienogest can inhibit the proliferation of the endometriotic stromal cells with G0/G1 arrest, suggesting a possible direct effect of dienogest in the treatment of endometriosis.

Fertil Steril. 2008 Jan;89(1):60-5. Epub 2007 May 16.

Survivin gene expression in granulosa cells from infertile patients undergoing in vitro fertilization-embryo transfer.

Fujino K, Yamashita Y, Hayashi A, Asano M, Morishima S, Ohmichi M.

Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan.

OBJECTIVE: To evaluate survivin gene expression in granulosa cells from infertile patients and examine the relationship between survivin gene expression and infertile clinical background. DESIGN: Prospective study. SETTING: IVF-ET program at Osaka Medical College. PATIENT(S): Twenty-eight patients underwent ovulation induction for IVF-ET performed because of tubal infertility, male factor infertility, or endometriosis. INTERVENTION(S): Granulosa cells obtained at oocyte retrieval were examined for survivin gene expression by quantitative reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Hormone environment, number of oocytes, fertilization rate, high-quality embryo rate, pregnancy rate, and expression of survivin genes. RESULT(S): Survivin gene expression was detected in all granulosa cells. The gene expression levels of survivin in patients with endometriosis were significantly lower than those in patients with male factor infertility. The gene expression levels of survivin in total pregnant patients were higher than those in total nonpregnant patients and than those in the male factor infertility group, and there was no correlation between gene expression level and serum E(2) level. CONCLUSION(S): Survivin may be used as an indicator of the success of IVF-ET, and the existence of endometriosis may elevate the apoptosis of granulosa cells.

Fertil Steril. 2008 Jan;89(1):232-6. Epub 2007 May 16.

Comment in:

Fertil Steril. 2008 Jul;90(1):242-3; author reply 243.

Infertility surgery is dead: only the obituary remains?

Feinberg EC, Levens ED, DeCherney AH.

Combined Federal Fellowship in Reproductive Endocrinology and Infertility at National Institutes of Health, Walter Reed Army Medical Center, National Naval Medical Center, and Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Despite the multiple advantages of assisted reproductive technology compared with surgery, there remain several diagnoses for which surgery is still widely performed: distal tubal occlusion, regret of permanent sterilization, and endometriosis. Assisted reproductive technology is superior to surgery and should be offered as first-line treatment.

Fertil Steril. 2008 Feb;89(2):465-7. Epub 2007 May 16.

Soluble HLA-G in the peritoneal fluid of women with endometriosis.

Eidukaite A, Tamosiunas V.

Department of Molecular Immunology, Institute of Immunology, Vilnius, Lithuania.

The aim of this study was to determine the level of soluble HLA-G molecules in the peritoneal fluid of endometriosis patients. The findings demonstrate that a soluble HLA-G level in the peritoneal fluid of women with endometriosis is similar to that of the control group.

Fertil Steril. 2008 Mar;89(3):538-45. Epub 2007 May 11.

Differences in characteristics among 1,000 women with endometriosis based on extent of disease.

Sinaii N, Plumb K, Cotton L, Lambert A, Kennedy S, Zondervan K, Stratton P.

Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1871, USA.

OBJECTIVE: To determine the relationship between disease severity and patient characteristics in endometriosis. DESIGN: Cross-sectional study of self-reported survey data. SETTING: Academic research setting. PATIENT(S): One thousand women in the Oxford Endometriosis Gene (OXEGENE) study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Participants were assigned to one of two groups with predominantly revised AFS stage I-II (group I, n = 423) or III-IV disease (group II, n = 517). Their characteristics were compared by disease extent. RESULT(S): Most participants were white (96%) and of reproductive age (81%). Women in group I were significantly younger on entering the study (39.9 +/- 0.5 vs. 44.5 +/- 0.4 years). Overall time to diagnosis did not differ between groups. The most common symptoms leading to a diagnosis were dysmenorrhea (79%) and pelvic pain (69%). In group II, subfertility (21.5% vs. 30.0%) and an ovarian mass (7.3% vs. 29.4%) more commonly led to a diagnosis, whereas dyspareunia (51.1% vs. 39.5%) was significantly more common in group I. Subfertility (41.5% vs. 53.4%) remained more common in group II throughout reproductive life, although birth and miscarriage rates were similar. CONCLUSION(S): Pelvic pain is common to all with endometriosis and those with more extensive disease report higher rates of subfertility. Remarkably, the time to diagnosis was similar among women.

