Am J Reprod Immunol. 2010 Jul 4. [Epub ahead of print]

Association of Interleukin-10 Promoter Polymorphism and Endometriosis.

Riiskjaer M, Nielsen K, Steffensen R, Erikstrup C, Forman A, Kruse C.

Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby, Aarhus, Denmark.

Citation Riiskjaer M, Nielsen K, Steffensen R, Erikstrup C, Forman A, Kruse C. Association of Interleukin-10 Promoter Polymorphism and Endometriosis. Am J Reprod Immunol 2010 Problem Inflammatory processes are believed to play an important role in the pathogenesis of endometriosis. Interleukin-10 (IL-10) is an important immunoregulatory cytokine. The biological actions are mainly inhibitory including inactivation of macrophages and inhibition of pro-inflammatory cytokines. Twin and family studies have shown that between 50 and 75% of the observed variability of IL-10 secretion was explained by genetic factors. Several single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 have been described, but the most investigated are located at positions -1082, -819 and -592 of the transcriptional start site. Method of Study Three SNPs in the promoter region of IL-10 (-1082)G>A, (-819)C>T and (-592)C>A were examined in 100 Danish patients with endometriosis and 358 healthy Danish blood donors, and haplotype associations were tested. Results We observed no strong single IL-10 marker effects and no single haplotype showed significant association. However, the ACC/ACC genotype showed a significant association because this genotype was significantly higher among patients with endometriosis than in healthy controls [OR = 3.55 (CI = 1.42-18.92); P = 0.006]. Conclusion Our results suggest that the IL-10 ACC/ACC genotype, which is known to be a ‘low-producer’ of IL-10, is associated with endometriosis.

Zentralbl Chir. 2010 Jul 8. [Epub ahead of print]

Abdominal Wall Endometriosis as Rare Differential Diagnosis of a Soft-tissue Tumor.

Cziupka K, Partecke LI, Thiele A, Paul H, Schreiber A, Heidecke CD, Busemann A.

Universitätsklinikum Greifswald, Klinik für Chirurgie, Abt. für Allgemein-, Viszeral-, Thorax und Gefässchirurgie, Greifswald, Deutschland.

Arch Gynecol Obstet. 2010 Jul 9. [Epub ahead of print]

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

Na YJ, Lee DH, Kim SC, Joo JK, Wang JW, Jin JO, Kwak JY, Lee KS.

Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Busan, 602-739, Korea.

PURPOSE: Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1alpha (MIP-1alpha) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. METHODS: Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. RESULTS: There was a positive correlation between the levels of MCP-1 and MIP-1alpha in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1alpha when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1alpha released by neutrophils and between the levels of MCP-1 and MIP-1alpha released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. CONCLUSIONS: These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1alpha in response to stimulation with ePF.

Hum Reprod. 2010 Jul 8. [Epub ahead of print]

Predicting aneuploidy in human oocytes: key factors which affect the meiotic process.

Gianaroli L, Magli MC, Cavallini G, Crippa A, Capoti A, Resta S, Robles F, Ferraretti AP.

S.I.S.Me.R., Reproductive Medicine Unit, Via Mazzini, 12, 40138 Bologna, Italy.

BACKGROUND To estimate the incidence of aneuploidy in relation to patients’ characteristics, the type of hormonal stimulation and their response to induction of multiple follicular growth, 4163 first polar bodies (PB1s) were analyzed. METHODS Five hundred and forty four infertile couples underwent 706 assisted conception cycles (640 with poor prognosis indications and 66 controls) in which chromosomal analysis of PB1 for the chromosomes 13, 15, 16, 18, 21 and 22 was performed. Results were evaluated in a multivariate analysis. RESULTS The proportion of normal oocytes was directly correlated (P < 0.01) with (i) the number of mature oocytes and (ii) the establishment of a clinical pregnancy; and inversely correlated (P < 0.01) with (i) female age, (ii) causes of female infertility (endometriosis, abortions, ovulatory factor), (iii) poor prognosis indications (female age, number of previous cycles, multiple poor prognosis indications), (iv) number of FSH units per oocyte and (v) number of FSH units per metaphase II oocyte. There was a weak significance of frequency (P < 0.05) between type of abnormality (originated by chromatid predivision, chromosome non-disjunction or combined mechanisms in the same oocyte) and groups of the studied variables, rather than to a specific abnormality or a specific chromosome. CONCLUSIONS The type of infertility had a significant effect on errors derived from the first meiotic division, whose incidence was significantly higher in the presence of endometriosis or of an ovulatory factor, and in women that experienced repeated abortions. Each aneuploidy event was found to be dependent not on a specific variable, but on groups of variables. In addition, the tendency of chromosomal abnormalities to occur simultaneously implies that the deriving aneuploidies can be of any type.

