J Womens Health (Larchmt). 2010 Sep 11. [Epub ahead of print]

Does Controlled Ovarian Hyperstimulation in Women with a History of Endometriosis Influence Recurrence Rate?

Coccia ME, Rizzello F, Gianfranco S.

1 Department of Gynaecology, Perinatology and Human Reproduction, University of Florence , Florence, Italy .

Background: Endometriosis is a common estrogen-dependent disease. The aim of this study was to assess whether controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART) was associated with an increased incidence in endometriosis recurrence as documented by transvaginal ultrasound (TV-US). Methods: In a retrospective cohort study of 592 patients submitted to laparoscopy for endometriosis, 177 with infertility-related endometriosis who underwent a periodic ultrasound follow-up after laparoscopy were selected. Women who started ART after laparoscopy (n = 90) were compared with the control group, who did not undergo ART (n = 87). Recurrence of endometriosis was defined as the presence of endometriotic lesions observed through TV-US. Results: During a long-term TV-US follow-up (1-15 years), 40 (22.6%) recurrences were observed. Patients submitted to ART showed a cumulative recurrence rate similar to that of the control group (28.6% and 37.9% respectively, p = 0.471). Recurrent lesions were ovarian cysts (47.5%), ovarian nodules (37.5%), and rectovaginal disease (15%). The stratified analysis based on stages of endometriosis and pelvic pain did not show differences. Conclusions: Gonadotropin treatments do not seem to affect the natural history of endometriotic lesions. The most important prognostic factors in recurrent disease observed by TV-US seem to be the stage of endometriosis and the presence of pelvic pain at the time of the first laparoscopic treatment.

Hum Reprod. 2010 Nov;25(11):2878-90. Epub 2010 Sep 9.

Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis, adenomyosis and uterine myoma.

Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, Ishimaru T, Masuzaki H.

Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

BACKGROUND We recently demonstrated the effect of gonadotrophin-releasing hormone agonist (GnRHa) on tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma. Here, we investigated expression of GnRH receptors (GnRHRs) and effect of GnRHa on the proliferation of cells derived from endometria and pathological lesions of women with these reproductive diseases. METHODS Biopsy specimens were collected from lesions and corresponding endometria of 35 women with pelvic endometriosis, 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma during laparoscopy or laparotomy. The gene and protein expressions of GnRHR in eutopic/ectopic cells and tissues were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The immunoreactivity of GnRHR in tissue was analysed by quantitative-histogram (Q-H) scores. The exogenous effect of GnRHa on cell proliferation was examined by 5-bromo-2-deoxyuridine incorporation assay. The Ki-67-immunoreactive cell proliferation index was analysed in biopsy specimens derived from GnRHa-treated and -non-treated women. RESULTS Types I and II GnRHRs mRNA and proteins were expressed in eutopic endometria and pathological lesions derived from women with endometriosis, adenomyosis and uterine myoma. GnRHR expression was the highest in the menstrual phase when compared with other phases of the menstrual cycle. Higher Q-H scores of GnRHR immunoreaction were found in blood-filled opaque red lesions than in other peritoneal lesions. Exogenous treatment with GnRHa significantly suppressed the proliferation of cells derived from respective endometria and pathological lesions when compared with GnRHa-non-treated cells. CONCLUSIONS Local tissue expression of GnRHR was detected in endometriosis, adenomyosis and uterine myoma. In addition to a hypo-estrogenic effect, a direct anti-proliferative effect of GnRHa may be involved in the regression of these reproductive diseases with consequent remission of clinical symptoms.

J Clin Endocrinol Metab. 2010 Sep 8. [Epub ahead of print]

Macrophage Migration Inhibitory Factor Elicits an Angiogenic Phenotype in Human Ectopic Endometrial Cells and Triggers the Production of Major Angiogenic Factors via CD44, CD74, and MAPK Signaling Pathways.

Veillat V, Carli C, Metz CN, Al-Abed Y, Naccache PH, Akoum A.

Laboratoire d’Endocrinologie de la Reproduction (V.V., C.C., A.A.), Centre de Recherche, Hôpital Saint-François d’Assise, and Centre de recherche en rhumatologie et immunologie (P.H.N.), Centre de recherche, Centre Hospitalier de l’Université Laval, Centre Hospitalier Universitaire de Québec, and Faculté de Médecine, Université Laval, Québec, Canada G1L 3L5; and Feinstein Institute for Medical Research (C.N.M., Y.A.-A.), Manhasset, New York 11030.

Context: An active angiogenesis is required for ectopic endometrial tissue growth. Our previous studies led to the identification of macrophage migration inhibitory factor (MIF), which is markedly elevated in active, vascularized, and early-stage endometriotic lesions, as a potent mitogenic factor for endothelial cells. Objective: Our objective was to study the mechanisms by which MIF may stimulate angiogenesis in ectopic endometrial implantation sites. Design: Primary cultures of ectopic endometrial cells were exposed to MIF, and the release of major angiogenic factors with targeted disruption of MIF signaling pathways was assessed. Patients: Patients were women found to have endometriosis during laparoscopy. Setting: The study was conducted at a hospital and reproduction research laboratory. Interventions: Biopsies were removed from endometriotic lesions. Main Outcome Measures: Vascular endothelial cell growth factor (VEGF), IL-8, and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels and expression and small interfering RNA silencing of MIF CD74/CD44 receptor complex and phosphorylation of ERK and p38 MAPKs were evaluated. Results: MIF markedly up-regulated VEGF, IL-8, and MCP-1 expression in endometriotic cells. Such an effect was abolished by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), a specific inhibitor of MIF, and significantly down-regulated after specific small interfering RNA silencing of CD44 or CD74. MIF treatment strongly activated ERK and p38 MAPKs, and specific inhibitors of both pathways completely blocked basal and MIF-induced VEGF, IL-8, and MCP-1 synthesis. Conclusions: These results show for the first time that MIF exerts a potent indirect angiogenic effect by interacting with ectopic endometrial cells and inducing the secretion of major angiogenic factors via CD44, CD74, and MAPK signaling pathways and provide evidence for a possible new mechanism underlying endometriosis development and pathophysiology.