Fertil Steril. 2008 Jan;89(1):243-5. Epub 2007 May 7.

Association between endometriosis and polymorphisms in endostatin and vascular endothelial growth factor and their serum levels in Korean women.

Kim JG, Kim JY, Jee BC, Suh CS, Kim SH, Choi YM.

Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea.

The aim of present study was to evaluate the relationship between endometriosis and polymorphisms in the endostatin and vascular endothelial growth factor (VEGF) genes, and their levels in serum in a Korean population. Serum endostatin levels (but not VEGF levels) were negatively correlated with the development of endometriosis, specifically in early-stage endometriosis patients, compared with women without endometriosis, but endometriosis was not associated with the endostatin G(4349)A and VEGF C(936)T polymorphisms.

J Reprod Immunol. 2008 Jan;77(1):63-74. Epub 2007 May 4.

Peritoneal fluid from endometriosis patients switches differentiation of monocytes from dendritic cells to macrophages.

Na YJ, Jin JO, Lee MS, Song MG, Lee KS, Kwak JY.

Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Busan, Republic of Korea.

Immunological abnormalities of cell-mediated and humoral immunity might be associated with the pathogenesis of endometriosis. This study has examined the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the phenotypic characteristics of macrophages and dendritic cells (DCs) derived from monocytes. Monocytes were obtained from healthy young volunteers and cultured with ePF (n=12) or a control PF (cPF) (n=5) in the presence or absence of macrophage-colony stimulating factor (M-CSF) or IL-4 plus granulocyte macrophage-colony stimulating factor (GM-CSF). The ePF was demonstrated to increase expression levels of CD14 and CD64 on isolated monocytes in the presence or absence of M-CSF. Compared with cPF, addition of 10% ePF to GM-CSF plus IL-4-treated monocytes significantly down-regulated CD1a expression and up-regulated CD64 expression, but did not enhance expression levels of class II MHC. ePF had no effect, however, on tumor necrosis factor-alpha-induced maturation of DC. Levels of IL-6, IL-10 and M-CSF production were higher in ePF-treated than cPF-treated monocytes for both cell culture conditions with GM-CSF plus IL-4 and M-CSF. A neutralizing IL-6 antibody, but not an IL-10 antibody, abrogated the ePF-induced down-regulation of CD1a, up-regulation of CD64 and secretion of M-CSF. These results suggest that ePF favorably induces monocyte differentiation toward macrophages rather than DCs, and that this effect is mediated by IL-6. A reciprocal mode of cell differentiation between macrophages and DCs in response to ePF may be related to the pathogenesis of endometriosis.

Fertil Steril. 2008 Jan;89(1):42-51. Epub 2007 May 4.

Role of interleukin-1 receptor type II in the pathogenesis of endometriosis.

Hou Z, Zhou J, Ma X, Fan L, Liao L, Liu J.

Center of Clinical Reproductive Medicine, Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China.

