Fertil Steril. 2009 Apr 25. [Epub ahead of print]

Coexistence of endometriosis in women with symptomatic leiomyomas.

Huang JQ, Lathi RB, Lemyre M, Rodriguez HE, Nezhat CH, Nezhat C.

Stanford University Medical Center, Department of Obstetrics and Gynecology, Palo Alto, California, USA.

OBJECTIVE: To investigate the coexistence of endometriosis in women presenting with symptomatic leiomyomas. DESIGN: Retrospective study. SETTING: Tertiary university medical center. PATIENT(S): We reviewed the medical records of 131 patients who underwent laparoscopic myomectomy or hysterectomy. All patients were consented for possible concomitant diagnosis and treatment of endometriosis. INTERVENTION(S): All patients underwent laparoscopic myomectomy or hysterectomy. MAIN OUTCOME MEASURE(S): The main outcome measure of the study was the presence or absence of endometriosis. RESULT(S): Of the 131 patients, 113 were diagnosed with endometriosis and fibroids, while 18 were diagnosed with fibroids alone. Patients with fibroids were on average 4.0 years older than those with endometriosis and fibroids (41 vs. 45). Patients with both diagnoses were also more likely to present with pelvic pain and nulliparity than those with fibroids alone. CONCLUSION(S): An overwhelming majority of patients with symptomatic fibroids were also diagnosed with endometriosis. Overlooking the concomitant diagnosis of endometriosis in these women may lead to suboptimal treatment of the patients. Further studies are needed to evaluate the impact of surgical treatments on symptom resolution.

Womens Health (Lond Engl). 2009 May;5(3):297-311.

Adenomyosis: new knowledge is generating new treatment strategies.

Benagiano G, Brosens I, Carrara S.

Department of Gynecology & Obstetrics, Sapienza University of Rome, Rome, Italy. [email protected]

In the early days, all mucosal invasions of abdominal organs were considered to be one pathological condition of uncertain origin, termed adenomyoma. It was only in the 1920s that endometriosis and adenomyosis were clearly separated and it took approximately 80 years to put forward a new theory reunifying their pathogenesis. Today, identification of adenomyosis is carried out exclusively through vaginal ultrasonography and MRI. These techniques have made a careful evaluation of a distinct anatomical structure and the inner myometrial layers underlying the endometrium, termed the junctional zone, possible. Adenomyosis is characterized by a homogeneous thickening of this portion of the myometrium. When this hyperplasia is associated to an alteration of spiral arterioles’ angiogenesis, then both adenomyosis and endometriosis may develop. Evidence is being accumulated that pre-eclampsia, fetal growth restriction and premature delivery may be linked, together representing a new, major obstetrical syndrome characterized by a modified uterine environment around the time of nidation. A dozen different medical or surgical techniques are utilized for the treatment of adenomyosis and novel approaches are being tested. These include use of inhibitors of angiogenesis that have been shown to cause reduced neo-angiogenesis, a significant modification of gene expression and a decrease in the percentage of active lesions. Encouraging results have also been obtained with the levonorgestrel-releasing intrauterine system.

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Endocrinology. 2009 Aug;150(8):3863-70. Epub 2009 Apr 23.

The progesterone receptor coactivator Hic-5 is involved in the pathophysiology of endometriosis.

Aghajanova L, Velarde MC, Giudice LC.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USA.

Endometriosis is an estrogen-dependent disorder primarily associated with pelvic pain and infertility in up to 10% of women of reproductive age. Recent studies suggest that resistance to progesterone action may contribute to the development and pathophysiology of this disorder. In this study we examined the in vivo and in vitro expression and function of one progesterone receptor (PR) coactivator, Hic-5, in human endometrium and endometrial stromal fibroblasts (hESFs) from 29 women with and 30 (control) women without endometriosis. Hic-5 was highly expressed in stromal, but not epithelial, cells in women without endometriosis, in a cycle-dependent manner. In contrast, Hic-5 expression was not regulated during the menstrual cycle in hESFs from women with endometriosis and was significantly reduced in hESFs from women with vs. without disease. Hic-5 mRNA expression throughout the cycle in endometrium from control women, but not those with endometriosis, correlated with expression of PR. Hic-5 mRNA in hESFs was significantly up-regulated in control but not endometriosis hESFs after treatment in vitro with 8-bromoadenosine-cAMP for 96 h but only modestly after 14 d of progesterone treatment. Hic-5 silencing did not influence cAMP-regulated gene expression but affected genes regulated solely by progesterone (e.g. DKK1 and calcitonin). Together the data suggest that the proposed progesterone resistance in endometrium from women with endometriosis derives, in part, from impaired expression of the PR coactivator, Hic-5, in endometrial tissue and cultured endometrial stromal fibroblasts.

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Pol Merkur Lekarski. 2009 Mar;26(153):231-3.


Pharmacotherapy for pelvic endometriosis in women

[Article in Polish]

Starczewski A, Brodowska A, Brodowski J.

Department of Reproduction and Gynecology, Pomeranian Medical University of Szczecin, Poland.

