J Magn Reson Imaging. 2010 May;31(5):1117-23.

Magnetic resonance imaging in the evaluation of (deep infiltrating) endometriosis: the value of diffusion-weighted imaging.

Busard MP, Mijatovic V, van Kuijk C, Pieters-van den Bos IC, Hompes PG, van Waesberghe JH.

Department of Radiology, Endometriosis Center VUMC, VU University Medical Center, Amsterdam, The Netherlands.

PURPOSE: To assess the value of magnetic resonance (MR) diffusion-weighted imaging (DWI) in the evaluation of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: In a prospective single-center study, DWI was added to the standard MRI protocol in 56 consecutive patients with known or suspected endometriosis. Endometriotic lesions as well as (functional) ovarian cysts were analyzed for location, size, and signal intensity on T1, T2, and DWI. Apparent diffusion coefficient (ADC) values were calculated using b-values of 50, 400, 800, and 1200 s/mm(2). Statistical analysis included the Spearman correlation coefficient, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: A total of 112 lesions (62 endometrial cysts and 48 DIE) were detected, 60 of which were large enough to analyze. Mean ADC values of endometrial cysts and functional ovarian cysts were 1.11 x 10(-3)/mm(2)/s and 2.14 x 10(-3)/mm(2)/s, respectively. Mean ADC values of DIE retrocervical, infiltrating the colon, and bladder were 0.70 x 10(-3)/mm(2)/s, 0.79 x 10(-3)/mm(2)/s, and 0.76 x 10(-3)/mm(2)/s, respectively. ADC values of DIE did not show a significant difference between varying pelvic locations (P = 0.63). CONCLUSION: Results of our study suggest that ADC values of DIE are consistently low, without significant difference between pelvic locations. Copyright 2010 Wiley-Liss, Inc.

Gynecol Obstet Fertil. 2010 Apr 27. [Epub ahead of print]

Aromatase and endometriosis: Myth or reality?

[Article in French]

Colette S, Donnez J.

 

Unité de gynécologie, faculté de médecine, université catholique de Louvain, 1200 Bruxelles, Belgique.

Gynecol Obstet Fertil. 2010 Apr 27. [Epub ahead of print]

Treatment of endometriosis by aromatase inhibitors: Efficacy and side effects.

[Article in French]

Racine AC, Legrand E, Lefebvre-Lacoeuille C, Hoppe E, Catala L, Sentilhes L, Descamps P.

Pôle de gynécologie-obstétrique, CHU d’Angers, 4, rue Larrey, 49933 Angers cedex 9, France.

The recent demonstration that aromatase is expressed at higher levels in endometriosis implants than in normal endometrium has led to pilot studies using inhibitor aromatasis in patients with endometriosis. We conducted a systematic review of the literature and studied the efficacy of aromatase inhibitors on endometriosis. There were seventeen studies (case reports/series) evaluating outcomes of aromatase inhibitors. Studies suggest that aromatase inhibitors alone or co-administered with progestins, oral contraceptives or gonadotrophin releasing hormone (GnRH) agonist could reduce pain and endometriosis. There is only one randomized controlled trial comparing aromatase inhibitor+GnRH agonist and GnRH agonist and one study with eighty patients. Side-effects profiles of aromatase inhibitor regimens are favorable; it does not appear a significant bone loss. Aromatase inhibitors seem to have a promising effect on endometriosis but randomized controlled trials are needed to prove their effects and their safety. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Eur J Obstet Gynecol Reprod Biol. 2010 Apr 27. [Epub ahead of print]

Luteinizing hormone beta-subunit gene (LHbeta) polymorphism in infertility and endometriosis-associated infertility.

Mafra FA, Bianco B, Christofolini DM, Souza AM, Zulli K, Barbosa CP.

Division of Gynecological Pathology and Human Reproduction, Department of Gynecology and Obstetrics, ABC School of Medicine, Avenida Príncipe de Gales 821, CEP: 09060-650, Santo André, SP, Brazil.

OBJECTIVE: To establish the frequency of LHbeta G1502A polymorphism in infertile women with endometriosis, infertile women without endometriosis and a control group. STUDY DESIGN: Case-control study including 110 infertile women with endometriosis, 84 infertile women without endometriosis and a control group consisting 209 healthy fertile women recruited from the ABC School of Medicine. The LHbeta G1502A polymorphism was studied by RPLP-PCR (restriction fragment length polymorphism-polymerase chain reaction). RESULTS: Genotypes GG, GA and AA of the LHbeta G1502A polymorphism presented frequencies of 54.6%, 31.8% and 13.6%, respectively, in the women with endometriosis (p=0.0398); of 52.4%, 38.1% and 9.5% (p=0.0123), respectively, in the infertile women without endometriosis; and of 68.9%, 21.5% and 9.6%, respectively, in the control group. In patients with minimal/mild endometriosis and moderate/severe endometriosis, the GG, GA and AA genotype frequencies were, respectively, 47.3%, 36.4% and 16.3% (p=0.0118); and 61.8%, 27.3% and 10.9% (p=0.5975). Considering the alleles, allele G was present in 70.5% of the patients with endometriosis, 71.4%% of the infertile women without endometriosis and in 79.7% of the controls, whereas allele A was present in 29.5%, 28.6% and 20.3%, respectively, in the infertile women with endometriosis (p=0.0121), infertile women without endometriosis (p=0.0409) and controls. Alleles G and A presented frequencies of 65.5% and 34.5% and 75.5% and 24.5%, respectively, in minimal/mild endometriosis (p=0.0026) and moderate/severe endometriosis (p=0.4062). CONCLUSION: The data suggest that LHbeta G1502A polymorphism may be involved in the predisposition to infertility and minimal/mild endometriosis-associated infertility, although endometriosis might be only a coincidental finding along with infertility. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Fertil Steril. 2010 Apr 27. [Epub ahead of print]

P(450)Arom induction in isolated control endometrial cells by peritoneal fluid from women with endometriosis.

Castro J, Torres M, Sovino H, Fuentes A, Boric MA, Johnson MC.

Institute of Maternal and Child Research, Faculty of Medicine, University of Chile, Santiago, Chile.

OBJECTIVE: To study the effect of peritoneal fluid from women with (PF-E) and without (PF-C) endometriosis on P(450)Arom expression in endometrial cells. DESIGN: Experimental study. SETTING: University research unit. PATIENT(S): Forty women of reproductive age with (n = 22) or without (control; n = 18) endometriosis. INTERVENTION(S): Peritoneal fluid and eutopic endometrial samples were obtained during surgery from women with (n = 13 and 9, respectively) and without (n = 4 and 14, respectively) endometriosis. MAIN OUTCOME MEASURE(S): Expression study for P(450)Arom, steroid factor 1 (SF-1), chicken ovalbumin upstream transcription factor I (COUP-TFI), and COUP-TFII messenger RNA (reverse transcriptase-polymerase chain reacion) and/or protein (immunoblot) in isolated endometrial epithelial cells transfected or not with expression vector containing SF-1, COUP-TFI, or COUP-TFII complementary DNAs. RESULT(S): Basal messenger RNA and/or protein expression of P(450)Arom and SF-1 were augmented in endometriosis, and that of COUP-TF was diminished. In control cells, (Bu)(2)cAMP and PF-E increased P(450)Arom and SF-1 expression (but not COUP-TF expression) in a dose-dependent way, an effect not observed with PF-C, adsorbed PF-E, or 10(-5) M indomethacin. Transfected cells confirmed these results. Any treatments modified the studied molecules in endometriosis cells. CONCLUSION(S): These data indicate that molecules contained in PF-E favor an estrogenic microenvironment, suggesting a role in the etiopathogenesis of endometriosis enabling the survival, maintenance, and growth of endometrial implants in the ectopic locations. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Am J Obstet Gynecol. 2010 Apr 27. [Epub ahead of print]

Racial and ethnic disparities in benign gynecologic conditions and associated surgeries.