Minerva Ginecol. 2010 Aug;62(4):373-80.

Treatment of endometriosis: a hormonal approach.

Budinetz T, Sanfilippo JS.

Department of Obstetrics and Gynecology Geisinger Medical Center, Danville, PA, USA – jsanfilippo@mail.magee.edu.

Endometriosis continues to plague women of reproductive age. It is a chronic disease leading to a decreased quality of life, infertility, and increased societal costs. The gold standard for diagnosis remains visualization and or biopsy of lesions at the time of intraoperative diagnosis, i.e. laparoscopy or laparotomy. The severity of pain does not correlate with the stage of endometriosis, which complicates the treatment process. Hormonal therapies have long been used as a treatment for endometriosis. Therapy is targeted at symptom relief as a cure is lacking. While some regimes use hormonal therapy exclusively, others combine such with surgical excision of lesions. Although hormonal modalities are successful in alleviating or suppressing symptoms, they fail to treat the infertility associated with endometriosis. Therefore, those, desiring to achieve pregnancy should be excluded from hormonal treatment in the short term. Future studies are needed to understand the pathophysiology and allow design of specific, targeted treatment.

J Clin Endocrinol Metab. 2010 Sep 8. [Epub ahead of print]

MUC1 as a Discriminator between Endometrium from Fertile and Infertile Patients with PCOS and Endometriosis.

Margarit L, Taylor A, Roberts MH, Hopkins L, Davies C, Brenton AG, Conlan RS, Bunkheila A, Joels L, White JO, Gonzalez D.

Institute of Life Science (L.M., A.T., M.H.R., A.G.B., R.S.C., J.O.W., D.G.), School of Medicine, Swansea University, Swansea SA2 8PP, Wales, United Kingdom; and Abertawe Bro Morgannwg University Trust (L.M., L.H., C.D., A.B., L.J.), Singleton Hospital, Swansea SA2 8QA, Wales, United Kingdom.

Context: Endometrium of fertile women expresses progesterone-regulated Mucin 1 (MUC1) that carries selectin ligands recognized by the human blastocyst. Altered MUC1 expression at the time of implantation may contribute to endometrial infertility. Objective: The aim was to assess the expression of MUC1 in the endometrium from polycystic ovary syndrome (PCOS), endometriosis, and fertile women in comparison with other hormone-regulated proteins [hydroxysteroid dehydrogenase (HSD) 1, HSD2, estrogen receptor (ER) and progesterone receptor (PR)]. Design and Patients: Endometrial samples were obtained from 33 fertile patients, 26 ovulatory PCOS patients, 15 anovulatory PCOS patients, and 25 endometriosis patients. Main Outcome Measure: Immunohistochemistry assessed the expression of MUC1 subunits ER, PR, HSD1, and HSD2 in endometrial epithelium. Endometrial MUC1 expression was quantified by immunoblots and RT-PCR. HSD1 and HSD2 expression was assayed by RT-PCR. Results: MUC1ND expression was significantly higher in ovulatory PCOS than in fertile and anovulatory PCOS patients, even after progesterone stimulation. MUC1ND and -CD expression was lower in anovulatory PCOS than in fertile patients. Only MUC1CD expression was lower in endometriosis patients. Endometrial ER expression was significantly higher in PCOS and endometriosis patients, whereas PR expression was significantly higher in PCOS than in fertile patients. The expression of HSD1 was significantly higher in anovulatory PCOS than in fertile patients. Expression of HSD2 was significantly higher in PCOS patients and lower in endometriosis patients. Conclusion: Expression of MUC1 subunits in the infertile endometrium is significantly different from fertile and appears to be a component of altered gene expression that potentially contributes to endometrial insufficiency.

Am J Reprod Immunol. 2010 Sep 5. [Epub ahead of print]

The Peritoneal Leptin, MCP-1 and TNF-α in the Pathogenesis of Endometriosis-Associated Infertility.

Tao Y, Zhang Q, Huang W, Zhu H, Zhang D, Luo W.

Department of Obstetrics/Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Citation Tao Y, Zhang Q, Huang W, Zhu H, Zhang D, Luo W. The peritoneal leptin, MCP-1 and TNF-α in the pathogenesis of endometriosis-associated infertility. Am J Reprod Immunol 2010 Problem  To explore the roles of leptin, monocyte chemotactic protein (MCP)-1, and tumour necrosis factor (TNF)-α in the peritoneal fluid (PF) in the pathogenesis of endometriosis-associated infertility. Method of study  Leptin, MCP-1, and TNF-α levels in the PF from 28 infertile women with endometriosis (study group), 23 women with fallopian-associated infertility (controls), and 24 women with myoma (controls) were determined by performing enzyme-linked immunosorbent assay (ELISA). Result  Leptin and TNF-α levels in the PF showed no significant difference among three groups. The MCP-1 level in patients with endometriosis was higher than those in fallopian-associated infertility group and myoma group (P < 0.01). There was a positive correlation between leptin and MCP-1 levels in the PF of patients with endometriosis (P < 0.05). Conclusion  Peritoneal leptin and MCP-1 play important roles in the pathogenesis of infertility in the early stage of endometriosis.

