Fertil Steril. 2009 Apr;91(4 Suppl):1414-6. Epub 2008 Aug 9.

Absence of association between a functional polymorphism of ALOX15 gene and infertility in endometriosis.

Borghese B, Gayet V, Chiche JD, Vernerey D, de Ziegler D, Bonaiti-Pellié C, Chapron C.

Service de Gynécologie-Obstétrique II et Médecine de la Reproduction, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, CHU Cochin – Saint Vincent de Paul, Paris, France.

bruno.borghese@inserm.fr

The aim of the present study, involving 463 women of reproductive age, was to evaluate for the first time the relationship between endometriosis, endometriosis-related infertility, and a recently described functional polymorphism in the ALOX15 gene, reported to be essential for implantation. In our study population, ALOX15 -292 C/T was not correlated either with the risk of developing an endometriosis or with the risk of infertility.

Fertil Steril. 2009 May;91(5 Suppl):2193-8. Epub 2008 Aug 9.

Increased matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 secretion but unaffected invasiveness of endometrial stromal cells in adenomyosis.

Yang JH, Wu MY, Chen MJ, Chen SU, Yang YS, Ho HN.

Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China.

OBJECTIVE: To investigate cell invasiveness and the production of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in endometrial stromal cells (ESCs) of adenomyosis. DESIGN: Prospective study. SETTING: Tertiary university hospital. PATIENT(S): Twenty-one women with adenomyosis (study group) and 25 women without adenomyosis (control group). INTERVENTION(S): Endometrial stromal cells were purified from eutopic endometrium and were cultured in vitro. MAIN OUTCOME MEASURE(S): Matrigel invasion assay and measurement of MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations. RESULT(S): Endometrial stromal cell invasiveness of adenomyosis was not different from that of the control group (0.95 vs. 1, using the latter as the bench mark) in ESCs cultured alone. After the ESCs were cultured with IL-6, anti-IL-6, or GM6001 for 24 hours, the indices of cell invasion were not different between the two groups. MMP-2 (median 7.3 vs. 3.5 ng/mL) and TIMP-1 (median 12.1 vs. 3.9 ng/mL), but not MMP-9 and TIMP-2, secreted by ESCs in women with adenomyosis were much higher than those in women without adenomyosis. CONCLUSION(S): The formation of adenomyosis does not result from altered invasiveness of ESCs. The concomitant elevation of MMP-2 and TIMP-1 may partially justify why invasiveness was not increased, but other enzymes should also be considered.

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Fertil Steril. 2009 Aug;92(2):453-7. Epub 2008 Aug 9.

Associated ovarian endometrioma is a marker for greater severity of deeply infiltrating endometriosis.

Chapron C, Pietin-Vialle C, Borghese B, Davy C, Foulot H, Chopin N.

Université Paris Descartes V, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Universitaire Ouest, CHU Cochin, Service de Gynécologie Obstétrique II et Médecine de la Reproduction, Paris, France. charles.chapron@cch.aphp.fr

OBJECTIVE: To investigate whether an associated ovarian endometrioma is a marker for severity of deep infiltrating endometriosis (DIE). DESIGN: Observational study between June 1992 and December 2005. SETTING: University tertiary referral center. PATIENT(S): Five hundred patients with histologically assessed DIE. INTERVENTION(S): Complete surgical exeresis of deep endometriotic lesions. MAIN OUTCOME MEASURE(S): Severity of the disease was quantified according to the mean number of DIE lesions and the type of main lesion. RESULT(S): In patients with associated ovarian endometrioma, the number of single isolated DIE lesions was statistically significantly lower (41.9% vs. 61.1%). The mean number of DIE lesions was statistically significantly higher in patients presenting with an associated ovarian endometrioma (2.51 +/- 1.72 vs. 1.64 +/- 1.0). For patients with associated ovarian endometrioma DIE lesions were more severe with an increased rate of vaginal, intestinal, and ureteral lesions. CONCLUSION(S): Associated ovarian endometrioma is a marker for the severity of the DIE. In a clinical context suggestive of DIE, when there is an ovarian endometrioma, the practitioner should investigate the extent of the disease to check for severe and multifocal DIE lesions.

Fertil Steril. 2009 Jul;92(1):35-40. Epub 2008 Aug 9.

Bladder psoas hitch in hydronephrosis due to pelvic endometriosis: outcome of urodynamic parameters.

Carmignani L, Ronchetti A, Amicarelli F, Vercellini P, Spinelli M, Fedele L.

Urology Unit, IRCCS Policlinico San Donato, University of Milan, Via Morandi 30, San Donato Milanese, Milan, Italy luca.carmignani@unimi.it

OBJECTIVE: To evaluate modifications in bladder sensitivity and function after ureteroneocystostomy with bladder psoas hitch for hydronephrosis due to deep pelvic endometriosis. DESIGN: Prospective study. SETTING: Center for the Treatment of Endometriosis of the Department of Obstetrics and Gynecology of the State University of Milan, Italy. PATIENT(S): Thirteen patients with deep endometriosis and ureteral involvement. Mean age of patients was 36.8 years (range, 31-48 years). INTERVENTION(S): Ureteroneocystostomy with a psoas hitch. Indications for performing psoas hitch ureteroneocystostomy were severe hydronephrosis, radiologic evidence of ureteral stricture measuring >4 cm, and the impossibility of performing ureterolysis. MAIN OUTCOME MEASURE(S): Impact on urodynamic parameters of bladder psoas hitch ureteroneocystostomy. RESULT(S): All patients showed normal bladder capacity 3 months after surgery. Two patients presented with stress incontinence immediately after surgery, which almost completely subsided at 3 months’ follow-up. In 4 patients the bladder was also involved; in these cases a bladder resection was performed, followed by ureteral reimplantation. Follow-up was at 6 months from surgery and then every 6 months thereafter, in which patients underwent urogynecologic examination, completed a questionnaire on urinary symptoms, and underwent renal ultrasound evaluation with no evidence of recurrence of obstructive uropathy. CONCLUSION(S): On the basis of the results of the present study, bladder psoas hitch along with ureteral resection and ureteroneocystostomy for infiltrating endometriosis do not seem to have a negative impact on urodynamic parameters.

Fertil Steril. 2009 Jul;92(1):75-87. Epub 2008 Aug 9.

Comment in:

The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis.

Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG.

Department of Obstetrics and Gynecology, Royal Lancaster Infirmary, Lancaster, United Kingdom.

