Bioorg Med Chem. 2010 Jun 1;18(11):3841-59. Epub 2010 Apr 20.

Synthesis and structure-activity relationships of 2-acylamino-4,6-diphenylpyridine derivatives as novel antagonists of GPR54.

Kobayashi T, Sasaki S, Tomita N, Fukui S, Kuroda N, Nakayama M, Kiba A, Takatsu Y, Ohtaki T, Itoh F, Baba A.

Takeda Pharmaceutical Company, Ltd, Ibaraki 300-4293, Japan. Kobayashi_Toshitake@takeda.co.jp

GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor has an essential role to modulate sex-hormones including GnRH. Though antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis, small molecule GPR54 antagonists have not been reported. We have synthesized a series of 2-acylamino-4,6-diphenylpyridines to identify potent GPR54 antagonists. Detailed structure-activity relationship studies led to compound 9l with an IC(50) value of 3.7nM in a GPR54 binding assay, and apparent antagonistic activity in a cellular functional assay.

Gynecol Obstet Fertil. 2010 May;38(5):304. Epub 2010 Apr 24.

If you are interested in endometriosis…

[Article in French]

Canis M.

Am J Reprod Immunol. 2010 Apr 30. [Epub ahead of print]

Resistin Concentration is Increased in the Peritoneal Fluid of Women with Endometriosis.

Yi KW, Shin JH, Park HT, Kim T, Kim SH, Hur JY.

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

Citation Yi KW, Shin J-H, Park HT, Kim T, Kim SH, Hur J-Y. Resistin concentration is increased in the peritoneal fluid of women with endometriosis. Am J Reprod Immunol 2010 Problem The aim of this study was to investigate the concentration of resistin and adiponectin in the peritoneal fluid (PF) of patients with endometriosis. Method of study PF sampling was obtained from women with (n = 48) and without endometriosis (n = 36), and the anthropometric indices of the patients were measured. Resistin and adiponectin concentrations in the PF were determined using the enzyme-linked immunosorbent assay. Results The mean concentration of PF resistin was significantly higher in women with endometriosis compared to the controls. PF resistin concentrations were not associated with any of the anthropometric indices. The PF adiponectin did not differ between the two groups, but showed a significant association with the weight, body mass index, and hip circumference. After adjusting for these factors, PF adiponectin expression was not associated with endometriosis. Conclusion The findings of this study suggest a potent role for resistin in endometriosis. Further studies are needed to elucidate the biological implications of resistin in endometriosis.

 

J Obstet Gynaecol. 2010 May;30(4):417-8.

Endometriosis of the round ligament. Is it really a rare entity?

Nikiteas N, Patsouras D, Kykalos S, Voutsarakis A, Mantas D, Dimitroulis D, Kouraklis G.

2nd Department of Propedeutic Surgery, Medical School of Athens University, Laiko General Hospital, Athens, Greece.

Ultrasound Obstet Gynecol. 2010 Aug;36(2):252-4.

Florid polypoid endometriosis of the cervix with left ureteric obstruction: a mimic of cervical malignancy.

Kwek JW, H’ng MW, Chew SH, Tay EH.

Department of Diagnostic Imaging, Kandang Kerbau Women’s and Children’s Hospital, Singapore.

Polypoid endometriosis, in contrast to typical (non-polypoid) endometriosis, presents as masses that project from a serosal or mucosal surface or from the lining of an endometriotic cyst. Generally large, these masses can simulate a malignant tumor on imaging and at surgery. We report a case of florid polypoid endometriosis arising from the cervix with extension into the left parametrium and involving the left ureter, mimicking a locally advanced cervical malignancy on ultrasound and magnetic resonance imaging. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Medicine (Baltimore). 2010 May;89(3):183-8.

Thoracic endometriosis: revisiting the association between clinical presentation and thoracic pathology based on thoracoscopic findings in 110 patients.

Channabasavaiah AD, Joseph JV.

UCSF Fresno, Division of Pulmonary & Critical Care Medicine, Fresno, California 93701, USA.