J Pathol. 2010 Oct;222(2):148-57.

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo.

Ngô C, Nicco C, Leconte M, Chéreau C, Arkwright S, Vacher-Lavenu MC, Weill B, Chapron C, Batteux F.

Université Paris Descartes, Faculté de Médecine, EA 1833 AP-HP Hôpital Cochin, 75679 Paris Cedex 14, France.

Endometriosis affects 6-10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans.

Copyright 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Arch Gynecol Obstet. 2010 Sep 7. [Epub ahead of print]

A systematic review: endometriosis presenting with ascites.

Gungor T, Kanat-Pektas M, Ozat M, Zayifoglu Karaca M.

Department of Gynecology, Dr. Zekai Tahir Burak Women Health Research and Education Hospital, Ankara, Turkey.

BACKGROUND: The present review aims to increase the awareness of the gynecologists by analyzing all the case reports which refer to endometriosis presenting either with only ascites or with massive ascites with pleural effusion.

METHODS: To conduct the present review, the CENTRAL (in the Cochrane Library, current issue), MEDLINE (Silver Platter, from 1950 to 2010), and EMBASE (from 1950 to 2010) electronic databases were searched. As a result, all the publications based on the keywords relating to the review topic were acquired.

RESULTS: Since the description of first case in 1954, endometriosis-related ascites was reported to occur in a total of 63 women who were aged between 19 and 51 years. Approximately 63.0% of the recruited women for whom ethnicity was specified were of African origin (29 out of 46). Of the 50 subjects with known obstetric history, 41 (82.0%) were nulliparous. Abdominal distention, anorexia/weight loss, abdominal pain, and menometrorrhagia were the most frequently encountered clinical symptoms, whereas pelvic mass was the most common physical finding. The serum concentrations of CA 125 were between 20 and 3,504 IU/ml for 19 women whose CA 125 levels were determined. Pleural effusion was also present in 38.1% of the reviewed subjects (24 out of 63). The clinical features of the women with endometriosis-related ascites and pleural effusion were similar to those of the women who had only endometriosis-related ascites.

CONCLUSION: Endometriosis-related ascites and/or pleural effusion refers to extensive disease with a high risk for recurrence which usually affects non-Caucasian, nulliparous women of reproductive age and leads to clinical symptoms resembling those of an ovarian malignancy. Therefore, clinicians should consider endometriosis in differential diagnosis of pelvic masses and also include endometriosis in diagnostic workup of ascites or pleural effusion.

J Assist Reprod Genet. 2010 Sep 7. [Epub ahead of print]

The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review.

Zanatta A, Rocha AM, Carvalho FM, Pereira RM, Taylor HS, Motta EL, Baracat EC, Serafini PC.

Huntington Medicina Reprodutiva, Av. República do Líbano, 529-Ibirapuera, 04501-000, São Paulo, SP, Brazil, alysson.zanatta@gmail.com.

PURPOSE: Endometriosis and its associated infertility have been the object of continuous research for over a century. To understand the molecular mechanisms underlying the disease, it has become necessary to determine the aspects of its etiology that are not explained by the retrograde menstruation theory. This could in turn elucidate how various clinical and surgical treatments might affect the evolution and remission of the disease.

METHODS: This review is focused on the most recent clinical and laboratory findings regarding the association of HOXA10 with endometriosis and infertility.

RESULT: The homebox (Hox/HOX) proteins are highly conserved transcription factors that determine segmental body identities in multiple species, including humans. Hoxa10/HOXA10 is directly involved in the embryogenesis of the uterus and embryo implantation via regulation of downstream genes. Cyclical endometrial expression of Hoxa10/HOXA10, with a peak of expression occurring during the window of implantation, is observed in the adult in response to estrogen and progesterone. Women with endometriosis do not demonstrate the expected mid-luteal rise of HOXA10 expression, which might partially explain the infertility observed in many of these patients. Recent studies also demonstrated HOXA10 expression in endometriotic foci outside the Müllerian tract.

CONCLUSIONS: Multiple lines of evidence suggest that the actions of the homeobox A10 (Hoxa10/HOXA10) gene could account for some aspects of endometriosis.

Abdom Imaging. 2010 Sep 5. [Epub ahead of print]

Deep rectosigmoid endometriosis: “mushroom cap” sign on T2-weighted MR imaging.

Yoon JH, Choi D, Jang KT, Kim CK, Kim H, Lee SJ, Chun HK, Lee WY, Yun SH.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.

PURPOSE: The purpose of this study is to evaluate the “mushroom cap” sign on T2-weighted MR imaging in patients with submucosal tumors in the rectosigmoid colon.

METHODS: From January 2001 to August 2009, 12 patients with four different diseases presenting or mimicking submucosal tumors in the rectosigmoid colon underwent colonic resection. All patients with deep endometriosis (n = 6), gastrointestinal stromal tumor (n = 4), metastasis from ovary cancer (n = 1), and carcinoid tumor (n = 1) had either an MRI of the rectum or pelvis before surgery. We evaluated the MRI findings and compared them with the macroscopic and microscopic observations in the resected specimens.

