Reprod Biomed Online. 2010 Apr 27. [Epub ahead of print]
Leicester Fertility Centre, University Hospitals of Leicester, Leicester, UK.
Management of endometrioma before IVF remains controversial. As well as some measurable benefits from surgical treatment, there are also potential risks that should be discussed with the patients to help them make an informed decision. When surgery is compared with expectant management, there appear to be no statistically significant differences in pregnancy rate and ovarian response to exogenous stimulation. The objectives of this European Society of Human Reproduction and Embryology (ESHRE)-sponsored survey were to acquire knowledge of current strategies for the management of endometrioma (>3cm) prior to IVF and to explore adherence to ESHRE guidelines. A validated, peer-reviewed online questionnaire made of 14 questions was sent to 396 members of the ESHRE Special Interest Groups (Reproductive Surgery and Endometriosis/Endometrium), with a response rate of 27%. Surgical management is the most common treatment (82.2%), with drainage and excision of the cyst wall being the preferred surgical approach (78.5%). Monthly depot gonadotrophin-releasing hormone analogues are the preferred choice of medical treatment of endometriomas before IVF, with an average duration of treatment of 3months. The findings demonstrate that surgery remains the commonest treatment offered for women with endometrioma before IVF. This is in line with the recommendations of the ESHRE guidelines. Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Mol Endocrinol. 2010 Aug 4. [Epub ahead of print]
Genome-Wide Profiling of Methylated Promoters in Endometriosis Reveals a Subtelomeric Location of Hypermethylation.
Institut Cochin (B.B., S.B., F.M., P.S., G.V., C.C., D.V.), Université Paris Descartes, Centre National de la Recherche Scientifique (Unite Mixte de Recherche 8104), 75014 Paris, France; Institut National de la Santé et de la Recherche Médicale (B.B., S.B., F.M., P.S., G.V., C.C., D.V.), U1016, 75014 Paris, France; and Service de Gynécologie Obstétrique 2 et Médecine de la Reproduction (B.B., P.S., C.C.), Groupe Hospitalier Cochin-Saint-Vincent de Paul, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
Several lines of evidence indicate that endometriosis could be partially due to selective epigenetic deregulations. Promoter hypermethylation of some key genes, such as progesterone receptor and aromatase, has been associated with the silencing of these genes and might contribute to the disease. However, it is unknown whether global alterations in DNA methylation patterns occur in endometriosis and to what extent they are involved in its pathogenesis. We conducted a whole-genome scanning of methylation status in more than 25,000 promoters, using methylated DNA immunoprecipitation with hybridization to promoter microarrays. We detailed the methylation profiles for each subtype of the disease (superficial endometriosis, endometriomas, and deep infiltrating endometriosis) and compared them with the profile obtained for the eutopic endometrium. In line with the current theory of the endometrial origin of endometriosis, the overall methylation profile was highly similar between the endometrium and the lesions. It showed promoter regions consistently hypomethylated or hypermethylated (more than 1.5-times, as compared with endometrium) and others specific to one given subtype. Albeit there was no systematic correlation between promoter methylation and expression of nearby genes, 35 genes had both methylation and expressional alterations in the lesions. These genes, reported here for the first time, might be of interest in the development of endometriosis. In addition, hypermethylated regions were located at the ends of the chromosomes, whereas hypomethylated regions were randomly distributed all along the chromosomes. We postulated that this original observation might participate to the chromosomal stability and protect the endometriotic lesion against malignancy.
Clin Ther. 2010 May;32(5):909-914.
Department of Cardiology, Clinical Hospital Centre Zemun, Belgrade, Serbia.
Background: Simvastatin, a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor, is indicated for the treatment of hypercholesterolemia and plays an important role in both the primary and secondary prevention of cardiovascular disease. Danazol is a steroid analogue approved for the treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema. Despite not being licensed, danazol has been used for other off-label indications, such as idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria, and aplastic anemia. Objective: We report a case of fatal rhabdomyolysis that occurred after concomitant administration of simvastatin and danazol in a patient with ITP. Case summary: An 80-year-old white male (height, 182 cm; weight, 90 kg) presented to the emergency department of the Clinical Hospital Centre Zemun, Belgrade, Serbia, with head injuries after an accidental fall caused by generalized weakness. He denied other complaints, except fatigue, mild pretibial edema, and progressive bilateral leg pain and cramping that began 7 days before. At the time of presentation, he was receiving aspirin 100 mg/d, clopidogrel 75 mg/d, ramipril 2.5 mg/d, pantoprazole 40 mg/d, danazol 600 mg/d, prednisone 60 mg/d, simvastatin 40 mg/d, and longacting insulin 24 IU/d. After the injuries were treated, he was diagnosed with collapse and nasal contusion, and discharged without any changes in his therapy. Two days after initial presentation, the patient was readmitted to the hospital due to nausea, dark urine, and oliguria. All clinical signs (oliguria, dark urine, muscle pain, and tenderness) and laboratory markers (creatine kinase levels approximately 100 times the upper limit of normal, along with hyperkalemia, hyperphosphatemia, and hypoalbuminemia) were consistent with severe rhabdomyolysis. Despite intravenous hydration, forced diuresis, and hemodialysis, oliguria persisted and the patient died 6 days after admission. A score of 5 on the Naranjo adverse drug reaction probability scale was consistent with a probable association of rhabdomyolysis and concomitant treatment with simvastatin and danazol in this patient. Conclusions: Statin-induced rhabdomyolysis must be considered whenever muscle or motor symptoms occur, especially when concomitant treatment with known inhibitors of statin metabolism is administered. Patients must be strictly monitored and the statin should be promptly discontinued with the onset of first signs and symptoms of myopathy. Clinicians should be aware of the potentially fatal consequences of both approved and unapproved treatments and be alert for the early detection of toxicity. Copyright © 2010 Excerpta Medica Inc. All rights reserved.
Eur J Obstet Gynecol Reprod Biol. 2010 Aug 2. [Epub ahead of print]
Genetic variations in vascular endothelial growth factor but not in angiotensin I-converting enzyme genes are associated with endometriosis in Estonian women.
Department of Obstetrics and Gynecology, University of Tartu, Puusepa 8, 51014 Tartu, Estonia.
OBJECTIVE: To determine plausible associations between endometriosis and vascular endothelial growth factor gene (VEGF -2578 A/C, -1154 G/A, -634 G/C and 936 C/T), also angiotensin I-converting enzyme gene (ACE -240 A/T and 2350 A/G) single nucleotide polymorphisms (SNPs), as well as their respective haplotypes. STUDY DESIGN: PCR-based restriction fragment length polymorphism analysis was used to detect SNPs in VEGF and ACE genes in 150 Estonian women with endometriosis and 199 control subjects. RESULTS: The CC genotype of the VEGF -2578 A/C SNP was correlated with a decreased risk of endometriosis (OR=0.40, 95% CI 0.20-0.78). Other VEGF and ACE SNPs and haplotypes were not associated with endometriosis. CONCLUSION: This case-control study demonstrated that the VEGF -2578 A/C SNP may influence susceptibility to endometriosis in the Estonian population, while associations between endometriosis and other VEGF and ACE SNPs, as well as the respective haplotypes are unlikely. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
J Med Case Reports. 2010 Aug 4;4(1):248. [Epub ahead of print]
Silent onset of postmenopausal endometriosis in a woman with renal failure in hormone replacement therapy: a case report.
ABSTRACT: Introduction Postmenopausal endometriosis is a rare form of a common disease, since the absence of estrogenic hormone production should halt disease progression. Case presentation We present the case of a 54-year-old Italian Caucasian woman in surgical menopause with a history of ovarian endometriosis, who underwent voluntary hormone replacement therapy for seven years. She developed postrenal renal failure due to bilateral compression of the pelvic ureteral tract caused by two large, deeply infiltrating endometriotic nodules with no pelvic pain. She underwent operative laparoscopy with adhesiolysis of enteroenteric adhesions and excision of the endometriotic nodules encompassing the juxtavesical tract of the ureters, without obtaining improvement of renal failure. Conclusion Postmenopausal endometriosis can manifest itself in an unpredictable and potentially very serious manner. It is therefore important to carefully evaluate the risks and benefits of administering hormone replacement therapy to patients with previous endometriosis.