Pelvic endometriosis in women is a very common disease. The incidence of this condition in Poland in reproductive age women is about 7-15%, and as much as 50% of cases is diagnosed in patients with co-existing infertility and/or pain and adhesion of a true pelvis. The choice of a therapeutic method depends on the patient’s age, stage of the disease, desire for pregnancy, the presence of adhesion, focus localization and a reaction to previous treatment. Currently, the most popular is surgical treatment sometimes followed by pharmacotherapy. Pharmacological treatment includes hormone therapy and symptomatic treatment, also the use of painkillers. Hormonal agents are administered to suppress ovarian activity and cause atrophy of ectopic foci of endometrium. At present, post-surgical pharmacotherapy for endometriosis uses mainly such hormones as: the Combined Oral Contraceptive Pill (COCP), progestagens, danazol, GnRh (gonadotropin-releasing hormone) analogues, aromatase inhibitors and other less common drugs. Also other therapeutic procedures are recommended in endometriosis treatment, procedures which support and in certain clinical situations even replace classical pharmacological methods. Some of them are immunotherapy and a diet rich in isoflavones, organic compounds which modulate estrogen receptor activity. Numerous clinical trials proved that preoperative pharmacotherapy does not improve treatment results and is not applicable to endometriomas in women. On the other hand, postoperative pharmacotherapy still ignites controversy. As maintained by the most recent literature, in the case of mild endometriosis (clinical Stage I and II according to the American Society for Reproductive Medicine) endometrial ablation has better effects than observation only, however postoperative pharmacotherapy does not improve the results of treatment. In more severe cases (clinical Stage III and IV), the best results are achieved by the combined treatment. Nevertheless, no randomized research has been carried out on a wide scale in this group of patients.

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Reprod Sci. 2009 Aug;16(8):727-33. Epub 2009 Apr 22.

Activin A, activin receptor type II, nodal, and cripto mRNA are expressed by eutopic and ectopic endometrium in women with ovarian endometriosis.

Torres PB, Florio P, Galleri L, Reis FM, Borges LE, Petraglia F.

Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy.

Activin A is a dimeric protein that regulates endometrial functions by signaling at its receptors, namely type I (ActRI) and type II (ActRII). Nodal is an activin competitor that requires the coreceptor cripto to assemble its signaling pathway through ActRI and ActRII. In the current study, we evaluated the expression of activin A, ActRII, nodal, and cripto in eutopic and ectopic endometrium collected from women with ovarian endometrioma (n = 15) and in eutopic endometrium of healthy participants (n = 15). Eutopic endometrial samples were evaluated according to the stage of menstrual cycle. Total RNA was extracted from tissue homogenates and analyzed by real-time polymerase chain reaction (PCR). Activin A messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis was significantly higher than in controls (P < .001) with a 10.2-fold and 7.3-fold increase in the proliferative and secretory phases, respectively. ActRII and nodal mRNA expression were found to be similar in patients with and without endometriosis, while cripto mRNA was markedly lower in eutopic (fold change = 0.03 at proliferative phase, P < .001) and ectopic endometrium (fold change = 0.14, P < .001) of women with endometriosis compared with eutopic endometrium from healthy controls. In conclusion, the altered endometrial expression of activin A and cripto during the menstrual cycle and the differences observed in the endometriotic tissue support the involvement of the activin system in endometrial changes of women with endometriosis.

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Hawaii Med J. 2009 Mar;68(2):40-6.


Ovarian cancer: risks.

Sueblinvong T, Carney ME.

Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawai’i, USA.

Publication Types:

Ginekol Pol. 2009 Mar;80(3):172-8.


Effects of presacral neurectomy on pelvic pain in women with and without endometriosis.

Jedrzejczak P, Sokalska A, Spaczyński RZ, Duleba AJ, Pawelczyk L.

Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, Poznan, Poland. [email protected]

OBJECTIVE: Presacral neurectomy (PSN) is used in treatment of central chronic pelvic pain (CPP); however, the confounding effect of concomitant resection of endometriosis remains uncertain. This study was undertaken to evaluate and compare the effectiveness of presacral neurectomy (PSN) in the presence and absence of endometriosis. MATERIAL AND METHODS: Twenty-three women with midline CPP (age 30.3 +/- 7.9, range 21-46) unresponsive to medical therapy were recruited to the study. Endometriosis was absent in seven and present in sixteen subjects. Laparoscopic PSN using a harmonic scalpel was performed in all subjects; simultaneous excision of endometriotic lesions was also carried out in subjects with endometriosis. Intensity of dysmenorrhoea and pelvic pain was measured by visual analogue pain scale (VAPS) at 3 and 12 months postoperatively. RESULTS: Dysmenorrhoea decreased at 3 months by 75% (P = 0.018) in those without endometriosis and by 78% (P = 0.001) in those with endometriosis. At 12-months, dysmenorrhea increased in women with endometriosis (P = 0.008), but not in those without endometriosis. Pelvic pain not related to menses decreased by 67% (P = -0.0007) and by 87% (P = 0.028), respectively, in women with and without endometriosis. Dyspareunia, declined dramatically at 3 and 12 months to a median score of 0 (the majority of subjects had no discomfort; P < 0.001); the change in dyspareunia between 3 and 12 months was in favour of patients without endometriosis (P = 0.02) CONCLUSIONS: PSN using a harmonic scalpel results in long-term pain relief, especially in patients without endometriosis.

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Reprod Sci. 2009 Apr 20. [Epub ahead of print]

Luminescence as a Tool to Assess Pelvic Endometriosis Development in Murine Models.

Defre Re S, Colette S, Lousse JC, Donnez J, Van Langendonckt A.

Classic murine endometriosis models may be insufficient to evaluate the effect of therapeutic agents on endometriosis development, because the process of identification and measurement of induced lesions is often impeded, as implants are small and embedded in murine tissue. In this context, as summarized in the current review, luminescence techniques have proved useful for identifying and visualizing or quantifying endometriotic transplants. They are also a valuable tool for endometrial cell tracking in live animals, yielding further information by adding spatial and temporal dimensions to biological processes in vivo. Such approaches involve transplanting luminescently labeled murine or human endometrium into animals. Two main strategies are applied to label endometrium before injection: use of genetically modified tissue or tissue labeled with a fluorescent dye. Each model has its advantages and disadvantages, the choice of model depends on the study objectives/design (long- or short-term studies, homologous or heterologous model).