Thoracic endometriosis (TE) is a rare disorder affecting women during their reproductive years. The etiopathogenesis of this disease is not well understood; the prevailing opinion is based on analysis obtained from case reports and small case series. A 1996 review of TE was not able to address the association between clinical presentation and thoracic pathology due to a paucity of thoracoscopic findings in these earlier cases. Since the year 2001, most published cases and series have included thoracoscopic findings. Therefore, we compiled data from case reports and case series published in English from January 2001 to July 2007 to analyze the demographics, clinical characteristics, and thoracoscopic findings, and to study the relationship between thoracoscopic findings and clinical presentation in patients with thoracic endometriosis. The clinical presentations in 110 patients were as follows: pneumothorax in 79 (72%), hemoptysis in 16 (14%), hemothorax in 13 (12%), and lung mass in 2 (2%). Ninety-one of the 110 (85%) patients underwent thoracotomy or thoracoscopy. The right hemithorax was more often affected (85%) than the left side (p = 0.008). The mean (standard deviation [SD]) age of all patients was 34 (7.6 yr). The mean age of patients presenting with hemoptysis (25.9 +/- 4.6 yr) was significantly lower than the age of those presenting with pneumothorax and hemothorax (p < 0.01). There was no significant association between the presence of diaphragmatic defects and pneumothorax (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.05-1.58; p = 0.23). The presence of parietal and visceral pleural implants was associated with a fivefold increase in hemothorax (OR, 5.55; 95% CI, 1.20-25.53; p < 0.01).Hemoptysis occurring in younger subjects may be the earliest manifestation of parenchymal lung involvement in TE. Diaphragmatic defects do not increase the risk for pneumothorax. Hemothorax reflects an increased burden of pleural implants in TE.

J Reprod Immunol. 2010 Jun;85(2):149-60. Epub 2010 May 7.

DNA microarray analysis in a mouse model for endometriosis and validation of candidate factors with human adenomyosis.

Kusakabe KT, Abe H, Kondo T, Kato K, Okada T, Otsuki Y.

Department of Laboratory Animal Science, Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Riku-Ourai kita, Izumisano, Osaka 598-8531, Japan. kkusakabe@vet.osakafu-u.ac.jp

Gene expression profiling can be of benefit in identifying critical factors in the process of disease initiation and development. However, in endometriosis it has proven difficult to identify common genes between DNA microarray studies, presumably because of tissue homogeneity in lesions and diversity in the patients’ conditions. We attempted DNA microarray analysis in a mouse model for endometriosis with stable lesions and a homogeneous genetic background. Data extracted from the mouse model was then evaluated in human tissues. Mice of the ddY strain underwent surgery to remove the left side of the uterine horn, and the uterine tissue was then minced into small segments and auto-transplanted onto the left peritoneum. After 8 weeks, most of the uterine grafts were enlarged and had regenerated lumens. Comparison of the intensity of mRNA expression between grafts and normal uteri showed that genes encoding immune regulators (e.g. CXCL10) and metabolic factors (e.g. calbindin D-28K) were highly up-regulated in the grafts. Strongly inhibited genes in the grafts included prostaglandin-related factors [e.g. prostaglandin E receptor 3 (subtype EP3) and prostaglandin I2 synthase]. Variation in some candidate factors detected in the mouse model was observed by immunohistochemical studies in human adenomyosis tissues. The gene list in the present study is available for re-evaluation of past studies and provides new candidate factors potentially involved in the pathogenesis of endometriosis. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Am J Obstet Gynecol. 2010 Aug;203(2):109.e1-6. Epub 2010 May 10.

Understanding cellular leiomyomas: a case-control study.

Taran FA, Weaver AL, Gostout BS, Stewart EA.

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA.