Tech Coloproctol. 2010 Aug 4. [Epub ahead of print]
Surgical Department of European Medical Center, Antheon 1, Panorama, 55236, Thessaloniki, Greece, [email protected]
We report on three cases of premenopausal female patients with large bowel endometriosis causing intermittent obstruction.
Zhong Yao Cai. 2010 Mar;33(3):401-6.
Inhibitory effect of Jiawei Sanleng pill medicated serum on estrogen production and its influence on apoptosis of human endometrial cells of endometriosis.[Article in Chinese]
College of Chemistry and Bioengineering, Chongqing University of Technology, Chongqing 400050, China. [email protected]
OBJECTIVE: To study the inhibitory effect on estradiol (E2) production of endometriosis by medicated serum of Jiawei Sanleng pill (SLW) and approach the mechanism of inducing apoptosis of human endometrial cells of endometriosis by medicated serum of SLW. METHODS: The eutopic endometrial cells of hysteromyoma and endometriosis patients were cultured. Taking that of the endometrial cells of hysteromyoma as control, the secretion level of E2 of endometrial cells in the culture media supernatant at different time point with the treatment of high, middle and low dose of SLW serum was detected by electrochemiluminescence immunoassay and the apoptosis percentage of endometrium cells in early stage and late stage was detected by flow cytometry and TUNEL method. After the optimal time for SLW to induce apoptosis of eutopic endometrial cells of endometriosis in early stage and late stage was identified based on time-effect relationship, another endometrium cells were divided into six groups: hysteromyoma endometrium group, eutopic endometrium of endometriosis group, eutopic endometrium of endometriosis + middle dose of SLW serum group, eutopic endometrium of endometriosis + anastrozole serum group, eutopic endometria of endometriosis + middle dose of SLW serum + E2 group and eutopic endometrium of endometriosis + E2 group. The apoptosis percentage of endometrial cells in early stage and late stage of each group was detected according to the optimal time point respectively. RESULTS: The secretion level of E2 of eutopic endometrium of endometriosis was decreased by SLW, which showed the dependence of concentration and time. The apoptosis percentage of endometrial cells in hysteromyoma endometrium group in early stage and late stage was increased along with the time and they was significantly higher than that of eutopic endometrium of endometriosis group at the same time point (P < 0.05 or P < 0.01). After 72 hours and 96 hours, with the treatment of middle dose of SLW serum, the apoptosis percentage of eutopic endometrial cells of endometriosis in early stage and late stage was 35.67 +/- 1.73 and 57.56 +/- 1.09 respectively, and the effect of inducing apoptosis was significantly stronger than that of the other time point. After 72 hours, with the combined treatment of middle dose of SLW serum and 5.30 ng/L E2, or after 96 hours, with the combined treatment of middle dose of SLW serum and 6. 36 ng/L E2, the apoptosis percentage of eutopic endometrial cells in early stage and late stage was decreased to 11.25 +/- 2.00 and 7.72 +/- 0.71 respectively, which had significant difference with that of middle dose of SLW serum group (P < 0.01). The apoptosis of the eutopic endometrial cells of endometriosis was induced by medicated serum of SLW could not be completely counteracted by E2 add-back treatment. Just with the treatment of 5.30 ng/L or 6.36 ng/L E2, the apoptosis percentage of eutopic endometrial cells of endometriosis in early stage and late stage tended to decrease, but there was no statistical significance (P > 0.05). Anastrozole, a specific aromatase inhibitor, had the contrary action to E2. CONCLUSION: SLW could decrease the secretion of E2 so as to induce apoptosis of the eutopic endometrial cells of endometriosis.
Ultrasound Obstet Gynecol. 2010 Aug;36(2):134-5.
Department of Radiology, Hôpital Tenon, 4 rue de la Chine, 75020, Paris, France.
Arch Gynecol Obstet. 2010 Aug 1. [Epub ahead of print]
Laparoscopic nerve-sparing surgery of deep infiltrating endometriosis: description of the technique and patients’ outcome.
Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Luebeck, Ratzeburgerallee 160, 23538, Luebeck, Germany, [email protected]
INTRODUCTION: The radical surgery of the deep infiltrating endometriosis of the rectovaginal septum and the uterosacral ligaments with or without bowel resection can cause a serious damage of the pelvic autonomic nerves with urinary retention and the need of self-catheterization. PATIENTS AND METHODS: We introduce a case series report of 16 patients with laparoscopic nerve-sparing surgery of deep infiltrating endometriosis. We describe the technique step by step and compare the patients’ outcome with patients who had undergone a non-nerve-sparing surgical technique. In 12 patients, a double-sided and in four patients, a single-sided identification of the inferior hypogastric nerve and plexus were performed. RESULTS: In all patients at least single-sided resection of the uterosacral ligaments were performed. Postoperatively dysmenorrhoea, pelvic pain, and dyspareunia disappeared in all patients. The average operating time was 82 min (range 45-185). Postoperatively, the overall time to resume voiding function was 2 days. The residual urine volume was in all patients <50 ml at two ultrasound measurements. DISCUSSION: Identification of the inferior hypogastric nerve and plexus was feasible. In comparison with non-nerve-sparing surgical technique, no cases of bladder self-catheterization for a long or even life time was observed, confirming the importance of the nerve-sparing surgical procedure.
J Reprod Med. 2009 Oct;54(10):625-30.
Tumor necrosis factor-alpha-induced cyclooxygenase-2 overexpression in eutopic endometrium of women with endometriosis by stromal cell culture through nuclear factor-kappaB activation.
Department of Obstetrics and Gynecology and Clinical Research Center, Ilan Paik Hospital, Inje University, Ilsan, lorea. [email protected]
OBJECTIVE: To investigate the role of NF-kappaB during the induction of COX-2 by TNF-alpha in the eutopic endometrium of women with and without endometriosis using stromal cell culture. STUDY DESIGN: Experimental study in cultured stromal cells of the eutopic endometrium of women with and without endometriosis in the presence of TNF-alpha. RESULTS: Within 5-20 minutes of stimulation with TNF-alpha, p-IkappaB was clearly observed in the eutopic endometrium of women with endometriosis and in that of women without endometriosis. COX-2 protein was significantly induced by treatment with TNF-alpha in both eutopic endometrial stromal cells of women with and without endometriosis (p < 0.05), but the degree of induction was significantly increased in eutopic endometrial stromal cells of women with endometriosis than those of women without endometriosis (p < 0.05). CONCLUSION: Overexpression of COX-2 by TNF-alpha in the eutopic endometrium of women with endometriosis may play a critical role in such pathophysiologic processes as endometriosis formation.
Fertil Steril. 2010 Jul 31. [Epub ahead of print]
Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.
This study analyzed by immunofluorescence staining the sympathetic innervation in the bowel adjacent to the endometriotic lesion and in the healthy tissue at the border of the resected specimen. Sympathetic nerve fibers are significantly reduced in the mucosal and muscular layer near the endometriotic lesions; in contrast, sensory nerve fiber density is not altered in the area near the endometriotic lesions. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Fertil Steril. 2010 Jul 30. [Epub ahead of print]
Department of Gynecology and Obstetrics, Sapienza, University of Rome, Rome, Italy.
Although uterine adenomyoma and endometriosis were described around the turn of the 19th century, the history of the identification of endometriosis has remained controversial and continues to confuse recent literature affecting the management of the disease. Using histologic parameters of endometrial structure and activity, the first scientist to identify the condition, under the name “adenomyoma,” was Thomas Cullen. John Sampson was the first to identify the pathogenesis of the condition. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
G Ital Nefrol. 2010 Jul-Aug;27(4):367-73.