OBJECTIVE: To determine the role of interleukin-1 receptor type II (IL-1RII) in the pathogenesis of endometriosis. DESIGN: Cultures of endometrial cells exposed to soluble IL-1RII or the recombinant adenovirus of IL-1RII (rAd-RII). SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Women with endometriosis undergoing hysterectomy. INTERVENTION(S): Cell culture media were collected 12 hours after addition of soluble IL-1RII or infection of rAd-RII. MAIN OUTCOME MEASURE(S): The levels of IL-6 and IL-8 in the culture media were measured via enzyme-linked immunoabsorbent assay. Furthermore, proteins of the cells were collected for two-dimensional electrophoresis and the differential protein expression was identified by the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULT(S): Addition of soluble IL-1RII (2.0 microg/mL) significantly inhibited IL-1 beta-induced IL-6 and IL-8 secretion by endometrial cells in vitro. Infection of endometrial cells with rAd-RII significantly decreased IL-1 beta-induced IL-8 secretion, compared with the PBS and rAd-LacZ controls but had no significant effect on IL-6 secretion. Proteins of the infected cells were collected for two-dimensional electrophoresis, and intensities of 62 spots were significantly increased or decreased when compared with those in the PBS group. Thirty-four proteins were identified by MALDI-TOF mass spectrometry. The majority of the identified proteins are related to cellular metabolism and proliferation. CONCLUSION(S): These results suggest that IL-1RII can neutralize IL-1 beta and counteract its effect on endometrial stromal cells, and may provide a new clinical strategy for the treatment of endometriosis.

Fertil Steril. 2008 Feb;89(2):478-80. Epub 2007 May 4.

Aberrant expression of keratinocyte growth factor receptor in ovarian surface epithelial cells of endometrioma.

Taniguchi F, Harada T, Iwabe T, Ohama Y, Takenaka Y, Terakawa N.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.

Ovarian surface epithelial cells (OSEs) are considered to be the common source of endometrioma and epithelial ovarian cancer. The present study reveals that keratinocyte growth factor receptor (KGFR) messenger RNA was expressed in OSEs of endometriomas but not in those of normal ovaries, suggesting that autocrine KGF/KGFR and paracrine fibroblast growth factor 10/KGFR signaling loops may be involved with the proliferation in OSEs of endometrioma.

Fertil Steril. 2008 Jan;89(1):206-11. Epub 2007 May 3.

Effects of a protein kinase C inhibitor on the initial development of ectopic implants in a syngeneic mouse model of endometriosis.

Matsuzaki S, Canis M, Darcha C, Déchelotte PJ, Pouly JL, Mage G.

Université d’Auvergne-Clermont I, Centre d’Endoscopie et des Nouvelles Techniques Interventionnelles, Clermont-Ferrand, France.

OBJECTIVE: To evaluate the effect of protein kinase C inhibition on surgically induced endometriosis in mice. DESIGN: Prospective, randomized study. SETTING: Academic facility. ANIMALS: Sixty adult female C57BJ6 mice. INTERVENTION(S): On day -7, oral gavage of a vehicle alone or of a protein kinase C inhibitor (100 mg/kg/day, once a day) was started and continued for 1 week in donor groups A and B, respectively. On day 0, uterine fragments from donor group A were implanted into recipient mice. Recipient mice were divided randomly into two groups: group 1 (vehicle) and group 2 (protein kinase C inhibitor). Uterine fragments from donor group B were implanted into recipient mice, and they were divided randomly into two groups: group 3 (vehicle) and group 4 (protein kinase C inhibitor). Oral gavage of a protein kinase C inhibitor (100 mg/kg/day, once a day) or vehicle was continued for 1 week. MAIN OUTCOME MEASURE(S): Presence and number of ectopic implants. RESULT(S): The number of mice that developed ectopic implants was significantly lower in groups 3 (40%) and 4 (30%) than in group 1 (100%). The number of ectopic implants was significantly lower in groups 2, 3, and 4 than in group 1. CONCLUSION(S): Protein kinase C inhibitor use partially prevented the development of ectopic implants in a mouse model of endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):204-9. Epub 2007 Mar 29.

Duration of dysmenorrhoea and extent of adenomyosis visualised by magnetic resonance imaging.

Kissler S, Zangos S, Kohl J, Wiegratz I, Rody A, Gätje R, Vogl TJ, Kunz G, Leyendecker G, Kaufmann M.