Scand J Work Environ Health. 2009 May;35(3):233-40. Epub 2009 Apr 17.

Lifetime occupational history and risk of endometriosis.

Marino JL, Holt VL, Chen C, Davis S.

Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide SA 5000, Australia. [email protected]

OBJECTIVES: Endometriosis is the presence of functioning endometrial glands and stroma outside the uterine cavity, most often in the pelvic peritoneal cavity. Women with endometriosis commonly have dysmenorrhea, dyspareunia, pain, menorrhagia, and/or metrorrhagia. Disease complications can include adhesions, chronic pain, and infertility. In this exploratory case-control study, we investigated the relationship between lifetime occupational history and surgically confirmed endometriosis in a population-based sample. METHODS: We conducted interviews with participants, all reproductive-aged female members of a large health-maintenance organization who were first diagnosed with surgically confirmed endometriosis between April 1, 1996 and March 31, 2001. Interviews were also conducted with randomly selected controls, reproductive-aged female enrollees of the same organization from the same time period. Each reported job was coded using US Census Occupations and Industries codes, and classified into categories. We used unconditional logistic regression to compare having worked in a given job class with never having done so. RESULTS: Our study found that an increased risk of endometriosis was associated with having worked as a flight attendant, service station attendant, or health worker, particularly as a nurse or health aide (flight attendant: odds ratio (OR) 9.80, 95% CI 1.08-89.02; service station attendant: OR 5.77, 95% CI 1.03-32.43; health worker: OR 1.49, 95% CI 1.03-2.15). Income and education did not make a difference in the OR estimates for the occupations examined. CONCLUSIONS: This exploratory study suggested that there might be an associated risk of endometriosis for those women who have worked as a flight attendant, service station attendant, or health worker, particularly a nurse.

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Fertil Steril. 2009 Apr 17. [Epub ahead of print]

Practice patterns and outcomes with the use of single embryo transfer in the United States.

Luke B, Brown MB, Grainger DA, Cedars M, Klein N, Stern JE; a Society for Assisted Reproductive Technology Writing Group.

Department of Obstetrics, Gynecology, and Reproductive Biology and Department of Epidemiology, Michigan State University, East Lansing, Michigan.

OBJECTIVE: To evaluate factors associated with the use of elective single embryo transfer (eSET) and its effect on assisted reproductive technology (ART) outcome. DESIGN: Historical cohort. SETTING: Clinic-based data. PATIENT(S): A total of 69,028 ART cycles of autologous fresh embryo transfers with additional embryos cryopreserved during the same cycle performed during 2004-06 and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Factors associated with the number of embryos transferred, and the odds of pregnancy, live birth, and multiple-infant live birth by number of embryos transferred as adjusted odds ratios (AORs). RESULT(S): Single embryo transfer was used more with uterine factor (AOR 1.76) and less with male factor, endometriosis, or tubal factor (AOR 0.81, 0.72, 0.83, respectively). Compared with women aged <30 years, eSET was used less among women aged 35-39 years and >/=40 years (AOR 0.74 and 0.39, respectively). Compared with White women, eSET was used more with Asian (AOR 1.52) and less with Black or Hispanic women (AOR 0.73 and 0.67, respectively). Compared with eSET, the likelihood of pregnancy, live birth, or multiple-infant live birth was more likely with two embryos (AOR 1.33, 1.34, and 27.4, respectively). CONCLUSION(S): Elective SET, used more for younger women with specific diagnoses, is associated with slightly reduced likelihood of a live birth but much reduced likelihood of multiples.

J Reprod Immunol. 2009 Jun;80(1-2):80-90. Epub 2009 Apr 18.

Intraperitoneal immune cell status in infertile women with and without endometriosis.

Tariverdian N, Siedentopf F, Rücke M, Blois SM, Klapp BF, Kentenich H, Arck PC.

Center of Internal Medicine and Dermatology, Division of PsychoNeuroImmunology, Charité, University Medicine Berlin, Berlin, Germany.

Endometriosis is a widespread chronic disease characterized by endometrial tissue located outside the uterine cavity. Clinical signs are chronic pelvic pain and infertility. Emerging evidence indicates that the immune system is profoundly involved in the onset and/or progression of endometriosis. However, mechanistic pathways have not yet been conclusively specified. In this study, women undergoing diagnostic laparoscopy due to infertility were recruited, and classified as early-stage endometriosis (n=30), advanced-stage endometriosis (n=8) or no endometriosis (n=31). The frequency and phenotype of leukocytes were evaluated in peritoneal fluid. While the frequency of lymphocytes was not significantly different, neutrophils were increased in endometriosis. Flow cytometry analysis revealed an increased frequency of CD4(+) and CD8(+) cells in peritoneal fluid of endometriosis patients. In addition, the frequency of CD4(+)CD25(+)CD103(+) cells and lineage(-)HLA-DR(+)CD11c(+)CD123(+) dendritic cells was decreased in peritoneal fluid in endometriosis, whereas CD57(+) NK cells and CD8(+)CD28(-) T suppressor cells remained largely unaltered. We conclude that therapeutic approaches in endometriosis might focus on peritoneal leukocytes as a target or surveillance marker; however, immune alterations in peritoneal fluid are subtle and their analysis will require highly standardized and harmonized protocols.

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Neuropeptides. 2009 Jun;43(3):229-34. Epub 2009 Apr 16.

Effects of the LHRH antagonist Cetrorelix on the brain function in mice.

