Hum Reprod. 2011 Apr 6. [Epub ahead of print]

The co-occurrence of endometriosis with multiple sclerosis, systemic lupus erythematosus and Sjogren syndrome.

Nielsen NM, Jørgensen KT, Pedersen BV, Rostgaard K, Frisch M.

Source

Department of Epidemiology Research, Statens Serum Institut, Copenhagen S, Denmark.

Abstract

BACKGROUND In a previous study, women with endometriosis were found to be at a 7-24-fold increased risk of multiple sclerosis (MS), systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). We examined these associations in a large population-based cohort study. METHODS We followed 37 661 women registered with endometriosis in the Danish Hospital Discharge Register 1977-2007 for subsequent hospitalizations with MS, SLE or SS. As measures of relative risk, we used ratios of observed to expected incidence rates of first hospitalizations for MS, SLE and SS among women with endometriosis, i.e. standardized incidence ratios (SIR) with accompanying 95% confidence intervals (CIs). RESULTS During slightly more than 456 000 person-years of follow-up, we identified 130, 54 and 86 cases of MS, SLE and SS, respectively, yielding SIRs of 1.2 (95% CI 1.05-1.5) for MS, 1.6 (1.2-2.1) for SLE and 1.6 (1.3-2.0) for SS. In a supplementary analysis restricted to 9191 women with laparoscopy or laparotomy confirmed endometriosis, associations were unchanged for MS (SIR = 1.4; 1.04-1.9), but lost statistical significance for SLE (SIR = 1.1; 0.6-2.1) and SS (SIR = 1.4; 0.9-2.3). CONCLUSIONS Our national cohort-based findings do not support prior claims of markedly increased risks of MS, SLE and SS in women with endometriosis. However, whether women with endometriosis are truly at a modestly (20-60%) elevated risk of one or more of the studied autoimmune diseases must await clarification in future large-scale prospective studies.

Reprod Biol Endocrinol. 2011 Apr 6;9:44.

TRIzol treatment of secretory phase endometrium allows combined proteomic and mRNA microarray analysis of the same sample in women with and without endometriosis.

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

Source

Leuven University Fertility Centre, Department of Obstetrics & Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium. thomas.dhooghe@uzleuven.be.

Eur J Obstet Gynecol Reprod Biol. 2011 Apr 5. [Epub ahead of print]

Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain.

Kitawaki J, Kusuki I, Yamanaka K, Suganuma I.

Source

Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.

Abstract

OBJECTIVE:

To examine whether long-term administration of dienogest following gonadotropin-releasing hormone agonist (GnRH-a) therapy would prolong the relief of pelvic pain while reducing the amount of irregular uterine bleeding.

STUDY DESIGN:

This was a prospective, non-randomized clinical trial. Among the patients suffering from chronic pelvic pain associated with recurrent endometriosis, Group G (n=38) received GnRH-a for 4-6months and then dienogest (1mg/day) for 12months. The dose of dienogest was increased to 1.5 or 2mg/day when a patient had uncontrollable uterine bleeding {n=15 (39%)}. Group D (n=33) received only dienogest (2mg/day) for 12months. Pelvic pain was assessed using a visual analog scale (VAS). Uterine bleeding was semi-quantified using a pictorial blood loss assessment chart (PBAC).

RESULTS:

In Group G, GnRH-a significantly reduced the VAS score for pelvic pain, and alleviation was maintained during the 12-month therapy with dienogest. There was no significant difference in pain reduction between Group G and Group D. The PBAC score during the first 6months on dienogest was significantly smaller in Group G than in Group D.

CONCLUSION:

Treatment with a GnRH-a followed by long-term dienogest therapy maintains the relief of endometriosis-associated pelvic pain achieved with GnRH-a therapy for at least 12months. This regimen reduces the amount of irregular uterine bleeding that often occurs during the early phase of dienogest therapy.

Fertil Steril. 2011 Apr 5. [Epub ahead of print]

Patients with endometriosis and patients with poor ovarian reserve have abnormal follicle-stimulating hormone receptor signaling pathways.