Jacoby VL, Fujimoto VY, Giudice LC, Kuppermann M, Washington AE.

Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA.

Common gynecologic conditions and surgeries may vary significantly by race or ethnicity. Uterine fibroid tumors are more prevalent in black women, and black women may have larger, more numerous fibroid tumors that cause worse symptoms and greater myomectomy complications. Some, but not all, studies have found a higher prevalence of endometriosis among Asian women. Race and ethnicity are also associated with hysterectomy rate, route, and complications. Overall, the current literature has significant deficits in the identification of racial and ethnic disparities in the incidence of fibroid tumors, endometriosis, and hysterectomy. Further research is needed to better define racial and ethnic differences in these conditions and to examine the complex mechanisms that may result in associated health disparities. Copyright © 2010 Mosby, Inc. All rights reserved.

Hum Reprod. 2010 Apr 28. [Epub ahead of print]

Effect of endometriosis on the protein expression pattern of follicular fluid from patients submitted to controlled ovarian hyperstimulation for in vitro fertilization.

Lo Turco EG, Souza GH, Garcia JS, Ferreira CR, Eberlin MN, Bertolla RP.

Department of Surgery, Division of Urology, Human Reproduction Section, Sao Paulo Federal University, R Embau, 231, Sao Paulo, SP 04039-060 Brazil.

BACKGROUND The aim of this study was to evaluate protein expression profile and quantify the proteins present in follicular fluid (FF) samples from women with endometriosis and pregnant women without endometriosis. METHODS A prospective case-control study was carried out including women with Stage III or IV endometriosis (Group I) and pregnant women without endometriosis (Group II), both at the maximum age of 35 years. Women were submitted to controlled ovarian stimulation for in vitro fertilization, and FF was collected after ultrasound-guided ovarian aspiration. FF from both ovaries was pooled, and patient samples were pooled according to Group I or II. Pooled protein samples were separated and analyzed by MudPIT (multidimensional protein identification technology followed by Expression(E) and label-free quantification with ProteinLynxGlobalServer 2.4v, Identity(E) and Expression(E) software). RESULTS A total of 416 proteins or randomic sequence were identified, 62 proteins differentially expressed between Groups I and II. One (1.6%) was expressed at a higher level and 36 (58.1%) were uniquely expressed in Group I, whereas 8 (12.9%) were expressed at a higher level and 17 (27.4%) were uniquely expressed in Group II. Of all these, 15 (24.2%) are related to binding, 1 (1.6%) to immune response, 8 (12.9%) to cell division, 3 (4.8%) to cellular metabolism, 16 (25.8%) to general function and 19 (30.6%) do not yet present an identified function. CONCLUSIONS Protein expression profiles of patients with and without endometriosis identified at least 64 proteins differentially expressed, which may be related to the physiopathology of endometriosis. These proteins may additionally be useful in determining potential biomarkers for diagnostics, as well as for therapeutic intervention in women with infertility due to endometriosis.

J Clin Endocrinol Metab. 2010 Apr 28. [Epub ahead of print]

Simvastatin Induces Apoptosis and Alters Cytoskeleton in Endometrial Stromal Cells.

Sokalska A, Wong DH, Cress A, Piotrowski PC, Rzepczynska I, Villanueva J, Duleba AJ.

Division of Reproductive Endocrinology and Infertility (A.S., D.H.W., A.C., J.V., A.J.D.), Department of Obstetrics and Gynecology, University of California Davis, Sacramento, California 95817; Division of Infertility and Reproductive Endocrinology (A.S., I.R.), Department of Gynecology, Obstetrics and Gynecological Oncology, Karol Marcinkowski University of Medical Sciences, 61-701 Poznan, Poland; and Polish Academy of Sciences, Medical Research Center (P.C.P.), 02-106 Warsaw, Poland.

Context: Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase, with antimitotic, antioxidant, antiinflammatory, and immunomodulatory properties. Recent studies have shown that statins reduce the growth of human endometrial stromal (HES) cells and protect from the development of endometriosis in animal models. Objectives: The present study was conducted to evaluate the effects of simvastatin on apoptosis and cytoskeleton of HES cells. Design and Setting: In vitro experiments were performed in the university research laboratory. Patients: HES cells were obtained from endometrial biopsies collected from nine subjects in the proliferative phase of their menstrual cycle. Main Outcome Measures: The effect of simvastatin (10 and 30 muM) and/or geranylgeranyl pyrophosphate (GGPP, 30 muM) on caspase 3 and 7 activity, DNA fragmentation, and HES cell morphology was evaluated. Results: Simvastatin induced significant time- and concentration-dependent apoptotic effects on HES cells as determined by increased activity of executioner caspases and DNA fragmentation. Simvastatin also caused profound alterations in HES cell morphology and F-actin cytoskeleton. This effect was abrogated by geranylgeranyl pyrophosphate, an important product of the mevalonate pathway. Conclusions: Simvastatin induces apoptosis and disruption of the cytoskeleton of HES cells by reducing isoprenylation in cultures of human endometrial stroma. The present findings may lead to the development of novel treatments for endometriosis involving statins.

G Chir. 2010 Mar;31(3):100-2.

Occlusione intestinale acuta da endometriosi ileale trattata in laparoscopia. Case report.

[Article in Italian]

Feroci F, De Prizio M, Kröning KC, Moraldi L, Scatizzi M.

Verisione italiana Riassunto: Occlusione intestinale acuta da endometriosi ileale trattata in laparoscopia. Case report. F. Feroci, M. De Prizio, K.C. Kröning, L. Moraldi, M. Scatizzi Il 10-20% delle donne in età fertile è affetto da endometriosi. La sua localizzazione ileale, solitamente nel tratto terminale, è solo del 7%. L’occlusione intestinale si verifica in non più dello 0,15% delle pazienti affette da endometriosi. Presentiamo un caso di occlusione intestinale acuta da endometriosi ileale, in una donna di 39 anni, in cui l’approccio diagnostico e terapeutico è stato condotto per via laparoscopico. English version Summary: Laparoscopic approach in acute bowel obstruction due to ileal endometriosis: case report. F. Feroci, M. De Prizio, K.C. Kröning, L. Moraldi, M. Scatizzi Endometriosis affects 10-20% of fertile women, and in 3-37% of them it extends to the bowel. Its location, in the ileal tract of the bowel, usually the end-part, is only the 7%; and the occurrence of intestinal obstruction is no more than 0.15% of patients affected by endometriosis. We present a case of acute bowel obstruction due to ileal endometriosis in a 39 years woman, diagnosed and treated by laparoscopic approach.

Curr Pain Headache Rep. 2010 Feb;14(1):22-32.

Interventional therapies for controlling pelvic pain: what is the evidence?

Green IC, Cohen SL, Finkenzeller D, Christo PJ.

Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21287, USA. igreen5@jhmi.edu

Chronic pelvic pain (CPP) has many potential causes and is often a complex disorder with multiple contributing etiologies. The evaluation and treatment of women with CPP often requires a multidimensional approach. The treatment of CPP consists of two approaches: 1) treatment of pain itself or global treatment, and 2) treatment of disease-specific etiologies. Most often, treatment requires a combination of both approaches. This article reviews recent literature in the global treatment of CPP, including pharmacologic, psychotherapy, and neuroablative, as well as specific interventions for endometriosis, interstitial cystitis, pelvic adhesive disease, adenomyosis, and pelvic venous congestion.

Neuro Endocrinol Lett. 2010 Apr 29;31(2):193-197. [Epub ahead of print]

Role of decidua in trophoblastic invasion.

Cohen M, Wuillemin C, Irion O, Bischof P.

Laboratoire d’Hormonologie, Department of Gynaecology and Obstetrics, Geneva, Switzerland. marie.cohen@hcuge.ch.

OBJECTIVE: Proliferation, migration and invasion of trophoblastic cells into the maternal endometrium are essential steps in human embryo implantation and placentation. Trophoblast invasion is normally limited in time, only during first and early second trimester of pregnancy, and in space, limited to the endometrium and the proximal third of myometrium. This process requires among other factors: the metalloproteinases (MMP) 2 and 9. Shallow trophoblast invasion is associated with pathologies including preeclampsia and fetal growth restriction whereas unlimited invasion is associated with hydatidiform moles and choriocarcinomas. METHODS: In order to understand the role of decidua in this endometrial invasion by trophoblastic cells, we have developed a model of coculture of decidual and cytotrophoblastic cells in which we can evaluate the effect of each partner on the proliferative and invasive properties of the other. RESULTS: Surprisingly, decidual cells secrete highest levels of MMPs, and their invasive potential seems to be increased in presence of cytotrophoblast (CTB). In contrast, invasive properties of CTB are not modified by decidual cells. CONCLUSION: CTB secrete factors that favour invasion whereas decidua seems not to play a major role in regulating CTB invasion in vitro. Moreover, it is interesting to note that decidual cells could have potent invasive capacity which could explain, at least in part, endometriosis.

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Apr;30(4):859-62.

Inhibitory effect of short hairpin RNA targeting survivin gene on human ectopic endometrial cells.

[Article in Chinese]

Peng DX, He YL, Qiu LW.

Department of Gynecology and Obstetrics, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. E-mail: pdx@ fimmu.com.

OBJECTIVE: To construct a lentiviral expression vector for short hairpin RNA (shRNA) of human survivin gene, and assess its gene silencing effect in human ectopic endometrial cells. METHODS: Human survivin gene shRNA sequence was designed using a software available on-line. The synthesized shRNA sequence was cloned into the pGCL-GFP vector to construct LV-survivin shRNA, which was confirmed by PCR and DNA sequence analysis. The packaging 293T cells were cotransfected with LV-survivin shRNA, pHelper 1.0 and pHelper 2.0, and the titer of the lentivirus was determined. The recombinant lentivirus was injected into human ectopic endometrial cells and the survivin mRNA expression was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in comparison with that in the non-transfected and blank vector-transfected human ectopic endometrial cells. RESULTS: PCR analysis and DNA sequencing confirmed correct insertion of the shRNA sequence into the lentiviral vector. The titer of virus after packaging was 8×10(8) U/ml. Survivin mRNA expression in human ectopic endometrial cells transfected by LV-survivin shRNA was significantly inhibited compared with those in the non-transfected and empty vector transfected human ectopic endometrial cells (P<0.01), and no significant difference was found between the latter two groups. CONCLUISON: The lentiviral shRNA vector of survivin gene constructed can effectively inhibit the expression of survivin gene in human ectopic endometrial cells in vitro. This vector provides a tool for investigating the role of survivin gene in the occurrence and progression of endometriosis and for searching new therapeutic targets.

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Apr;30(4):851-4.

Establishment of serum peptidome pattern-based diagnostic model of endometriosis.

[Article in Chinese]

Li LA, Wang N, Liang TT, Li AL, Li YL.

General Hospital of PLA, Beijing 100853, China.

OBJECTIVE: To establish a diagnostic model of endometriosis by analyzing serum peptidome patterns in patients with endometriosis using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). METHODS: Serum samples from 21 endometriosis patients and 29 healthy control subjects were analyzed using MALDI-TOF-MS and Clinprotools 2.0 software to establish the diagnostic model of endometriosis, which was validated using the serum samples from 10 endometriosis patients and 15 healthy controls. RESULTS: Eighteen statistically significant peptide peaks were obtained with the m/z value ranging from 1 000 to 10 000 (P<0.01). Among the peaks, 12 were down-regulated and 6 up-regulated. The sensitivity and specificity of the model was 90.9% and 100.0%, respectively, with a diagnostic accuracy of 96.2%. CONCLUISON: This model shows the feasibility of using MALDI-TOF-MS and Clinprotools software to identify the biomarkers of endometriosis.

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Apr;30(4):750-4.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in human and nude mouse ectopic endometrium and the effect of estrogen and progestin on their expression.

[Article in Chinese]

Lou YH, Guo XH, Jiang H, Xia YF.

Department of Gynecology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China. E-mail: lyh7497@163.com.

OBJECTIVE: To explore the roles of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the pathogenesis of endometriosis and the effects of estrogen and progestin on their expression. METHODS: Immunohistochemistry and RT-PCR were employed to detect the expression of MMP-1 and TIMP-1 in the ectopic tissues of 35 patients with endometriosis, 22 eutopic endometrium tissues from women with endometriosis and 28 normal controls. Fifty-nine nude mice were injected with human late secretory endometrial chippings and randomized into estrogen group, progestin group, estrogen-progestin group and control group with corresponding treatments. The implantation rates and graft morphology were observed and MMP-1 and TIMP-1 expressions in the grafts detected by immunohistochemistry. RESULTS: Typical endometrial glands and stroma were observed in all the groups with comparable implantation rates. The administration of progestin was associated with multiple peritoneal implantation sites and significantly larger implants. The transplanted endometria showed proliferative or secretory changes with estrogen or progestin administration. MMP-1 expression significantly increased and TIMP-1 expression decreased with increased MMP-1/TIMP-1 ratio in human and nude mouse ectopic endometria in comparison with those in normal endometria (P<0.05, P<0.01). MMP-1 expression was higher in estrogen and estrogen-progestin groups than in the control group, and was lower in the 3 sexual hormone-treated groups than in the control group. MMP-1 mRNA expression in the eutopic endometrium was significantly higher than that in the normal endometria. CONCLUSION: Progestrin can not inhibit MMP-1 expression or the effect of estrogen on ectopic endometrium known as progestin resistance. The high expression of MMP-1 and low expression of TIMP-1 in endometriotic tissues confer strong invasiveness of ectopic endometrial tissue, especially in eutopic endometrial tissue, and may play an important role in the pathogenesis of endometriosis.

Environ Health Perspect. 2010 Apr 27. [Epub ahead of print]

Non-Dioxin-Like Polychlorinated Biphenyls and Risk of Endometriosis.

Trabert B, De Roos AJ, Schwartz SM, Peters U, Scholes D, Barr DB, Holt VL.

National Cancer Institute.