Telegdy G, Tanaka M, Schally AV.

Department of Pathophysiology, University of Szeged, Semmelweis 1, 6701 Szeged, Csongrad, Hungary. [email protected]

The decapeptide Cetrorelix, an LHRH antagonist, inhibits gonadotropin and sex steroid secretion. Cetrorelix is used for IVF-ET procedures and for the treatment of patients with prostate carcinoma, benign prostatic hyperplasia, endometriosis, leiomyomas and, ovarian cancer. However little is known about the effects of Cetrorelix on the brain function. In the present work the influence of Cetrorelix on different aspects of the brain function was studied following its administration into the lateral brain ventricle in mice. The effects tested included the impairment of the consolidation of a passive avoidance reflex caused by beta-amyloid 25-35, anxiolytic action in the plus-maze, antidepressive action in a forced swimming test and a tail suspension test and open-field behavior. In the passive avoidance test, beta-amyloid 25-35 administered immediately after the learning trial impaired the consolidation of passive avoidance learning. Cetrorelix fully blocked the impairment of the consolidation of passive avoidance learning when given icv 30 min following beta-amyloid 25-35 administration. If beta-amyloid 25-35 and Cetrorelix icv were given simultaneously, the Cetrorelix attenuated, but did not block the action of the beta-amyloid 25-35. Cetrorelix elicited anxiolytic action in the plus-maze, depending on the dose used. In the forced swimming and tail suspension tests, Cetrorelix demonstrated antidepressive-like action. Concerning open-field behavior, Cetrorelix displayed no action on locomotion, rearing or grooming. The results demonstrate that Cetrorelix affects brain function: and is able to correct the impairment of the memory consolidation caused by beta-amyloid 25-35. Cetrorelix also elicits anxiolytic and antidepressive action, but it does not influence the open-field activity. Further experimental work with Cetrorelix is necessary, but the results imply the possible merit of a clinical trial with Cetrorelix in patients with anxiety, depression and Alzheimer’s disease.

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Indian J Biochem Biophys. 2009 Feb;46(1):59-65.


Curcumin arrests endometriosis by downregulation of matrix metalloproteinase-9 activity.

Swarnakar S, Paul S.

Department of Physiology, Drug Development Diagnostics and Biotechnology Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India. [email protected]

Curcumin, a polyphenol derived from turmeric (Curcuma longa) possesses diverse pharmacological properties including antioxidant, anti-inflammatory and antiproliferative activities. Endometriosis is a gyneocological disorder characterized by growth of endometrial tissues outside uterus that involves aberrant matrix remodeling. In this study the effect of curcumin was studied on surgically developed endometriosis in mice. Endometriosis with varying severity was developed in mice by peritoneal implantation of uterine fragments. The changes in matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloprotease (TIMP)-1 were investigated in endometriotic tissues following curcumin pre- and posttreatment. Results showed that MMP-9 activity increased gradually in endometriotic tissues with severity and curcumin treatment reversed the MMP-9 activity near to control value. Curcumin administered either post- or pre-endometriosis arrested endometriosis in a dose-dependent manner. It inhibited both MMP-9 activity and its expression at the level of secretion, during regression of endometriotic lesion. In addition, the attenuated activity of MMP-9 was associated with decreased expression of tumor necrosis factor-alpha (TNF-alpha) during healing, suggesting the anti-inflammatory property of curcumin. Moreover, curcumin pretreatment prevented lipid peroxidation and protein oxidation in endometriotic tissues. We reported here for the first time the anti-endometriotic property of curcumin via MMP-9 dependent pathway that may lead to new therapeutic intervention.

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Jpn J Radiol. 2009 Jan;27(1):45-7. Epub 2009 Feb 8.

Magnetic resonance imaging findings of extrapelvic endometriosis of the round ligament.

Tokue H, Tsushima Y, Endo K.

Department of Diagnostic and Interventional Radiology, Gunma University Hospital, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan. [email protected]

A 31-year-old woman presented with a mass in her groin accompanied by intense pain during the menstrual period. A poorly circumscribed, elastic, hard mass was palpable in her right inguinal region. Magnetic resonance imaging showed that the mass had continuity with the inguinal course of the round ligament of the uterus. The mass lesion was well enhanced with high intensity on diffusion-weighted imaging. An operation was performed, and the histological diagnosis was endometriosis of the round ligament. After operation, she was completely relieved of pain. It is important to include endometriosis in the differential diagnosis in women with painful inguinal mass lesions at risk for endometriosis.

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J Reprod Med. 2009 Mar;54(3):155-9.

Abdominal wall endometriomas.

Chang Y, Tsai EM, Long CY, Chen YH, Kay N.

Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

OBJECTIVE: Abdominal wall endometriosis is rare, with an incidence of 0.03-0.47% following cesarean delivery. STUDY DESIGN: The study reviewed abdominal wall endometriomas during an 8-year period in the Department of Obstetrics and Gynecology of the Kaohsiung Municipal Hsiao-Kang Hospital. RESULTS: Of 166 patients with endometriosis treated surgically in the hospital during an 8-year period, 20 (12%) had abdominal wall endometriomas. The mean interval between the prior operation and the appearance of the first symptoms was 39.3 months. Preoperative diagnosis was correct in 14 patients (70%). CONCLUSION: Abdominal wall endometrioma is more common than generally assumed in patients visiting the hospital. In patients with a palpable subcutaneous mass near surgical scars associated with cyclic or constant pain, a thorough history and physical examination are sufficient to establish the presence of endometriomas. A surgical-wide excision with clear margins is the single treatment of choice.

J Reprod Med. 2009 Mar;54(3):145-50.