González-Fernández R, Peña O, Hernández J, Martín-Vasallo P, Palumbo A, Avila J.

Source

Departamento de Bioquímica y Biología Molecular, Universidad de la Laguna, Tenerife, Spain.

Abstract

OBJECTIVE:

To study the integrity of the FSH receptor (FSHR) signaling pathway in granulosa-lutein cells at the time of egg retrieval and its relationship with the infertility diagnosis.

DESIGN:

In vitro assays.

SETTING:

University laboratory and private IVF center.

PATIENT(S):

Patients undergoing IVF: 35 controls (no ovarian factor, NOF), 28 poor responders (PR), 32 patients with endometriosis (EM), and 22 patients with polycystic ovary syndrome (PCOS).

INTERVENTION(S):

Quantitative reverse transcriptase-polymerase chain reaction (PCR) in granulosa-lutein cells from pooled follicles.

MAIN OUTCOME MEASURE(S):

Correlation between expression of FSHR and FSH-regulated genes PAPP/Cyp19A1.

RESULT(S):

Positive correlations among FSHR, PAPP, and Cyp19A1 expression levels are observed in NOF and are lost, with different patterns, in poor responder patients and those with endometriosis. Patients with endometriosis are an heterogeneous group including patients with poor ovarian reserve who behave like other poor responders patients (endometriosis-A) and patients with good response to ovarian stimulation (endometriosis-B) who show a specific alteration of the FSHR signaling pathway.

CONCLUSION(S):

These preliminary data suggest that the different signaling pathways activated through the FSHR in normal ovaries (NOF) are disrupted in poor responders and in patients with endometriosis. A better knowledge of the molecular origin of these errors may guide clinicians in the choice of personalized ovulation induction protocols for each type of ovarian dysfunction.

Eur J Obstet Gynecol Reprod Biol. 2011 Apr 4. [Epub ahead of print]

Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system.

Engemise SL, Willets JM, Taylor AH, Emembolu JO, Konje JC.

Source

Reproductive Science Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom.

Abstract

OBJECTIVES:

The levonorgestrel (LNG) intrauterine system (LNG-IUS) has been shown to improve symptoms in women with minimal to moderate endometriosis. The precise mechanism for this is unknown. We hypothesized that this involves alteration in the expression of estrogen receptors (ER) and progesterone receptors (PR).

STUDY DESIGN:

A prospective study of tissues obtained prospectively from 28 women with laparoscopically confirmed minimal to moderate endometriosis treated with LNG-IUS for 6months. Endometrial and endometriotic biopsies obtained before and 6months after treatment were processed and stained for ER-α, ER-β and PR expression by immunohistochemistry. Photographs were obtained and the receptors quantified.

RESULTS:

The mean (±SD) age of the 28 women was 31±7.2 (range 18-42) years. Eight of them at initial biopsy were in the proliferative phase and 20 in the secretory phase. ER-α, ER-β and PR expression decreased significantly in the glandular (P<0.0001) and stromal (P<0.0001) compartments of the eutopic endometrium after treatment with LNG-IUS. Similarly, ER-α, ER-β and PR were significantly decreased in the stromal compartment of ectopic endometrium (P<0.0001), and significantly decreased in the ectopic glands of ER-α (P<0.0001), ER-β (P=0.0002) and PR (P=0.0064) expression.

CONCLUSION:

The ameliorative effect of LNG-IUS on the symptoms of minimal to moderate endometriosis is likely modulated through a decrease in the expression of glandular and stromal ER-α, ER-β and PR in the ectopic endometrium.

Invest Radiol. 2011 Apr 4. [Epub ahead of print]

In Vivo Detection of Choline in Ovarian Tumors Using 3D Magnetic Resonance Spectroscopy.

Esseridou A, Di Leo G, Sconfienza LM, Caldiera V, Raspagliesi F, Grijuela B, Hanozet F, Podo F, Sardanelli F.