Division of Gynaecologic Endocrinology and Reproductive Medicine, Johann-Wolfgang-Goethe-University, Frankfurt/Main, Germany. <>

OBJECTIVE: Enlargement of the junctional zone (JZ) on T2-weighted resonance imaging of the uterus has recently been established as the major criterion for adenomyosis in patients with endometriosis. This study was conducted to analyse the extent of adenomyosis using magnetic resonance imaging (MRI) and relate it to the duration of dysmenorrhoea. STUDY DESIGN: This was a prospective study of 70 patients presenting with the complaint of severe dysmenorrhoea. Forty patients (57%) reported dysmenorrhoea as their major complaint and 30 patients (43%) suffered additionally from infertility. Group I (n=40) consisted of patients with dysmenorrhoea of between 1 and 10 years’ duration, group II (n=30) consisted of patients with dysmenorrhoea of longer than 11 years’ duration. All patients underwent laparoscopy to detect the presence and degree of endometriosis, and all patients underwent T2-weighted resonance imaging of the uterus to detect the extent of adenomyosis by measurement of the “junctional zone”. RESULTS: In group I, adenomyosis could be detected via MRI in 21 patients (52.5%), while 19 patients (47.5%) showed no signs of adenomyosis. By contrast, in group II a distinct enlargement of the JZ, as the major radiological criterion of adenomyosis, could be observed in 26 patients (87%), while only 4 patients (13%) revealed no signs of adenomyosis (p=0.04). The mean thickness of the JZ was significantly enlarged in group II (11.07 mm) compared with group I (6.38 mm; p<0.0001). The prevalence of adenomyosis in endometriosis after dysmenorrhoea of more than 11 years’ duration was 87%. CONCLUSIONS: In deep infiltrating endometriosis, a correlation between a specific localisation and dysmenorrhoea can often not be found. Recently, endometriosis and adenomyosis have been believed to result from a common uterine disease, the dislocation of the basal endometrium. Our data clearly show that dysmenorrhoea of long duration in patients who have had endometriosis for over a threshold value of 11 years is significantly related to adenomyosis of the uterus. Hence, evaluation of adenomyosis using MRI should become a standard procedure in cases of dysmenorrhoea and endometriosis. Severe dysmenorrhoea of long duration should always focus clinical interest on adenomyosis of the uterus.

Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):198-203. Epub 2007 Mar 21.

Histone deacetylase inhibitors trichostatin A and valproic acid induce cell cycle arrest and p21 expression in immortalized human endometrial stromal cells.

Wu Y, Guo SW.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

OBJECTIVE: Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA and VPA do so by inducing cell cycle arrest and p21 expression. STUDY DESIGN: A recently established immortalized endometrial stromal cell line was treated with TSA, VPA, and/or all-trans retinoic acid (ATRA) and the consequent cell cycle progression was measured by flow cytometry and p21 protein expression by Western blot analysis. RESULTS: Both TSA and VPA induced cell cycle arrest and p21 expression in a concentration-dependent manner. Treatment with ATRA alone also induced cell cycle arrest and moderate increase in p21 expression but joint treatment of ATRA and TSA/VPA did not further enhance cell cycle arrest as compared with TSA/VPA treatment alone. CONCLUSIONS: HDACIs suppress proliferation of endometrial stromal cells through induction of cell cycle arrest and possibly also through apoptosis as well. RA also induces cell cycle arrest but it does not synergize with HDACIs in inducing cell cycle arrest. HDACIs may be promising compounds for treating endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2008 May;138(1):121-2. Epub 2007 Mar 19.

Extraperitoneal endometriosis as a differential diagnosis of an inguinal lump.

Chalouhi GE, Harb CA, Atallah DM, Golfier FR.

Int J Colorectal Dis. 2008 Jan;23(1):133-4. Epub 2007 Feb 9.

Long-segment hypoplasia of the left hemicolon 4 months after sigmoid resection and loop transversostomy in a patient with intestinal endometriosis.

Steger U, Hoeller S, Boenicke L, Thiede A, Dietz U.

Fertil Steril. 2008 Jan;89(1):246-50. Epub 2007 Jan 18.

Comment in:

Fertil Steril. 2008 Jul;90(1):238; author reply 238-9.

A pilot study on the off-label use of valproic acid to treat adenomyosis.

Liu X, Guo SW.