Nefrologia e Dialisi, Ospedale ”S. Giovanni Bosco”, Torino – Italy.
Isolated asymptomatic hematuria is frequently encountered in clinical practice but there are no established recommendations for its evaluation and management. There is controversy regarding which tests are necessary and whether renal biopsy is indicated. In the pediatric population, renal biopsy should be considered if there is evidence of progressive renal disease or when parents are worried about their child’s diagnosis or prognosis. In adults, examinations for isolated microhematuria should include exclusion of pharmacological causes, journeys to endemic areas for S. haematobium or tuberculosis, sickle-cell disease, endometriosis and, in patients older than 40 years, kidney, ureteral or bladder cancer. Examination of urinary sediment may help in identifying the origin of microhematuria. If it is decided to perform a renal biopsy, the patient should be carefully informed of the possible complications of renal biopsy, including the possibility of finding normal renal tissue.
Nat Rev Drug Discov. 2010 Aug;9(8):584-5.
Nurs Stand. 2010 Jun 30-Jul 6;24(43):25.
Despite being a specialist nurse, Jo Johnson lacked confidence in dealing with professionals treating her for endometriosis.
Endocrinology. 2010 Jul 28. [Epub ahead of print]
Department of Obstetrics and Gynaecology (J.R.A.S.), The Whittington Hospital National Health Service Trust, London N19 5NF, United Kingdom; Human Reproductive Sciences Unit (J.M.H.), Medical Research Council, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Beckman Institute (K.S.J.), Urbana, Illinois, 61801-4161; Department of Obstetrics and Gynecology (P.A.M.), University of Illinois at Chicago, Chicago, Illinois 60212-7313; Department of Pathology (A.M.S.), Cambridge CB2 1QP, United Kingdom; and Department of Obstetrics, Gynecology, and Reproductive Biology (A.T.F.), Michigan State University, College of Human Medicine, Grand Rapids, Michigan, 49503-2532.
Endometriosis-associated infertility has a multifactorial etiology. We tested the hypothesis that the endometrial response to the early embryonic signal, human chorionic gonadotropin (hCG), alters over time in a nonhuman primate model of endometriosis. Animals with experimental or spontaneous endometriosis were treated with hCG (30 IU/d), from d 6 after ovulation for 5 d, via an oviductal cannula. Microarray analysis of endometrial transcripts from baboons treated with hCG at 3 and 6 months of disease (n = 6) identified 22 and 165 genes, respectively, whose levels differed more than 2-fold compared with disease-free (DF) animals treated with hCG (P < 0.01). Quantitative RT-PCR confirmed abnormal responses of known hCG-regulated genes. APOA1, SFRP4, and PAPPA, which are normally down-regulated by hCG were up-regulated by hCG in animals with endometriosis. In contrast, the ability of hCG to induce SERPINA3 was lost. Immunohistochemistry demonstrated dysregulation of C3 and superoxide dismutase 2 proteins. We demonstrate that this abnormal response to hCG persists for up to 15 months after disease induction and that the nature of the abnormal response changes as the disease progresses. Immunohistochemistry showed that this aberrant gene expression was not a consequence of altered LH/choriogonadotropin receptor distribution in the endometrium of animals with endometriosis. We have shown that endometriosis induces complex changes in the response of eutopic endometrium to hCG, which may prevent the acquisition of the full endometrial molecular repertoire necessary for decidualization and tolerance of the fetal allograft. This may in part explain endometriosis-associated implantation failure.
Eur J Obstet Gynecol Reprod Biol. 2010 Jul 26. [Epub ahead of print]
Department of Obstetrics and Gynecology, Faculty of Medicine, Abant Izzet Baysal University, Gölköy, Bolu, Turkey.
OBJECTIVE: To determine the effects of pinealectomy on endometrial explants in rats and evaluate the activity of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in the rat endometriosis model. STUDY DESIGN: Rats with experimentally induced endometriosis were randomly divided into three groups after second-look laparotomies. Group 1 (pinealectomy, n=8) and Group 2 (pinealectomy+melatonin, n=8) underwent pinealectomies after the second-look laparotomies. Group 3 was presented as control group (vehicle solution+without pinealectomy (n=6)). Melatonin was administered intraperitoneally for 4 weeks in Group 2, whereas an equal volume of vehicle solution was given to Groups 1 and 3. Evaluation of the volume of the endometrial explants, histopathological examination and preservation of explant epitheliums according to the scoring system were undertaken. RESULTS: There was a statistically significant increase in spherical explant volumes of Group 1 compared to Groups 2 and 3. In Group 1, the level of MDA was significantly higher and SOD and CAT activity was significantly lower compared to Groups 2 and 3. A statistically significant increase in the epithelial lining scores of explants was noted in Group 1 compared to Groups 2 and 3. CONCLUSION: The effects of pinealectomy on the progression of endometriosis explants were reversed by melatonin. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
J Obstet Gynaecol Res. 2010 Aug;36(4):916-9.
Department of Obstetrics and Gynaecology, Liverpool Hospital, University of New South Wales, Sydney, New South Wales, Australia. [email protected]
Cervical endometriosis is uncommon and usually an incidental or retrospective finding on histopathology reports. It can be asymptomatic or present with a diverse range of persistent symptoms and even life-threatening hemorrhage. The condition can be managed expectantly in asymptomatic patients, however persistent symptoms may warrant surgery. We encountered four cases of histologically proven cervical endometriosis at our tertiary hospital in New South Wales, Australia. All our patients had different symptoms, presentations and indications for their surgery leading to their diagnosis. This review is to report these cases followed by discussion with a review of the literature.
J Obstet Gynaecol Res. 2010 Aug;36(4):902-6.
Division of Obstetrics and Gynaecology, C. Magati Hospital, Scandiano, Reggio Emilia, Italy. [email protected]
The abdominal wall is an uncommon site of extrapelvic endometriosis, which usually develops in a previous surgical scar and it should be considered in the differential diagnosis of any abdominal swelling. Endometriosis involving the rectus abdominis muscle is a very rare event and its rarity explains the incomplete nature of the reports in the literature. Up to the present, 18 cases with lesions contained entirely within the rectus abdominis muscle were clearly documented in medical literature with only four cases as a primary location. We report a case, which came to our observation, of primary endometriosis of the rectus abdominis muscle. The patient underwent only surgery without any medical treatment. Currently, the patient is in follow up for four years with no recovery of the disease. In our experience, surgery is the treatment of choice and it is decisive. We reviewed the literature and summarized all reported cases.
J Obstet Gynaecol Res. 2010 Aug;36(4):825-31.
Genetic contribution of the interferon gamma dinucleotide-repeat polymorphism in South Indian women with endometriosis.
Fertility Services MHRT Hospital and Research Centre, Deccan College of Medical Sciences, Hyderabad, India.
AIM: To investigate whether the interferon-gamma (IFNG) gene dinucleotide (CA)-repeat polymorphism is responsible in part for genetic susceptibility to endometriosis in South Indian women. METHODS: Following extraction of genomic DNA, genotyping of interferon-gamma CA-repeat polymorphism was performed using genescan technology. RESULTS: The global IFNG allele frequencies in all patients with endometriosis were significantly different from those in the control women (chi(2) = 37.062; 6 degrees of freedom; P < or = 0.0001). Significant difference was observed in global allele frequencies between the control women and each clinical subgroup of patients with endometriosis except for patients suffering from endometriosis associated with adenomyosis. The difference was due to an increase in a12 (112 bp) allele in the patients with endometriosis and each clinical subgroup of patients with endometriosis. The distribution of the IFNG a12 genotypes was significantly different between patients with endometriosis and the control women. (chi(2) = 10.635; 2 degrees of freedom; P = 0.0049). A significant difference in the IFNG a12 genotypes was found only among the three clinical subgroups. CONCLUSION: These results suggest that the IFNG gene CA-repeat polymorphism is associated with susceptibility to endometriosis in South Indian women.