Source

From the *Unità di Radiologia, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy; †Scuola di Specializzazione in Radiodiagnostica, Facoltà di Medicina e Chirurgia, Università degli Studi di Milano, Milan, Italy; ‡Struttura Complessa di Chirurgia Ginecologica, IRCCS Istituto Nazionale Tumori, Milan, Italy; §Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy; and ¶Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, IRCCS Policlinico San Donato, Unità di Radiologia, San Donato Milanese, Milan, Italy.

Abstract

OBJECTIVES:

To assess the clinical feasibility of 3-dimensional (3D) proton magnetic resonance spectroscopy (MRS) of ovarian masses at 1.5 T.

MATERIALS AND METHODS:

We prospectively evaluated 16 patients with 23 ovarian masses using contrast-enhanced magnetic resonance imaging and 3D chemical shift imaging MRS (time of reception/time of echo = 700/135 ms, number of excitations = 6, interpolated voxel = 5 × 5 × 5 mm, water and fat suppression). Spectral editing consisted of water reference, filtering, zero-filling, Fourier transformation, frequency shift, automatic baseline and phase correction, and curve fitting. The volume of interest was placed to encompass both solid and cystic tumor components as well as apparently healthy pelvic tissues. The presence of a choline peak at 3.14 to 3.34 ppm was considered as a marker of malignancy. All patients underwent surgery and histopathological evaluation.

RESULTS:

Of 23 masses, 19 were malignant and the remaining 4 benign lesions were a fibrothecoma, an endometriosis, a cyst, and a cystadenofibroma. A choline peak was detected in 17/19 malignant tumors (sensitivity 89%), absent in 2 G1 tumors. It was visible in 16 solid components of 19 malignant tumors (in one of them, a choline peak was detected only in the cystic component, in 6 in both solid and cystic components). The choline peak was absent in 20/21 apparently healthy pelvic tissues, with a very low choline peak being detected in one intraperitoneal fluid collection with malignant cells at cytologic analysis; 3/4 benign tumors showed a choline peak (overall specificity 21/25 = 84%). A significant difference between the mean choline peak integral detected within the solid component and that within the cystic component was observed (P = 0.002). No correlation between the choline peak integral and the tumor size was found (r = 0.120, P = 0.615).

CONCLUSIONS:

3D MRS of ovarian masses is clinically feasible at 1.5 T. This opens new research strategies for early diagnosis of ovarian cancer.

J Obstet Gynaecol Res. 2011 Apr 4. doi: 10.1111/j.1447-0756.2010.01467.x. [Epub ahead of print]

Rectal endometriosis with invasion into lymph nodes.

Namkung J, Kim SJ, Kim JH, Kim J, Hur SY.

Source

Departments of GynecologyPathology, College of Medicine, Catholic University of Korea, Seoul, Korea.

Abstract

Although endometriosis is a common disease in women of reproductive age, rectal endometriosis is rare and lymph node involvement by endometriosis is considered uncommon. We report a 37-year-old woman who had irregular lower abdominal pain and changes in bowel habits. She was operated on with suspected rectal cancer, but the histological diagnosis was rectal endometriosis with lymph node involvement. In women who suffer from digestive complaints, endometriosis should be considered in differential diagnosis. Rectal endometriosis has the ability to invade adjacent tissue as true malignant tumors. Therefore, lymph node involvement should be considered in rectal endometriosis.

Am J Obstet Gynecol. 2011 Apr;204(4):303.e1-6. Epub 2011 Jan 21.

Urinary dysfunction after colorectal resection for endometriosis: results of a prospective randomized trial comparing laparoscopy to open surgery.

Ballester M, Chereau E, Dubernard G, Coutant C, Bazot M, Daraï E.

Source

Department of Gynecology and Obstetrics, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, CancerEst, Université Pierre et Marie Curie, Paris, France.

Abstract

OBJECTIVE:

To evaluate urinary symptoms before and after colorectal resection for endometriosis using validated questionnaires.

STUDY DESIGN:

We randomly assigned 52 patients with colorectal endometriosis to undergo laparoscopically assisted or open colorectal resection. The median follow-up was 19 months. Urinary symptoms were evaluated using the International Prostate Score Symptom and the Bristol Female Low Urinary Tract Symptoms questionnaires.

