Fertil Steril. 2009 Feb;91(2):622-3. Epub 2008 Apr 25.

Endometriosis entrapment of the obturator nerve after previous cervical cancer surgery.

Langebrekke A, Qvigstad E.

Department of Obstetrics and Gynecology, Ullevål University Hospital, Oslo, Norway. anton.langebrekke@uus.no

A 26-year-old patient underwent pelvic lymphadenectomy and trachelectomy because of cervical cancer stage IB. Later she developed symptoms from obturator nerve entrapment. Examinations could not reveal metastatic cancer disease, but endometriosis surrounding the obturator nerve was discovered. Laparoscopic removal of the endometriotic tissue surrounding the nerve was performed and the patient’s symptoms then disappeared.

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Arch Gynecol Obstet. 2009 Jan;279(1):17-22. Epub 2008 Apr 23.

Laparoscopy-assisted cystectomy for large adnexal cysts.

Göçmen A, Atak T, Uçar M, Sanlikal F.

Department of Obsterics and Gynecology, Umraniye Education and Research Hospital, Istanbul, Turkey. gocmenahmet@yahoo.com

OBJECTIVE: To evaluate the feasibility and surgical outcome of laparoscopy-assisted surgery for large adnexal cysts. METHODS: From January 1998 to October 2007, 46 women underwent laparoscopy-assisted surgery for large adnexal cysts whose maximum diameter were between 10 and 20 cm, radiologic and laboratory features suggestive of benign disease. All the patients had a pre-operative ultrasound with or without computed tomography and CA-125 assessment. Patients’ demographics, clinical and ultrasound features, CA-125 values, surgical procedures, operative and post-operative complications, estimated amount of blood loss (EBL), operative time, conversion to laparotomy and the pathological findings were recorded. RESULTS: Fourty-six consecutive patients underwent laparoscopy-assisted surgery over 9 years. The mean and range of the patients’ age and body mass index were 34.1 +/- 6.3 and (21-45) years and 27.4 +/- 5.9 and (22-40), respectively. In all the patients, except one with borderline ovarian tumor, laparoscopy-assisted surgery was successful. There were no operative or post-operative complications. The mean and range of the operative time, EBL and hospital stay were 48.4 +/- 7.3 and (35-65) min, 55.0 +/- 28.9 and (25-150) mL, 1.49 +/- 0.50 and (1-3) days, respectively. The mean and range of the extracorporeal cystectomy time were 10.2 +/- 2.7 and (8-14) min. The surgical procedures performed were: ovarian and paraovarian cystectomy (n = 45), unilateral salpingo-oophorectomy, pelvic-paraaortic lymphadenectomy and omentectomy (n = 1). Pathologic findings included serous cystadenoma (n = 26), mucinous cystadenoma (n = 7), dermoid (n = 6), endometriosis (n = 6), and borderline ovarian tumor (n = 1). CONCLUSION: Laparoscopy-assisted surgery is feasible and safe for women with large benign adnexal cysts and result s in a short surgery time.

Fertil Steril. 2009 Jan;91(1):278-80. Epub 2008 Apr 18.

Rectosigmoid endometriosis with unusual presentation at magnetic resonance imaging.

Biscaldi E, Ferrero S, Remorgida V, Fulcheri E, Rollandi GA.

Department of Radiology, Galliera Hospital, Genoa, Italy.

We report on a patient with a bowel endometriotic nodule that was hypointense on both T1- and T2-weighted magnetic resonance imaging (MRI); histologic examination revealed that the MRI appearance of the nodule was due to the presence of extensive fibrosis. Bowel endometriotic nodules with extensive fibrosis and limited endometrial tissue have a signal intensity similar to that of the muscle on both T1- and T2-weighted images. In these patients, additional techniques such as multislice computed tomography enteroclysis may be used for adequate diagnosis before surgery.

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Fertil Steril. 2009 Apr;91(4 Suppl):1326-8. Epub 2008 Apr 14.

Fibrotic tissue in the endometrioma capsule: surgical and physiopathologic considerations from histologic findings.

Vicino M, Scioscia M, Resta L, Marzullo A, Ceci O, Selvaggi LE.

Department of Gynaecology, Obstetrics and Neonatology, University of Medical Science of Bari, Bari, Italy.

Ovarian tissue inadvertently excised along with endometriomas was associated with the presence of pericystic fibrosis and serum levels of CA-125, representing the only clinical parameter for predicting follicle loss before surgery. A consecutive series of 91 ovarian endometriotic cysts were studied, and an inverse relationship between serum CA-125 and the thickness of the fibrotic tissue of the endometrioma capsule was demonstrated.

Fertil Steril. 2009 May;91(5):1662-7. Epub 2008 Apr 14.

Endometriosis of the ureter and bladder are not associated diseases.

Abrao MS, Dias JA Jr, Bellelis P, Podgaec S, Bautzer CR, Gromatsky C.