Fertil Steril. 2010 Jul 19. [Epub ahead of print]
GROW: School for Oncology and Developmental Biology and Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Fertil Steril. 2010 Jul 15. [Epub ahead of print]
Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes.
Department of Obstetrics, Gynecology, and Reproductive Medicine, Université Paris Descartes-Assistance Publique Hôpitaux de Paris, CHU Cochin, Paris, France.
In women with endometriosis, including those with endometriomas, 6 to 8 weeks of continuous use of oral contraception (OC) before assisted reproduction treatment (ART) maintains ART outcomes comparable with the outcomes of age-matched controls without endometriosis. In contrast, ART outcomes are markedly compromised in endometriosis patients who are not pretreated with OC. Ovarian responsiveness to stimulation was not altered by 6 to 8 weeks’ use of pre-ART OC, including in poor responders with endometriomas. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Crit Rev Toxicol. 2010 Aug;40(7):633-52.
Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications.
Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada.
Reproductive function and fertility are thought to be compromised by behaviors such as cigarette smoking, substance abuse, and alcohol consumption; however, the strength of these associations are uncertain. Furthermore, the reproductive system is thought to be under attack from exposure to environmental contaminants, particularly those chemicals shown to affect endocrine homeostasis. The relationship between exposure to environmental contaminants and adverse effects on human reproductive health are frequently debated in the scientific literature and these controversies have spread into the lay press drawing increased public and regulatory attention. Therefore, the objective of the present review was to critically evaluate the literature concerning the relationship between lifestyle exposures and adverse effects on fertility as well as examining the evidence for a role of environmental contaminants in the purported decline of semen quality and the pathophysiology of subfertility, polycystic ovarian syndrome, and endometriosis. The authors conclude that whereas cigarette smoking is strongly associated with adverse reproductive outcomes, high-level exposures to other lifestyle factors are only weakly linked with negative fertility impacts. Finally, there is no compelling evidence that environmental contaminants, at concentrations representative of the levels measured in contemporary biomonitoring studies, have any effect, positive or negative, on reproductive health in the general population. Further research using prospective study designs with robust sample sizes are needed to evaluate testable hypotheses that address the relationship between exposure and adverse reproductive health effects.
DNA Cell Biol. 2010 Jul 27. [Epub ahead of print]
Association of an Interleukin-16 Gene Polymorphism with the Risk and Pain Phenotype of Endometriosis.
1 Department of Gynecology and Obstetrics, West China Secondary Hospital, Sichuan University , Chengdu, P.R. China .
Interleukin-16 (IL-16), a proinflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of endometriosis. The aim of this study was to evaluate the association of IL-16 gene polymorphisms with the risk and clinical phenotypes of endometriosis in Chinese women. We analyzed rs4778889 T/C, rs11556218 T/G polymorphisms of the IL-16 gene in 230 patients with endometriosis and 203 controls in a Chinese population, using a polymerase chain reaction-high resolution melting analysis strategy and DNA sequencing methods. There was no significant difference in the genotype and allele frequencies of the rs11556218 T/G polymorphism between patients with endometriosis and controls (p > 0.05). In contrast, the genotype and allele frequencies of the rs4778889 T/C polymorphism were statistically different between patients with endometriosis and controls, which resulted from a significantly increased proportion of TC heterozygote and CC homozygote carriers among patients with endometriosis (p = 0.001 and 0.012, respectively); moreover, further subgroup analysis found that the genotype difference was more evident in patients with endometriosis who also experienced pain symptoms (p < 0.001) than in patients without pain symptoms (p = 0.625) when compared with controls. Our results suggest that the rs4778889 T/C polymorphism of the IL-16 gene may be associated with risk of endometriosis in the Chinese population, especially in patients with pain phenotype.
Arch Gynecol Obstet. 2010 Jul 27. [Epub ahead of print]
A comparison of the effect of short-term aromatase inhibitor (letrozole) and GnRH agonist (triptorelin) versus case control on pregnancy rate and symptom and sign recurrence after laparoscopic treatment of endometriosis.
Division of Infertility and Endoscopic Surgery, Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, P.O. Box 71345-1818, Shiraz, Iran, [email protected]
PURPOSE: To compare the role of an aromatase inhibitor (letrozole) with a GnRH agonist (triptorelin) versus case control on the pregnancy rate and recurrence of symptoms and signs in patients with endometriosis. METHODS: In a prospective randomized clinical trial, after treatment of 144 infertile women in their reproductive age by laparoscopy (whose endometriosis was confirmed by prior laparoscopy), they were divided into 3 groups: group 1 (47 cases) who received letrozole for 2 months, group 2 (40 patients) who were prescribed triptorelin for 2 months and group 3 who were 57 patients in the control group and did not receive any medication. We followed up each group at least for 12 months after their restoration of regular cycle. RESULTS: Pregnancy rate was 23.4% in group 1, 27.5% in group 2, and 28.1% in group 3. The results did not show significant differences among the 3 groups. Recurrence rate of endometriosis was 6.4% in group 1, 5% group 2 and 5.3% in group 3, which was not statistically significantly different as well. CONCLUSION: Pregnancy rate and endometriosis recurrence rate are comparable among the 3 groups.
J Minim Invasive Gynecol. 2010 Jul 24. [Epub ahead of print]
IRCAD (Research Institute Against Digestive Cancer) and University Hospitals Strasbourg (Hautepierre Hospital and CMCO [Centre Medico-Chirurgical et Obstetrical] Hospital), Strasbourg, France.
STUDY OBJECTIVE: To describe outcomes after laparoscopic excision of deep bladder endometriosis. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University hospitals. PATIENTS: Twenty-one consecutive patients with endometriotic nodule on the bladder (infiltrating detrusor muscle) from a series of 169 patients were included in the study. The primary outcome studied was resolution of bladder symptoms. Secondary outcomes included complication rates, recurrence rates, and pregnancy rates after laparoscopic surgery. INTERVENTIONS: Laparoscopic excision of bladder endometriosis. MEASUREMENTS AND MAIN RESULTS: Laparoscopy was feasible in all cases without the need for conversion. Median follow-up was 20 months. Ten patients (47.6%) underwent partial cystectomy, and the remaining patients underwent partial-thickness excision of the detrusor muscle. Sixteen patients (76%) had associated deep lesions in the pelvis. The most common associated lesions were rectovaginal nodules (38%) and ureteric lesions (14%), with signs of obstruction. Major complications developed in 3 patients (14%), primarily related to bowel resection. Six patients became pregnant (60%). No patients experienced disease recurrence. CONCLUSION: Laparoscopic excision is feasible in all types of bladder endometriosis but often involves multiple procedures to manage associated lesions, especially rectovaginal nodules and ureteric lesions. Previous reports have suggested that ureteric lesions are not associated with bladder endometriosis; however, this was not true in our series. Complications are primarily related to severity of the disease and associated procedures. Partial cystectomy is not required in all cases to achieve adequate clearance. Complete excision of the disease is associated with resolution of bladder symptoms and low recurrence rates. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.
Eur J Obstet Gynecol Reprod Biol. 2010 Jul 23. [Epub ahead of print]
Rotunda Hospital, Royal College of Surgeons in Ireland, Parnell Square, Dublin 1, Ireland.
Int J Gynaecol Obstet. 2010 Jul 23. [Epub ahead of print]
Department of Obstetrics and Gynaecology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
Fertil Steril. 2010 Jul 22. [Epub ahead of print]
Department of Obstetrics, Gynecology and Women’s Health, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey.