RESULTS:

Dysuria was observed in 29% of cases postoperatively. Using Bristol Female Low Urinary Tract Symptoms and International Prostate Score Symptom scores, an alteration was observed for voiding symptoms (P = .01 and P = .006, respectively). No difference was observed between the laparoscopy and the open surgery group. An alteration of the International Prostate Score Symptom voiding symptoms was observed in the group that did not undergo nerve sparing surgery (P = .048). An alteration of the International Prostate Score Symptom voiding symptoms was observed for patients who underwent vaginal resection (P = .01) and parametrial resection (P = .02).

CONCLUSION:

Our findings confirm that colorectal resection for endometriosis is a source of urinary dysfunction whatever the surgical route.

Am J Pathol. 2011 Apr;178(4):1782-91.

Circulating endothelial progenitor cells are up-regulated in a mouse model of endometriosis.

Becker CM, Beaudry P, Funakoshi T, Benny O, Zaslavsky A, Zurakowski D, Folkman J, D’Amato RJ, Ryeom S.

Source

Vascular Biology Program, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts; Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.

Abstract

Endometriosis is a debilitating disease characterized by the growth of ectopic endometrial tissue. It is widely accepted that angiogenesis plays an integral part in the establishment and growth of endometriotic lesions. Recent data from a variety of angiogenesis-dependent diseases suggest a critical role of bone marrow-derived endothelial progenitor cells (EPCs) in neovascularization. In this study we examined the blood levels of EPCs and mature circulating endothelial cells in a mouse model of surgically induced endometriosis. Fluorescence-activated cell sorting analysis revealed elevated levels of EPCs in the blood of mice with endometriosis compared with control subject that underwent a sham operation. EPC concentrations positively correlated with the amount of endometriotic tissue and peaked 1 to 4 days after induction of disease. In a green fluorescent protein bone marrow transplant experiment we found green fluorescent protein-positive endothelial cells incorporated into endometriotic lesions but not eutopic endometrium, as revealed by flow cytometry and immunohistochemistry. Finally, treatment of endometriosis-bearing mice with the angiogenesis inhibitor Lodamin, an oral nontoxic formulation of TNP-470, significantly decreased EPC levels while suppressing lesion growth. Taken together, our data indicate an important role for bone marrow-derived endothelial cells in the pathogenesis of endometriosis and support the potential clinical use of anti-angiogenic therapy as a novel treatment modality for this disease.

Am J Reprod Immunol. 2011 Apr;65(4):403-6. doi: 10.1111/j.1600-0897.2010.00920.x. Epub 2010 Sep 6.

The peritoneal leptin, MCP-1 and TNF-α in the pathogenesis of endometriosis-associated infertility.

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

Source

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

Abstract

PROBLEM:

To explore the roles of leptin, monocyte chemotactic protein (MCP)-1, and tumour necrosis factor (TNF)-α in the peritoneal fluid (PF) in the pathogenesis of endometriosis-associated infertility.

METHOD OF STUDY:

Leptin, MCP-1, and TNF-α levels in the PF from 28 infertile women with endometriosis (study group), 23 women with fallopian-associated infertility (controls), and 24 women with myoma (controls) were determined by performing enzyme-linked immunosorbent assay (ELISA).

RESULT:

Leptin and TNF-α levels in the PF showed no significant difference among three groups. The MCP-1 level in patients with endometriosis was higher than those in fallopian-associated infertility group and myoma group (P < 0.01). There was a positive correlation between leptin and MCP-1 levels in the PF of patients with endometriosis (P < 0.05).

CONCLUSION:

Peritoneal leptin and MCP-1 play important roles in the pathogenesis of infertility in the early stage of endometriosis.

Arch Gynecol Obstet. 2011 Apr;283(4):799-804. Epub 2010 Mar 24.

Efficacy of anti-tumor necrosis factor therapy on endometriosis in an experimental rat model.

Zulfikaroglu E, Kılıc S, Islimye M, Aydin M, Zergeroglu S, Batioglu S.