Correlation of anterior vaginal wall pain with endometriosis in infertile patients.

Paulson JD.

Eastern Virginia Medical School, Norfolk, USA. [email protected]

OBJECTIVE: To investigate whether anterior vaginal wall tenderness in a patient with unexplained infertility correlated to a high percentage of finding endometriosis on laparoscopy. METHOD: Fifty-five consecutive patients with unexplained infertility had vaginal examinations with anterior wall palpation to determine whether there was tenderness (AVWT). As part of the infertility workup, laparoscopy, biopsies and cystoscopy with hydrodistention were performed. RESULTS: The prevalence ofendometriosis in this study was 78%. The sensitivity of positive AVWT on palpation with patients who were found to have endometriosis was 84%, and the specificity was 75%. The positive predictive value was 86% and the negative predictive value was 69%. CONCLUSION: Unexplained infertility may be amenable to treatment in finding problems such as endometriosis, adhesions or subtle other problems that can be corrected by use of laparoscopy instead of going directly to in vitro fertilization. AVWT is a test that may be able to aid physicians in choosing a management to treat a patient with a laparoscopy early in the workup.

Cochrane Database Syst Rev. 2009 Apr 15;(2):CD004753.

Update of:

Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis.

Allen C, Hopewell S, Prentice A, Gregory D.

Cochrane Collaboration Secretariat, Summertown Pavilion, 18-24 Middle Way, Oxford, UK, OX2 7LG. [email protected].

BACKGROUND: Endometriosis is a common gynaecological condition that affects women and can lead to painful symptoms and infertility. It greatly affects women’s quality of life, impacting on their careers, everyday activities, sexual and non-sexual relationships, and fertility. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used first-line treatment for endometriosis. OBJECTIVES: To assess the effects of NSAIDs used for the management of pain in women with endometriosis compared to placebo, other NSAIDs, other pain management drugs, or no treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (April 2008) published in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (1966 to April 2008), EMBASE (1980 to April 2008), and the reference lists from relevant publications. Experts in the field were also contacted for information about possible studies. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) describing the use of NSAIDs in the treatment of endometriosis in women of all ages. DATA COLLECTION AND ANALYSIS: Two review authors (CA and SH) independently read and extracted data from each of the included studies. Crossover trials were analysed using the inverse variance method in RevMan to calculate the odds ratio for binary outcomes. MAIN RESULTS: Two trials were identified but only one trial, with 24 women, was included in the analysis. Comparing NSAIDs (naproxen) to placebo, there was no evidence of a positive effect on pain relief (odds ratio (OR) 3.27, 95% CI 0.61 to 17.69) in women with endometriosis. There was also inconclusive evidence to indicate whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12, 95% CI 0.01 to 1.29) or to experience side effects (OR 0.46, 95% CI 0.09 to 2.47) when compared to placebo. AUTHORS’ CONCLUSIONS: There is inconclusive evidence to show whether or not NSAIDs (naproxen) are effective in managing pain caused by endometriosis. There is no evidence on whether any individual NSAID is more effective than another. As shown in other Cochrane reviews, women using NSAIDs need to be aware of the possibility that these drugs may cause unintended effects.

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J Clin Endocrinol Metab. 2009 Jul;94(7):2489-94. Epub 2009 Apr 14.

Simvastatin protects against the development of endometriosis in a nude mouse model.

Bruner-Tran KL, Osteen KG, Duleba AJ.

Women’s Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

CONTEXT: Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. OBJECTIVE: The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. METHODS: Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg x d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. PRIMARY OUTCOME: The number and size of endometriotic implants were measured. RESULTS: Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1alpha). CONCLUSIONS: Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins.

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JSLS. 2009 Jan-Mar;13(1):14-8.

Natural orifice-assisted laparoscopic appendectomy.

Nezhat C, Datta MS, Defazio A, Nezhat F, Nezhat C.

Atlanta Center for Special Minimally Invasive Surgery and Reproductive Medicine, Atlanta, Georgia, USA. [email protected]

BACKGROUND AND OBJECTIVES: Natural orifice transluminal endoscopic surgery involves the introduction of instruments through a natural orifice into the peritoneal cavity to perform diagnostic and therapeutic surgical interventions. We report the utilization of the vaginal opening at the time of laparoscopic-assisted vaginal hysterectomy or total laparoscopic hysterectomy as a natural orifice for appendectomy. METHODS: We reviewed cases of 42 patients who underwent total laparoscopic hysterectomy or laparoscopic-assisted vaginal hysterectomy followed by appendectomy, performed by applying a stapler and removing the appendix transvaginally. By using a small-diameter laparoscope, the appendix was mobilized, especially in patients with adhesions, endometriosis, or retrocecal appendix, to facilitate transvaginal access with the stapler. RESULTS: All procedures were performed successfully without intraoperative or major postoperative complications. The appendectomy portion of the procedure took approximately 5 minutes to 10 minutes. Appendiceal pathology included serosal adhesions (14), fibrous obliteration of the lumen (12), endometriosis (4), serositis (2), and carcinoid tumor (1), among others. CONCLUSIONS: Appendectomy performed with an endoscopic stapler introduced transvaginally for amputation and retrieval following total laparoscopic hysterectomy or laparoscopically assisted vaginal hysterectomy appears to be a safe and effective modification of established techniques with acceptable outcomes.

Acta Cytol. 2009 Mar-Apr;53(2):195-7.

Chronic ovarian pregnancy mimicking an ovarian tumor diagnosed by peritoneal washing cytology: a case report.

Su CC, Tzeng CC, Huang KF.