Our studies demonstrate significantly lower expression of relaxin and its receptor in ectopic endometriotic tissues than their expression in eutopic endometrium and in endometrium from normal controls. These data suggest that in normal and eutopic endometrium, relaxin may exert a protective effect against endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Fertil Steril. 2010 Jul 22. [Epub ahead of print]
Institute of Neurobiology and Molecular Medicine, National Research Council, Rome, Italy.
N-acetyl-L-cysteine exerts a complex action on endometrial cells, involving regulation of gene expression and protein activity and location, all converging into a decreased proliferation and a switch toward a differentiating, less invasive, and less inflammatory phenotype. Also considering the lack of undesired side effects, including unaffected fertility potential, this suggests a beneficial use of NAC in endometriosis clinical treatment. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Fertil Steril. 2010 Jul 22. [Epub ahead of print]
Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues.
Department of Biosignaling, Tottori University Faculty of Medicine, Yonago, Japan.
OBJECTIVE: To search for the demethylated cytosine-phosphate-guanine (CpG) islands within the aromatase gene in stromal cells derived from endometriotic chocolate cysts. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology and Department of Biosignaling, Tottori University, Yonago, Japan. PATIENT(S): Twenty-eight women who underwent laparoscopy (n = 14) and laparotomy (n = 14). INTERVENTION(S): Endometrial and endometriotic stromal cells were obtained from the uterus and chocolate cyst lining of the ovary. MAIN OUTCOME MEASURE(S): We searched for the CpG island and examined methylation profile and the association of methyl-binding proteins with the CpG island. RESULT(S): Up-regulation of aromatase messenger RNA (mRNA) expression was demonstrated in endometriotic cells. Three proximal promoters drove the mRNA expression. In endometrial cells, a marginal level of aromatase mRNA expression was observed. Treating endometrial cells with the demethylating agent 5-aza-2′-deoxycytidine markedly enhanced aromatase mRNA expression. The same promoters as in the endometriotic cells were used. To identify the unmethylated CpGs in endometriotic cells, we searched for CpG islands within the aromatase gene and subsequently examined the methylation profiles. Sequence analysis of bisulfite-treated genomic DNA demonstrated a stretch of CpG demethylation within a nonpromoter CpG island of the aromatase gene in endometriotic cells. In endometrial cells, the CpG sequences were heavily methylated and associated with methyl-CpG-binding proteins. CONCLUSION(S): The up-regulation of the aromatase gene in endometriosis may be ascribed to the epigenetic disorder associated with aberrant DNA demethylation in a nonpromoter CpG island. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Recent Pat Food Nutr Agric. 2010 Jun;2(2):166-77.
Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis.
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Oxidative stress results from an imbalance in the production of reactive oxygen species (ROS) and cell’s own antioxidant defenses that in part lead to numerous carcinogenesis. Several phytochemicals, derived from vegetables, fruits, herbs and spices, have demonstrated excellent chemopreventive properties against carcinogenesis by regulating the redox status of the cells during oxidative stress. I3C (indole-3-carbinol) and DIM (diindolylmethane) are the phytochemicals that are found in all types of cruciferous vegetables and demonstrated exceptional anti-cancer effects against hormone responsive cancers like breast, prostate and ovarian cancers. Novel analogs of I3C were designed to enhance the overall efficacy, particularly with respect to the therapeutic activity and oral bioavailability and that results in several patent applications on symptoms associated with endometriosis, vaginal neoplasia, cervical dysplasia and mastalgia. Likewise, DIM and its derivatives are patented for treatment and prevention of leiomyomas, HPV infection, respiratory syncytial virus, angiogenesis, atherosclerosis and anti-proliferative actions. On the other hand, phytochemicals in cardamom have not been explored in great details but limonene and cineole demonstrate promising effects against carcinogenesis. Thus studies with selected phytochemicals of cardamom and bioavailability research might lead to many patent applications. This review is focused on the patents generated on the effects of I3C, DIM and selected phytochemicals of cardamom on carcinogenesis.
Fertil Steril. 2010 Jun 19. [Epub ahead of print]
Department of Obstetric, Gynecology, and Reproductive Medicine,University of Saint Etienne, Saint-Etienne, France.
OBJECTIVE: To report the usefulness of three-dimensional (3D) ultrasonography for the assessment of parietal endometriosis. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A 35-year-old woman with a noncyclic, painful abdominal nodule near a caesarean delivery scar. INTERVENTION(S): 3D ultrasonography and wide surgical resection with healthy margins. MAIN OUTCOME MEASURE(S): 3D ultrasonographic assessment of the endometriotic nodule. RESULT(S): We found that 3D ultrasonography offered a more specific description of parietal endometriosis with irregular and spiculated margins and depth infiltration as well as provided preoperative evaluation of volume measurements. CONCLUSION(S): Three-dimensional ultrasonography is a useful, noninvasive tool in extrapelvic endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):269-72.
Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
OBJECTIVE: To evaluate the quality of literatures and the accuracy of ultrasonography in diagnosis of deeply infiltrating endometriosis (DIE). METHODS: The database of Medline (1966 to 2009), the excerpta medica database (EMBASE, 1980 to 2009), Chinese biological medicine on disc (CBMdisc, 1978 to 2009), China national knowledge infrastructure (CNKI, 1979 to 2009) and VIP for Chinese technology periodical database (VIP, 1989 to 2009) Cochrane library of studies about the diagnosis of ultrasound for DIE were searched and analyzed. Quality assessment of diagnostic accuracy studies (QUADAS) items were used to evaluate the quality of literatures. The sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic test odds ratio (DOR) for the pooled analysis and heterogeneity test were analyzed for transvaginal ultrasonography (TVUS), transrectal ultrasonography (TRUS) and rectal endoscopic sonography (EUS) by Meta-disc software, and drew the summary receiver operating characteristic (SROC) curves for those without heterogeneity. RESULTS: Totally 15 literatures in English were enrolled into this study. The positive rate of 10 items of QUADAS were above 60%, whereas that of the 11th item “Were the reference standard results interpreted without knowledge of the results of the index test” was 46.7%; none of studies had mentioned the 13th item “Were uninterpretable/intermediate test results reported”. All researches had no heterogeneity by explored threshold effect. The results of pooled sensitivity, specificity, +LR, -LR, DOR were 0.925, 0.986, 30.036, 0.107, 299.25 for TRUS, 0.799, 0.944, 11.972, 0.187, 69.126 for transvaginal ultrasonography (TVUS), and 0.635, 0.928, 8.022, 0.320, 39.606 for EUS, respectively. Area under the curve of EUS was 0.9479, and that of TVUS was 0.9246. CONCLUSIONS: TRUS, TVUS and EUS all showed optimal value in diagnosis of DIE. The bias identified from the 15 studies might be mainly resulted from reference standard review bias.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):264-8.
Effect of gonadotropin-releasing hormone agonist on fertility potential in patients with stage I endometriosis after laparoscopy.[Article in Chinese]
Reproductive Medicine Center, Peking University People’s Hospital, Beijing 100044, China.
OBJECTIVE: To investigate the impact on fertility potential of patients with stage I endometriosis treated by gonadotropin-releasing hormone agonist (GnRH-a) treatment followed by laparoscopy surgery. METHODS: From Jan. 2006 to Jun. 2008, medical documents of 102 patients with minimal or mild endometriosis (stage I) treated by laparoscopy and hysteroscopy surgery and excluded the other causes of infertility were reviewed retrospectively in Peking University People’s Hospital. The pelvic endometriosis leisions were destructed by electric burning. Those patients were divided into GnRH-a treatment group (n = 60) and non-GnRH-a treatment group(n = 42) after surgery. The patients in GnRH-a treatment group were administered by GnRH-a injection once or twice after surgery, in the mean time, no adjuvant therapy were given for the patients in the other group. All the patients were followed-up for 24 months after surgery to evaluate the effect of postoperative GnRH-a treatment on pregnancy outcome and fertility potential (number of pregnancy per 100 women in one month, expressed as percentage). RESULTS: The total pregnancy rate of 78% (47/60) in GnRH-a treatment group is significantly higher than 55% (23/42) in non-GnRH-a treatment group(P = 0.012). There is no significant difference in spontaneous abortion rate between the GnRH-a treatment group and non GnRH-a treatment group (19% vs. 13%, P = 0.465). The fecundity rate of were 6.17% in GnRH-a treatment group and 3.26% in non-GnRH-a treatment group, which the relative risk is 1.9 (95%CI: 1.1 – 3.0). CONCLUSION: Low-dose GnRH-a treatment after laparoscopy can improve the pregnancy rate and fertility potential of patients with stage I endometriosis.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):260-3.