Source

Department of Obstetrics and Gynecology, Ankara Dr Zekai Tahir Burak Women Health Teaching and Research Hospital, 7.Cadde 70 A/14, Bahcelievler, 06490 Ankara, Turkey. zebru33@hotmail.com

Abstract

OBJECTIVE:

To show the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in an experimental model.

DESIGN:

A randomized, placebo-controlled, blinded study using rat endometriosis model.

SETTING:

Experimental research center of Ankara Education and Research Hospital.

ANIMAL(S):

Twenty-two Wistar female rats.

INTERVENTION(S):

After peritoneal implantation of endometrial tissue, rats were randomized to two equal intervention groups: control and etanercept-treated groups. After measuring implant volume, blood and peritoneal fluid samples were obtained. Vehicle treatments of 2 mL saline to rats in control and 0.4 mg/kg etanercept SC once weekly were administered in treatment group. Four weeks later, a third laparotomy was performed to remeasure implant volumes, blood, and peritoneal fluid samples.

MAIN OUTCOME MEASURE(S):

To compare spherical volume, peritoneal fluid and serum levels of VEGF, IL-6, and TNF-α between groups.

RESULT(S):

There was a significant difference in spherical volume between control [131.0 (60.3-501.2)] and treatment groups [72.8 (31.2-149.6)] (p < 0.025). In etanercept-treated group, a significant difference was found between peritoneal fluid and serum levels of VEGF, IL-6, and TNF-α (p < 0.01).

CONCLUSION(S):

These results indicate that etanercept was found to effectively reduce the development of endometriosis.

Bioanalysis. 2011 Apr;3(7):763-78.

Bioanalytical determination of unstable endogenous small peptides: RFRP3 & its metabolites in rat blood.

Haynes JJ, Jones H, Gibson D, Clark GT.

Source

Department of Pharmacokinetics, Dynamics and Metabolism (PDM), PGRD, Sandwich Laboratories, Kent, UK.

Abstract

Background: Targeting the gonadotropin-releasing hormone pathway for the treatment of endometriosis leads to an interest in monitoring for endogenous modulators of this pathway (RFRP3 and kisspeptin) as baseline controls for treatment development. Results: Stabilization of RFRP3 was shown to be extremely difficult in a highly enzymatically active matrix, such as rat blood. Sample denaturing with solvent at collection was necessary due to enzyme inhibition being unsuccessful at stabilization leading to difficulties in sample processing. Monitoring multiple fragments formed in blood can aid in profiling these peptides once in-source conversion is controlled. Conclusion: generic high-sensitivity LC-MS/MS assay was developed for RFRP3 and the fragments formed from it in whole blood. Use of 2D chromatography circumvents concentration and retention issues related to small fragments with a normal flow setup, making a more open-access approach feasible.

Biol Reprod. 2011 Apr;84(4):801-15. Epub 2010 Sep 23.

Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.

Aghajanova L, Tatsumi K, Horcajadas JA, Zamah AM, Esteban FJ, Herndon CN, Conti M, Giudice LC.

Source

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

Abstract

Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P(4)) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P(4), we compared early (6-h), intermediate (48-h), and late (14-Day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESF) from women with endometriosis (hESF(endo)) with hESF from women without endometriosis (hESF(nonendo)). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESF were isolated and treated with P(4) (1 μM) plus estradiol (E(2)) (10 nM), E(2) alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P(4) in both hESF(nonendo) and hESF(endo), although a blunted response to P(4) was observed in the latter. The normal response of hESF to P(4) involves a tightly regulated kinetic cascade involving key components in the P(4) receptor and MAPK signaling pathways that results in inhibition of E(2)-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESF(endo) early response to P(4). The abnormal response of this cell type to P(4) may contribute to compromised embryonic implantation and infertility in women with endometriosis.

Curr Opin Immunol. 2011 Apr;23(2):265-71. Epub 2011 Feb 1.

Epidemiologic perspective on immune-surveillance in cancer.

Cramer DW, Finn OJ.