BACKGROUND: Endometriosis, a gynecologic disorder affecting 8-10% of US reproductive age women, is defined as the presence of endometrial tissue outside the uterus and is linked to pelvic pain and infertility. Environmental contaminants, including polychlorinated biphenyls (PCBs), are hypothesized to contribute to endometriosis risk through effects on steroid hormones. OBJECTIVE: We evaluated serum concentrations of certain non-coplanar PCBs, which have no- or only weak dioxin-like properties, as risk factors for endometriosis. METHODS: In a case-control study of Group Health enrollees in western Washington state twenty PCB congeners were measured in serum from surgically confirmed endometriosis cases newly diagnosed between 1996 and 2001 (n=251), and age and reference year matched female controls (n=538). RESULTS: Summed and estrogenic PCB concentrations were not associated with endometriosis risk [summed: odds ratio (OR) = 1.3 (95% confidence interval (CI) = 0.8, 2.2); estrogenic: OR = 1.1 (95% CI = 0.8, 1.4)]. Although several congener-specific ORs were statistically above or below the null, [PCB 170: third vs. lowest: OR = 0.5 (95% CI = 0.3, 0.9); PCB 196: third vs. lowest: OR = 0.4 (95% CI = 0.2, 0.7); PCB 201: second vs. lowest: OR = 0.5 (95% CI = 0.3, 0.8), third vs. lowest: OR = 0.4 (95% CI = 0.2, 0.7)] there were no overall consistent patterns of endometriosis risk. CONCLUSIONS: Taken in context with other North American studies, our findings suggest that non-coplanar PCB concentrations consistent within the range of exposure currently observed in western Washington State do not contribute meaningfully to endometriosis risk.

Arch Gynecol Obstet. 2010 Apr 27. [Epub ahead of print]

Intercellular adhesion molecule-1 (ICAM-1) gene polymorphism and endometriosis in northern Iran.

Aghajanpour L, Mashayekhi F, Rajaei F.

Department of Biology, Faculty of Sciences, University of Guilan, 1914, Rasht, Iran.

PURPOSE: Endometriosis is a chronic pleomorphic disorder with pelvic or systemic manifestations, and is characterized by the presence of endometrial glands and stroma. It is generally considered to involve genetic, environmental, immunological, angiogenic and endocrine processes. The aim of this study was to evaluate the frequency of intercellular adhesion molecule-1 (ICAM-1) polymorphism at position 241 in exon 4 of the ICAM-1 gene in patients with endometriosis and in healthy control subjects in northern Iran. METHODS: A total of 84 unrelated patients and 120 consecutive unrelated healthy controls from the northern Iran were recruited for the study. ICAM-1 codon 241 polymorphism analysis was performed by two independent PCR reactions, based on the two set of oligoprimers specific for Arg (AGG) or Gly (GGG) coding sequence, respectively. RESULTS: Genotype distributions of ICAM-1 gene show significant difference between patients and controls. The R241 allele was detected in 23% of endometriosis patients and in 6% of controls (P = 0.001; odds ratio 4.67; 95% confidence interval 1.81-12.07). Comparing patients with different stage of endometriosis, we found a trend to higher frequency of R241 in patients with stage IV (65 vs 6%; P < 0.0001). CONCLUSION: Our results suggest that ICAM-1 polymorphism in codon 241 is associated with the development of endometriosis susceptibility in the population of northern Iran.

Arch Gynecol Obstet. 2010 Apr 27. [Epub ahead of print]

Cutaneous endometriosis: review of 15 cases diagnosed at a single institution.

Fernández-Aceñero MJ, Córdova S.

Department of Surgical Pathology, Fundación Jiménez Díaz, Avda Reyes Católicos 2, 28040, Madrid, Spain, mgg10167@gmail.com.

INTRODUCTION: Endometriosis is a disease characterized by the presence of endometrial glands and/or stroma outside the uterine cavity. The main location is the ovary, but it has been described in many other extragenital locations, mainly the intestinal wall and the epiplon, but also the lung and the skin. MATERIALS AND METHODS: In this report we review the cases of cutaneous endometriosis diagnosed at Fundación Jiménez Díaz in Madrid in the last decade. RESULTS: In this time period we have seen 376 specimens with endometriosis, 330 from ovarian origin, 11 cases involving the appendix, 3 affecting the uterine cervix, 3 involving the epiplon, 1 in an ileal lymph node, 5 in the small intestine, 6 in the large intestine, 2 affecting the lung (with recurring pneumothorax) and 15 involving the skin. CONCLUSION: We comment on the features of the patients with cutaneous endometriosis and their gynaecological history.

Zhonghua Fu Chan Ke Za Zhi. 2010 Feb;45(2):93-8.

Clinico-pathologic characteristics of posterior deeply infiltrating endometriosis lesions, pain symptoms and its treatment using laparoscopic surgery.

[Article in Chinese]

Dai Y, Leng JH, Lang JH, Liu ZF, Li XY, Wang YY.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

OBJECTIVE: To investigate the characteristics of the anatomical distribution of posterior deeply infiltrating endometriosis (PDIE) lesions, pain symptoms and effects of laparoscopic surgery. METHODS: Clinical data of 176 PDIE patients with laparoscopically diagnosed and histologically confirmed were analyzed and compared with data of 179 cases with non-PDIE. According to the invasion of rectum or vaginal fornix, 176 PDIE cases were divided into three groups: simple (144 cases), fornix (18 cases) or rectum group (14 cases). RESULTS: Compared with the non-PDIE patients, the risk of pain symptoms in PDIE patients were significantly increased, OR for dysmenorrhea, chronic pelvic pain, deep dyspareunia, dyschezia were 6.73 (95%CI, 3.66 – 12.40), 1.90 (95%CI, 1.17 – 3.05), 3.09 (95%CI, 1.94 – 4.92) and 4.90 (95%CI, 2.07 – 8.11), respectively (all P < 0.05). The highest incidence of dyschezia was observed in rectum group (50.0%, P < 0.05), while deep dyspareunia in fornix group (72.2%, P < 0.05). The longest operative duration (82 +/- 31) minutes and the postoperative hospitalization (7.7 +/- 2.1) days were observed in rectum group (P < 0.01). The median pain relief time was 56 months in the patients with complete excision of PDIE lesions, which was significantly longer than that in patients with incomplete excision (25 months, P < 0.01). Multivariate analysis demonstrated that only incomplete excision of PDIE lesions was the risk factor for shorter pain relief time (P < 0.05). CONCLUSION: Conservative laparoscopic surgery may effectively relieve pelvic pain symptoms in patients with PDIE, while incomplete excision of PDIE lesions was the only significant predictor of shorter pain relief time.

Clin Exp Obstet Gynecol. 2010;37(1):19-20.

Endometriosis: a possible cause of right shoulder pain.

Seoud AA, Saleh MM, Yassin AH.

Department of Obstetrics and Gynaecology, Rochdale Infirmary, Whitehall Street, Rochdale, Lancashire, UK. seoud85@hotmail.com

Although endometriosis is a common condition it can present with a wide range of symptoms. We report a case of chronic right hypochondrial and shoulder pain which proved to be due to endometriosis.

J Pak Med Assoc. 2010 Apr;60(4):257-60.

Chronic pelvic pain: a dilemma.

Santosh A, Liaquat HB, Fatima N, Liaquat S, Anwar MA.

Department of Obstetrics & Gynaecology, Karachi, Pakistan.