Department of Gynecology, Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Following on the heels of the discovery that endometriosis is an epigenetic disease, we conducted a pilot study on the off-label use of valproic acid to treat adenomyosis. We found that by the end of the 3-month treatment, all three recruited patients reported complete disappearance of dysmenorrhea, with an average of one-third reduction in uterus size.

Int J Colorectal Dis. 2008 Jan;23(1):127-8. Epub 2007 Jan 18.

Ileus due colon endometriosis and the role of MRI scan.

Hampe T, Kulaksiz H.

Eur J Obstet Gynecol Reprod Biol. 2008 Feb;136(2):243-8. Epub 2007 Jan 8.

The effect of intraperitoneal interleukin-2 on surgically induced endometriosis in rats.

Quereda F, Bermejo R, Velasco I, Campos A, Acién P.

Division of Gynecology, School of Medicine, Miguel Hernández University, Alicante, Spain.

OBJECTIVE: To evaluate the effect of interleukin-2 (IL-2) on an experimental model of endometriosis. STUDY DESIGN: Double blind and randomized experimental prospective placebo-controlled study. Experimental endometriosis was induced in 66 three-month-old female Wistar rats, by auto-transplanting fragments of endometrium to the peritoneum. After four weeks, the size of each implant was measured in millimeters by laparotomy (L2), and animals were randomly distributed for intraperitoneal administration of human-IL-2, rat-IL-2 or placebo. Four weeks later, the implants were measured (L3) and a second dose was given. After four weeks, endometriosis size was evaluated again (L4). RESULTS: We found a reduction of experimental endometriosis at L3 that was only significant in IL-2 treated groups: 20.1% and 30.3% with human-IL-2 and rat-IL-2, respectively (p<0.001 with respect to L2 size), versus a non-significant reduction of 9.0% found in placebo group, but the differences were not statistically significant between groups. The decrease after a second dose (L4) was: 49.8%, 41.8% and 11.4% with human-IL-2, rat-IL-2 and placebo, respectively (p<0.001 in IL-2 groups versus L2 and L3, and p<0.05 in both groups versus placebo at L4). CONCLUSION: Intraperitoneal administration of IL-2 reduces experimental endometriosis, and this effect is similar using rat-IL-2 or human IL-2 (non specie-specific effect).

Eur J Obstet Gynecol Reprod Biol. 2008 Feb;136(2):243-8. Epub 2007 Jan 8.

The effect of intraperitoneal interleukin-2 on surgically induced endometriosis in rats.

Quereda F, Bermejo R, Velasco I, Campos A, Acién P.

Division of Gynecology, School of Medicine, Miguel Hernández University, Alicante, Spain.

OBJECTIVE: To evaluate the effect of interleukin-2 (IL-2) on an experimental model of endometriosis. STUDY DESIGN: Double blind and randomized experimental prospective placebo-controlled study. Experimental endometriosis was induced in 66 three-month-old female Wistar rats, by auto-transplanting fragments of endometrium to the peritoneum. After four weeks, the size of each implant was measured in millimeters by laparotomy (L2), and animals were randomly distributed for intraperitoneal administration of human-IL-2, rat-IL-2 or placebo. Four weeks later, the implants were measured (L3) and a second dose was given. After four weeks, endometriosis size was evaluated again (L4). RESULTS: We found a reduction of experimental endometriosis at L3 that was only significant in IL-2 treated groups: 20.1% and 30.3% with human-IL-2 and rat-IL-2, respectively (p<0.001 with respect to L2 size), versus a non-significant reduction of 9.0% found in placebo group, but the differences were not statistically significant between groups. The decrease after a second dose (L4) was: 49.8%, 41.8% and 11.4% with human-IL-2, rat-IL-2 and placebo, respectively (p<0.001 in IL-2 groups versus L2 and L3, and p<0.05 in both groups versus placebo at L4). CONCLUSION: Intraperitoneal administration of IL-2 reduces experimental endometriosis, and this effect is similar using rat-IL-2 or human IL-2 (non specie-specific effect).

Eur J Obstet Gynecol Reprod Biol. 2008 Mar;137(1):67-76. Epub 2007 Jan 4.