Source

Obsterics-Gynecology Epidemiology Center, Department of Obsterics and Gynecology, Brigham and Women’s Hospital, Boston, MA 02115, USA.

Abstract

Common ‘themes’ in epidemiology related to cancer risk beg a comprehensive mechanistic explanation. As people age, risk for cancer increases. Obesity and smoking increase the risk for many types of cancer. History of febrile childhood diseases lowers the risk for melanomas, leukemias, non-Hodgkin’s lymphoma (NHL), and ovarian cancer. Increasing number of ovulatory cycles uninterrupted by pregnancies correlate positively with breast, endometrial, and ovarian cancer risk while pregnancies and breastfeeding lower the risk for these cancers as well as cancers of the colon, lung, pancreas, and NHL. Chronic inflammatory events such as endometriosis or mucosal exposure to talc increase the risk for several types of cancer. Mechanisms so far considered are site specific and do not explain multiple associations. We propose that most of these events affect cancer immunosurveillance by changing the balance between an effective immune response and immune tolerance of an emerging cancer. We review recently published data that suggest that immune mechanisms underlie most of these observed epidemiologic associations with cancer risk.

Eur J Obstet Gynecol Reprod Biol. 2011 Apr;155(2):221-4. Epub 2011 Jan 14.

Single port transumbilical laparoscopic surgery for adnexal lesions: a single center experience in Korea.

Jung YW, Choi YM, Chung CK, Yim GW, Lee M, Lee SH, Paek JH, Nam EJ, Kim YT, Kim SW.

Source

Department of Obstetrics and Gynecology, CHA University School of Medicine, Seoul, Republic of Korea.

Abstract

OBJECTIVES:

The purpose of this study was to demonstrate the feasibility of single port transumbilical laparoscopic surgery (SPLS) for the treatment of adnexal lesions.

METHODS:

We have performed SPLS to treat adnexal lesions using a single three-channel port system with a wound retractor and surgical glove since October 2008. All patients who underwent SPLS for adnexal lesions between October 2008 and September 2009 were included in the study. We retrospectively reviewed their medical records and analyzed demographic data and surgical outcomes including age, medico-surgical illness, surgical indications, operative times and pathologic results.

RESULTS:

Eighty-six patients underwent SPLS for adnexal lesions. The median age of the patients was 31 years (range 14-78 years), the median body mass index was 21.0kg/m(2) (range 16.7-32.2kg/m(2)), and the median operation time was 64.5min (range 21-176min). The median blood loss was 10ml (range 10-300ml). The median length of postoperative hospital stay was 2 days (range 1-7 days). Endometriosis was the most frequently diagnosed etiology (34.9%). Other laparoscopic approaches were employed in two cases (2.3%). There were four cases (4.7%) with complications: three with pelvic infections and one with postoperative hemorrhage.

CONCLUSIONS:

SPLS is a feasible approach for the treatment of adnexal lesions.

Eur J Obstet Gynecol Reprod Biol. 2011 Apr;155(2):183-7. Epub 2010 Dec 18.

Efficacy of transient abdominal ovariopexy in patients with severe endometriosis.

Carbonnel M, Ducarme G, Dessapt AL, Yazbeck C, Hugues JN, Madelenat P, Poncelet C.

Source

Services de Gynécologie Obstétrique et Médecine de la Reproduction, Centre Hospitalier Universitaire Jean Verdier, Paris, France.

Abstract

OBJECTIVE:

To assess adhesion formation and fertility outcome after transient abdominal ovariopexy performed in patients with severe endometriosis.

STUDY DESIGN:

Retrospective study including 218 patients who underwent surgery for severe endometriosis from 1997 to 2009. One hundred and thirty-nine (64%) patients were infertile. The initial ASRM stage was IV in 139 cases, III in 43 cases and II in 36 cases. Adnexal adhesions were scored by using the Operative Laparoscopy Study Group (OLSG) and modified AFS scoring systems. Unilateral or bilateral transient abdominal ovariopexy of 336 ovaries was performed to prevent adhesion formation or reformation for extensive surgery. In patients who underwent a second operation, adnexal adhesion scores were reported. Fertility outcome was evaluated by a questionnaire.