Am J Epidemiol. 2010 Aug 1;172(3):237-43. Epub 2010 Jul 8.

Pelvic endometriosis diagnosed in an entire nation over 20 years.

Gylfason JT, Kristjansson KA, Sverrisdottir G, Jonsdottir K, Rafnsson V, Geirsson RT.

Department of Obstetrics and Gynecology, Landspitali University Hospital/University of Iceland, Reykjavik, Iceland.

The annual incidence of pelvic endometriosis among women aged 15-49 years and up to age 69 years was ascertained for the Icelandic population between 1981 and 2000 by using Iceland’s extensive record linkage systems. Comprehensive, state-financed health care and unique personal identification numbers enabled care to be tracked from first diagnosis. To identify cases, a centralized discharge-code registry was searched, as well as all hospital databases and, for individual patients, all hospital records. Each case of visually diagnosed and histologically verified endometriosis was cross-checked against the nationwide pathology registry. The revised American Society for Reproductive Medicine classification system was used for staging. Recorded was type of operation at diagnosis and presence of disease at 5 sites: deep pelvis, appendages, central pelvis, vesicouterine pouch, and ovaries. A total of 1,383 women were diagnosed surgically, with histologic verification of 811 (58.6%). All but 6 cases could be staged; 297 (36.9%) had minimal/mild and 508 (63.1%) had moderate/severe disease. The estimates of crude annual incidence were 0.1% for visually confirmed and 0.06% for histologically verified endometriosis, and respective age-standardized annual incidence was 0.1% and 0.05% for women aged 15-49 years. The most common site was the ovary, followed by deep pelvis, central pelvis, appendages, and vesicouterine pouch.

Uterine stem cells.

Teixeira J, Rueda BR, Pru JK.

In: StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008-.
2008 Sep 30.

The uterus is essential for reproduction in most mammalian species and is arguably the most naturally plastic organ in terms of tissue remodeling in mammals. Histologically, the uterus is divided into the endometrium and the outer smooth muscle layer called the myometrium. The endometrium harbors epithelial (glandular and luminal) and fibroblast-like stromal cells, and is separated physiologically into the functionalis (inner most region nearest the lumen) and basalis layers. The key morphological changes that the uterus undergoes are in response to cyclical hormonal cues from the ovary and from the implanting embryo during pregnancy. During menses and following parturition, the functionalis layer of the endometrium regresses and is lost in primates and must be replaced. During pregnancy, the wet weight of the uterus increases 10-fold largely due to myometrial smooth muscle cell hypertrophy and hyperplasia. We believe that the remodeling of the uterus in response to these stimuli and its return to a basal state requires adult stem (or progenitor) cells that reside in the individual endometrial and myometrial compartments. Furthermore, we suspect that several pathological conditions, such as endometrial cancer, endometriosis, and leiomyomata (i.e., uterine fibroids), can be attributed to dysregulation of these same stem cells, or are derived from committed cells that acquire stem-like features. We will review uterine development and its response to hormonal cycling and pregnancy, uterine neoplasia, and the evidence for a role for uterine stem cells in these settings.

Curr Opin Obstet Gynecol. 2010 Aug;22(4):344-53.

The feasibility of laparoscopic bowel resection performed by a gynaecologist to treat endometriosis.

Pereira RM, Zanatta A, Serafini PC, Redwine D.