OBJECTIVE: To investigate the effect of surgical treatment of endometrioma on pregnancy rate and ovarian response to gonadotrophin stimulation in women undergoing IVF. DESIGN: A systematic review and meta-analysis. SETTING: Tertiary referral center for reproductive medicine. PATIENT(S): Subfertile women with endometrioma undergoing IVF. INTERVENTION(S): Surgical removal of endometrioma or expectant management. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and ovarian response to gonadotrophins (number of gonadotrophin ampoules, peak E(2) levels, number of oocytes retrieved, and number of embryos available for transfer). RESULT(S): A search of three electronic databases for articles published between January 1985 and November 2007 yielded 20 eligible studies. Meta-analysis was conducted for five studies that compared surgery vs. no treatment of endometrioma. There was no significant difference in clinical pregnancy rate between the treated and the untreated groups. Similarly, no significant difference was found between the two groups with regard to the outcome measures used to assess the response to controlled ovarian hyperstimulation with gonadotrophins. CONCLUSION(S): Collectively the available data in the literature show that surgical management of endometriomas has no significant effect on IVF pregnancy rates and ovarian response to stimulation compared with no treatment. Randomized controlled trials are needed before producing best-practice recommendations on this topic.

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Fertil Steril. 2009 May;91(5 Suppl):2061-8. Epub 2008 Aug 9.

Cumulus cell apoptosis changes with exposure to spermatozoa and pathologies involved in infertility.

Díaz-Fontdevila M, Pommer R, Smith R.

Institute of Maternal and Child Research, School of Medicine, University of Chile, San Borja Arriarán Clinical Hospital, Santiago, Chile. diazfontdevila@gmail.com

OBJECTIVE: To determine whether the incidence of apoptosis in mature oocyte cumulus cells changes after insemination related to infertility. DESIGN: Prospective study. SETTING: Public hospital and university. PATIENT(S): One hundred women undergoing in vitro fertilization and embryo transfer (IVF-ET). INTERVENTION(S): Collection of cumulus cells from IVF-ET cycles with different infertility etiologies. MAIN OUTCOME MEASURE(S): Detection of apoptosis in cumulus cells; fertilization, embryo quality, and pregnancy rate. RESULT(S): The incubation of cumulus-oocyte-complexes with spermatozoa led to an increase in cumulus cell apoptosis from 34.2 +/- 3.7 to 44.5 +/- 6.3%. After insemination, cumulus cells of poor quality embryos showed a statistically higher apoptotic rate versus cumulus cells of good quality embryos (61.5 +/- 6.4 vs. 40.6 +/- 3.9%). Cumulus cells arising from oocytes with >or=50% fertilization rates after insemination showed higher apoptosis rates did cumulus cells from oocytes with <50% fertilization rates (46.0 +/- 3.7 vs. 33.8 +/- 4.0%). Patients with endometriosis presented higher apoptotic rates before insemination (77.6 +/- 9.06%). Cumulus cells obtained after aspiration showed no differences in their apoptosis rates for the following factors: age of women, aspirated oocytes, estradiol level, fertilization rate, and embryo quality or pregnancy. The apoptotic profile from pregnant women was less than (but not statistically significantly different from) profiles from nonpregnant women. CONCLUSION(S): These results suggest that the incidence of apoptosis in cumulus cells is associated with exposure to spermatozoa and the cause of infertility.

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Fertil Steril. 2009 Jul;92(1):54-60. Epub 2008 Aug 8.

Association of estrogen receptor alpha and interleukin-10 gene polymorphisms with endometriosis in a Chinese population.

Xie J, Wang S, He B, Pan Y, Li Y, Zeng Q, Jiang H, Chen J.

Central Laboratory of Nanjing First Hospital affiliated to Nanjing Medical University, Nanjing, People’s Republic of China.

OBJECTIVE: To determine whether polymorphisms of the estrogen receptor alpha (ERalpha) and interleukin-10 (IL-10) genes are associated with endometriosis in a Chinese population. DESIGN: Association study. SETTING: University hospital. PATIENT(S): Chinese women diagnosed with endometriosis by laparotomy or laparoscopy. INTERVENTION(S): Determination of polymorphisms of the ERalpha and IL-10 genes was performed by polymerase chain reaction and restriction fragment length polymorphism analysis in 214 affected women and 160 controls. MAIN OUTCOME MEASURE(S): Frequency and distribution of PvuII and XbaI polymorphisms of ERalpha and of BslI, SspI, and RsaI polymorphisms of IL-10. RESULT(S): There was no significant difference between the endometriosis patients and the control groups in the genotype frequency of ERalpha-PvuII and promoter of IL-10 gene polymorphisms in the position of -1082. However, the frequency of ERalpha-XbaI and -592 or -819C alleles of IL-10 in the endometriosis group was significantly higher than that of controls, and further analysis showed that the X allele of ERalpha-XbaI was associated with endometriosis. CONCLUSION(S): The X allele of ERalpha-XbaI and the -592 or -819 C allele of IL-10 are associated with endometriosis.

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Fertil Steril. 2009 Jul;92(1):41-6. Epub 2008 Aug 5.

Fertility after bowel resection for endometriosis.

Ferrero S, Anserini P, Abbamonte LH, Ragni N, Camerini G, Remorgida V.

Department of Obstetrics and Gynaecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1, Genoa, Italy. dr@simoneferrero.com

OBJECTIVE: To determine the pregnancy rate after bowel resection for rectosigmoid endometriosis. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENT(S): Forty-six symptomatic women with bowel endometriosis requiring colorectal resection. INTERVENTION(S): Bowel resection by either laparoscopy or laparotomy. MAIN OUTCOME MEASURE(S): Pregnancy rate after surgery. RESULT(S): The pregnancy rate was higher in women who underwent bowel resection by laparoscopy (57.6%) than in those who underwent laparotomy (23.1%). No significant difference was observed in pregnancy rate and mode of conception between women with different fertility status before bowel resection. Women who conceived were significantly younger than those who did not conceive; only 26.7% of women aged > or =35 years conceived after bowel resection. Uterine adenomyosis was more frequently present in women who did not conceive than in those who conceived. Infertile women who conceived had a shorter length of infertility before surgery than those who did not conceive. CONCLUSION(S): Laparoscopic colorectal resection is less likely to impact negatively on fertility than the laparotomy approach. Previous laparotomies, age > or =35 years, uterine adenomyosis, and longer duration of infertility before surgery are associated with decreased pregnancy rate.

Fertil Steril. 2009 May;91(5 Suppl):2185-92. Epub 2008 Aug 5.

Interleukin-10 attenuates TNF-alpha-induced interleukin-6 production in endometriotic stromal cells.