OBJECTIVE: To determine the frequency of gynaecological factors leading to chronic pelvic pain via diagnostic laparoscopy. To see the association of these factors with demographic variables of the patients. METHODS: Fifty patients underwent the study over a period of 1.5 years from 1st January 2007 to 30th June 2008 at the Department of Gynaecology and Obstetrics, Jinnah Postgraduate Medical Centre, Karachi. All patients fulfilling inclusion criteria were admitted via Out Patient Department, underwent initial investigations and later Diagnostic Laparoscopy. RESULTS: Twenty nine patients were in 25-34 years age group and had parity between 1 to 5, and 56% of the patients belonged to poor socioeconomic and educational status. Pelvic Inflammatory disease was the most frequently found gynaecological etiology of Chronic Pelvic Pain (20% of patients) followed by endometriosis (14%) and Pelvic Congestion Syndrome (12%). CONCLUSION: Chronic Pelvic Pain is a common problem of women with multifactorial etiology. Laparoscopy was found be very effective in diagnosing the various gynaecological causes of the disorder.

Fertil Steril. 2010 Apr 21. [Epub ahead of print]

Rescue radical trachelectomy for preservation of fertility in benign disease.

Del Priore G, Klapper AS, Gurshumov E, Vargas MM, Ungar L, Smith JR.

Department of Obstetrics and Gynecology, New York Downtown Hospital, New York, New York.

OBJECTIVES: To report a series of patients treated with modified radical abdominal trachelectomy to preserve fertility in benign disease that would normally result in hysterectomy. DESIGN: We reviewed all cases of radical abdominal trachelectomy performed for nonneoplastic indications. PATIENT(S): Of the >160 radical abdominal trachelectomies we performed, four cases were performed for benign indications. One patient had a 10-year history of progressive endometriosis with worsening hydronephrosis, failed medical therapy, and infertility. Two myomectomy patients had intraoperative consultation and a third had preoperative consultation for large lower segment/cervical myomas with conversion to trachelectomy rather than hysterectomy. INTERVENTION(S): Modified radical trachelectomy was successfully completed in all patients. MAIN OUTCOME MEASURE(S): We measured the successful completion of the surgery without hysterectomy, complications, and follow-up. RESULT(S): Hysterectomy was avoided in all patients, and all resumed normal menses. There were no intraoperative or postoperative complications. One required hysterectomy for recurrence 1 year later, and the remainder were symptom free at 1-5 years of follow-up. CONCLUSION(S): Although traditionally performed with cervical cancer, radical abdominal trachelectomy can be modified to preserve fertility for benign indications that would otherwise require hysterectomy. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Bioorg Med Chem. 2010 Mar 29. [Epub ahead of print]

Novel estrone mimetics with high 17beta-HSD1 inhibitory activity.

Oster A, Klein T, Werth R, Kruchten P, Bey E, Negri M, Marchais-Oberwinkler S, Frotscher M, Hartmann RW.

Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), PO Box 15 11 50, D-66041 Saarbrücken, Germany.

17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyzes the reduction of estrone into estradiol, which is the most potent estrogen in humans. Lowering intracellular estradiol concentration by inhibition of this enzyme is a promising new option for the treatment of estrogen-dependent diseases like breast cancer and endometriosis. Combination of ligand- and structure-based design resulted in heterocyclic substituted biphenylols and their aza-analogs as new 17beta-HSD1 inhibitors. The design was based on mimicking estrone, especially focusing on the imitation of the D-ring keto group with (substituted) heterocycles. Molecular docking provided insights into plausible protein-ligand interactions for this class of compounds. The most promising compound 12 showed an inhibitory activity in the high nanomolar range and very low affinity for the estrogen receptors alpha and beta. Thus, compound 12 is a novel tool for the elucidation of the pharmacological relevance of 17beta-HSD1 and might be a lead for the treatment of estrogen-dependent diseases. Copyright © 2010 Elsevier Ltd. All rights reserved.

Fertil Steril. 2010 Apr 21. [Epub ahead of print]

Possible roles of oxytocin receptor and vasopressin-1alpha receptor in the pathomechanism of dysperistalsis and dysmenorrhea in patients with adenomyosis uteri.

Mechsner S, Grum B, Gericke C, Loddenkemper C, Dudenhausen JW, Ebert AD.

Endometriosis Research Center, Department of Obstetrics and Gynecology, Campus Benjamin Franklin, Berlin, Germany.

OBJECTIVE: To investigate the expression of oxytocin (OTR) and/or vasopressin (VP1alphaR) receptor in patients with and without adenomyosis uteri. DESIGN: Retrospective nonrandomized study. SETTING: University hospital endometriosis research center. PATIENT(S): Forty patients with histologically proven adenomyosis and 40 patients without adenomyosis who had undergone hysterectomy for dysmenorrhea, bleeding disorders, and fibroids. INTERVENTION(S): Immunohistochemical examination of both OTR and VP1alphaR expression in endometrium, myometrium, and adenomyotic lesions, and identification of smooth muscle cells using antibodies against OTR, VP1alphaR, and smooth muscle actin (sm-actin). MAIN OUTCOME MEASURE(S): The immunoreactive score (IRS) was used for expression of OTR, VP1alphaR, and sm-actin. RESULT(S): Expression of OTR in epithelial cells of adenomyotic lesions and surrounding myometrial cells was detectable. VP1alphaR was expressed only in myometrial cells and blood vessels. Using a specific anti-sm-actin antibody, another spindle cell population was characterized to represent smooth muscle cells which are in direct contact with the adenomyotic stroma. Compared with the unaffected myometrium, the surrounding adenomyosis-associated myometrium overexpressed OTR and showed changes in morphology. In the uteri of patients with adenomyosis, the junctional zone was often seen to be quite fissured. CONCLUSION(S): In addition to the specific expression of VP1alphaR, OTR expression and morphologic changes in the myometrial architecture of uteri having adenomyosis support the hypothesis that dysperistalsis plays an essential role in the development of endometriosis and dysmenorrhea. In the near future, specific inhibition of this receptor might yield a promising treatment for therapy. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Biol Reprod. 2010 Apr 21. [Epub ahead of print]

Neutralizing TIMP1 Restores Fecundity in a Rat Model of Endometriosis and Treating Control Rats with TIMP1 Causes Anomalies in Ovarian Function and Embryo Development.

Stilley JA, Birt JA, Nagel SC, Sutovsky M, Sutovsky P, Sharpe-Timms KL.

Human and rat endometriotic lesions synthesize and secrete tissue inhibitor of metalloproteinase 1 (TIMP1). More TIMP1 localizes in the ovarian theca in an established rat model for endometriosis (Endo) when compared to surgical controls (Sham). We hypothesized that endometriotic TIMP1 secreted into peritoneal fluid (PF) negatively impacts ovarian function and embryogenesis by altering the balance of matrix metalloproteinases (MMPs) and TIMPs. Three experiments were performed modulating TIMP1 in vitro and in vivo to investigate ovarian and embryonic anomalies. The first experiment demonstrated control embryos treated in vitro with endometriotic PF concentrations of TIMP1 developed abnormally. In the second experiment where TIMP1 was modulated in vivo, TIMP1 treated Sham rats had fewer zygotes, ovarian follicles and corpora lutea (CLs) and poorer embryo quality and development, analogous to Endo rats. Importantly, Endo rats treated with a TIMP1 function blocking antibody had zygote, follicle and CL numbers and embryo quality similar to Sham rats. More TIMP1 inhibitory activity was found in ovaries from Endo and TIMP1 treated Sham rats than in ovaries from Sham or TIMP1 antibody-treated Endo rats. In experiment three, control rats (no surgery) treated with Endo PF had fewer follicles and CLs and increased TIMP1 localization in the ovarian theca whereas Endo PF stripped of TIMP1 or Sham PF had no effect, providing further evidence that endometriotic TIMP1 sequesters in the ovary and inhibits MMPs necessary for ovulation. Collectively, these results showed that excessive TIMP1 was deleterious to ovulation and embryo development. Thus, novel TIMP1 modulating therapies may be developed to alleviate infertility in women with endometriosis.