RESULTS: In all six cases of deep endometriosis, a characteristic “mushroom cap” shaped appearance was found on T2-weighted MR imaging. Heterogeneous low signal intensity of the hypertrophic muscularis propria, covered with high signal intensity of the mucosa and submucosa on T2-weighted MR images, looked like a “mushroom cap” with the pattern of intraluminal endophytic growth. In histological findings, deep endometriosis involved the submucosa (n = 4) or mucosa (n = 2). The “mushroom cap” sign was not present in any of the six other tumors.

CONCLUSION: The “mushroom cap” sign on T2-weighted MR imaging may be a characteristic sign for diagnosing deep rectosigmoid endometriosis.

Chin Med J (Engl). 2010 Aug;123(16):2190-4.

Increased expression of stathmin in eutopic endometrium of patients with endometriosis.

Li CY, Liu HY, Lang JH, Wang HQ, Fan XL.

Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

BACKGROUND: Stathmin was identified as an endometriosis-related protein by comparative proteomics in our previous study. As a microtubule-destabilizing factor, stathmin was shown to participate in the relay and integration of diverse intracellular signaling pathways involved in cell proliferation, differentiation, and many other cellular activities. To investigate whether stathmin is involved in the pathogenesis of endometriosis, we examined the expression of stathmin in eutopic endometrium of women with or without endometriosis.

METHODS: Eutopic endometrium samples were collected from thirty-six patients who were diagnosed as endometriosis and the nineteen age-matched patients who were confirmed to be free of endometriosis surgically and histologically. The expression of stathmin mRNA was detected by real-time PCR, and its protein was detected by Western blotting and immunohistochemistry.

RESULTS: Stathmin was overexpressed in eutopic endometrium of women with endometriosis detected by real-time PCR in mRNA levels and by Western blotting in protein levels, without significant difference between proliferative and secretory phase. Immunohistochemistry showed that stathmin protein was localized in both endometrial glandular and stromal cells throughout the menstrual cycle.

CONCLUSIONS: Stathmin is overexpressed in endometrium of patients with endometriosis and may play a role in the pathogenesis of endometriosis.

Chin Med J (Engl). 2010 Aug;123(16):2176-80.

Effect of interval after surgery on in vitro fertilization/ intracytoplasmic sperm injection outcomes in patients with stage III/IV endometriosis.

Huang XW, Qiao J, Xia EL, Ma YM, Wang Y.

Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University Third Hospital, Beijing 100191, China.

BACKGROUND: For patients with severe endometriosis, the spontaneous pregnancy rates have been reported to be near 0 due to extreme distortion of normal pelvic anatomy. Surgery is one of the treatment options; however, if patients failed to conceive after surgery, in vitro fertilization (IVF) is effective. The objective of this retrospective study was to determine the clinical characteristics of IVF/intracytoplasmic sperm injection (ICSI) in patients with stage III/IV endometriosis, and to determine the impact of the interval from surgery to IVF/ICSI on outcome.

METHODS: One hundred and sixty patients who were diagnosed with stage III/IV endometriosis underwent IVF/ICSI cycles between February 2004 and June 2009 were enrolled. The mean interval from surgery to IVF, number of oocytes retrieved, fertilization rate, implantation rate, embryos transferred, and good embryos transferred were compared between two age groups (<or=35 years and >35 years).

RESULTS: The mean interval from surgery to IVF was (37.9+/-28.9) months for the group<or=35 years of age and (57.6+/-39.7) months for the group>35 years of age. Twenty-five IVF/ICSI cycles (12.8%) were performed during the first year after surgery, and 34.9% IVF/ICSI cycles were performed 2 years after surgery. No significant differences existed between the two groups with respect to the fertilization rate, implantation rate, number of embryos transferred, number of good embryos, clinical pregnancy rates, live birth rates, and cumulative clinical pregnancy rates (P>0.05). The probability of cumulative clinical pregnancies was 75%, 50%, and 25% ((29.0+/-4.8), (61.0+/-7.6), and (120.0+/-16.9) months after surgery, respectively).

CONCLUSIONS: For infertile patients with stage III/IV endometriosis, the optimal time to conceive by IVF/ICSI is <2 years after surgery; nevertheless, most of the patients took a longer time to conceive.

Chin Med J (Engl). 2010 Jun;123(12):1610-1.

Appendiceal endometriosis differentially diagnosed from acute appendicitis.

Astroza G, Faundes V, Nanjarí R, Fleiderman M, Rodríguez C.

Servicio de Urgencia General, Hospital Ramón Barros Luco Trudeau, Santiago 8900085, Chile. gaeulufi@hotmail.com

J Int Med Res. 2010 May-Jun;38(3):987-93.

Differences in mitochondrial proteins in the eutopic endometrium of patients with adenomyosis and endometriosis identified using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

Ding X, Wang L, Ren Y, Zheng W.