Tagashira Y, Taniguchi F, Harada T, Ikeda A, Watanabe A, Terakawa N.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.

OBJECTIVE: To determine whether high levels of interleukin (IL)-10 can attenuate the production of tumor necrosis factor (TNF)-alpha-induced proinflammatory cytokines in endometriotic stromal cells. DESIGN: Prospective study. SETTING: Department of Ob/Gyn, Tottori University, Japan. PATIENT(S): Thirty-five patients with ovarian endometrioma and ten patients with uterine myoma. INTERVENTION(S): Endometriotic stromal cells were obtained from chocolate cyst linings of ovaries. Endometrial stromal cells obtained from patient with uterine myoma. MAIN OUTCOME MEASURE(S): Expression of IL-10 gene in endometriotic or endometrial stromal cells was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We performed immunohistochemical staining to find the presence of IL-10 and IL-10 receptors 1 and 2. We examined the effects of TNF-alpha and IL-10 on the expression of IL-6 or IL-8 by real-time RT-PCR and ELISA. We examined the activation of intracellular signal transduction molecules in endometriotic stromal cells by Western blotting. RESULT(S): Addition of IL-10 suppressed the expressions of IL-6 induced by TNF-alpha and IL-10 induced the phosphorylation of STAT3 in endometriotic stromal cells. TNF-alpha induced the expression of phosphorylated ERK1/2, JNK1/2, and I kappaB. Adding IL-10 suppressed the phosphorylation of these signal molecules. CONCLUSION(S): Interleukin-10 attenuates TNF-alpha-induced IL-6 synthesis via NF-kappaB and MAPK pathways in endometriotic cells.. Interleukin-10 may play a significant role in the pathogenesis of endometriosis.

Fertil Steril. 2009 Jul;92(1):68-74. Epub 2008 Aug 5.

High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners.

Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D’Hooghe T.

Leuven University Fertility Centre, Department of Obstetrics and Gynecology, University Hospital Leuven, Herestraat 49, Leuven, Belgium.

OBJECTIVE: To determine the prevalence of histologically proven endometriosis in a subset of infertile women. DESIGN: Retrospective case series with electronic file search and multivariable logistic regression analysis. SETTING: Tertiary academic fertility center. PATIENT(S): Two hundred twenty-one infertile women without previous surgical diagnosis for infertility with regular cycles (variation, 21-35 days) whose partners have a normal semen analysis. INTERVENTION(S): Diagnostic laparoscopy and, if necessary, operative laparoscopy with CO(2) laser excision. MAIN OUTCOME MEASUREMENT(S): The prevalence of endometriosis and of fertility-reducing nonendometriotic tubal and/or uterine pathology. RESULT(S): The prevalence of endometriosis was 47% (104/221), including stage I (39%, 41/104), stage II (24%, 25/104), stage III (14%, 15/104), and stage IV (23%, 23/104) endometriosis, and was comparable in patients with (54%, 61/113) and without (40%, 43/108) pelvic pain. The prevalence of fertility-reducing nonendometriotic tubal and/or uterine pathology was 29% in all patients (15% in women with and 40% in women without endometriosis). A multivariate logistic regression model including pain, ultrasound data, age, duration of infertility, and type of fertility was not or not sufficiently reliable for the prediction of endometriosis according to the revised American Fertility Society (rAFS) classifications I-II and rAFS III-IV, respectively. CONCLUSION(S): Reproductive surgery is indicated in infertile women belonging to the study population, regardless of pain symptoms or transvaginal ultrasound results, since half of them have endometriosis and 40% of those without endometriosis have fertility-reducing pelvic pathology.

Fertil Steril. 2009 Jul;92(1):47-53. Epub 2008 Aug 5.

Expression and possible implication of growth hormone-releasing hormone receptor splice variant 1 in endometriosis.

Fu L, Osuga Y, Yano T, Takemura Y, Morimoto C, Hirota Y, Schally AV, Taketani Y.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.

OBJECTIVE: To determine possible involvement of splice variant 1 (SV1), a variant of the pituitary growth hormone-releasing hormone (GHRH) receptor, in the development of endometriosis. DESIGN: Comparative and laboratory study. SETTING: University teaching hospital reproductive endocrinology and infertility practice. PATIENT(S): Eutopic and ectopic endometrial tissues, and peritoneal bone marrow-derived cells were collected from women with or without endometriosis. Normal ovarian tissues were collected from women without endometriosis. INTERVENTION(S): Ectopic endometrial stromal cells (ESC) were isolated and cultured with or without GHRH. MAIN OUTCOME MEASURE(S): Gene expression of GHRH and SV1 in the sample tissues was determined by reverse transcriptase (RT) nested polymerase chain reaction (PCR). Cyclic adenosine monophosphate (cAMP) production and 5-bromo-2′-deoxyuridine (BrdU) incorporation in ESC were measured using specific assay systems. RESULT(S): We detected SV1 messenger RNA (mRNA) in 17 out of 27 (63%) ectopic endometrial tissues, which was statistically significantly higher than that detected in eutopic endometrial tissues (2 out of 47, 4%) and normal ovarian tissues (0 out of 14). A relatively low rate of GHRH mRNA was detected in ectopic endometrial tissues (6 out of 27, 24%) and in eutopic endometrial tissues (12 out of 47, 26%). In contrast, relatively high rates were detected in normal ovarian tissues (14 out of 14, 100%) and peritoneal bone marrow-derived cells (13 out of 16, 81%). We found that GHRH stimulated the production of cAMP and the incorporation of BrdU in SV1-expressing ESC. CONCLUSION(S): GHRH and SV1 may play a role in promoting the development of endometriosis.

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Fertil Steril. 2009 Jul;92(1):226-30. Epub 2008 Aug 3.

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

Weitzman VN, Engmann L, DiLuigi A, Maier D, Nulsen J, Benadiva C.

Center for Advanced Reproductive Services, Department of Obstetrics and Gynecology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6224, USA.

OBJECTIVE: To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. DESIGN: Retrospective analysis. SETTING: University-based IVF center. PATIENT(S): Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. MAIN OUTCOME MEASURE(S): Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. RESULT(S): The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. CONCLUSION(S): This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

Fertil Steril. 2009 May;91(5):1686-91. Epub 2008 Jul 30.

Reduced expression of biomarkers associated with the implantation window in women with endometriosis.

Wei Q, St Clair JB, Fu T, Stratton P, Nieman LK.

Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

OBJECTIVE: To evaluate the expression of biomarkers of implantation, glycodelin A (GdA), osteopontin (OPN), lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis. DESIGN: Prospective observational study. SETTING: Clinical research center. PATIENT(S): Twenty-four women with endometriosis and 23 healthy volunteers of similar age. INTERVENTION(S): Secretory phase endometrial biopsy. MAIN OUTCOME MEASURE(S): Expression of immunohistochemical staining intensity and localization of GdA, OPN, LPA3, and HOXA10 in eutopic endometrium. RESULT(S): Endometrial GdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases. CONCLUSION(S): The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis, providing one explanation for the subfertility observed even in women with few pelvic implants. Because many of these markers are P dependent, these findings suggest the possibility of reduced endometrial P action in this population.

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Arch Gynecol Obstet. 2009 Mar;279(3):361-4. Epub 2008 Jul 30.

Peritoneal fluid and serum leptin concentrations in women with primary infertility.

Gungor T, Kanat-Pektas M, Karayalcin R, Mollamahmutoglu L.

Department of Infertility, Dr Zekai Tahir Burak Women Health Research and Education Hospital, Ankara, Turkey.

AIM: Leptin is proposed to participate in the reproductive system of women by acting on either ovaries or hypothalamic-pituitary axis. The objective of the present study is to investigate the leptin concentrations in peritoneal fluid and serum samples of women diagnosed with primary infertility. METHODS: A prospective study was carried out in women who underwent laparoscopy within the diagnostic process of primary infertility between January 2005 and January 2007. Leptin concentrations were determined in blood samples obtained before surgery and in peritoneal fluid samples collected during laparoscopy. RESULTS: Peritoneal fluid was obtained from 112 subjects; 21 with unexplained infertility 28 with polycystic ovary syndrome (PCOS), 30 with bilateral tubal occlusion, and 33 with endometriosis. Subjects with PCOS have significantly higher body weights, BMI values and plasma leptin levels when compared to other study groups. Peritoneal fluid levels of leptin were significantly higher in the endometriosis group compared to other three study groups. A positive correlation was found between peritoneal fluid leptin levels and the endometriosis stage (r=0.51, P=0.01). However, plasma leptin levels were unrelated to the disease extent. DISCUSSION: It might be hypothesized that leptin may be an active factor in the pathogenesis of PCOS and endometriosis, which are two major causes of primary infertility. A mild leptin deficiency in peritoneal environment may interrupt follicular development and ultimately lead to PCOS. Leptin has angiogenic and mitogenic properties, which trigger inflammatory cytokines and eventually result in the development of endometriosis implants. Significantly, higher levels of leptin in peritoneal environments of endometriosis subjects strongly imply the important role of this common pathology.

Fertil Steril. 2009 Mar;91(3):675-81. Epub 2008 Jul 23.

Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis–a randomized, double-blind, multicenter, controlled trial.

Harada T, Momoeda M, Taketani Y, Aso T, Fukunaga M, Hagino H, Terakawa N.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan. tasuku@grape.med.tottori-u.ac.jp

OBJECTIVE: To compare the efficacy and safety of dienogest (DNG) with intranasal buserelin acetate (BA) in patients with endometriosis. DESIGN: Phase III, randomized, double-blind, multicenter, controlled trial. SETTING: Twenty-four study centers in Japan. PATIENT(S): Two hundred seventy-one patients with endometriosis. INTERVENTION(S): Dienogest (2 mg/day, orally) or BA (900 microg/day, intranasally) for 24 weeks. MAIN OUTCOME MEASURE(S): The pre- to posttreatment changes in the scores of five subjective symptoms during nonmenstruation (lower abdominal pain, lumbago, defecation pain, dyspareunia, and pain on internal examination) and two objective findings (induration in the pouch of Douglas and limited uterine mobility). RESULT(S): Dienogest reduced the scores of all symptoms and findings at the end of treatment, and the mean changes in the scores of all symptoms and findings except induration in the pouch of Douglas were comparable to those obtained with BA. Compared with BA, DNG was associated with irregular genital bleeding more frequently and with fewer hot flushes. The reduction in bone mineral density (BMD) during DNG treatment was significantly lower than that during BA treatment. CONCLUSION(S): DNG is as effective as intranasal BA in alleviating endometriosis, and causes less BMD loss.

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Fertil Steril. 2009 Jun;91(6):2315-23. Epub 2008 Jul 21.

Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium.

Di Carlo C, Bonifacio M, Tommaselli GA, Bifulco G, Guerra G, Nappi C.

Department of Obstetrics and Gynecology, University of Naples Federico II, Naples, Italy.

OBJECTIVE: To evaluate the expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and 2 (ANGPT1/ANGPT2), and matrix metalloproteinases 1, 2, and 9 (MMP-1, MMP-2, MMP-9) in eutopic and ectopic endometrium. DESIGN: Experimental retrospective study. SETTING: University hospital. PATIENT(S): Eutopic and ectopic endometrium samples from 30 women with endometriosis and endometrium biopsy samples from 30 healthy women. INTERVENTION(S): Biopsies of ovarian endometriomas and eutopic endometrium. MAIN OUTCOME MEASURE(S): Immunohistochemical staining to evaluate the expression of VEGF, ANGPT1, ANGPT2, MMP-1, MMP-2, and MMP-9, and real-time polymerase chain reaction analysis to quantify mRNA expression. RESULT(S): Patients with endometriosis had higher levels of angiogenic factors and metalloproteinases in endometriotic cysts than in eutopic endometrium. These substances were also overexpressed in eutopic endometrium of patients with endometriosis when compared with normal controls. CONCLUSION(S): Overexpression of angiogenic factors and metalloproteinases may be the characteristic feature of endometrium with greater potential to transform into endometriotic lesions in the peritoneal cavity. Structural and/or functional differences of eutopic endometrium could have a role in the pathogenesis of endometriosis secondary to the backward passage of endometrial cells into the peritoneal cavity. Whether these local factors may induce, promote, and/or regulate this transformation remains to be determined.

Arch Gynecol Obstet. 2009 Mar;279(3):419-21. Epub 2008 Jul 19.

Recurrent endometriosis following total hysterectomy with oophorectomy mimicking a malignant neoplastic lesion: a diagnostic and therapeutic challenge.

Giarenis I, Giamougiannis P, Speakman CT, Nieto JJ, Crocker SG.