J Clin Endocrinol Metab. 2010 Apr 21. [Epub ahead of print]

Impaired Down-Regulation of E-Cadherin and {beta}-Catenin Protein Expression in Endometrial Epithelial Cells in the Mid-Secretory Endometrium of Infertile Patients with Endometriosis.

Matsuzaki S, Darcha C, Maleysson E, Canis M, Mage G.

Centre Hospitalier Universitaire Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction (S.M., E.M., M.C., G.M.); and Service d’Anatomie et Cytologie Pathologiques (C.D.), 63058 Clermont-Ferrand, France.

Context: Only a few, small, human studies on E-cadherin and beta-catenin expression in normal cycling human endometrium have been reported. It remains unclear whether expression of these molecules might be altered in the endometrium of infertile patients with endometriosis. Objectives: The aim of the present study was to investigate E-cadherin and beta-catenin expression in the endometrium of infertile patients with endometriosis, those with uterine fibromas, and patients with unexplained infertility. Design: Expression levels of E-cadherin and beta-catenin mRNA and/or protein in the endometrium of infertile patients with endometriosis (n = 151), those with uterine fibromas (n = 41), patients with unexplained infertility (n = 9), as well as healthy fertile controls (n = 57) were measured. This study utilized laser capture microdissection, real-time RT-PCR, and immunohistochemistry. Results: No significant differences in E-cadherin or beta-catenin mRNA expression in microdissected epithelial cells were observed among the different groups throughout the menstrual cycle. However, very low or no protein expression of E-cadherin, total beta-catenin, or dephosphorylated beta-catenin in luminal and glandular epithelial cells was detected in the mid-secretory endometrium of healthy fertile controls. E-cadherin, total beta-catenin, and dephosphorylated beta-catenin protein expression in the mid-secretory endometrium of infertile patients with endometriosis or unexplained infertility was significantly higher compared to that of healthy fertile controls in both luminal and glandular epithelial cells. Conclusions: These findings suggest that impaired down-regulation of E-cadherin and beta-catenin protein expression, along with Wnt/beta-catenin signaling pathway activation during the window of implantation, might be one of the potential molecular mechanisms of infertility in patients with endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2010 Apr 19. [Epub ahead of print]

Adenomyosis has no adverse effects on IVF/ICSI outcomes in women with endometriosis treated with long-term pituitary down-regulation before IVF/ICSI.

Mijatovic V, Florijn E, Halim N, Schats R, Hompes P.

Endometriosis Center VUmc/Department of Reproductive Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HVAmsterdam, The Netherlands.

OBJECTIVES: To establish the effect of adenomyosis on IVF/ICSI outcomes in infertile patients with endometriosis who were pretreated with long-term (>/=3 months) GnRH-agonist prior to IVF/ICSI. STUDY DESIGN: Retrospective study in 74 infertile patients with surgically proven endometriosis who were treated with IVF/ICSI between January 2002 and March 2007. The diagnosis of adenomyosis was based on transvaginal ultrasound criteria. All patients were pretreated with long-term (>/=3 months) GnRH-agonist prior to IVF/ICSI. RESULTS: 90.4% of the patients were diagnosed with endometriosis rASRM stages III-IV. Adenomyosis was demonstrated in 27% of them and was predominantly located in the posterior wall of the uterus. The following IVF/ICSI outcomes were found: a mean duration of GnRH-agonist use prior to IVF/ICSI of 5.35 months (3-26); a mean dosage of FSH used of 208IU (75-450); the mean number of oocytes retrieved was 8.73 (1-30); the mean number of embryos obtained was 3.86 (0-16); the mean number of embryos transferred was 1.6; a mean fertilization rate of 43.6%; a mean implantation rate of 26.3%; a mean miscarriage rate of 24.3%; and a clinical pregnancy rate (fetal heart activity on ultrasound beyond 12 weeks of gestation) of 31.7%. No significant differences were found for any of the IVF/ICSI outcomes between women with and without adenomyosis. CONCLUSIONS: Adenomyosis had no adverse effects on IVF/ICSI outcomes in infertile women with proven endometriosis who were pretreated with long-term GnRH-agonist. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

J Obstet Gynecol Neonatal Nurs. 2010 Mar;39(2):220-5; quiz 225-6.

Coping with endometriosis.

Kaatz J, Solari-Twadell PA, Cameron J, Schultz R.

Sanford Women’s Health, Sioux Falls, SD, USA.

Endometriosis not only has physical implications for women but also may affect their sexuality, self-image, and hopes for childbearing. This article discusses the role of parish nurses in a community faith-based setting collaborating to provide comprehensive care for women who are diagnosed with endometriosis. Physical, emotional, and spiritual dimensions of care are highlighted. Traditional and complimentary treatments are described. Examples of outcomes for women in the described program are included in case study exemplars.

J Huazhong Univ Sci Technolog Med Sci. 2010 Apr;30(2):188-92. Epub 2010 Apr

Change profiles in matrix metalloproteinase-2 and -9 in induced endometriosis in mice.

Chen Q, Qiu N, Pu D, Zhou Y, Li T, Yang H.

Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China, cqhua@126.com.

To examine the changes in matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in the development and progression of endometriosis, real time quantitative polymerase chain reaction, enzyme-linked immunoabsorbent assay and gelatin zymography were employed to determine the mRNA and protein levels and activities of MMP-2 and MMP-9 from the first day to the 21(st) day after the induction in mice with induced endometriosis (experimental group) and sham-operated animals (controls). The results showed that the mRNA and protein levels and activities of the MMP-2 and MMP-9 were significantly increased on the first day after the induction and the level of MMP-2 stayed at a level higher than that in the control group. MMP-9 had two or three peaks during the 21 days, taking place at day 1, 4 and 15. It is concluded that the changes in the MMP-2 and MMP-9 might be involved in pathogenesis of endometriosis.

Int J Gynecol Pathol. 2010 May;29(3):248-51.

Melanosis tubae: histogenesis and appropriate terminology.

Zorzi MG, Pusiol T, Piscioli F.

Institute of Anatomic Pathology, S.Maria del Carmine Hospital Rovereto, Rovereto, Trento, Italy. mariagrazia.zorzi2@apss.tn.it

We report 2 cases of abnormal localized deposition of lipofuscin-laden macrophages in the lamina propria of the fallopian tube. In both cases there was evidence of ovarian and tubal endometriosis. The authors propose the term “melanosis tubae” (MT) as the most appropriate terminology in the diagnosis of the disease, whose pathogenesis is similar to that occurring in gastrointestinal tract pigmented conditions. The lesion is not of an inflammatory nature so that the term “pseudoxanthomatous salpingitis” is inaccurate and should not be used. Other definitions such as “pseudoxanthomatous salpingiosis,” “pigmentosis salpingiosis,” “pigmentosis tubae” may be used, but these are descriptive terms that are not suitable for denoting histogenesis. None of the previously reported MT cases showed coexisting tubal endometriosis. Our cases are the first examples of MT associated with tubal endometriosis.