RESULTS:

Second-look surgery was performed after 11.7±2.4 months in 24 patients (11%) who had undergone 38 ovariopexies. Transient abdominal ovariopexy significantly decreased adnexal adhesion scores (p<0.05). Regarding fertility outcome, the median follow up was 19.6±1.5 months. Fifty-eight patients, out of 105 infertile women who actively tried to conceive after surgery, conceived, 21 (36%) spontaneously and 37 (64%) after ART. The median time interval for conception was 8.6±1 months.

CONCLUSION:

In patients with severe endometriosis, transient abdominal ovariopexy is an effective technique in preventing postoperative adhesion formation and in improving fertility outcome. CONDENSATION: In 218 patients with severe endometriosis, transient abdominal ovariopexy was an effective technique in preventing adhesion formation and improving fertility outcome.

Fertil Steril. 2011 Apr;95(5):1560-1567.e3. Epub 2011 Feb 21.

Proteolytic tailoring of the heat shock protein 70 and its implications in the pathogenesis of endometriosis.

Chehna-Patel N, Warty N, Sachdeva G, Khole V.

Source

Department of Gamete Immunobiology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Parel, Mumbai, India.

Abstract

OBJECTIVE:

To investigate the mechanism underlying the appearance of a 20-kd HSP70 fragment and its consequences in the ectopic endometrium of endometriosis patients.

DESIGN:

Experimental study.

SETTING:

Research institute and obstetrics and gynecology clinic.

PATIENT(S):

Participants with (n = 18) and without (n = 20) endometriosis.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Reverse-transcription polymerase chain reaction, protease assays, and in silico tools were used to investigate the origin of the 20-kd HSP70 fragment. Immunocolocalization studies were carried out to determine whether subtilisin/kexin isozyme 1 (SKI-1) and HSP70 are colocalized. Expression and localization of surrogate markers of inflammation, such as nuclear factor NF-κB and interleukin IL-6 were examined by immunoblotting and in situ studies.

RESULT(S):

HSP70 is posttranslationally processed into a 20-kd fragment by SKI-1, a protease of the subtilisin family, in ectopic endometrium (ECE). Immunocolocalization studies revealed spatial proximity of SKI-1 and HSP70 in ECE. Furthermore, ECE demonstrated nuclear localization of the transcription factor, NF-κB and high expression of its target protein, IL-6.

CONCLUSION(S):

This study hints at the possible mechanisms underlying the trimming of HSP70 in ECE and also at the role of proteases in the pathogenesis of endometriosis. The possible repercussions of HSP70 fragmentation include dysregulation of key regulatory proteins, resulting in the escalation of inflammatory events in endometriotic lesions.

Fertil Steril. 2011 Apr;95(5):1574-8.

Comparison of revised American Fertility Society and ENZIAN staging: a critical evaluation of classifications of endometriosis on the basis of our patient population.

Haas D, Chvatal R, Habelsberger A, Wurm P, Schimetta W, Oppelt P.

Source

General Hospital Linz, Department of Obstetrics and Gynecology, Linz, Austria.

Abstract

OBJECTIVE:

To develop a classification that takes deep infiltrating endometriosis into account, the ENZIAN score was introduced. The ENZIAN classification supplements the revised American Fertility Society (AFS) score with regard to the description of deep infiltrating endometriosis, retroperitoneal structures, and other organs. The null hypothesis was that classifying a lesion by the revised AFS as well as the ENZIAN system is not meaningful, because the two systems express different locations.

DESIGN:

Retrospective.

SETTING:

Hospital admissions.

PATIENT(S):

Two hundred nineteen women admitted for endometriosis.

INTERVENTION(S):

Surgical interventions.

MAIN OUTCOME MEASURE(S):

Classification of the severity of endometriosis according to the revised AFS and the ENZIAN classification, focusing on the distribution pattern in deep infiltrating endometriosis, and the identification of duplicate classifications of the same lesions in the revised AFS as well as the ENZIAN systems.