Department of Obstetrics and Gynecology, Norfolk and Norwich University Hospital, Norwich, UK. elgiaren@yahoo.gr

CASE REPORT: A woman with a previous hysterectomy and bilateral salpingo-oophorectomy for endometriosis presented with painless vaginal bleeding. Imaging revealed a heterogeneous soft tissue pelvic mass suggestive of a malignant neoplastic lesion. Radical surgery was performed including excision of the pelvic mass and anterior resection of the sigmoid colon. Histopathology revealed endometriosis. CONCLUSION: The risk of malignant transformation and the difficulty in achieving a preoperative diagnosis make radical surgery inevitable in the management of recurrent endometriosis. The use of hormone replacement therapy after bilateral salpingo-oophorectomy for endometriosis remains controversial and requires careful counseling about recurrence and close follow-up.

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Genet Epidemiol. 2009 Feb;33(2):105-13.

Common genetic influences underlie comorbidity of migraine and endometriosis.

Nyholt DR, Gillespie NG, Merikangas KR, Treloar SA, Martin NG, Montgomery GW.

Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, QLD, Australia. daleN@qimr.edu.au

We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12-2.21, P=0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (r(G) = 0.27, 95% CI: 0.06-0.47) and bivariate heritability (h(2)=0.17, 95% CI: 0.08-0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes.

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Abdom Imaging. 2009 Jan-Feb;34(1):94-106.

Transitional cell carcinoma of upper urinary tract vs. benign lesions: distinctive MSCT features.

Wang J, Wang H, Tang G, Hou Z, Wang G.

Department of Radiology, Peking University First Hospital, Beijing, China. wb62877701@yahoo.com

The transitional cell carcinoma (TCC) of the upper urinary tract is relatively uncommon. The clinical presentation of TCCs and many other diseases of the upper urinary tract are nonspecific, and most of these lesions are usually necessary to be evaluated by computed tomography (CT) urography. CT appearances of TCCs can be classified as papillary, infiltrating papillary, and diffusely infiltrating tumor. Most TCCs of the upper urinary tract can be identified on the bases of characteristic CT appearances. However, some benign lesions may mimic different categories of TCCs and should be taken into account for differentiating diagnosis. These lesions include endometriosis, nephrogenic adenoma, mycetomas, malacoplakia, and inflammatory pseudotumor which are similar to infiltrating papillary TCCs; complex urolithiasis, passed stone of ureter and ureteropelvic junction, chronic ureteropelvic junction obstruction with superimposed infection, atypical pyelonephritis, and tuberculosis which mimic diffusely infiltrating TCCs, and fibroepithelial polyp which has the same CT appearances as papillary TCCs. The useful CT signs to make differential diagnosis involve enhanced pattern, location of lesion, induration of urinary tract, and range of thickening of urinary wall. The three-dimension (3D) reconstructed images is useful in making differential diagnosis.

Pathol Oncol Res. 2009 Mar;15(1):81-8. Epub 2008 Jun 25.

Pelvic endometriosis is rarely associated with ovarian borderline tumours, cytologic and architectural atypia: a clinicopathologic study.

Bedaiwy MA, Hussein MR, Biscotti C, Falcone T.

Department of Obstetrics and Gynaecology, The Cleveland Clinic Foundation, Cleveland, OH, USA.

Endometriotic foci, especially ovarian ones, with epithelial cytologic atypia may be precursors of cancer. This study presents an overview of the atypical cytological and histopathological findings associated with endometriosis. Six cases of endometriosis, with atypical histological and cytological changes, were obtained from the archives of the Department of Pathology at Cleveland Clinic Foundation between year 2000 and 2003. The size of the base from which these cases were drawn was 2000 cases of endometriosis. The age range of the patients was from 29 to 52 years. The clinical presentations included infertility (three cases), pelvic pain (three cases), adenexal and pelvic masses (four cases). Stage IV endometriosis with extensive pelvic involvement was found in two patients. Intraoperatively, the endometriotic lesions involved the ovaries (all cases); Cul de sac (four cases); urinary bladder (two cases); sigmoid colon, hemidiaphragms, and uterine vessels (one case each). The endometriotic lesions were associated with uterine leiomyomas (two patients) and adenocarcinoma of the vagina (one patient). Histologically, in addition to endometrial type glands and stroma, usually found in endometriosis, we observed both cytologic and pattern atypism involving the epithelium in all cases. The features of cytologic atypia included nuclear stratification, hyperchromatism, and pleomorphism. The features of pattern atypia were complex glandular pattern, papillary formations and psammoma bodies. In two cases, these features were sufficient for diagnosis of borderline Mullerian seromucinous tumours. One patient had recurred with metastatic adenocarcinoma of the vault. She died later from disseminated metastatic disease. There is a rare association between pelvic endometriosis and borderline ovarian tumours (three cases), cytologic and pattern atypia (two cases); mesothelial hyperplasia, endosalpingiosis (two cases), and metastasis (one case). Cytologic and pattern atypia can develop in the endometriotic foci and therefore, these lesions should be thoroughly scrutinized for presence of these changes. Our findings recommend surgical excision of these foci rather than their simple cauterization.

Fertil Steril. 2009 Jun;91(6):2709-13. Epub 2008 Jun 20.

Effectiveness of ultrasound-guided aspiration and sclerotherapy with 95% ethanol for treatment of recurrent ovarian endometriomas.

Hsieh CL, Shiau CS, Lo LM, Hsieh TT, Chang MY.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China.

OBJECTIVE: To evaluate the effectiveness of transvaginal ultrasound aspiration and ethanol sclerotherapy in patients with recurrent ovarian endometriomas. DESIGN: Retrospective study. SETTING: Teaching hospital affiliated with Chang Gung University, Taipei. PATIENT(S): Patients (n = 108) with recurrent ovarian endometriomas >or=3 cm. INTERVENTION(S): Preoperative evaluation of previous pathology, midcycle serum CA-125 level, and color Doppler ultrasonography to exclude possibility of malignancies. After aspiration, sclerotherapy with 95% ethanol irrigation of the cystic cavity was performed (group 1, n = 78, 0-10 minutes of retention; group 2, n = 30, ethanol left in situ [retention]). MAIN OUTCOME MEASURE(S): Ultrasonography was performed at 3, 6, 9, and 12 months to determine persistence and size of cysts and the number of antral follicles. Pelvic pain score was also determined at those time points. RESULT(S): The 1-year recurrence rate for group 2 patients was significantly lower than for group 1 patients (13.3% vs. 32.1%). Antral follicle count was increased and pain score was decreased in both groups to a similar level. No significant change in CA-125 was observed. CONCLUSION(S): Ultrasound-guided sclerotherapy with 95% ethanol is an effective therapy for ovarian endometriomas. Retention of ethanol is more effective than irrigation only.

Fertil Steril. 2009 May;91(5 Suppl):2142-7. Epub 2008 Jun 20.