Huntington Reproductive Medicine Center, São Paulo, São Paulo, São Paulo, Brazil.

PURPOSE OF REVIEW: Intestinal endometriosis is commonly diagnosed in the setting of deeply infiltrating endometriosis. A multidisciplinary team that includes gynaecologists and general surgeons traditionally performs laparoscopic bowel resections for symptomatic patients. Recently, Pereira et al. has published the results of a series of patients who underwent laparoscopic bowel resection for endometriosis performed by a team of gynaecologic surgeons, after a period of experimental training with animals and joining participation with general surgeons in the first cases. It is suggested that gynaecologic surgeons may be able to perform laparoscopic bowel resections for endometriosis, if properly trained, although the results may not be reproducible. RECENT FINDINGS: A review of recent literature related to laparoscopic bowel resections for endometriosis showed that the learning curve and experience of the surgeon may be the most important predictive factors for the effectiveness of the procedure. Results concerning major operative complications and clinical remission were considered satisfactory in both single and multidisciplinary approaches, that is, laparoscopic bowel resections performed by gynaecologic and colorectal surgeons. Protective colostomies or ileostomies could not reduce the rate of rectovaginal fistulae in multidisciplinary experiences. SUMMARY: The single-surgeon model approach in laparoscopic excision of endometriosis that includes bowel resection may provide advantages for both the patients and healthcare system. The best model should be decided on the maximum benefit of the patient.

Curr Opin Obstet Gynecol. 2010 Aug;22(4):309-14.

Laparoscopic conservative management of ureteral endometriosis.

Camanni M, Delpiano EM, Bonino L, Deltetto F.

GINTEAM Unit of Minimally Invasive Gynaecology, Corso Marconi, 10125 Turin, Italy.

PURPOSE OF REVIEW: The surgical management of deeply infiltrating endometriosis involving the ureter is a complex procedure that requires an accurate balance between the need for complete excision of endometriotic foci and the need to avoid any morbidity associated with radical surgery. Owing to its rarity, a clear surgical strategy to deal with this condition (e.g. ureterolysis vs. ureteroneocystostomy) has not as yet been identified. RECENT FINDINGS: A few studies present data about the conservative management of ureteral endometriosis. We reported the experience of some surgical topics dealing with ureteral endometriosis and their strategies for the conservative treatment of this condition. SUMMARY: Ureterolysis could be used as the initial surgical step for patients with ureteral endometriosis. For patients displaying extended severe ureteral involvement, stenosis, or moderate or severe hydronephrosis with a high risk of having intrinsic ureteral disease, ureteroneocystostomy is likely to be a wiser surgical strategy. Moreover the crucial role of the primary surgeon in the treatment definition will hardly be replaced by objective reproducible referral pattern.

J Pineal Res. 2010 Jul 1. [Epub ahead of print]

Melatonin protects against endometriosis via regulation of matrix metalloproteinase-3 and an apoptotic pathway.

Paul S, Bhattacharya P, Mahapatra PD, Swarnakar S.

Department of Physiology, Indian Institute of Chemical Biology, Kolkata, India.

The role of matrix metalloproteinases (MMPs) in endometriosis, a gynecological disease of women, is unclear. The study investigated the activity of MMP-3 and its interplay with MMP-9 during the onset of endometriosis. Additionally, the importance of MMP-3 on the apoptotic pathway in endometriosis and effect of melatonin thereon were investigated. A Significant increase in the activity of MMP-3 with the severity of endometriosis in human was observed which was found similar in mice also. During the early phase of endometriosis, MMP-3 but not MMP-9 was increased and associated with the expression of transcription factor, c-Fos. Moreover, urokinase plasminogen activator and tissue inhibitor of metalloproteinase (TIMP)-3 were involved in MMP-3 regulation during endometriosis. Furthermore, MMP-3 activity that was parallel to c-Fos expression in endometriosis was reduced by melatonin pretreatment as characterized by diminished activator protein (AP)-1 DNA-binding activity. Because decreased apoptosis is an explanation for the perpetuation of endometriosis, we tested the role of melatonin on apoptotic pathway in preventing endometriosis. Significant regression of glandular epithelium was observed in melatonin-treated when compared to untreated mice. Melatonin treatment increased apoptotic cells in endometriotic zones. This was related to reduced Bcl-2 expression along with increased Bax expression and caspase-9 activation. In summary, early induction of MMP-3 was distinct from MMP-9 during endometriosis, which was regulated by c-Fos and TIMP-3. Melatonin suppressed MMP-3 activity and amplified apoptosis while regressing endometriosis through a caspase-3 mediated pathway. Thus, melatonin may be a therapeutic agent for resolving endometriosis.