Department of Gynaecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Adenomyosis and endometriosis have a similar pathogenesis; indeed, adenomyosis has been considered by some as a variant of endometriosis (‘internal endometriosis’). This study aimed to detect differences in mitochondrial proteins in eutopic endometrial samples from women with adenomyosis (n = 13) and endometriosis (n = 24), and from control patients (n = 29) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein chip technology. A total of 82 and 78 mitochondrial protein peaks were found in adenomyosis and endometriosis individuals, respectively. Of these, 14 were common to women with adenomyosis and women with endometriosis, although only one of these (mass-to-charge [m/z] ratio 3499) was significantly different between the adenomyosis and endometriosis groups. It is concluded that, compared with control patients, there are differences in the mitochondrial proteins isolated from the eutopic endometrium of patients with adenomyosis and those with endometriosis. Although the changes in mitochondrial proteins in eutopic endometrium from patients with adenomyosis and endometriosis were largely similar, significant differences were also detected. Further identification of these proteins and elucidation of the differences will help towards the differential diagnosis of adenomyosis and endometriosis and new therapeutic approaches.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Aug;35(8):896-902.

Activin and activin receptors in related gynecologic and obstetric diseases.

[Article in Chinese]

Li H, Huang F.

Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Activin is a member of the transforming growth factor-beta (TGF-beta) superfamily that result from the assembly of disulphide-linked betaA and betaB subunits. Activin receptors are transmembrane proteins and activin fulfils the biological function through the signal transduction of the receptor system. In recent years, many studies have suggested that activins have wide biological activities. It is the basic medium in regulating histiocytic function and plays a role in maintaining the normal function of cells. Moreover, abnormal expression of activin in the tissues of many gynecologic and obste-tric diseases,such as epithelial ovarian tumor, endometrial carcinoma, pre-eclampsia, polycystic ovary syndrome, endometriosis and so on affects the development of these diseases.

Fertil Steril. 2010 Sep 2. [Epub ahead of print]

A mutant single nucleotide polymorphism of follicle-stimulating hormone receptor is associated with a lower risk of endometriosis.

Wang HS, Cheng BH, Wu HM, Yen CF, Liu CT, Chao A, Wang TH.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Six hundred thirty-seven Taiwanese Chinese women including 300 patients with endometriosis and 337 controls without endometriosis were enrolled to investigate the association between nonsynonymous single nucleotide polymorphism of the FSH receptor gene and the risk of endometriosis. For the A/G polymorphism of FSH receptor gene (Asn680Ser), a univariate analysis for women with endometriosis demonstrated that both the GG genotype (680(Ser/Ser)) and GA genotype (680(Ser/Asn)) were associated with a significantly lower risk of endometriosis.

Copyright © 2010. Published by Elsevier Inc.

Fertil Steril. 2010 Sep 2. [Epub ahead of print]

Bronchobiliary fistula: a rare complication of hepatic endometriosis.

Schuld J, Justinger C, Wagner M, Bohle RM, Kollmar O, Schilling MK, Richter S.

Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of the Saarland, Homburg/Saar, Germany.

OBJECTIVE: To report the case and surgical therapy of a patient with bilioptysis after vaginal delivery, caused by bronchobiliary fistula. Histologic analysis revealed endometrial glands embedded in the decidual stroma neighboring the liver and the lung.

DESIGN: Case report.

SETTING: University hospital.

PATIENT(S): A 39-year-old patient, 7 days after vaginal delivery, without endometrial history.

INTERVENTION(S): Synchronous liver and lung resection of a bronchobiliary fistula by laparotomy and a transdiaphragmatic approach.

MAIN OUTCOME MEASURE(S): For complicated brochobiliary fistula caused by endometriosis, radical surgical treatment is mandatory.

RESULT(S): Histopathologic analyses confirmed the presence of clusters of endometrial glands embedded in the decidual stroma that were neighboring the liver, and perifistulous lung tissue was shown to contain biliary pigment absorbed by macrophages and their derivatives.

CONCLUSION(S): Hepatic and perihepatic endometriosis can cause a bronchobiliary fistula. Exacerbation of the symptoms can be triggered by high estrogen levels, physiologically dominating the last trimester. For such a rare case, surgery is mandatory.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Zhongguo Zhong Yao Za Zhi. 2010 Jun;35(12):1607-11.

Inhibitory effect on estrogen production and its influence on invasive ability of human endometrial cells of endometriosis by medicated serum of SLW.

[Article in Chinese]

Li A, Wang Y, Dong W, Xu X.

College of Chemistry and Bioengineering, Chongqing University of Technology, Chongqing 400050, China. ao_livip@tom.com

OBJECTIVE: To study the inhibitory effect of medicated serum of SLW on estrogen production and to approach on the key mechanism of SLW in inhibiting the invasion ability of endometrial cells of endometriosis.

METHOD: First, the model of eutopic primary cultured endometrial cells of endometriosis and hysteromyoma in vitro was successfully established. Taking that of endometrial cells of hysteromyoma as control, the secretion level of E2 of endometrial cells in the culture media supernatant at different time point with the treatment of high, middle and low dose of SLW serum was detected by electrochemiluminescence immunoassay, the activities of matrix metalloproteinase-2, 9 (MMP-2, 9) were detected by gelatinase zymography assay, and the expression of tissue inhibitor of metalloproteinase-1, 2 (TIMP-1, 2) protein was observed by immunofluorescence. After the optimal time for SLW to inhibit invasion ability of endometrial cells was identified based on time-effect relationship, another endometrial cells were divided into six groups: hysteromyoma endometrium group, eutopic endometrium of endometriosis group, eutopic endometrium of endometriosis + middle dose of SLW serum group, eutopic endometrium of endometriosis + middle dose of SLW serum + E2 group, eutopic endometrium of endometriosis + anastrozole serum group , and eutopic endometrium of endometriosis + E2 group. The activities of MMP-2, 9 and the expression of TIMP-1, 2 protein were detected according to the optimal time point.