Peroxisome proliferator-activated receptor-gamma and retinoid X receptor agonists synergistically suppress proliferation of immortalized endometrial stromal cells.

Wu Y, Guo SW.

Taussig Cancer Center, Center for Hematology and Oncology Molecular Therapeutics, Cleveland, Ohio, USA.

OBJECTIVE: To examine whether trichostatin A (TSA), a histone deacetylase inhibitor (HDACI), can induce up-regulation of peroxisome proliferator-activating receptor gamma (PPAR gamma) and to see whether LG100268, a retinoid X receptor (RXR) ligand, can inhibit proliferation of endometriotic cells alone or in synergy with ciglitazone, a PPAR gamma agonist. DESIGN: One endometrial stromal cell line and two endometriotic cell lines used as a model system: Western blot analysis to determine whether TSA can up-regulate PPAR gamma expression, and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) proliferation assay to see whether ciglitazone and LG100268 have any antiproliferative effects individually or jointly. SETTING: Academic. PATIENT(S): None. INTERVENTION(S): Culture of immortalized endometrial and endometriotic cell lines with TSA, or ciglitazone or LG100268. MAIN OUTCOME MEASURE(S): PPAR gamma protein expression levels in cells treated with or without TSA, and number of viable cells treated with or without ciglitazone, LG100268, or both. RESULT(S): The TSA treatment resulted in up-regulation of PPAR gamma expression in all cell lines in a dose-dependent fashion. Both ciglitazone and LG100268 inhibited proliferation in a dose-dependent manner, and the antiproliferative effects appeared to be synergistic. In addition, endometriotic cells were more sensitive than endometrial stromal cells to LG100268 treatment. CONCLUSION(S): The up-regulation of PPAR gamma induced by TSA indicates that the action of HDACIs also includes the PPAR gamma signaling pathway, suggesting that the activation of PPAR gamma is a desirable way to contain endometriosis phenotypes. The higher sensitivity of endometriotic cells than their endometrial counterpart to LG100268 treatment suggests that the sensitivity differential could be exploited effectively to eradicate unwanted ectopic endometrial tissues while minimizing the collateral damage to the normal endometrial tissues.

Acta Histochem. 2009;111(1):61-7. Epub 2008 Jun 16.

Heterogeneous appearance of VEGF (vascular endothelial growth factor) immunopositivity in cyst capsules of endometrioma.

Tuncay G, Kilic S, Yuksel B, Elmas C, Lortlar N, Erdogan D, Ozogul C.

Department of Reproductive Endocrinology, Dr. Zekai Tahir Burak Women’s Health and Research Hospital, Süleymanbey Sok. 29/10, Maltepe, PK: 06570 Ankara, Turkey.

The aim of the research was to reveal vascular endothelial growth factor (VEGF) immunolocalization in endometrioma cysts and endometrial tissues. The study group (group1) included 15 patients laparoscopically operated on for endometrioma and the control group (group 2) included 13 patients prepared for diagnostic laparoscopy for primary infertility. Biopsies from endometrioma cyst capsules, disease-free peritoneum and pipelle biopsies from the endometrium were taken from group 1. Biopsies from parietal peritoneum and endometrium were taken from group 2. Results showed VEGF immunoreactivity of peritoneal biopsies of group 1 was more intense than that of the control biopsies. A positive correlation was seen between the diameter of cyst capsules and VEGF labeling intensity and as the size of cyst enlarged, the appearance of non-homogeneous distribution of VEGF immunolocalization became more frequent. We conclude that the variation of VEGF immunolocalization in endometrioma cysts may be attributed to other possible angiogenic molecules in the pathogenesis and may cause unexpected responses to anti-angiogenic therapies.

Fertil Steril. 2009 Jun;91(6):2331-7. Epub 2008 Jun 13.

Mass spectrometry and serum pattern profiling for analyzing the individual risk for endometriosis: promising insights?

Wölfler MM, Schwamborn K, Otten D, Hornung D, Liu H, Rath W.

Department of Obstetrics and Gynecology, RWTH Aachen University, Aachen, Germany. mwoelfler@ukaachen.de

OBJECTIVE: To evaluate whether distinct patterns of serum proteins in symptomatic women are of value to predict endometriosis before laparoscopy. DESIGN: Prospective exploratory cohort study. SETTING: Tertiary care center. PATIENT(S): A total of 91 consecutive symptomatic patients suffering from dysmenorrhea, dyspareunia, chronic pelvic pain, or unexplained infertility. INTERVENTION(S): Collection of serum samples and a standardized protocol for patients’ history before laparoscopic diagnosis. MAIN OUTCOME MEASURE(S): Protein expression was analyzed by mass spectrometric analysis according to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) standards. The analysis of data was performed using a genetic algorithm (ClinProTools 2.0 software) and a rule-based decision-tree algorithm (XLminer software). RESULT(S): A total of 90 out of 91 samples were eligible for analysis. At laparoscopy, 51 of 90 patients (56.7%) exhibited endometriosis and 39 of 90 (43.3%) were disease free. Analyzing the serum samples, the software revealed a unique selection of mass peaks between 2,000 and 20,000 Da, which allowed for discrimination between patients suffering from endometriosis and control subjects. Overall recognition capacity was 70.8%, exhibiting a sensitivity of 81.3% (95% confidence interval [CI] 66.5-92.5) and a specificity of 60.3% (95% CI 46.1-74.2]) using the genetic algorithm, and a sensitivity of 78.4% and a specificity of 59.0% using the rule-based decision-tree algorithm. CONCLUSION(S): These findings provide direct evidence that screening for serum protein patterns using SELDI-TOF MS before laparoscopy might be of discriminative value in the prediction of disease and partly confirms recently published data. However, in this prospective setting, we found both low sensitivity and low specificity, which disqualifies the screening for serum protein patterns by SELDI-TOF MS as a “quick fix” diagnostic test.

Publication Types:

Fertil Steril. 2009 Jun;91(6):2324-30. Epub 2008 Jun 12.

Haplotype analysis of the matrix metalloproteinase-9 gene associated with advanced-stage endometriosis.

Han YJ, Kim HN, Yoon JK, Yi SY, Moon HS, Ahn JJ, Kim HL, Chung HW.

Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, South Korea.