OBJECTIVE: Reports exist in which cellular leiomyomas (CLs) appear to have clinical characteristics or genetic profiles similar to leiomyosarcomas. This study aimed to determine whether most CLs differ clinically from typical uterine leiomyomas (ULs). STUDY DESIGN: A case-control study was conducted with women who underwent surgical procedures between January 1989 and December 2008 and who were diagnosed with a CL (n = 99). Control subjects, who were matched in a 2:1 ratio, were women with a diagnosis of UL (n = 198). Hospital and ambulatory records were reviewed. RESULTS: In multivariable logistic regression analyses, women with CLs were more likely to have surgery for the indication of enlarging leiomyoma and less likely to have concomitant endometriosis or adenomyosis. Uteri that contained CLs were also more likely to have larger and fewer leiomyomas when compared with control subjects. CONCLUSION: CLs have a distinct clinical phenotype compared with ULs and have some characteristics in common with leiomyosarcomas. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Intern Emerg Med. 2010 May 7. [Epub ahead of print]

Endometriosis, need for a multidisciplinary clinical setting: the internist’s point of view.

Montalto M, Santoro L, D’Onofrio F, Gallo A, Campo S, Campo V, Gasbarrini A, Gasbarrini G.

Institute of Internal Medicine, Catholic University, Largo Agostino Gemelli 8, 00168, Rome, Italy, mmontalto@rm.unicatt.it.

Endometriosis is a common condition characterized by proliferation of endometrial tissue outside the uterus, both in the pelvis and in other extra-pelvic sites. The clinical picture of endometriosis is widely heterogeneous. A correct diagnostic work-up of these patients can sometimes be very difficult, since there are a number of gynecological, intestinal and systemic diseases mimicking endometriosis, as well as other conditions that could be associated with or are a consequence of this disorder. Therefore, multidisciplinary care should be encouraged to ensure correct evaluation and improve the management of these patients.

Indian J Cancer. 2010 Apr-Jun;47(2):224-5.

Endometriosis with massive hemorrhagic ascites.

Suchetha S, Rema P, Mathew AP, Sebastian P.

Placenta. 2010 Jun;31(6):499-505. Epub 2010 May 5.

Genetic polymorphisms in the fibrinolytic system of placentas with massive perivillous fibrin deposition.

Uxa R, Baczyk D, Kingdom JC, Viero S, Casper R, Keating S.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Canada. ruchitauxa@hotmail.com

Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) of the placenta are rare related conditions associated with poor perinatal outcome including antepartum stillbirth. The diseases are characterized by pathologic accumulation of fibrinoid deposits that surround the placental villi (in the case of MFI predominantly in the basal regions adjacent to the decidual plate). These findings suggest either overproduction and/or defective clearance of fibrinoid within the intervillous space. Recently genetic polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene have been found in association with impaired fibrinolysis in the pelvis predisposing to endometriosis. We hypothesized that polymorphisms in one or more of four genes that regulate fibrinolysis were associated with MPFD and MFI placentas. We retrospectively identified 20 consecutive cases of MPFD/MFI from our placental pathology database and generated 2 random gestational age-matched controls for each case. Clinical charts were reviewed. DNA was extracted from archived paraffin blocks of placental tissue from cases and controls. Single nucleotide repeat polymorphisms (SNPs) in loci within PAI-1 gene, thrombin activated fibrinolysis inhibitor (TAFI) gene, plasminogen activator urokinase (u-PA) gene and plasminogen activator tissue (t-PA) gene were studied using PCR methods. Outcomes in the study group included perinatal death (8), preterm IUGR (6), preeclampsia (4) and only 3 normal term deliveries. A spectrum of placental ultrasound abnormalities was observed. No SNP polymorphism was found to associate with MPFD/MFI. MPFD/MFI are associated with significant abnormal perinatal outcomes but have not been shown to be mediated by polymorphisms in candidate genes that are predicted to impair fibrinolysis in our study.

Tunis Med. 2010 Apr;88(4):285-7.

Ovarian abscess as a complication of assisted reproduction techniques: a case report.

Ben Saad M, Attia L, Ben Temime R, Kilani M, Makhlouf T, Chachia A, Koubâa A.