Differential flow cytometric detection of intracellular cytokines in peripheral and peritoneal mononuclear cells of women with endometriosis.

Gmyrek GB, Sieradzka U, Goluda M, Gabryś M, Sozański R, Jerzak M, Zbyryt I, Chrobak A, Chełmońska-Soyta A.

Laboratory of Reproductive Immunology, Institute of Immunology and Experimental Therapy, Rudolfa Weigla 12, 53-114 Wroclaw, Poland.

OBJECTIVE: The pathogenesis of endometriosis is related to functional changes in CD3+ and CD14+ cells observed both at the local and systemic level. Here we investigated whether, and if so, how the body compartment influences cytokine expression in stimulated peritoneal and peripheral CD3+ and CD14+ cells of women with endometriosis. STUDY DESIGN: Isolated peripheral blood (PB) and peritoneal fluid (PF) mononuclear cells from women with endometriosis were cultured under non-adherent conditions and stimulated with PMA and ionomycin for 6h to induce intracellular cytokine synthesis of TNF-alpha, IFN-gamma, and IL-8 by CD3+ cells or with LPS for 9h to produce TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 by CD14+ cells. RESULTS: The percentages of positive CD3+ cells stained for TNF-alpha and IFN-gamma were significantly higher and those stained for IL-8 were significantly lower in PF compared with PB, this being independent of the stage of endometriosis. In contrast, the percentages of CD14+ cells producing TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 were significantly higher in PB than PF of women with endometriosis. CONCLUSIONS: Monocytes/macrophages and lymphocytes derived from the peripheral and peritoneal compartments of women with endometriosis differentially respond to stimulated cytokine synthesis induction. However, it is difficult to state whether the observed phenomenon is more related to body compartment influence per se or to the presence of endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2008 Feb;136(2):194-8. Epub 2006 Dec 18.

A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis.

Loverro G, Carriero C, Rossi AC, Putignano G, Nicolardi V, Selvaggi L.

Department of Gynecology, Obstetrics, and Neonatology, University of Bari, Italy.

OBJECTIVE: To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis. STUDY DESIGN: Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients). RESULTS: Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test). CONCLUSION: Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.

Eur J Obstet Gynecol Reprod Biol. 2008 Feb;136(2):199-209. Epub 2006 Dec 1.

Expression of heparanase and angiopoietin-2 in patients with endometriosis.

Jingting C, Yangde Z, Yi Z, Mengxiong L, Rong Y, Yu Z, Guoqing P, Lixiu P.

Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

OBJECTIVE: The objective was to investigate the expression of heparanase (Hpa) and angiopoietin-2 (Ang-2) in endometriosis. STUDY DESIGN: In ectopic and eutopic endometrium of patients undergoing laparoscopy for endometriosis (n=86) and in normal endometrium of patients undergoing laparoscopic tubal ligation or hysteroscopic resection because of uterus septus (n=30), we determined Hpa and Ang-2 gene expression by RT-PCR. To support the mRNA data, the expression of Hpa and Ang-2 protein was measured by Western blot analysis. Finally, Hpa and Ang-2 in these tissues was localized by immunohistochemical staining. RESULT(S): The positive rate of Hpa and Ang-2 mRNA in ectopic and eutopic endometrium in the study group was significantly higher than that in normal endometrium in the control group. In the study group, ectopic and eutopic endometrium expressed a higher positive rate of Hpa and Ang-2 protein, whereas in the control group, normal endometrium expressed a lower positive rate of Hpa and Ang-2 protein. In eutopic and ectopic endometrium, there was balanced expression between Hpa and Ang-2. Both Hpa and Ang-2 showed a balanced expression between eutopic and ectopic endometrium. In ectopic endometrium, strong staining for Hpa and Ang-2 was observed both in epithelial cells and in stromal cells, but in eutopic endometrium, Hpa and Ang-2 were mainly expressed in epithelial cells. CONCLUSION: The higher expression of Hpa and Ang-2 in ectopic and eutopic endometrium may play an important role in the pathogenesis and development of endometriosis.


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