OBJECTIVE: To investigate whether the -1562C>T, R279Q, P574R, and R668Q polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene are related to endometriosis. DESIGN: Case-control study. SETTING: University-based hospital in Korea. PATIENT(S): Patients with endometriosis stage III/IV (n = 225) who underwent pelvic surgery and controls (n = 198) with no endometriosis in a Korean population. INTERVENTION(S): Peripheral blood samples were collected by venipuncture. MAIN OUTCOME MEASURE(S): Frequencies of genotypes and haplotypes were compared with the risk of endometriosis including -1562C>T, R279Q, P574R, and R668Q polymorphisms of MMP-9. RESULT(S): In the two-locus haplotype analyses using the four single nucleotide polymorphisms (SNPs), an increase in the distribution of the R279Q/P574R (2678G>A/4859C>G) (AC haplotype: odds ratio [OR] = 3.180, 95% confidence interval [CI] = 1.956-5.170; GG haplotype: OR = 4.374, 95% CI = 2.376-8.053) and -1562C>T/R668Q (-1562C>T/5546G>A) (CA haplotype: OR = 3.280, 95% CI = 1.406-7.653) haplotypes was significantly associated with endometriosis. By contrast, the risk of endometriosis was not associated with the individual SNPs studied. CONCLUSION(S): These findings suggest that haplotype analysis was more informative than SNP analysis. The haplotypes in the MMP-9 gene may correlate with the progression of endometriosis, and further study of these variations might improve our understanding of the pathogenesis of endometriosis.

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Fertil Steril. 2009 Jun;91(6):2477-80. Epub 2008 Jun 12.

Semen profiles of male partners in females presenting with endometriosis-associated subfertility.

Botha DJ, Kruger TF, Van Der Merwe JP, Nosarka S.

Department of Obstetrics and Gynecology, Stellenbosch University and Tygerberg Academic Hospital, Tygerberg, South Africa.

OBJECTIVE: To establish fertile and subfertile groups of males in couples presenting with endometriosis-related infertility in the female. DESIGN: Retrospective study of semen profiles on partners of women undergoing surgery for endometriosis-related infertility. SETTING: University-affiliated assisted reproduction center. PATIENT(S): One hundred seventeen partners of females undergoing surgery for endometriosis related infertility. MAIN OUTCOME MEASURE(S): Fertility potential according to Tygerberg strict criteria for sperm evaluation. RESULT(S): A total of 65.8% of the semen analysis were reported normal according to the Tygerberg strict criteria and 34.2% were reported subfertile. Of the total, 11.96% of the patients studied had a severe defect (azoospermia, double, and triple defects). CONCLUSION(S): Labeling of the male in couples presenting with infertility as fertile, subfertile, or infertile plays an important role in decision making regarding management of the female presenting with endometriosis-related infertility. It is important that in future studies on the effect of surgery on improving pregnancy outcome in patients with endometriosis the semen profile be reported and thresholds used should be mentioned. This will contribute significantly to the future comparison of data on the impact of the male factors in couples presenting with endometriosis-related infertility.

Fertil Steril. 2009 Jun;91(6):2501-7. Epub 2008 May 23.

Letrozole co-treatment in infertile women 40 years old and older receiving controlled ovarian stimulation and intrauterine insemination.

Bedaiwy MA, Shokry M, Mousa N, Claessens A, Esfandiari N, Gotleib L, Casper R.

Toronto Centre For Advanced Reproductive Technologies (TCART), and Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.

OBJECTIVE: To investigate the effect of a combination of letrozole and gonadotropins in advanced reproductive age infertile women who were treated with IUI. DESIGN: A retrospective case control study. SETTING: A private practice affiliated with an academic institute. PATIENT(S): Infertile women 40 years old and older who were treated with IUI and controlled ovarian hyperstimulation (COH) using either letrozole in combination with FSH (n = 90) or FSH alone (n = 69). MAIN OUTCOME MEASURE(S): Pregnancy rates (PR), mature follicles, serum levels of E(2), P, LH, endometrial thickness, rates of cycle cancellation, and FSH dose. RESULT(S): Pregnancy rates were comparable between the letrozole-FSH co-treatment group and the FSH alone group. Significantly fewer cycles were cancelled in the letrozole co-treatment group. The E(2) levels and the number of follicles were significantly higher in the FSH-only group. Serum levels of LH were significantly higher in the co-treatment group on cycle day 7. The P levels were significantly higher in the FSH alone group on the day of hCG administration. CONCLUSION(S): Letrozole co-treatment compared with using FSH alone has significantly modified the cycle characteristics without reducing PRs and could be of potential benefit in IUI cycles in older infertile women.

Arch Gynecol Obstet. 2009 Feb;279(2):183-7. Epub 2008 May 10.

A rare case of coexistence of carcinoid tumor of appendix vermicularis and ileal endometriosis.

Azordegan N, Yazdankhah A, Moghadasian MH.

Pathology Research Laboratory, and Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada. nazordegan@sbrc.ca

BACKGROUND: Carcinoid tumor is the most common tumor of appendix with overall good prognosis. Endometriosis is the implantation of endometrial glands and stroma outside the uterus. CASE REPORT: We here report the coexistence of carcinoid tumor of appendix and ileal endometriosis in a 37-year-old nulliparous woman who came to the emergency room with right lower abdominal pain mimicking acute appendicitis. The main clinical and laboratory findings included fever, leukocytosis and elevated ESR. With preoperative suspicion of acute appendicitis, laparatomy was performed and revealed apparently normal looking appendix, along with a nodule in the terminal ileum. Both the appendix and ileal nodule were removed. Histological examinations revealed carcinoid tumor of appendix and ileal endometriosis. The case was discharged 4 days after surgery with no pain and symptoms and remained symptom free for the 1 year period of follow up. CONCLUSION: Many cases of carcinoid tumor of the appendix and ileal endometriosis are diagnosed incidentally. Overall prognosis of these conditions is very good. Surgical treatment seems to be the best intervention for these disorders.

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Arch Gynecol Obstet. 2009 Feb;279(2):217-9. Epub 2008 May 10.

Caesarean scar endometriosis.

Singh M, Sivanesan K, Ghani R, Granger K.

Department of Obstetrics and Gynaecology, Royal Lancaster Infirmary, Lancaster, UK. manikasuri@yahoo.co.in

INTRODUCTION: Caesarean section incidence is rising and caesarean scar endometriosis could be encountered more in the day to day clinical practice. MATERIALS AND METHODS: We present three cases of caesarean scar endometriosis which were managed in our unit with excision biopsy. CONCLUSIONS: Complete excision is both diagnostic and therapeutic. FNAC could be a tool to exclude malignancy and allows a quick diagnosis.

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Anim Reprod Sci. 2009 Apr;111(2-4):261-78. Epub 2008 Mar 30.

The equine endometrosis: new insights into the pathogenesis.

Hoffmann C, Ellenberger C, Mattos RC, Aupperle H, Dhein S, Stief B, Schoon HA.