Department of Obstetrics & Gynaecology “A” Charles Nicolle Hospital, Tunis, Tunisia.

BACKGROUND: AMP makes true great strides these last decades. Logically some complications were noticed even due to ovarian puncture such as hemorrhage, perforation or infection. The aim of this report is to try, through a review of literature, to draw the attention of physicians to a rare entity, ovarian abscess after follicle aspiration for in-vitro fertilization, and to means of prevention. CASE REPORT: We report a 38-year-old woman who was plainting from lower abdominal pain located in the left iliac fossa one month after failed IVF trial. The pain was associated with fever and vomiting. The patient’s past medical history involves 2 myomectomys (2003-2007). On admission, her temperature was 38.9 degrees C and her blood pressure was 90/60 mm Hg. Physical examination found nondistended abdomen. Tenderness to deep palpation in the left lower quadrant, without peritoneal signs, was detected. No masses were palpated. Mild tenderness in the left cul-de-sac was found. A full blood count showed a white cell count of 17,500 cells/mm3 with 84.5% polymorph nuclear cells, CRP 173 mg/dl. Pelvic ultrasound shows a left latero uterine mass; right ovary and the uterus are unremarkable; there was no free abdominal fluid. The laparotomy was performed 24 hours later and a left ovarian abscess was found. The treatment was conservative. Antibiotics were associated during 15 days. The clinical evolution was satisfying. CONCLUSION: The ovarian puncture might be technically difficult, incomplete, and even impossible which exposes to a greater infection risk. An ultrasound evaluation of ovarian accessibility is necessary before starting an IVF attempt, especially in case of overweight or history of abdominal or pelvic surgery, endometriosis, tubal abnormalities or myomas. The treatment is based on surgery and antibiotics.

Eur J Obstet Gynecol Reprod Biol. 2010 Aug;151(2):193-8. Epub 2010 May 5.

Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study.

Strowitzki T, Faustmann T, Gerlinger C, Seitz C.

Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Vossstrasse 9, 69115 Heidelberg, Germany. Thomas_strowitzki@med.uni-heidelberg.de

OBJECTIVE: To investigate the efficacy and safety of oral dienogest 2mg compared with placebo in the treatment of endometriosis-associated pelvic pain (EAPP). STUDY DESIGN: This was a 12-week, randomized, double-blind, placebo-controlled, multicenter (n=33) study in Germany, Italy, and Ukraine of 198 women aged 18-45 years with laparoscopically confirmed endometriosis and EAPP score > or =30 mm on a visual analog scale (VAS). Dienogest 2mg or placebo was administered orally once daily. The primary efficacy variable was absolute change in EAPP from baseline to Week 12, as determined by the target variables of change in VAS score and change in intake of supportive analgesic medication (ibuprofen) for pelvic pain. RESULTS: Mean reductions in VAS score between baseline and Week 12 in the full analysis set were 27.4 mm and 15.1mm in the dienogest and placebo groups, respectively-a significant score difference of 12.3 mm in favor of dienogest (P<0.0001). Changes in intake of supportive analgesic medication were modest in both groups. The primary efficacy measure of absolute change in EAPP demonstrated the superiority of dienogest over placebo. Dienogest was generally well tolerated and few adverse events were associated with therapy. CONCLUSIONS: Dienogest at a dose of 2mg daily for 12 weeks was significantly more effective than placebo for reducing EAPP. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

PLoS One. 2010 Apr 28;5(4):e10387.

Stem cell-like properties of the endometrial side population: implication in endometrial regeneration.

Masuda H, Matsuzaki Y, Hiratsu E, Ono M, Nagashima T, Kajitani T, Arase T, Oda H, Uchida H, Asada H, Ito M, Yoshimura Y, Maruyama T, Okano H.

Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

BACKGROUND: The human endometrium undergoes cyclical regeneration throughout a woman’s reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerative capacity of the human endometrium at eutopic and ectopic sites suggests the existence of stem/progenitor cells and a unique angiogenic system. The objective of this study was to isolate and characterize putative endometrial stem/progenitor cells and to address how they might be involved in the physiology of endometrium. METHODOLOGY/PRINCIPAL FINDINGS: We found that approximately 2% of the total cells obtained from human endometrium displayed a side population (SP) phenotype, as determined by flow cytometric analysis of Hoechst-stained cells. The endometrial SP (ESP) cells exhibited preferential expression of several endothelial cell markers compared to endometrial main population (EMP) cells. A medium specific for endothelial cell culture enabled ESP cells to proliferate and differentiate into various types of endometrial cells, including glandular epithelial, stromal and endothelial cells in vitro, whereas in the same medium, EMP cells differentiated only into stromal cells. Furthermore, ESP cells, but not EMP cells, reconstituted organized endometrial tissue with well-delineated glandular structures when transplanted under the kidney capsule of severely immunodeficient mice. Notably, ESP cells generated endothelial cells that migrated into the mouse kidney parenchyma and formed mature blood vessels. This potential for in vivo angiogenesis and endometrial cell regeneration was more prominent in the ESP fraction than in the EMP fraction, as the latter mainly gave rise to stromal cells in vivo. CONCLUSIONS/SIGNIFICANCE: These results indicate that putative endometrial stem cells are highly enriched in the ESP cells. These unique characteristics suggest that ESP cells might drive physiological endometrial regeneration and be involved in the pathogenesis of endometriosis.

Clin Obstet Gynecol. 2010 Jun;53(2):449-66.

Extragenital endometriosis.

Veeraswamy A, Lewis M, Mann A, Kotikela S, Hajhosseini B, Nezhat C.

Center for Special Minimally Invasive and Robotic Surgery, Stanford University Medical Center, Palo Alto, California, USA.

In recent years, there have been significant changes in many aspects of extragenital endometriosis ranging from the epidemiology to the management of the disease. Advances in minimally invasive surgery and expansion of the field have lead to further research in management of extragenital endometriosis. As a result, treatment has shifted from medical management toward a surgical, multidisciplinary approach. Surgery for extragenital endometriosis clearly improves outcome through relief of symptoms, improved quality-of-life, increased fertility rates, and reduced recurrences. Endoscopy has a pivotal role as both a diagnostic and therapeutic tool.

Clin Obstet Gynecol. 2010 Jun;53(2):439-48.

Management of endometriosis-associated pain.

Hansen KA, Chalpe A, Eyster KM.

Department of Obstetrics and Gynecology, Sanford School of Medicine of University of South Dakota, Sioux Falls and Vermillion, South Dakota, USA. kahansen@usd.edu

Endometriosis, a common cause of morbidity in reproductive-age females, results in pelvic pain and infertility. Endometriosis-associated pain can be approached with surgical or medical therapies. Conservative surgery maintains reproductive organs and is effective in the treatment of endometriosis-associated pain. A more radical surgical approach of hysterectomy with bilateral salpingo-oophorectomy remains a mainstay of therapy for patients who have completed childbearing. Current medical therapies rely upon interruption of normal cyclic ovarian hormone production resulting in an environment not conducive to the growth of endometriosis. Genomics promises to further characterize endometriosis and tailor therapies based on a woman’s symptoms and reproductive goals.

Clin Obstet Gynecol. 2010 Jun;53(2):429-38.

Endometriosis and infertility.

Holoch KJ, Lessey BA.

Department of Obstetrics and Gynecology, Greenville Hospital System, Greenville, South Carolina 29605, USA.

Endometriosis is an enigmatic disease affecting up to 10% of reproductive-aged women causing pain and infertility. Up to 50% of women with endometriosis are infertile, and agreement about treatment options has been difficult to establish. The association between endometriosis and infertility is derived from comparisons of fertile and infertile women, animal models, donor sperm studies, and in vitro fertilization results. Diagnostic approaches based on endometrial changes associated with endometriosis are also providing insights into possible mechanisms of infertility, especially in women with milder forms of the disease. Treatment of endometriosis, including surgical ablation or resection, is cost-effective and offers the potential for improvement in cycle fecundity. Medical management of endometriosis-associated infertility has not been proven outside of in vitro fertilization.