Department of Clinical Pathology, Buddhist Dalin Tzu Chi General Hospital, 2, Minsheng Road, Dalin Town, Chiayi County 622, Taiwan. [email protected]

BACKGROUND: Chronic ectopic pregnancy is an enigma. The clinical presentation can be mild, with absent or subtle symptoms. Ovarian pregnancy usually ends with rupture. We report the first case of unruptured chronic ovarian pregnancy that was initially diagnosed by peritoneal washing cytology. CASE: A 35-year-old woman suffered from low abdominal pain during the presumed menstrual period for 6 months. Abdominal computed tomography revealed a huge cystic mass with intralesional hematoma and soft tissue components located in the pelvic cavity. Mild right hydronephrosis caused by tumor obstruction of the right ureter were noted. Right ovarian cancer was suspected. Peritoneal washing cytology revealed both cytotrophoblasts and syncytiotrophoblasts. Patient received enucleation of the right ovary. Microscopically, the ovarian mass exhibited extensive hemorrhage and necrosis, embedding degenerated chorionic villi. CONCLUSION: When a patient experiences low abdominal pain during a menstrual period, the possibility of ectopic pregnancy should be considered in addition to possible endometriosis. Ovarian or other abdominal pregnancies, even untruptured, may be discriminated from other lesions in cases of abdominal pain by peritoneal washing cytology.

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Gynecol Obstet Invest. 2009;68(1):40-52. Epub 2009 Apr 9.

Toll-like receptors in innate immunity: role of bacterial endotoxin and toll-like receptor 4 in endometrium and endometriosis.

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

Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan. [email protected]

Macrophages, dendritic cells, and Toll-like receptors (TLRs) are integral components of the innate immune system. This rapidly reactive system responds immediately to infectious or other non-self agents, thereby inducing an inflammatory response to protect the host until the activation of the slower adaptive immune system. The fundamentals of the innate immune system, functional characteristics of TLRs, and signaling pathways of TLR4 are discussed for the easy understanding by readers. Studies showed that the growth and progression of endometriosis continue even in ovariectomized animals. This indicates that besides ovarian steroid hormones, the growth of endometriosis can be regulated by the innate immune system in the pelvic environment. As a component of the innate immune system, increased infiltration of macrophages has been described in the intact tissue and peritoneal fluid of women with endometriosis. In this review article, we discuss the role of bacterial endotoxin and TLR4 in endometrium and endometriosis and outline the involvement of endotoxin in causing adverse reproductive outcome.

Publication Types:

Arch Gynecol Obstet. 2009 Apr 12. [Epub ahead of print]

OC-125 immunostaining in endometriotic lesion samples.


Barbosa CP, de Souza AM, Bianco B, Christofolini DM, Mafra FA, de Lima GR.

Disciplina de Genética e Reprodução Humana, Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina do ABC, FMABC, Avenida Príncipe de Gales, 821, Prédio CEPES, 2 degrees . Andar, Santo André, São Paulo, CEP 09060-650, Brazil, [email protected].

PURPOSE: To determine the presence of OC-125 staining in endometriotic lesions and to verify whether there is an association with endometriosis stage. METHODS: Thirteen patients from the Family Planning programs (group I) and 53 patients from the Chronic Pelvic Pain outpatient clinic (group II) were studied. Endometriotic lesions were excised from areas of endometriosis incidence and studied by histopathological assay and by immunohistochemistry for OC-125 staining. RESULTS: The histopathological study disclosed that all patients from group I had minimal/mild endometriosis. In group II, 39.6% had minimal/mild endometriosis, and 60.4% had moderate/severe endometriosis. OC-125 staining was negative in all samples from group I. In group II, OC-125 staining was positive in 52.4% patients with minimal/mild endometriosis and in 81.2% with moderate/severe endometriosis. CONCLUSION: The data suggest that the OC-125 antibody is probably related to endometriosis activity and, consequently, to the progression and severity of the illness.

Hum Reprod. 2009 Aug;24(8):1818-24. Epub 2009 Apr 10.

Decidualized ovarian endometriosis in pregnancy: a challenging diagnostic entity.

Barbieri M, Somigliana E, Oneda S, Ossola MW, Acaia B, Fedele L.

Department of Obstetrics, Gynecology and Neonatology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Via Commenda 12, 20122 Milan, Italy.

BACKGROUND: The hormonal milieu that characterizes pregnancy may determine profound modifications of ovarian endometriomas leading to lesions mimicking malignancy. In this study, we report on our experience and perform a review of the literature on this issue. METHODS: Data from women evaluated at our referral center for prenatal diagnosis were reviewed in order to identify those who were detected with an ovarian endometrioma in pregnancy mimicking malignancy. A review of the literature on this issue (1990-2008) was also performed, using the PubMed database. RESULTS: Three cases were identified at our center. The literature reports on a further 19 cases (11 studies). Sonographic and color Doppler examination consistently documented rapidly growing and abundantly vascularized intracystic excrescences. Conversely, the presence of septations or significant free fluid was never reported. The vast majority of cases underwent surgical removal. Interestingly, in our experience, in a woman who declined surgery and had spontaneous miscarriage at 10 weeks’ gestation, the sonographic examination performed 6 weeks after dilatation and curettage revealed an unremarkable typical endometrioma, thus suggesting that it is a transitory transformation. CONCLUSIONS: Pregnancy-related modifications of an ovarian endometrioma leading to the rapid development of vascularized intracystic excrescences are an uncommon but possible event. An expectant management and serial monitoring should first be envisaged in these cases provided that other features of malignancy, such as septations or free fluid, are absent.

Publication Types:

Fertil Steril. 2009 Apr 8. [Epub ahead of print]

Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery.