Institute of Pathology, University of Leipzig, Germany. christine.hoffmann@fli.bund.de

This paper describes the histomorphological and immunohistochemical characterisation of phenotypic variations of endometrosis as well as potential etiological factors which may influence disease progression. In total, 779 endometrial biopsies were examined. These biopsies were taken in the breeding and non-breeding season (n=509), on defined days during the estrous cycle (n=70) and before and after experimentally induced bacterial endometritis (n=200). In addition to conventional histopathology, selected biopsies were investigated using alcianblue staining as well as immunohistochemical methods for the detection of steroid hormone receptors, Ki-67-antigen, vimentin, desmin, fibronectin, smooth-muscle-alpha-actin and laminin. The equine endometrosis can be divided into a destructive and a non-destructive form. Based on the morphology of the stromal cells involved, an active or inactive state can be distinguished in fibrotic foci. In all types of endometrosis, fibrotic stromal cells show a distinctly reduced expression of steroid hormone receptors in comparison to the intact stroma, indicating their dedifferentiation. However, the steroid hormone receptor expression of involved glandular epithelia seems to depend on the activity of the fibrosis. These results suggest an independency of all fibrotic foci from the hormonal control mechanism of the uterus. The characteristical features of destructive endometrosis are a large number of smooth-muscle-alpha-actin containing myofibroblasts, a pronounced epithelial vimentin expression, excessive extracellular matrix accumulation and a progressive alteration of the basal lamina. Furthermore, the frequently seen cystic glandular dilatation and mechanical destruction of the uterine glands may occur due to the contractibility of the myofibroblasts involved. As shown in this study, a simultaneous endometritis can cause a temporary activation of fibrotic stromal cells. However, cyclic and seasonal endocrine changes seem to have no effects on progression of the disease. It can be concluded that the various types of endometrosis represent different stages in the fibrotic process, possibly leading to the destruction of the glands and subsequently resulting in the development of a stromal fibrosis.

Fertil Steril. 2009 Jan;91(1):51-5. Epub 2008 May 7.

A logistic model for the prediction of endometriosis.

Stegmann BJ, Funk MJ, Sinaii N, Hartmann KE, Segars J, Nieman LK, Stratton P.

Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1109, USA.

OBJECTIVE: To develop a model that uses individual and lesion characteristics to help surgeons choose lesions that have a high probability of containing histologically confirmed endometriosis. DESIGN: Secondary analysis of prospectively collected information. SETTING: Government research hospital in the United States. PATIENT(S): Healthy women 18-45 years of age, with chronic pelvic pain and possible endometriosis, who were enrolled in a clinical trial. INTERVENTION(S): All participants underwent laparoscopy, and information was collected on all visible lesions. Lesion data were randomly allocated to a training and test data set. MAIN OUTCOME MEASURE(S): Predictive logistic regression, with the outcome of interest being histologic diagnosis of endometriosis. RESULT(S): After validation, the model was applied to the complete data set, with a sensitivity of 88.4% and specificity of 24.6%. The positive predictive value was 69.2%, and the negative predictive value was 53.3%, equating to correct classification of a lesion of 66.5%. Mixed color; larger width; and location in the ovarian fossa, colon, or appendix were most strongly associated with the presence of endometriosis. CONCLUSION(S): This model identified characteristics that indicate high and low probabilities of biopsy-proven endometriosis. It is useful as a guide in choosing appropriate lesions for biopsy, but the improvement using the model is not great enough to replace histologic confirmation of endometriosis.

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Fertil Steril. 2009 Jun;91(6):2338-43. Epub 2008 Apr 28.

Feasibility of laparoscopic high-intensity focused ultrasound treatment for patients with uterine localized adenomyosis.

Yang Z, Cao YD, Hu LN, Wang ZB.

Department of Obstetrics & Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China. cqyangz@vip.163.com

OBJECTIVE: To investigate the feasibility of laparoscopic high-intensity focused ultrasound (HIFU) ablation in the treatment of patients with uterine localized adenomyosis. DESIGN: A prospective clinical trial. SETTING: University teaching hospital. PATIENT(S): Seven patients with uterine localized adenomyosis. INTERVENTION(S): Using a hand-held focused ultrasound transducer, the HIFU procedure was performed by the same gynecologist for the treatment of a targeted adenomyosis during the surgical procedure, followed by hysterectomy. MAIN OUTCOME MEASURE(S): Feasibility and effectiveness of HIFU treatment of localized adenomyomas. RESULT(S): Macroscopic and microscopic examinations showed that HIFU induced thermal ablation of a targeted adenomyosis in all patients. The treated adenomyosis presented typical characteristics of coagulation necrosis, and the margin between the treated and untreated regions was clear in 2,3,5-triphenyltetrazolium chloride staining. By using electronic microscopy and nicotinamide adenine dinucleotide-diaphorase stain, complete loss of cellular viability was identified in the treated tissue. CONCLUSION(S): The HIFU treatment is feasible and effective in the treatment of patients with uterine localized adenomyosis. It may provide a promising laparoscopic treatment for localized adenomyosis.

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Fertil Steril. 2009 May;91(5):1681-5. Epub 2008 Apr 25.

Expression of interleukin-10 in patients with adenomyosis.

Wang F, Li H, Yang Z, Du X, Cui M, Wen Z.

Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China.

OBJECTIVE: To investigate the expression of interleukin-10 (IL-10) in adenomyosis. DESIGN: Laboratory study using human tissue. SETTING: University hospital. PATIENT(S): Thirty-four patients with adenomyosis and 30 women without adenomyosis who underwent hysterectomy for nonendometrial pathology. INTERVENTION(S): Tissue sections were immunostained with murine monoclonal antihuman IL-10 antibodies. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and localization of IL-10 throughout the menstrual cycle in both eutopic endometrial and adenomyotic tissues of women with adenomyosis and compare it with IL-10 expression in the normal endometrium. RESULT(S): In the eutopic and ectopic endometrium of women with adenomyosis, epithelial cells showed higher staining intensity than the normal controls. However, no significant differences were found in the epithelial IL-10 immunostaining H score values between the eutopic endometrium and adenomyosis foci. Nonetheless, we observed a cyclic variation in the eutopic epithelial IL-10 immunoreactivity throughout the menstrual cycle with higher H score values in the secretory phase than in the proliferative phase. CONCLUSION(S): These findings suggest that an abnormality of inflammatory response may be present in the eutopic and ectopic endometrium of women with adenomyosis and that IL-10 may contribute to the pathogenesis and pathophysiology of adenomyosis.

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