RESULT(S):

Deep infiltrating endometriosis was diagnosed in 160 of 219 patients (73%). These patients had 236 lesions of deep infiltrating endometriosis, which were classified by ENZIAN as follows: compartment a (vertical): 26%; compartment b (horizontal): 41%; compartment c (dorsal): 24%; uterine adenomyosis: 4%; bladder disease: 2%; ureter disease: 1%; and bowel disease: 2%. The severity of deep infiltrating endometriosis according to ENZIAN (grades 1 = mild to 4 = severe) was as follows: grade 1: 45%; grade 2: 26%; grade 3: 19%; grade 4: 10%. Fifty-eight patients were classified according to ENZIAN although they did not fulfill the criteria of deep infiltrating endometriosis and had previously been classified according to the revised AFS classification. Adaptation of the ENZIAN score would reduce the diagnoses of deep infiltrating endometriosis by 36% (95% confidence interval [CI] 29%-44%).

CONCLUSION(S):

The ENZIAN score is a helpful aid to describe deep infiltrating endometriosis, but needs to be adapted.

Fertil Steril. 2011 Apr;95(5):1568-73.

Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain.

Guzick DS, Huang LS, Broadman BA, Nealon M, Hornstein MD.

Source

University of Florida Health Science Center, Gainesville, Florida.

Abstract

OBJECTIVE:

To compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis-associated pain.

DESIGN:

Prospective, randomized, double-blind controlled trial.

SETTING:

Academic medical centers in Rochester, New York, and Boston, Massachusetts.

PATIENT(S):

Forty-seven women with endometriosis-associated pelvic pain.

INTERVENTION(S):

Forty-eight weeks of either depot leuprolide, 11.25 mg IM every 12 weeks with hormonal add-back using norethindrone acetate 5 mg orally, daily; or a generic monophasic oral contraceptive (1 mg norethindrone + 35 mg ethinyl estradiol) given daily.

MAIN OUTCOME MEASURE(S):

Biberoglu and Behrman (B&B) pain scores, numerical rating scores (NRS), Beck Depression Inventory (BDI), and Index of Sexual Satisfaction (ISS).

RESULT(S):

Based on enrollment of 47 women randomized to continuous oral contraceptives and to leuprolide, there were statistically significant declines in B&B, NRS, and BDI scores from baseline in both groups. There were no significant differences, however, in the extent of reduction in these measures between the groups.

CONCLUSION(S):

Leuprolide and continuous oral contraceptives appear to be equally effective in the treatment of endometriosis-associated pelvic pain.

Fertil Steril. 2011 Apr;95(5):1579-83. Epub 2011 Feb 4.

Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin.

Imesch P, Samartzis EP, Schneider M, Fink D, Fedier A.

Source

Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.

Abstract

OBJECTIVE:

To investigate whether the histone deacetylase (HDAC) inhibitor romidepsin down-regulates VEGF (vascular endothelial growth factor) gene expression and abrogates VEGF protein secretion in human epithelial endometriotic cells.

DESIGN:

In vitro study with human immortalized epithelial endometriotic cells.

SETTING:

University hospital.

PATIENT(S):

Not applicable.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Real-time reverse-transcriptase polymerase chain reaction to evaluate VEGF gene expression, immunoblot analysis to evaluate protein expression, and enzyme-linked immunosorbent assay to evaluate VEGF protein secretion into the culture medium.

RESULT(S):

Treatment of 11z human endometriotic cells with romidepsin statistically significantly inhibited VEGF gene transcription and down-regulated VEGF protein expression. Moreover, romidepsin abrogated the secretion of VEGF protein into the culture medium. Romidepsin also reduced the expression of hypoxia-inducible factor-1α (HIF-1α), which is implicated in the transcription of the VEGF gene, in cobalt chloride-pretreated (to mimic hypoxic conditions) 11z cultures.

CONCLUSION(S):

Romidepsin targets VEGF at the transcriptional level, which subsequently leads to the reduction of secreted VEGF (the “active” form of VEGF). Therefore, romidepsin may be a potential therapeutic candidate against angiogenesis in endometriosis.

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