RESULT: The secretion level of E2 of eutopic endometrium in endometriosis could be decreased by SLW, which showed the dependence of time and concentration. The result of gelatinase zymography assay and immunofluorescence respectively showed that along with the time the activities of MMP-2, 9 of eutopic endometrial cells of endometriosis were significantly higher than those of hysteromyoma at the same time point (P < 0.01). After 48 hours, with the treatment of middle dose of SLW serum, the activities of MMP-2, 9 of eutopic endometrial cells of endometriosis could be decreased (P < 0.01) while the expression of TIMP-1, 2 protein could be increased obviously (P < 0.01). The malignant invasion ability improved by SLW of eutopic endometrial cells of endometriosis was partly recruited by add-back E2 treatment. There was no significant difference in the activity of MMP-2 and the expression of TIMP-1, 2 protein between eutopic endometrium of endometriosis + middle dose of SLW serum + E2group and untreated group. The behavior of invasion of endometrial cells of endometriosis could be deteriorated treated by E2 as contrast to anastrozole, a specific aromatase inhibitor.

CONCLUSION: SLW could decrease the secretion of E2 so as to inhibit the invasion of the eutopic endometrial cells of endometriosis.

Hum Reprod. 2010 Nov;25(11):2851-8. Epub 2010 Sep 2.

Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model.

Katayama H, Katayama T, Uematsu K, Hiratsuka M, Kiyomura M, Shimizu Y, Sugita A, Ito M.

Department of Obstetrics & Gynecology, Graduate School of Medicine, Ehime University, Shitsukawa Toon, Ehime 791-0295, Japan.

BACKGROUND We aimed to establish an endometrial autograft model in rats that would allow for repetitive in vivo analyses of angiogenesis. Dienogest (DNG) is an orally active progestin used for the treatment of endometriosis. We investigated whether DNG would affect angiogenesis of the ectopic endometrium in our model. METHODS Mechanically isolated endometrial fragments were transplanted into dorsal skinfold chambers in rats. We analyzed the effect of DNG on angiogenesis of the ectopic endometrium on Days 0, 2, 4, 7, 10 and 14 after transplantation using intravital fluorescence microscopy. RESULTS The DNG-administered group showed significant suppression of angiogenesis of endometrial autografts, as indicated by the reduced size of the microvascular network and decreased microvessel density compared with those of control animals. The newly formed microvessels of the DNG-administered group showed consistently elevated diameters and centerline red blood cell velocity was decreased. Immunohistochemistry revealed a significant reduction in the level of perivascular α-smooth muscle actin within endometrial grafts of the DNG-administered group. CONCLUSIONS DNG inhibited angiogenesis of the ectopic endometrium, with confirmed structural changes in the microvessels.

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Aug;30(8):1874-6.

Effect of sinomenine on tumor necrosis factor-alpha and nuclear factor-kappaB in the heterotopic tissue in rats with endometriosis.

[Article in Chinese]

Yi H, Lu Y, Chen JK, DU BY, Liu AJ, Luo H.

Basic Medical School, Second Clinical Medical College, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, China. E-mail: yihuayi-027@163.com.

OBJECTIVE: To investigate the effect of sinomenine on the level of tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) and in the heterotopic tissue in rats with endometriosis.

METHODS: The rats with endometriosis were divided into sinomenine lavage group, blank control group, model group and dannazol group, and the levels of TNF-alpha and NF-kappaB in the heterotopic tissues of the rats were detected with immunohistochemistry.

RESULTS: Sinomenine lavage and dannazol treatment both significantly decreased the levels of levels of TNF-alpha and NF-kappaB in the heterotopic tissues of the rats as compared with the model group (P<0.05), and lesions were significantly smaller in sinomenine lavage group than in dannazol group.

CONCLUSION: Sinomenine can inhibit the production and activity of TNF-alpha and NF-kappaB to suppress the adhesion, implantation, infiltration and growth of the endometrial cells in the rat model of endometriosis.

J Control Release. 2010 Sep 8. [Epub ahead of print]

Route of administration-dependent anti-inflammatory effect of liposomal alendronate.

Haber E, Afergan E, Epstein H, Gutman D, Koroukhov N, Ben-David M, Schachter M, Golomb G.

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel.

Innate immunity and inflammation are of major importance in various pathological conditions. Intravenous (IV) and intraperitoneal (IP) liposomal alendronate (LA) treatments have been shown to deplete circulating monocytes and peritoneal macrophages resulting in the inhibition of restenosis and endometriosis (EM), respectively. Nevertheless, the correlation between the extent of circulating monocyte depletion and liposome biodistribution is unknown, and the route of administration-dependent bioactivity in restenosis and EM has not been determined. We found that, LA treatment resulted in a dose-response modified biodistribution following both IV and IP administrations. The biodistribution of high-dose LA (10mg/kg), but not that of the low-dose (1mg/kg), was similar in healthy and diseased animals. It is concluded that LA impedes its own elimination from the circulation by depleting circulating monocytes and/or inhibiting their endocytic activity, in a dose-dependent manner. Both IV and IP administration of LA mediated by the partial and transient depletion of circulating monocytes effected inhibition of restenosis. Inhibition of EM was effected only by IP administration, which depleted both intraperitoneal and circulating monocytes. Thus, EM should be considered as a local inflammatory condition with systemic manifestations as opposed to restenosis, a systemic inflammatory disease.