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.

BACKGROUND: 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.

AIM: 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.

Technological 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 –

AIM: 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 –

17b-Hydroxysteroid 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.

Gynecol Endocrinol. 2010 Jun 29. [Epub ahead of print]

Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis.

Lamp M, Peters M, Reinmaa E, Haller-Kikkatalo K, Kaart T, Kadastik U, Karro H, Metspalu A, Salumets A.

Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.

Objective. To investigate whether polymorphisms in genes involved in biosynthesis and signalling of sex steroids influence susceptibility to endometriosis and to infertility associated with it. Materials and methods. Patients with endometriosis (n = 150) and fertile controls (n = 199) were genotyped for polymorphisms in oestrogen receptor genes ESR1 (rs2234693 – T/C single nucleotide polymorphism (SNP), dinucleotide (TA)(n) repeat) and ESR2 (dinucleotide (CA)(n) repeat), progesterone receptor gene PGR (rs10895068 – G/A SNP, 306-bp Alu-insertion), 17beta-hydroxysteroid dehydrogenase type 1 gene HSD17B1 (rs605059 – A/G SNP), and aromatase gene CYP19A1 (rs10046 – C/T SNP, (TTTA)(n) tetranucleotide repeat, 3-bp TCT insertion/deletion polymorphism). Results. The HSD17B1 A/G SNP A allele increased overall endometriosis risk and the risk of stage I-II disease, while ESR1 longer (TA)(n) repeats only correlated with susceptibility to stage I-II endometriosis. When considering patients’ fertility status, HSD17B1 A/G SNP A allele and ESR1 longer (TA)(n) repeats were associated with endometriosis accompanied by infertility, while ESR2 shorter (CA)(n) repeats were linked with endometriosis without infertility. Other polymorphisms were distributed similarly among patients and controls. Conclusions. Genetic variants in ESR1, ESR2, and HSD17B1 genes could modify susceptibility to endometriosis and might influence the fertility status in endometriosis patients.

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Jun;30(6):1318-20.

Ultrastructural change of the ectopic endometrium and its significance in endometriosis.

[Article in Chinese]

Jin HY, Zhou LS.

Department of Gynecology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou 510260, China. E-mail:

OBJECTIVE: To analyze the ultrastructural characteristics of ectopic endometrium in endometriosis. METHODS: Ectopic endometria collected from patients with adenomyosis and ovarian endometriosis were examined under transmission electron microscope (TEM). RESULTS: In comparison to normal human endometrium, the ectopic glandular epithelium of adenomyosis patients showed reduced and shortened microvilli covering the surface of the secretory cells, with obviously increased, elongated and irregularly aligned cilia of ciliated cells projecting into the lumen. Numerous microvilli and cilia broke off from the cell surface and shed into the lumen. The mitochondria were enlarged, and multiple polyribosomes were present on the surface of RER. The Golgi apparatus with electron-lucent vacuoles was seen frequently. The glandular cells contained many lysosomes, lipofuscins and myelinosomes, and the cell nuclei showed varying shape and size. The nuclear membrane of the epithelial cells was irregularity. Cytoplasm protrusion containing a few organells occurred and shed into the lumen. Some ectopic epithelial cells showed characteristic features of necrosis. The basement membrane became markedly tortuous and focal lysis of the extracellular matrix was seen. Ultrastructurally, the ectopic glandular epithelium in ovarian endometriosis showed short and sparse microvilli on the free surface of the secretory cells. Some microvilli broke off from the surface. The short cilia of the ciliated cells were seldom seen. The mitochondria were enlarged. The glandular cells contained small amounts of RER, many free ribosomes, Golgi apparatus, lipofuscins and myelinosomes. The nuclear membrane showed obvious irregularity. Some ectopic epithelial cells had giant nuclei. Cytoplasmic protrusions containing small amounts of organells were observed in some ectopic epithelial cells. Apoptotic cell death occurred in some ectopic glandular epithelium cells. The basement membrane became markedly tortuous, and the decidual-like cells containing abundant short and club-shaped RER were observed. The number of macrophages was obviously increased. CONCLUSION: The ultrastructural change of the ectopic glandular epithelium in endometriosis promotes its transformation into endometriotic lesions.