J Hum Reprod Sci. 2010 Jan;3(1):20-4.Role of laparohysteroscopy in women with normal pelvic imaging and failed ovulation stimulation with intrauterine insemination.Jayakrishnan K, Koshy AK, Raju R.Fertility Research and Gynecology Centre, KJK Hospital, Trivandrum – 695 015, Kerala, India.CONTEXT: Women with primary infertility and no obvious pelvic pathology on clinical evaluation and imaging are either treated empirically or further investigated by laparoscopy. AIMS: The role of diagnostic laparoscopy in women who fail to conceive after empirical treatment with ovulation induction and intrauterine insemination was evaluated. SETTINGS AND DESIGN: Retrospective study at a private infertility center. MATERIALS AND METHODS: A study of patients who underwent diagnostic laparoscopy between 1(st) January 2001 and 31(st) December 2008 was performed. Those patients who had no detectable pathology based on history, physical examination, and ultrasound and had treatment for three or more cycles in the form of ovulation induction and IUI were included in the study. Moderate and severe male factor infertility and history of any previous surgery were exclusion criteria. STATISTICAL ANALYSIS USED: Data were statistically analyzed using Statistics Package for Social Sciences (ver. 16.0; SPSS Inc., Chicago). RESULTS: Of the 127 women who underwent diagnostic laparoscopy and hysteroscopy, 87.4% (n = 111) of patients had positive findings. Significant pelvic pathology (moderate endometriosis, pelvic inflammatory disease, and tubal pathology) was seen in 26.8% of cases. CONCLUSION: One in four women had significant pelvic pathology where treatment could possibly improve future fertility. Diagnostic laparoscopy has a role in infertile women with no obvious abnormality before they proceed to more aggressive treatments.Fertil Steril. 2010 Jun 2. [Epub ahead of print]Smoking habits of 411 women with histologically proven endometriosis and 567 unaffected women.Chapron C, Souza C, de Ziegler D, Lafay-Pillet MC, Ngô C, Bijaoui G, Goffinet F, Borghese B.Service de Gynécologie Obstétrique II et Médecine de la Reproduction (Professeur Chapron), Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France; Institut Cochin, CNRS UMR 8104, Paris, France; INSERM U1016, Paris, France.Smoking habits did not influence either the risk of any form of endometriosis (superficial peritoneal endometriosis, ovarian endometriomas, and deep infiltrating endometriosis) and did not correlate with the revised American Fertility Society stages or scores. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Fertil Steril. 2010 Jun 2. [Epub ahead of print]Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhibits proliferation, and activates apoptosis in immortalized epithelial endometriotic cells.Imesch P, Fink D, Fedier A.Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.Romidepsin inhibited HDAC activity, produced acetylation of the histone proteins, up-regulated p21, and down-regulated cyclins B1 and D1, resulting in proliferation inhibition and apoptosis activation in 11z immortalized epithelial endometriotic cells. Our findings provide evidence that endometriotic cells are sensitive to the epigenetic effects of romidepsin and suggest that endometriosis may be therapeutically targeted by romidepsin. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Chemosphere. 2010 Jul 3. [Epub ahead of print]Theoretical targets for TCDD: A bioinformatics approach.Olivero-Verbel J, Cabarcas-Montalvo M, Ortega-Zúñiga C.Environmental and Computational Chemistry Group, University of Cartagena, Cartagena, Colombia.Dioxins are a group of highly toxic molecules that exert their toxicity through the activation of the aryl hydrocarbon receptor (AhR). The most important agonist of the AhR, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic compound. Although most of the effects related to TCDD exposure have been linked to the activation of AhR, the objective of this work was to use a bioinformatics approach to identify possible new targets for TCDD. The Target Fishing Docking (TarFisDock) Server was used to find target proteins for TCDD. This virtual screening allowed the identification of binding sites with high affinity for TCDD in diverse proteins, such as metallopeptidases 8 and 3, oxidosqualene cyclase, and myeloperoxidase. Some of these proteins are well known for their biochemical role in some pathological effects of dioxin exposure, including endometriosis, diabetes, inflammation and liver damage. These results suggest that TCDD could also be interacting with cellular targets though AhR-independent pathways. Copyright © 2010 Elsevier Ltd. All rights reserved.Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2010 Jun;32(3):297-302. doi: 10.3881/j.issn.1000-503X.2010.03.013.Application values of four risk of malignancy indices in the preoperative evaluation of patients with adnexal masses.[Article in Chinese]Lou HY, Meng H, Zhu QL, Zhang Q, Jiang YX.Department of Ultrosonography, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.OBJECTIVE: To evaluate the diagnostic values of four risk of malignancy indices (RMI) for malignant adnexal masses. METHODS: The data of 223 women with adnexal masses admitted to the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital for surgical exploration between June 2008 and December 2008 were retrospectively analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of RMI1, RMI2, RMI3, and RMI4 in the diagnosis of malignant adnexal masses were calculated. RESULTS: When the cutoff levels of RMI1, RMI2, RMI3 were set at 200 and RMI4 at 450, the sensitivities for diagnosing malignant adnexal masses ranged 59.0%-67.2%, the specificities ranged 94.4%-96.9 %, the positive predictive values ranged 82.0%-87.8%, and the negative predictive values ranged 90.9%-92.6%. The Youdens indexes (YI) of RMI1, RMI2, RMI3, and RMI4 were 0.559,0.606,0.576, and 0.559, respectively. RMI2 was significantly different from RMI1 (P=0.000), RMI3 (P=0.008), and RMI4 (P=0.000) in terms of diagnostic efficiency. RMI1, RMI2, RMI3, and RMI4 at a cutoff level of 75.688.679.1, 177.2 respectively, according to ROC curves, yielded sensitivities of 77.8%-82.5%, specificities of 84.6%-90.1%, positive predictive values of 69.0%-75.4%, and negative predictive values of 90.9%-92.6%; the relevant YI of RMI1, RMI2, RMI3, and RMI4 were 0.635, 0.665, 0.651 and 0.705, respectively. Under this cutoff level, the difference between RMI1, RMI2, RMI3, and RMI4 in diagnosing malignancy had no statistic significant. The primary histological types arising false negative were early stage epithelial ovarian cancer and non-epithelial ovarian cancer. The primary histological types arising false positive were endometriosis masses and degenerative sex cord-stromal tumor. CONCLUSIONS: RMIs are useful indices for the differentiation between benign and malignant pelvic diseases. Meanwhile, their cutoff levels for Chinese populations need further study.Nat Genet. 2010 Aug;42(8):707-10. Epub 2010 Jul 4.A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese.Uno S, Zembutsu H, Hirasawa A, Takahashi A, Kubo M, Akahane T, Aoki D, Kamatani N, Hirata K, Nakamura Y.Institute of Medical Science, The University of Tokyo, Tokyo, Japan.Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.Reprod Sci. 2010 Jul 2. [Epub ahead of print]Reciprocal Communication Between Endometrial Stromal Cells and Macrophages.Eyster K, Hansen K, Winterton E, Klinkova O, Drappeau D, Mark-Kappeler C.This study tested the hypothesis that reciprocal communication occurs between macrophages and cultured human endometrial stromal cells and that this communication may contribute to the pathology of endometriosis. An endometrial stromal cell line (telomerase-immortalized human endometrial stromal cell [T-HESC]) was treated with macrophage-conditioned medium (CM) +/- estradiol + progesterone. Macrophages were treated without or with T-HESC CM. DNA microarray identified 716 differentially expressed genes in T-HESCs in response to factors secreted by macrophages. Upregulated genes in T-HESC included interleukin 8 (IL-8)/chemokine (C-X-C motif) ligand 8 (CXCL8), matrix metalloproteinase 3 (MMP3), phospholamban, cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), tenascin C, and nicotinamide N-methyltransferase (NNMT), whereas integrin alpha-6 was downregulated. In contrast, 15 named genes were differentially expressed in macrophages in response to factors secreted by endometrial stromal cells. The data document reciprocal communication between macrophages and endometrial stromal cells and suggest that interaction with macrophages stimulates the expression of genes in endometrial stromal cells that may support the establishment of endometriosis.Interact Cardiovasc Thorac Surg. 2010 Jul 2. [Epub ahead of print]Endometriosis-related spontaneous diaphragmatic rupture.Triponez F, Alifano M, Bobbio A, Regnard JF.University Hospital of Geneva, Geneva, Switzerland.Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months. Keywords: Catamenial pneumothorax; Diaphragmatic rupture; Diaphragmatic hernia; Diaphragmatic repair.Health Qual Life Outcomes. 2010 Jul 2;8:64.The development and validation of the daily electronic Endometriosis Pain and Bleeding Diary.Deal LS, DiBenedetti DB, Williams VS, Fehnel SE.Patient Reported Outcomes, Pfizer, 500 Arcola Road, Collegeville, PA 19426, USA. [email protected]: The objective of this study was to develop and validate a daily electronic Endometriosis Pain and Bleeding Diary (EPBD) for assessing treatment-related changes in endometriosis symptoms from the patient’s perspective in a clinical trial setting. METHODS: The EPBD items were developed based on clinician input and the results of 5 focus groups (N = 38) and 3 iterative sets of cognitive interviews (N = 22). The psychometric properties were evaluated using data collected in a usual-practice, non-intervention study conducted at 4 sites in the United States. Existing questionnaires were also administered to explore the construct validity of the EPBD. The development and validation processes were consistent with the recommendations in the 2009 FDA Patient Reported Outcomes Guidance to Industry. RESULTS: Focus group participants described 2 distinct types of pain (intermittent and continuous), which they felt were relevant and important to monitor. Participants also indicated that pain and bleeding/spotting associated with intercourse were important symptoms related to endometriosis. Cognitive interviews with additional endometriosis patients served to optimize item content, wording, and response options. Psychometric analyses found the EPBD items to behave as expected, for example, item-level means for subjects with severe endometriosis symptoms were higher (i.e., worse) compared with subjects with mild symptoms. Item-total correlations for the EPBD pain items (range 0.40-0.89) indicated that the items were related but not redundant. EPBD pain ratings correlated highly with the modified Brief Pain Inventory-Short Form Pain Intensity score (range 0.46-0.61). Women with severe endometriosis symptoms reported significantly higher intermittent and continuous dysmenorrhea and intermittent and continuous pelvic pain ratings and greater interference with daily activities compared with women with mild symptoms (all p < 0.01). CONCLUSIONS: The results of this study show that the 17-item EPBD reliably and validly characterizes the types of pain that endometriosis patients identified as being important. As a daily patient-reported assessment, it overcomes the significant potential for intra- and inter-rater variability and rater and recall bias that is inherent in the Biberoglu and Behrman Scale. Additional studies are required to confirm the dimensionality and optimal scoring of the EPBD, to corroborate the present results, and to assess other important measurement properties, such as responsiveness.J Obstet Gynaecol Res. 2010 Jun;36(3):611-8.Uterine junctional zone at magnetic resonance imaging: a predictor of in vitro fertilization implantation failure.Maubon A, Faury A, Kapella M, Pouquet M, Piver P.Limoges University Hospital, Radiology and Medical Imaging Department-MAP Center, Limoges, Cedex, France. [email protected]: To prospectively study the influence of the uterine junctional zone thickness measured on pelvic magnetic resonance imaging (MRI), on implantation rates during in vitro fertilization (IVF). METHODS: A prospective clinical-imaging study was conducted and included 152 female patients. Patients had a positive diagnosis of infertility and an indication for IVF. All patients had a pelvic MRI scan on a 1.5T magnet with T2-weighted sequences prior to IVF. The average junctional zone thickness value and the maximal junctional zone thickness values were measured. Implantation outcomes were correlated with junctional zone values and with infertility subtypes (endometriosis, tubal, dysovulation, male, unexplained). RESULTS: The mean number of embryo transfers per patient was 1.63, with a total pregnancy rate of 54%. Junctional zone thickness increase was significantly correlated with implantation failure at IVF: implantation failure rate was 95.8% for patients with an average junctional zone superior to 7 mm and a maximal junctional zone superior to 10 mm, versus 37.5% in other patient groups (P < 0.0001), independently from the cause of infertility or patients’ age. CONCLUSION: In a group of infertile patients engaged in an IVF program, a pelvic MRI scan showing a thickened uterine junctional zone is a negative predictive factor for embryo implantation after IVF.Womens Health (Lond Engl). 2010 Jul;6(4):551-63.Acupuncture in reproductive medicine.So EW, Ng EH.Department of Obstetrics & Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong.Acupuncture is increasingly being used in reproductive medicine. This review summarizes the evidence of acupuncture in pain relief for oocyte retrieval, improving pregnancy outcomes of in vitro fertilization treatment, management of ovulation disorders, male subfertility, primary dysmenorrhea, endometriosis and menopausal symptoms. However, most of the studies are nonrandomized uncontrolled trials, case reports or case series. For randomized controlled trials, the sample size is underpowered and blinding of assessors is lacking. Different acupuncture protocols and controls are used. These heterogeneities make it difficult to compare studies and draw any firm conclusions. Further studies should also evaluate the cost-effectiveness of acupuncture and investigate the underlying mechanism of acupuncture treatment.Womens Health (Lond Engl). 2010 Jul;6(4):531-48, quiz 548-9.Fallopian tube recanalization: lessons learnt and future challenges.Allahbadia GN, Merchant R.Deccan Fertility Clinic, Mumbai, India. [email protected] advances in fiberoptics and endoscopy have resulted in the development of minimally invasive transcervical tubal catheterization procedures with the potential of improved diagnostic accuracy of tubal disease and transcervical treatment of proximal tubal obstruction (PTO) with reduced risks, costs and morbidity compared with surgical procedures. Fallopian tube recanalization can be performed with catheters, flexible atraumatic guidewires or balloon systems under endoscopic (falloposcopy/hysteroscopy/laparoscopy), sonographic, fluoroscopic or tactile guidance. Falloposcopy provides a unique possibility to accurately visualize and grade endotubal disease, characterize and document endotubal lesions, identify the segmental location of tubal pathology without complications, objectively classify the cause of PTO and guide future patient management. This is in contrast to the surgical and radiological gold standards, laparoscopy and hysterosalpingography, respectively, that are often associated with poor or misdiagnosis of PTO. Nonhysteroscopic transuterine falloposcopy using the linear eversion catheter is a successful, well-tolerated, outpatient technique with a good predictive value for future fertility. Hysteroscopic-falloposcopic-laparoscopic tubal aquadissection, guidewire cannulation, guidewire dilatation and direct balloon tubuloplasty may be used therapeutically to breakdown intraluminal adhesions or dilate a stenosis in normal or minimally diseased tubes with high patency and pregnancy rates. However, guidewire cannulation of proximally obstructed tubes yields much lower pregnancy rates compared with other catheter techniques, despite the high tubal patency rates. Laparo-hysteroscopic selective tubal catheterization with insufflation of oil-soluble radiopaque dye has been reported to be an effective treatment for infertility associated with endometriosis. The various disadvantages associated with fluoroscopic and sonographic techniques limit their application, despite the reportedly high patency and intrauterine pregnancy rates. Recanalization is contraindicated in florid infections and genital tuberculosis, obliterative fibrosis and long tubal obliterations that are difficult to bypass with the catheter, severe tubal damage, male subfertilitY and previously performed tubal surgery. Distal tubal obstruction is not amenable to catheter recanalization techniques. Tuberculosis, salpingitis isthmica nodosa, isthmic occlusion with club-changed terminal, ampullar or fimbrial occlusion, and tubal fibrosis have been cited as reasons for recanalization failure. In lieu of the poor pregnancy outcomes in patients with severe tubal disease and poor mucosal health following tubal recanalization, as well as poor available technical skills and results with microsurgery, in vitro fertilization and embryo transfer is a valid option in such women. Despite the high diagnostic and therapeutic power of falloposcopic interventions, technical shortcomings with falloposcopy must be overcome before the procedure gains widespread acceptance.Minerva Ginecol. 