Clin Obstet Gynecol. 2010 Jun;53(2):420-8.

Endometriosis and the adolescent.

Dovey S, Sanfilippo J.

University of Pittsburgh Medical Center/Magee Women’s Hospital, Pittsburgh, Pennsylvania 15213, USA. doveysl@mail.magee.edu

The majority of women with endometriosis report symptoms starting in adolescence, yet endometriosis is often a delayed diagnosis in this patient population. Given that endometriosis is felt to be a progressive disease with increasing morbidities over time, such as structural defects and infertility, being more aggressive with pursuing the diagnosis is warranted. Once the diagnosis of endometriosis is made, various medical and surgical treatment modalities are available, and this article will review the most current treatment recommendations.

Clin Obstet Gynecol. 2010 Jun;53(2):413-9.

Invasive and noninvasive methods for the diagnosis of endometriosis.

Hsu AL, Khachikyan I, Stratton P.

Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Endometriosis has been associated with pain and infertility. The gold standard for the diagnosis of endometriosis has been visual inspection by laparoscopy, preferably with histologic confirmation. Because there is no good noninvasive test for endometriosis, there is often a significant delay in diagnosis of this disease. Imaging that confirms an endometriotic cyst or deep infiltrating endometriosis may help guide surgical therapeutic approaches. No serum marker has been found to diagnose endometriosis with adequate sensitivity and specificity. There has been a recent focus on the presence of nerve fibers in the eutopic endometrium of patients with endometriosis.

Clin Obstet Gynecol. 2010 Jun;53(2):403-12.

Genetics and genomics of endometriosis.

Hansen KA, Eyster KM.

Department of Obstetrics and Gynecology, Sanford School of Medicine of University of South Dakota, Vermillion and Sioux Falls, South Dakota 57107, USA. kahansen@usd.edu

 

Endometriosis is a common cause of morbidity in women with an unknown etiology. Studies have demonstrated the familial nature of endometriosis and suggest that inheritance occurs in a polygenic/multifactorial fashion. Studies have attempted to define the gene or genes responsible for endometriosis through association or linkage studies with candidate genes or DNA mapping technology. A number of genomics studies have demonstrated significant alterations in gene expression in endometriosis. A more thorough understanding of the genetics and genomics of endometriosis will facilitate understanding the basic biology of the disease and open new inroads to diagnosis and treatment of this enigmatic condition.

Clin Obstet Gynecol. 2010 Jun;53(2):397-402.

Immunology of endometriosis.

Barrier BF.

Department of Obstetrics, Gynecology and Women’s Health, University of Missouri, Columbia, Missouri, USA. barrierb@health.missouri.edu

Endometriosis is a common condition with a varied phenotype. Symptomatic cases have been associated with progesterone resistance and dysregulated cytokine production in both ectopic and eutopic endometrium. In at least some cases, this seems to be associated with chronic local inflammation and antibody self-reactivity. Coexistence of endometriosis with autoimmune disease has been documented in a small number of cases, and the presence of autoreactive antibodies in the serum of some patients with endometriosis is commonly reported. This paper briefly reviews the association between endometriosis and autoimmune disease and describes the potential role of inflammation in the development of immunologic self-reactivity in these patients.

Clin Obstet Gynecol. 2010 Jun;53(2):389-96.

Epidemiology of endometriosis: an assessment of risk factors.

McLeod BS, Retzloff MG.

Department of Obstetrics and Gynecology, Wilford Hall Medical Center, SAUSHEC, Lackland Air Force Base, Texas, USA.

Endometriosis is the third leading cause of gynecologic hospitalization in the United States. This disease impacts both a woman’s physical and mental well being. This impact is often compounded by the frequent delay from the onset of symptoms to a confirmed diagnosis, which may average 6 years or more. The precise incidence and prevalence of endometriosis remains elusive for a multitude of reasons, and their measurement remains difficult to accurately assess. None the less, there are many unique and interesting components to the disease which arise when population-based analyses are performed. The goal of this paper is to investigate and summarize the existing epidemiologic parameters, primarily risk factors, associated with endometriosis.