Copyright © 2010 Elsevier B.V. All rights reserved.

Int J Surg. 2010 Sep 6. [Epub ahead of print]

Scar endometriosis – A series of six patients.

Goel P, Devi L, Tandon R, Saha PK, Dalal A.

Department of Obstetrics and Gynaecology, Government Medical College and Hospital, Sector 32, Chandigarh 160030, India.

INTRODUCTION: Scar endometriosis is a rare form of extrapelvic endometriosis that is usually confused with other surgical or dermatological conditions leading to delay in diagnosis.

METHODS: We reviewed the case records of patients with the diagnosis of scar endometriosis seen in our hospital from January 1996 to December 2008.

RESULTS: We found six patients of scar endometriosis in 13 years making it one of the rare conditions. The median age of the patients was 32.5 years (range 28-37 years) and median interval from symptoms to treatment was 2 years (range 1-6 years). Four patients had first presented to either the surgery or dermatology physicians. Cyclic pain and swelling at local site was the most common presenting symptoms. All patients underwent wide excision of the mass with no recurrence of symptoms at a follow up ranging from 9 months to 12 years.

CONCLUSIONS: Increasing awareness of this condition among doctors can help in early diagnosis and treatment with gratifying results.

Copyright © 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Gastroenterol Clin Biol. 2010 Aug 27. [Epub ahead of print]

Endometriosis of the appendix presenting as acute appendicitis: Report of a case.

Maghrebi H, Khalfallah M, Bedoui R, Nouira R, Sabbegh Znaïdi N, Dziri C.

Department B of General Surgery, Charles Nicolle’s Hospital, Tunis, Tunisia.

Lancet. 2010 Aug 28;376(9742):730-8.

Endometriosis and infertility: pathophysiology and management.

de Ziegler D, Borghese B, Chapron C.

Université Paris Descartes, Centre Hospitalier Universitaire Cochin, Service de Gynécologie Obstétrique II et Médecine de la Reproduction, Paris, France. ddeziegler@orange.fr

Endometriosis and infertility are associated clinically. Medical and surgical treatments for endometriosis have different effects on a woman’s chances of conception, either spontaneously or via assisted reproductive technologies (ART). Medical treatments for endometriosis are contraceptive. Data, mostly uncontrolled, indicate that surgery at any stage of endometriosis enhances the chances of natural conception. Criteria for non-removal of endometriomas are: bilateral cysts, history of past surgery, and altered ovarian reserve. Fears that surgery can alter ovarian function that is already compromised sparked a rule of no surgery before ART. Exceptions to this guidance are pain, hydrosalpinges, and very large endometriomas. Medical treatment-eg, 3-6 months of gonadotropin-releasing hormone analogues-improves the outcome of ART. When age, ovarian reserve, and male and tubal status permit, surgery should be considered immediately so that time is dedicated to attempts to conceive naturally. In other cases, the preference is for administration of gonadotropin-releasing hormone analogues before ART, and no surgery beforehand. The strategy of early surgery, however, seems counterintuitive because of beliefs that milder non-surgical options should be offered first and surgery last (only if initial treatment attempts fail). Weighing up the relative advantages of surgery, medical treatment and ART are the foundations for a global approach to infertility associated with endometriosis.

Copyright 2010 Elsevier Ltd. All rights reserved.

Talanta. 2010 Sep 15;82(4):1581-7. Epub 2010 Aug 3.

Enzyme-linked immunosorbent assays for the synthetic steroid gestrinone.

Brun EM, Hernández-Albors A, Ventura R, Puchades R, Maquieira A.

Departamento de Química, Instituto de Reconocimiento Molecular y Desarrollo Tecnológico, Universidad Politécnica de Valencia, Camino de Vera s/n, 46071 Valencia, Spain.

Gestrinone is a synthetic steroid hormone with anti-estrogenic and anti-progesterone properties. It is used to treat endometriosis, shrink uterine fibroids and reduce menorrhagia; besides, it has been investigated for use as contraceptive. Also, due to its anabolic effects, it has been included in the banned list of performance enhanced drugs in sport. Polyclonal antibodies raised against bovine serum albumin coupled to gestrinone 3-carboxymethyloxime (3OCMO-G) were used to develop two highly sensitive and specific enzyme-linked immunosorbent assays for gestrinone. One of them, based on direct format, shows a detection limit (LD) of 0.09+/-0.03 ng L(-1). The second assay, hapten-protein coating format, can detect until (LD) 0.14+/-0.05 ng L(-1). Both immunoassays were also highly specific, showing negligible or no cross-reactivity to other anabolic steroids. The developed ELISAs detected lower amounts of gestrinone than those determined by the reference chromatographic HPLC/MS/MS methods. The direct format was applied to quantify this steroid in spiked human urine without sample pre-treatment, with recovery values between 76 and 122%.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

Reprod Biomed Online. 2010 Oct;21(4):581-5. Epub 2010 Jun 16.

Possible role of endometriosis in the aetiology of spontaneous miscarriage in patients with septate uterus.

Gergolet M, Gianaroli L, Suster NK, Verdenik I, Magli MC, Gordts S.