2010 Jun;62(3):179-85.Transvaginal ultrasonography with water-contrast in the rectum in the diagnosis of bowel endometriosis.Morotti M, Ferrero S, Bogliolo S, Venturini PL, Remorgida V, Valenzano Menada M.Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy – [email protected]: The rectosigmoid is the most frequent location of intestinal endometriosis. Although several techniques have been proposed for the diagnosis of intestinal endometriosis, no gold standard is currently available. In this review, we describe in details a new technique for the diagnosis of rectosigmoid endometriosis: rectal water-contrast transvaginal ultrasonography. METHODS: During transvaginal ultrasonography, an assistant inserts a 6-mm flexible catheter through the anal os into the rectal lumen; the insertion of this catheter is evaluated under ultrasonographic control. Water contrast is instilled slowly in the rectum to permit intestinal distension. The colonic wall evaluation is obtained by positioning the transvaginal probe against a length of the sigmoid colon to obtain either axial or longitudinal images. The injection of the saline solution facilitates the identification of recto-sigmoid endometriotic nodules which appear as rounded or triangular hypoechoic masses, located anterior or lateral to the bowel. RESULTS: This technique has high sensitivity and specificity in the diagnosis of rectal infiltration in women with rectovaginal endo-metriosis. The distance between the nodules and the mucosal layer permits to estimate the depth of infiltration of these endometriotic lesions within the intestinal wall. Rectal distensibility can be estimated. The procedure is well tolerated by the patients. CONCLUSION: Water distension of the rectum facilitates the identification of intestinal endometriosis during transvaginal ultrasonography.Minerva Endocrinol. 2010 Jun;35(2):87-108.17b-Hydroxysteroid dehydrogenase inhibitors.Day JM, Tutill HJ, Purohit A.Department of Endocrinology and Metabolic Medicine and Sterix Ltd., Imperial College London, St. Mary’s Hospital, London, UK – [email protected] dehydrogenases (17b-HSDs) are enzymes which require NAD(P)(H) for activity and are responsible for reduction or oxidation of hormones, fatty acids and bile acids in vivo, regulating the amount of the active form which is available to bind to its receptor. Fifteen 17b-HSDs have been identified to date, and with one exception, 17b-HSD Type 5 (17b-HSD5), an aldo-keto reductase, they are all short chain dehydrogenases/reductases. Although named as 17b-HSDs, reflecting the major redox activity at the 17b-position of the steroid, overall homology between the enzymes is low and the activities of these fifteen enzymes vary, with several of the 17b-HSDs able to reduce and / or oxidise multiple substrates at various positions. These activities are involved in the progression of a number of diseases, including those related to steroid metabolism. Many groups are now working on inhibitors specific for several of these enzymes for the treatment of steroid-dependent diseases, including breast and prostate cancer, and endometriosis, with demonstrable efficacy in in vivo disease models, although none have yet reached clinical trials. In this review the recent advances in the development of specific inhibitors of the 17b-HSD1, 3 and 5 enzymes as targets for the treatment of these diseases and the models used for their evaluation will be discussed.J Reprod Immunol. 2010 Jun 29. [Epub ahead of print]Endometriosis research: animal models for the study of a complex disease.Tirado-González I, Barrientos G, Tariverdian N, Arck PC, García MG, Klapp BF, Blois SM.Charité, Department of Internal Medicine and Dermatology, Medicine University of Berlin, Berlin, Germany.Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence of events involved in disease establishment and progression. Also, because this disease occurs spontaneously only in humans and non-human primates and there are practical problems associated with studying the disease, animal models have been developed for the evaluation of endometriosis. This review describes the animal models for endometriosis that have been used to date, highlighting their importance for the investigation of disease mechanisms that would otherwise be more difficult to elucidate, and proposing new alternatives aimed at overcoming some of these limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.Case Report Med. 2010;2010:472162. Epub 2010 Jun 13.Ovarian splenosis: a case report.Talati H, Radhi J.Department of Pathology, McMaster University, 1200 Main Street West, Hamilton, ON, Canada L8N 3V7.Splenosis is auto transplantation of splenic tissue following traumatic rupture of the spleen. In females it can mimic endometriosis when symptomatic. Asymptomatic splenosis is common than previously suspected and it can also involve ovary. In a patient with a history of splenectomy, splenosis can act and provide the function of the spleen and thus should not be routinely excised. We report a case of an asymptomatic, incidental ovarian splenosis of left ovary accompanying multiple pelvic and serosal splenotic nodules. To our best knowledge, total three cases of ovarian splenosis have been reported previously including two cases of ovarian splenosis accompanying pelvic and serosal splenotic nodules and one case of solitary ovarian splenosis.Arch Pathol Lab Med. 2010 Jul;134(7):1020-3.Ovarian frozen section diagnosis: use of whole-slide imaging shows excellent correlation between virtual slide and original interpretations in a large series of cases.Fallon MA, Wilbur DC, Prasad M.Department of Pathology, University of Massachusetts,Worcester, MA, USA.CONTEXT: Whole-slide images (WSI) are a tool for remote interpretation, archiving, and teaching. Ovarian frozen sections (FS) are common and hence determination of the operating characteristics of the interpretation of these specimens using WSI is important. OBJECTIVES: To test the reproducibility and accuracy of ovarian FS interpretation using WSI, as compared with routine analog interpretation, to understand the technology limits and unique interpretive pitfalls. DESIGN: A sequential series of ovarian FS slides, representative of routine practice, were converted to WSI. Whole-slide images were examined by 2 pathologists, masked to all prior results. Correlation characteristics among the WSI, the original, and the final interpretations were analyzed. RESULTS: A total of 52 cases, consisting of 71 FS slides, were included; 34 cases (65%) were benign, and 18 cases (35%) were malignant, borderline, and of uncertain potential (9 [17%], 7 [13%], and 2 [4%] of 52 cases, respectively). The correlation between WSI and FS interpretations was 96% (50 of 52) for each pathologist for benign versus malignant, borderline, and uncertain entities. Each pathologist undercalled 2 borderline malignant cases (4%) as benign cysts on WSI. There were no overcalls of benign cases. Specific issues within the benign and malignant groups involved endometriosis versus hemorrhagic corpora lutea, and granulosa cell tumor versus carcinoma, respectively. CONCLUSIONS: The correlation between original FS and WSI interpretations was very high. The few discordant cases represent recognized differential diagnostic issues. Ability to examine gross pathology and real-time consultation with surgeons might be expected to improve performance. Ovarian FS diagnosis by WSI is accurate and reproducible, and thus, remote interpretation, teaching, and digital archiving of ovarian FS specimens by this method can be reliable.