Reprod Toxicol. 2010 Apr 18. [Epub ahead of print]

Upper control limit of reactive oxygen species in follicular fluid beyond which viable embryo formation is not favorable.

Jana SK, K NB, Chattopadhyay R, Chakravarty B, Chaudhury K.

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, W.B., India.

Though the role of reactive oxygen species (ROS) in female infertility has been a subject of rigorous research worldwide, there is inadequate information on the cut-off value of ROS in the oocyte microenvironment beyond which ART outcome may be adversely affected. An upper ROS level in follicular fluid (FF) samples of women undergoing IVF beyond which good quality embryo formation is unlikely, is established. ROS, lipid peroxidation and total antioxidant capacity were estimated. The upper cut-off ROS level beyond which viable embryo formation is not favorable was found to be approximately 107cps/400mul FF. This level, determined in women with tubal factor infertility, was further validated in women with endometriosis and PCOS and correlated with fertilization and pregnancy rate and embryo quality. Summarizing, a threshold level in FF has been established for the first time beyond which ROS may be considered toxic for viable embryo formation and pregnancy outcome. Copyright © 2010. Published by Elsevier Inc.

Acta Clin Croat. 2009 Sep;48(4):439-43.

Rectus abdominis muscle endometriosis after cesarean section–case report.

Dordević M, Jovanović B, Mitrović S, Dordević G, Radovanović D, Sazdanović P.

University Department of Obstetrics and Gynecology, Kragujevac Clinical Center, Kragujevac. mogidj@ptt.rs

Endometriosis is defined by the presence of functional endometrial tissue outside the uterus, where it is normally located. Endometriosis is one of the most common gynecologic entities affecting 8%-18% of menstrual women. Endometriosis can occur at intra- and extrapelvic localizations. The most common intrapelvic localizations are those involving the ovaries, Douglas’ area, pelvic peritoneum, uterus, bladder and rectum. Abdominal endometriosis is the most common localization of extrapelvic endometriosis and usually develops in connective tissue. Extra-pelvic implantation of endometrial tissue may develop in any organ including the skin, lungs, liver, extremities, brain and stomach. Three years after cesarean section, a 35-year-old female was operated on for suspected anterior abdominal hernia at the site of previous section. An egg-sized tumor was removed from the rectus abdominis muscle and referred for histopathologic and immunohistochemical analyses. The results showed endometriosis of the muscle with positive estrogen and progesterone receptors. A year after the procedure, treatment with gonadotropin-releasing hormone analogs was continued due to recurrent pain in the scar area, along with ultrasonography and biochemical marker (carbohydrate antigen 125) follow-up. Clinical diagnosis of scar endometriosis can be made by thorough history and physical, ultrasonography and biochemical examinations. Scar endometriosis should always be considered when the symptoms occur in a cyclic and hormone-dependent pattern, mostly after gynecologic operations, and worsening during menstruation. Definitive diagnosis is based on histopathologic analysis.

Fertil Steril. 2010 Apr 17. [Epub ahead of print]

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis.

Nabeta M, Abe Y, Haraguchi R, Kito K, Kusanagi Y, Ito M.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Ehime, Japan; Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Ehime, Japan.

OBJECTIVE: To establish a novel serum marker for endometriosis, serum autoantibodies (autoAbs) were investigated using a proteomic approach. DESIGN: Retrospective study. SETTING: Departments of Molecular Pathology and Obstetrics and Gynecology in Ehime University and University Hospital. PATIENT(S): Sixty-nine patients with endometriosis, 38 disease control patients without endometriosis, and 44 healthy volunteers. INTERVENTION(S): Autoantibodies in sera of endometriotic patients and healthy controls were investigated using a human fibroblast cell line, two-dimensional gel electrophoresis, and Western blotting. Proteins in reacted spots were identified using MALDI time of flight mass spectrometry with MASCOT analysis. ELISAs were established using recombinant proteins, and autoAb-titers were estimated in sera of endometriotic patients and controls. MAIN OUTCOME MEASURE(S): Identification of serum autoAb useful for diagnosis of endometriosis. RESULT(S): Several autoAbs were identified. ELISAs were established and serum autoAb titers were estimated. Among those identified, anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients. Sensitivity (59.4%) and accuracy (72.8%) of serum anti-PDIK1L-autoAb assay were better than those of serum CA125 levels (36.2% and 62.9%, respectively) in diagnosis of endometriosis. Additionally, anti-PDIK1L-autoAb could detect endometriotic patients in early stages. CONCLUSION(S): Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis. This study validates further clinical evaluation of this novel marker. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

J Pediatr Adolesc Gynecol. 2010 Apr 17. [Epub ahead of print]

Endometriosis in Young Women: The Experience of GISE.

Gruppo Italiano di Studio sull’Endometriosi, Vicino M, Parazzini F, Cipriani S, Frontino G.

II Clinica Ginecologica Ostetrica, Bari.

STUDY OBJECTIVE: To analyze the clinical manifestations of endometriosis in adolescents. DESIGN: prospective clinical study. SETTING: University and General hospitals. PARTICIPANTS: A total of 38 females aged </=21 years who had a first surgically confirmed diagnosis of endometriosis during the period including years 2005-2006 at 12 participating centers were identified. Endometriotic lesions were staged according to the 1985 revised American Fertility Society [renamed American Society for Reproductive Medicine (ASRM)] classification. RESULTS: The mean age at diagnosis was 18.6 years, except in 3 cases (7.9%) in which it was made at </=15 years of age. None of the patients had a prior diagnosis of genital malformations, nor were any cases of diagnosed familiarity for endometriosis. Pelvic pain was present in all cases, although in 3 cases the presence of a pelvic mass was the indication for surgery. CONCLUSIONS: The main clinical finding emerging from this analysis suggests that pelvic pain is the main symptom. In our series pain was present in all cases and an ovarian endometrioma was present in three cases. With regard to the stage and site of the disease, the frequency of minimal-mild endometriosis was lower than in adult cases observed in the experience of GISE. Copyright © 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Apr 16. [Epub ahead of print]

Prokineticin 1, homeobox A10, and progesterone receptor messenger ribonucleic acid expression in primary cultures of endometrial stromal cells isolated from endometrium of healthy women and from eutopic endometrium of women with endometriosis.

Tiberi F, Tropea A, Romani F, Apa R, Marana R, Lanzone A.

Istituto Scientifico Internazionale “Paolo VI,” Università Cattolica del Sacro Cuore (UCSC), Rome.

OBJECTIVE: To examine prokineticin 1 (PROK1), homeobox (HOX) A10, and P receptor (PR) messenger ribonucleic acid (mRNA) expression in primary cultures of endometrial stromal cells (ESC) obtained from eutopic endometrial samples of patients with endometriosis and to clarify whether in vitro steroid hormone dependence of PROK1 gene expression is altered in endometriosis. DESIGN: Prospective laboratory study. SETTING: Tertiary university hospital. PATIENT(S): Twelve normal women (controls) and 12 patients affected by moderate to severe endometriosis in the midsecretory phase of the menstrual cycle. INTERVENTION(S): Endometrial specimens were obtained from control women and from women affected by endometriosis; ESC were isolated from endometrial biopsies, and primary cultures were established. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction analysis of PROK1, HOXA10, and PR mRNA expression in ESC after 1-4 days of steroid hormone treatment and after decidual differentiation. RESULT(S): Contrary to ESC from control women, in ESC obtained from women affected by endometriosis PROK1 and PR mRNA expression was not induced by 1-4 days of treatment with steroid hormones. Nevertheless, when ESC from both groups of women were differentiated to decidual phenotype, PROK1 mRNA was up-regulated and PR and HOXA10 mRNA were down-regulated to the same extent. CONCLUSION(S): Our results provide additional evidence for P resistance in endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Apr 16. [Epub ahead of print]

Rare case of perplexing ovarian endometriosis.

van der Merwe JL, Siebert I, van Wyk AC.