Am J Reprod Immunol. 2010 Jun 24. [Epub ahead of print]

Lymphocytes in Endometriosis.

Osuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.

Osuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y. Lymphocytes in Endometriosis. Am J Reprod Immunol 2010. Endometriosis is a disease characterized by the presence of endometriotic tissue outside the uterine cavity. Although its pathogenesis remains to be elucidated, immune status is suggested to play an important role in the initiation and the progression of the disease. In particular, immune cells in lymphoid lineage that comprised T and B lymphocytes and natural killer cells play essential roles in determining either accept or reject survival, implantation, and proliferation of endometrial and endometriotic cells. Numerous studies have shown aberrant functions of these immune cells in women with endometriosis. The abnormalities include reduced activity of cytotoxic T cells and NK cells, cytokine secretion by helper T cells, and autoantibody production by B lymphocytes. These alterations are suggested to be induced by various manners and promote the disease. Understanding of these immune aspects in endometriosis is thus expected to benefit the treatment of the disease.

Surg Today. 2010 Jul;40(7):672-5. Epub 2010 Jun 26.

Rectal endometriosis masquerading as dissemination in a patient with rectal cancer: report of a case.

Uchiyama S, Haruyama Y, Asada T, Nagaike K, Hotokezaka M, Yorita K, Chijiiwa K.

Department of Surgical Oncology and Regulation of Organ Function, Miyazaki University School of Medicine, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.

A 57-year-old woman was diagnosed as having rectal cancer. A barium enema study showed the apple-core sign at the rectosigmoid colon, and colonoscopy revealed an encircled ulcerated tumor. A laparoscope-assisted resection of the rectum was planned; however, the rectal cancer directly invaded the uterus body. The operation was converted to open surgery. An elastic hard tumor suspected of being peritoneal dissemination at the peritoneal reflection was detected and excised together with the rectum below the peritoneal reflection. A histological examination of this tumor revealed that cystic glands lined by nonmucinous columnar epithelial cells were seen on the serosal side and were embedded in the proper muscle of the rectum. This tumorous lesion was diagnosed as endometriosis.

Reprod Toxicol. 2010 May 16. [Epub ahead of print]

Organochlorine pesticides and endometriosis.

Cooney MA, Buck Louis GM, Hediger ML, Vexler A, Kostyniak PJ.

Epidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, 6100 Executive Blvd, Rm. 7B05, Rockville, MD 20852, United States.

Limited study of persistent organochlorine pesticides (OCPs) and endometriosis has been conducted. One hundred women aged 18-40 years who were undergoing laparoscopy provided 20cm(3) of blood for toxicologic analysis and surgeons completed operative reports regarding the presence of endometriosis. Gas chromatography with electron capture was used to quantify (ng/g serum) six OCPs. Logistic regression was utilized to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for individual pesticides and groups based on chemical structure adjusting for current cigarette smoking and lipids. The highest tertile of aromatic fungicide was associated with a fivefold risk of endometriosis (aOR=5.3; 95% CI, 1.2-23.6) compared to the lowest tertile. Similar results were found for t-nonachlor and HCB. These are the first such findings in a laproscopic cohort that suggest an association between OCP exposure and endometriosis. More prospective studies are necessary to ensure temporal ordering and confirm these findings. Copyright © 2010. Published by Elsevier Inc.

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