S.I.F.E.S. Slovene Institute for Fertility and Endoscopic Surgery, Nova Gorica, Slovenia. marco.gergolet@gmail.com

A recent study found a significant correlation between endometriosis and non-obstructive forms of Müllerian anomalies. Other studies described an increased miscarriage rate in patients with endometriosis. This study assessed the effect of endometriosis on pregnancy outcome in a group of patients with endometriosis and septate uterus. Spontaneously achieved pregnancies were taken into consideration. The outcome of 179 infertile women who underwent surgery for septate uterus was analysed in a retrospective study. Stage I or II endometriosis was found by laparoscopy in 36 patients. The pregnancy outcomes, before and after metroplasty, of the group of 36 patients with septum and endometriosis were compared with the pregnancy outcomes of 143 patients with septate uterus with no endometriosis. Before metroplasty the incidence of pregnancy loss was 67% in patients without endometriosis and 75% in patients with endometriosis and the difference was not significant. After metroplasty, no significant differences have been found between the two groups, suggesting that endometriosis could be an occasional finding not influencing pregnancy outcome.

2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Fertil Steril. 2010 Aug 26. [Epub ahead of print]

Evaluation of endometrial biomarkers for semi-invasive diagnosis of endometriosis.

Kyama CM, Mihalyi A, Gevaert O, Waelkens E, Simsa P, Van de Plas R, Meuleman C, De Moor B, D’Hooghe TM.

Leuven University Fertility Center, Leuven, Belgium; Experimental Gynecology Laboratory, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Leuven, Belgium; Division of Reproductive Health and Biology, Institute of Primate Research, Nairobi, Kenya.

OBJECTIVE: To test the hypothesis that specific proteins and peptides are expressed differentially in eutopic endometrium of women with and without endometriosis and at specific stages of the disease (minimal, mild, moderate, or severe) during the secretory phase.

DESIGN: Patients with endometriosis were compared with controls.

SETTING: University hospital.

PATIENT(S): A total of 29 patients during the secretory phase were selected for this study on the basis of cycle phase and presence or absence of endometriosis.

INTERVENTION(S): Endometriosis was confirmed laparoscopically and histologically in 19 patients with endometriosis of revised American Society for Reproductive Medicine stages (9 minimal-mild and 10 moderate-severe), and the presence of a normal pelvis was documented by laparoscopy in 10 controls.

MAIN OUTCOME MEASURE(S): Protein expression of endometrium was evaluated with use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The differential expression of protein mass peaks was analyzed with use of support vector machine algorithms and logistic regression models.

RESULT(S): Data preprocessing resulted in differential expression of 73, 30, and 131 mass peaks between controls and patients with endometriosis (all stages), with minimal-mild endometriosis, and with moderate-severe endometriosis, respectively. Endometriosis was diagnosed with high sensitivity (89.5%) and specificity (90%) with use of five down-regulated mass peaks (1.949 kDa, 5.183 kDa, 8.650 kDa, 8.659 kDa, and 13.910 kDa) obtained after support vector machine ranking and logistic regression classification. With use of a similar analysis, minimal-mild endometriosis was diagnosed with four mass peaks (two up-regulated: 35.956 kDa and 90.675 kDa and two down-regulated: 1.924 kDa and 2.504 kDa) with maximal sensitivity (100%) and specificity (100%). The 90.675-kDa and 35.956-kDa mass peaks were identified as T-plastin and annexin V, respectively.

CONCLUSION(S): Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis of secretory phase endometrium combined with bioinformatics puts forward a prospective panel of potential biomarkers with sensitivity of 100% and specificity of 100% for the diagnosis of minimal to mild endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Acta Obstet Gynecol Scand. 2010 Nov;89(11):1424-31. Epub 2010 Aug 30.

Unilateral renal agenesis and female genital tract pathologies.

Acién P, Acién M.

Service of Obstetrics and Gynecology, University Hospital of San Juan, Alicante, Spain.

Objectives. To analyze the gynecological pathologies and extragenital anomalies associated with unilateral renal agenesis (URA) and the possible origin of these congenital anomalies. Design. Retrospective case-control study. Setting. University Hospital. Population. This study included 276 women with genitourinary malformations who had undergone hysterosalpingography (and/or laparoscopy) and pyelography with images available for review. Methods. There were 60 cases of women diagnosed with genital malformations and congenital URA and 216 control cases of women with genital tract malformations and both kidneys present. All cases were categorized according to an embryological-clinical classification and the type of Müllerian malformation (American Society for Reproductive Medicine (ASRM) classification) and then compared by type for the presence of gynecological and extragenital pathologies. Main outcome measures. Genital malformations, endometriosis, leiomyomas and skeletal anomalies. Results. URA was generally associated with either agenesis of all of the derivatives of the urogenital ridge on the same side of the body, which were usually found on the left, or distal mesonephric anomalies such as a double uterus with a blind hemivagina or unilateral cervico-vaginal atresia, which were most frequently on the right. The uterine malformations that were most commonly seen in women with renal agenesis were bicornis-bicollis, didelphys and unicornuate uteri. Women with bicornuate or didelphys uteri and renal agenesis had more gynecological pathologies, such as endometriosis, than those with both kidneys present. Conclusions. URA and major uterine malformations are frequently related, and individuals with bicornuate or didelphys uteri have endometriosis more often than those without renal agenesis. Those malformations that seem to be caused by the absence or anomaly of a mesonephric duct lead to renal agenesis, ipsilateral vaginal anomalies (blind or atretic hemivagina) and failure of the induction function of the Wolffian ducts on the Müllerian ducts, causing uterine malformations.

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