Clin Obstet Gynecol. 2010 Jun;53(2):379-88.

Evolving spectrum: the pathogenesis of endometriosis.

Jensen JR, Coddington CC 3rd.

Division of Reproductive Medicine, Mayo Clinic, Rochester, Minnesota, MN 55901, USA.

Although the exact etiology of endometriosis is unknown, several hypotheses about its origin exist. Of these, Sampson’s theory of retrograde menstruation is the most widely accepted. Multiple in-vitro and in vivo models have been developed to study endometriosis. Several key steps are required to establish an endometriotic implant: presence of ectopic endometrial glands and stroma, attachment of endometrial cells to the peritoneum, invasion into the mesothelium, and survival and growth of the ectopic tissue. Many of these steps are similar to those associated with neoplasia, and numerous biologic pathways are involved. It is likely that both intrinsic factors within the ectopic endometrium and permissive alterations within the host are important to the development of endometriosis.

Clin Obstet Gynecol. 2010 Jun;53(2):377-8.

Endometriosis. Foreword.

Hansen KA.

Department of Obstetrics and Gynecology, Sanford School of Medicine of The University of South Dakota, Sioux Falls, South Dakota, USA. kahansen@usd.edu

J Pharmacol Exp Ther. 2010 Aug;334(2):460-6. Epub 2010 Apr 30.

A long-acting tumor necrosis factor alpha-binding protein demonstrates activity in both in vitro and in vivo models of endometriosis.

Altan ZM, Denis D, Kagan D, Grund EM, Palmer SS, Nataraja SG.

Reproductive Health, EMD Serono Research Institute Inc, Rockland, Massachusetts 02370, USA.

Endometriosis is characterized by the presence of elevated proinflammatory cytokines such as tumor necrosis factor (TNF) alpha in the peritoneal cavity. Blocking interaction of TNFalpha with its receptor by the addition of excess TNFalpha-binding protein (TBP)-1 (a soluble form of TNF receptor-1) was effective in animal models of endometriosis. Recently, a novel, high-affinity inhibitor of TNFalpha, TNF-soluble high-affinity receptor complex (TNF-SHARC), was created by fusing TBP to both the alpha and beta subunits of inactive human chorionic gonadotropin. This dimeric protein was effective in inhibiting collagen-induced arthritis in mice. In the present study, the efficacy of TNF-SHARC in cellular and in vivo models of endometriosis was examined. TBP and TNF-SHARC dose-dependently inhibited TNFalpha-induced secretion of interleukin (IL)-6, IL-8, granulocyte macrophage-colony-stimulating factor, and monocyte chemoattractant protein-1 in immortalized human endometriotic cells. An in vivo mouse model of experimentally induced endometriosis using cycling C57BL/6 mice was established. Antide treatment (0.5 mg/kg), used as positive control, initiated 7 days after the establishment of the disease, reduced the weight of the lesions compared with control. TNF-SHARC at 3 mg/kg was not effective in inhibiting the disease, whereas at 9 mg/kg there was reduction in the lesion weight. In addition, antide and TNF-SHARC treatment in vivo increased in vitro natural killer cell activity compared with untreated animals. Thus, we provide evidence for supporting the development of TNF-SHARC as a therapeutic candidate for treating endometriosis in human.

Fertil Steril. 2010 Apr 28. [Epub ahead of print]

Results of first in vitro fertilization cycle in women with colorectal endometriosis compared with those with tubal or male factor infertility.

Mathieu d’Argent E, Coutant C, Ballester M, Dessolle L, Bazot M, Antoine JM, Daraï E.

Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.

This retrospective study of women undergoing IVF (29 with colorectal endometriosis, 157 with tubal factor infertility, and 340 with male factor infertility) found similar fertility outcomes between the groups. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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