Donnez J, Lousse JC, Jadoul P, Donnez O, Squifflet J.

Department of Gynecology, Université Catholique de Louvain, Brussels, Belgium.

OBJECTIVE: To describe and evaluate a new technique of laparoscopic treatment of endometriomas that combines excisional and ablative surgery. DESIGN: Descriptive and prospective study. SETTING: Gynecology research unit in a university hospital. PATIENT(S): Fifty-two women under 35 years of age presenting for infertility and/or pelvic pain with endometriomas larger than 3 cm were included in the study. None had undergone any surgery for endometriosis. INTERVENTION(S): A large part of the endometrioma wall was first excised according to the cystectomy technique. After this first step, CO(2) laser was used to vaporize the remaining 10%-20% of the endometrioma wall close to the hilus. MAIN OUTCOME MEASURE(S): The feasibility of this new technique was assessed. Ovarian volume and antral follicle count (AFC) were compared between operated ovaries and nonoperated ovaries of patients with endometriosis and controls (women with male factor infertility). RESULT(S): The combined technique was possible in all cases. The volume of the ovary after the combined technique was similar to that of the contralateral normal ovary, as well as to that observed in infertile women without endometriosis presenting for male factor infertility. The AFC on day 2-5 showed the same number of antral follicles in all subgroups. Histopathology of the excised part of the endometrioma revealed the presence of follicles in only one case (2%). The pregnancy rate was 41% at a mean follow-up of 8.3 months. Recurrence of a small endometrioma was observed in only one case (2%). CONCLUSION(S): The combined technique (stripping and ablation) has proved not to be deleterious to the ovary.

Zhong Xi Yi Jie He Xue Bao. 2009 Apr;7(4):360-5.

Effects of Caulis Sargentodoxae Granule on expressions of vascular endothelial growth factor and its receptor-2 in rats with endometriosis

[Article in Chinese]

Cao Y, Zhang TT, Xie SW, Zhu Y, Shu LD, Song ZL, Cao L, Dai DY.

Department of Gynecology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China.

OBJECTIVE: To investigate the effects of Caulis Sargentodoxae Granule (CSG), a compound traditional Chinese herbal medicine for treating endometriosis, on expressions of vascular endothelial growth factor (VEGF) and its receptor-2 fetal liver kinase-1 (Flk-1) in rats with endometriosis. METHODS: A rat model of endometriosis was established by autotransplant of endometria. Forty-eight endometriosis rats were randomly divided into 6 groups: untreated group, castrate group, mifepristone group (5 mg/kg) and low- (20 g/kg), medium- (40 g/kg) and high-dose (80 g/kg) CSG group. After 21-day consecutive treatment, the expressions of VEGF and its receptor Flk-1 in ectopic endometria were detected by immunohistochemical method, and the volume of the ectopic endometria was also measured by using electronic digital calipers. RESULTS: Compared with the untreated group, the endometrial volumes in the treated groups were significantly decreased (P<0.05) except for the low-dose CSG group. Histopathologic observation showed that the epithelial layer of ectopic endometrium was less and the thickness of epithelial layer was thinner than those in the untreated group (P<0.01), but the low-dose CSG group had few changes. The VEGF and its receptor Flk-1 expressed abundantly in the cytoplasm of the glandular epithelium and vascular endothelial cell in all the groups. Compared with the untreated group, the expressions of VEGF and Flk-1 of ectopic endometrium in the CSG-treated groups, the mifepristone group and the castrate group were significantly decreased (P<0.05, P<0.01). CONCLUSION: CSG can treat the endometriosis in rats, and its action may be associated with decreasing the expressions of VEGF and its receptor Flk-1 in ectopic endometrium.

Publication Types:

J Womens Health (Larchmt). 2009 Apr;18(4):519-27.

Diagnosis of the most frequent benign ovarian cysts: is ultrasonography accurate and reproducible?

Guerriero S, Alcazar JL, Pascual MA, Ajossa S, Gerada M, Bargellini R, Virgilio B, Melis GB.

Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. [email protected]

OBJECTIVE: To evaluate the reproducibility and the accuracy of B-mode ultrasonographic features of three different kinds of benign ovarian cysts: ovarian endometrioma, mature teratoma, and serous cyst. METHODS: Digitally stored B-mode sonographic images of 98 women submitted to surgery for the presence of an adnexal mass were evaluated by five different examiners with different degrees of experience. The histological type of each mass was predicted on the basis of the B-mode typical benign findings, as in the case of endometrioma (groundglass endocystic pattern), cystic teratoma (echogenic pattern with or without acoustic shadow), and serous cyst (anechoic cyst without endocystic vegetations). To assess the reproducibility of the B-mode findings, intraobserver and interobserver agreements were calculated using the kappa index. RESULTS: The intraobserver agreement was good or very good for all examiners and for all patterns (kappa = 0.71-1) except for the dermoid cyst, which showed moderate agreement (kappa = 0.42) for the highly experienced operator. The interobserver agreement was good for all experts for endometrioma (kappa = 0.66-0.78) and for serous cyst (kappa = 0.82-1), whereas it was moderate or good for cystic teratoma (kappa = 0.51-0.72). Interobserver agreement between experts and highly experienced operators was fair (kappa = 0.33-0.36) for teratoma and good or very good for endometrioma (kappa = 0.70-0.83) and serous cyst (kappa = 0.76-0.82). For different kinds of cysts, the accuracy was comparable among different operators. CONCLUSIONS: Typical features of benign masses using grayscale transvaginal ultrasonography are reproducible even in moderately experienced examiners, although more experience was associated with better interobserver agreement. The diagnostic performance of different operators with different degrees of experience is similar.