Department of Obstetrics and Gynaecology, Tygerberg Hospital and Stellenbosch University, Tygerberg, South Africa.

OBJECTIVE: To document a rare case of coexisting endometriosis and mature cystic teratoma in the same ovary. DESIGN: Case report. SETTING: Gynecology unit in a tertiary training and teaching hospital in Cape Town, South Africa. PATIENT(S): A 30-year-old healthy nulligravida woman with a large ovarian tumor. INTERVENTION(S): After a basic examination, a diagnostic and management laparotomy was performed. A unilateral oophorectomy and staging laparotomy were performed. MAIN OUTCOME MEASURE(S): Final diagnosis of a complex ovarian tumor. RESULT(S): Histologic analysis confirmed endometriosis of the pelvis and concomitant compound pathology in the right ovary, which included endometriosis, mature teratoma, and mucinous cystadenoma. CONCLUSION(S): Co-existence of varied pathology in a single organ presents a challenge to the pathologist and the clinician. Accurate clinical (i.e., surgical) assessment and decisive histologic verification forms a critical part in this process. This case of coexisting endometriosis and teratoma in a single ovary is, to our knowledge, only the third case reported in literature. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

J Gynecol Obstet Biol Reprod (Paris). 2010 Apr 14. [Epub ahead of print]

Endometriosis and genetics: What responsibility for the genes?

[Article in French]

Borghese B, Vaiman D, de Ziegler D, Chapron C.

Service de gynécologie obstétrique 2 et médecine de la reproduction, centre hospitalier universitaire Cochin-Saint-Vincent-de-Paul, groupe hospitalier universitaire Ouest, AP-HP, université Paris Descartes, 74-82, avenue Denfert-Rochereau, 75014 Paris, France; CNRS UMR 8104, institut Cochin, 75014 Paris, France; U1016, Inserm, 75014 Paris, France.

Endometriosis is a very frequent and debilitating disease responsible for a considerable socio-economic toll. In spite of that, its pathogenesis remains enigmatic. Endometriosis is hold for a multifactorial pathology resulting from the mixed effects of environmental and genetic factors. To date, few susceptibility factors have been reported, with the exception of some polymorphisms in estrogen and progesterone receptors. Large-scale expressional studies have clearly demonstrated that endometriosis is a hormone-dependant disease, characterized by three main features: (i) inflammation, (ii) excessive production of estrogens, and (iii) progesterone resistance. Endometriosis is also considered as a benign metastatic disease, closely linked to cancer. However, the risk of malignant transformation appears to be very limited, likely by a systematic repression of the genes involved in cell cycle and a specific regulation of the HOX genes. Lastly, endometriosis might result from abnormalities of the eutopic endometrium, which show the same molecular alterations than the ectopic endometrium, to a lesser extent however. These alterations, possibly occurring during the embryonic life through epigenetic and genetic predisposition, could lead to an earlier and non-invasive diagnosis for endometriosis. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Ann Surg. 2010 May;251(5):887-95.

Complete surgery for low rectal endometriosis: long-term results of a 100-case prospective study.

Dousset B, Leconte M, Borghese B, Millischer AE, Roseau G, Arkwright S, Chapron C.

Department of Digestive and Endocrine Surgery, University Hospital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France. bertrand.dousset@cch.aphp.fr

OBJECTIVE: We conducted a prospective study to assess the long-term results of complete surgery for low rectal endometriosis (LRE), paying particular attention to surgical complications, functional results, and disease recurrence after a follow-up of at least 5 years. SUMMARY BACKGROUND DATA: Deep infiltrating endometriosis (DIE) may infiltrate the midlow rectum and lead to severe pelvic pain. Complete resection of LRE is reluctantly considered by young women of childbearing age. METHODS: From 1995 to 2003, 100 women with severe pelvic pain and previous incomplete surgery (n=82) underwent complete open surgery for LRE after thorough preoperative imaging work-up. This included total or subtotal rectal excision with combined resection of all extrarectal endometriotic lesions. Univariate analysis of predictive factors for transient neurogenic bladder and surgical complications was performed. Mean follow-up was 78+/-15 months. RESULTS: All patients underwent rectal resection with straight coloanal (n=16) or low colorectal anastomosis (n=84). A concomitant extrarectal procedure was required in all instances, including gynecologic procedures (n=100), additional intestinal (n=45), and urologic (n=23) resections. A fertility-preserving procedure was possible in 92% of the patients. Mean numbers of DIE and endometriotic lesions were 3.9+/-1.4 and 5.5+/-1.6 per patient, respectively. There were no deaths and the surgical morbidity rate was 16%. Sixteen patients developed a transient peripheral neurogenic bladder, which was more frequently observed after colonanal anastomosis (P<0.001) or concomitant hysterectomy (P<0.01) and in patients with more than 4 DIE lesions (P<0.05). At last follow-up, 94 patients had complete (n=83) or very satisfactory (n=11) relief of symptoms. Urine voiding and fecal continence was satisfactory in all cases. There was no recurrence of colorectal and/or urologic endometriosis and the overall DIE recurrence rate was 2%. CONCLUSIONS: Complete surgery for LRE provides excellent long-term functional results in 94% of the patients, provided all extraintestinal endometriotic lesions are resected during the same surgical procedure. In that setting, the overall 5-year recurrence rate is very low.

Reprod Biomed Online. 2010 May;20(5):699-706. Epub 2010 Feb 1.

Administration of betaHCG leads to dose-dependent changes of gene expression signature of endometriotic stromal cells.

Hudelist G, Huber A, Auer M, Knöfler M, Saleh L, Hrachowitz C, Huber JC, Kubista E, Manavi M, Bilban M, Singer CF.

Division of Special Gynecology, Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Department of OB/GYN, Center for Endometriosis, Villach General Hospital, Vienna, Austria.

Preliminary studies have shown that systemic beta-human chorionic gonadotrophin (betaHCG) therapy alleviates endometriosis-related chronic pelvic pain. The underlying mechanism, however, is completely unknown. This study has investigated the dose-dependent alterations in the overall gene expression profile of endometriosis-derived stromal cells under increasing concentrations of betaHCG by using the Affymetrix GeneChip U133 Set. It has been previously shown that betaHCG concentrations of 0.1U/ml and higher lead to a significant and dose-dependent increase in the expression of 68 genes. This study reports on a cluster analysis which identified three clusters of genes with a comparable expression pattern in response to increasing concentrations of betaHCG. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix remodelling, apoptosis and inflammation. Stromal monocultures from eight patients, treated with and without 50U/ml of betaHCG, were then incubated and real-time polymerase chain reaction for the highly up-regulated genes PAI2, DUSP6, PLAU and MMP1 performed in order to validate the cDNA array findings in patients with endometriosis. Taken together, this study shows that betaHCG induces dose-dependent characteristic response clusters in the gene expression profile of stromal cells obtained from endometriotic lesions which could explain the differential biological responses of betaHCG in endometriosis. Copyright © 2010. Published by Elsevier Ltd.

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