Publication Types:

Gynecol Obstet Fertil. 2009 Apr;37(4):325-33. Epub 2009 Apr 8.

How does peritoneal fluid flow influence anatomical distribution of endometriotic lesions?

[Article in French]

Bricou A, Borghese B, Batt RE, Piketty M, de Ziegler D, Chapron C.

Clinique universitaire Baudelocque, CHU Cochin-Saint-Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris (AP-HP), université Paris-Descartes, 123, boulevard de Port-Royal, 75014 Paris, France.

Endometriosis is a common disease in gynecology. Many theories were proposed to explain the endometriosis pathogenesis. The distribution of the endometriosis lesions seems to be interesting in order to understand the endometriosis pathogenesis. This distribution is asymmetric. This asymmetric distribution of endometriosis is explained by the anatomy of the peritoneal cavity and by the intraperitoneal fluids. It strongly confirms the role of menstrual regurgitation and peritoneal fluid in the endometriosis genesis. The similar asymmetric distribution for all types of endometriosis (superficial lesions, ovarian endometriosis cyst, deep endometriosis) is an argument in favor of a unique origin for the different types of lesions.

Publication Types:

J Exp Clin Cancer Res. 2009 Apr 9;28:49.

Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer.

Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M, Baldi A.

Fondazione Italiana Endometriosi, Rome, Italy. [email protected]

BACKGROUND: Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Women with endometriosis have an increased risk of different types of malignancies, especially ovarian cancer and non-Hodgkin’s lymphoma. Though there are several theories, researchers remain unsure as to the definitive cause of endometriosis. Our objective was to test the validity of the theory of müllerianosis for endometriosis, that is the misplacing of primitive endometrial tissue along the migratory pathway of foetal organogenesis METHODS: We have collected at autopsy 36 human female foetuses at different gestational age. We have performed a morphological and immunohistochemical study (expression of oestrogen receptor and CA125) on the pelvic organs of the 36 foetuses included en-block and totally analyzed. RESULTS: In 4 out of 36 foetuses we found presence of misplaced endometrium in five different ectopic sites: in the recto-vaginal septum, in the proximity of the Douglas pouch, in the mesenchimal tissue close to the posterior wall of the uterus, in the rectal tube at the level of muscularis propria, and in the wall of the uterus. All these sites are common location of endometriosis in women. CONCLUSION: We propose that a cause of endometriosis is the dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis.

Publication Types:

J Obstet Gynaecol. 2009 Apr;29(3):259-60.

Severe anaemia due to bleeding from caesarean section scar endometriosis.

Melendez J, Ayinde O, Bhatia R, Yoong W.

Department of Obstetrics and Gynaecology, North Middlesex University Hospital, London, UK.

Publication Types:

Surg Endosc. 2009 Sep;23(9):2073-7. Epub 2009 Apr 9.

The role of diagnostic laparoscopy for chronic abdominal conditions: an evidence-based review.

Richardson WS, Stefanidis D, Chang L, Earle DB, Fanelli RD.

Department of Surgery, Ochsner Clinic, New Orleans, LA, USA. [email protected]

BACKGROUND: Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of intraabdominal diseases. The aim of this review is a critical examination of the available literature on the role of laparoscopy for chronic intraabdominal conditions. METHODS: A systematic literature search of English-language articles on MEDLINE, the Cochrane database of evidence-based reviews, and the Database of Abstracts of Reviews of Effects was performed for the period 1995-2006. The level of evidence in the identified articles was graded. The search identified and reviewed six main categories that have received attention in the literature: pelvic pain and endometriosis, primary and secondary infertility, nonpalpable testis, and liver disease. RESULTS: The indications, contraindications, risks, benefits, diagnostic accuracy of the procedure, and its associated morbidity are discussed. CONCLUSIONS: The limitations of the available literature are highlighted, and evidence-based recommendations for the use of laparoscopy to stage intraabdominal cancers are provided.

Hum Reprod. 2009 Jul;24(7):1619-25. Epub 2009 Apr 8.

Laparoscopic treatment of bowel endometriosis in infertile women.

Stepniewska A, Pomini P, Bruni F, Mereu L, Ruffo G, Ceccaroni M, Scioscia M, Guerriero M, Minelli L.

Departments of Obstetrics and Gynecology, Ospedale Sacro Cuore, Via Don Sempreboni 5, Negrar 37024, Verona, Italy. [email protected]

BACKGROUND: The purpose of the study was to determine the influence of bowel endometriosis on fertility, and to study whether its removal improves fecundity in women with endometriosis-associated infertility. METHODS: Three groups of infertile patients were included in the study. Group A (60 women) consisted of patients who underwent surgery for endometriosis with colorectal segmental resection. In group B, 40 patients with evidence of bowel endometriosis underwent endometriosis removal without bowel resection. Group C consisted of 55 women who underwent surgery for moderate or severe endometriosis with at least one endometrioma and deep infiltrating endometriosis but without bowel involvement. The women were clinically evaluated before laparoscopy and then at 1 month, at 6 months and at each year up to 4 years after surgery. Main outcome measures were surgical complications as well as post-operative pregnancy rate, time to conception and monthly fecundity rate. RESULTS: The monthly fecundity rates (MFR) in groups A, B and C were 2.3, 0.84 and 3.95%, respectively. The difference in the MFR between groups was significant (P < 0.05). CONCLUSIONS: The presence of bowel infiltration by endometriosis seems to negatively influence the reproductive outcome in women with endometriosis-associated infertility. The complete removal of endometriosis with bowel segmental resection seems to offer better results in terms of post-operative fertility. 

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