Department of Obstetrics and Gynecology, University of São Paulo Medical School, São Paulo, Brazil. msabrao@attglobal.net

OBJECTIVE: To verify whether bladder and ureter endometriosis had the same clinical features and disease behavior. DESIGN: Case-control study. SETTING: Multidisciplinary group in Sao Paulo, Brazil. PATIENT(S): A total of 690 patients were submitted to laparoscopy with histologically diagnosis of endometriosis between July 1999 and December 2006. Twelve of these patients had lesions affecting the ureter and 26 had lesions affecting the bladder. A control group consisted of 652 patients in whom endometriosis was not affecting either the ureter or the bladder. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and surgical features of patients with ureteral or bladder endometriosis. RESULT(S): No patients with ureteral endometriosis had lesions affecting the bladder. Compared with the control group, patients with ureteral endometriosis had more advanced disease (Stages III and IV) according to the American Society of Reproductive Medicine (ASRM) staging classification (100% vs. 65.5%); they also had more retrocervical (83.3% vs. 21.6%) and rectum-sigmoid lesions (91.7% vs. 17.9%). Compared with the control group, more patients with bladder endometriosis had cyclic dysuria and/or hematuria (34.6% vs. 9.8%), more advanced stages of the disease (88.4% vs. 65.5%), and an association with endometriosis of the rectum-sigmoid (65.3% vs. 17.9%). CONCLUSION(S): Ureter endometriosis is not associated with the bladder disease; however, it is associated with advanced ASRM stages and with retrocervical and rectum-sigmoid lesions.

Fertil Steril. 2009 May;91(5 Suppl):2172-6. Epub 2008 Apr 9.

Letrozole stimulates the growth of human endometrial explants cultured in three-dimensional fibrin matrix.

Khazaei M, Montaseri A, Casper RF.

Reproduction Research Center, Kermanshah University of Medical Science, Kermanshah, Iran. mkhazaei1345@yahoo.com

OBJECTIVE: To investigate the effects of an aromatase inhibitor, letrozole, on the growth of human endometrium in a three-dimensional fibrin matrix model of endometriosis. DESIGN: Experimental study of human endometrial biopsies in a three-dimensional fibrin matrix culture system. SETTING: Academic research center. PATIENT(S): Eight normal women with benign gynecologic problems. INTERVENTION(S): Endometrial biopsy samples were washed, cut into small pieces, and placed between two layers of fibrin gel in the presence or absence of letrozole in the culture medium. Tissue changes were assessed by histological and immunohistochemical staining using an inverted microscope, image analysis, and a semiquantitative scoring system. MAIN OUTCOME MEASURE(S): Stromal and epithelial cell outgrowth into the fibrin matrix and angiogenesis comprising endothelial cell invasion of the matrix. RESULT(S): Letrozole (0.1 micromol/L, 1 micromol/L, and 10 micromol/L) exerted a significant growth stimulation effect on endometrial tissue in this model. CONCLUSION(S): In contrast to our expectations, letrozole stimulated growth of normal human endometrium in an in vitro model of endometriosis. Normal endometrium may respond differently than endometriotic lesions to therapeutic agents. Our findings should be kept in mind when considering future research to explore new clinical treatments for endometriosis.

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Fertil Steril. 2009 May;91(5):1676-80. Epub 2008 Apr 9.

Glycodelin expression in the endometrium of healthy women and in the eutopic and ectopic endometrium of women with endometriosis.

Meola J, Dentillo DB, Rosa e Silva JC, Ferriani RA, Veiga LC, Paro de Paz CC, Giuliatti S, Martelli L.

Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. jumeola@yahoo.com.br

OBJECTIVE: To analyze the expression of the glycodelin gene to better understand the molecular environment of endometriotic lesions and to elucidate the potential mechanisms that underlie the complex physiopathology of endometriosis. DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENT(S): Eleven healthy fertile women and 17 patients with endometriosis in the early proliferative phase of the menstrual cycle. INTERVENTION(S): Endometrial biopsy specimens were obtained from the endometrium of healthy women without endometriosis (controls) and from eutopic and ectopic endometrium tissues (pelvic and ovarian endometriotic implants) of endometriosis patients. MAIN OUTCOME MEASURE(S): The glycodelin relative expression level by real-time polymerase chain reaction (PCR) analysis. RESULT(S): The glycodelin down-regulation found in the endometriotic lesions was 332.26 and 123.17-fold lower, respectively, when compared with the eutopic tissue and the control endometrium. CONCLUSION(S): Glycodelin may be one of the molecules that contributes to the loss of cellular homeostasis in endometriotic lesions.

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Fertil Steril. 2009 May;91(5):1668-75. Epub 2008 Apr 8.

Iron storage is significantly increased in peritoneal macrophages of endometriosis patients and correlates with iron overload in peritoneal fluid.

Lousse JC, Defrère S, Van Langendonckt A, Gras J, González-Ramos R, Colette S, Donnez J.

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

OBJECTIVE: To further investigate peritoneal iron disruption in endometriosis by studying iron storage in peritoneal macrophages of patients with endometriosis compared with controls. DESIGN: Cross-sectional study. SETTING: Academic gynecology research unit in a university hospital. PATIENT(S): Fifty patients undergoing laparoscopy. INTERVENTION(S): Collection of peritoneal fluid samples (N = 50) from patients with (n = 27) and without (n = 23) endometriosis undergoing laparoscopy. MAIN OUTCOME MEASURE(S): Quantification of peritoneal macrophage ferritin by immunocytochemical staining and immunodensitometry and measurement of peritoneal iron, transferrin, ferritin, and prohepcidin concentrations. RESULT(S): The optical density of peritoneal macrophage ferritin staining was statistically significantly higher in endometriosis patients than in controls. Higher iron concentrations, transferrin saturations, and ferritin concentrations were also detected in case of endometriosis. A statistically significant positive correlation was found between the optical density of macrophage ferritin staining and peritoneal iron concentrations in endometriosis and control patients. CONCLUSION(S): Iron storage is statistically significantly increased in peritoneal macrophages of patients with endometriosis and correlates with iron overload in peritoneal fluid. The potential implications of iron accumulation in peritoneal macrophages in case of endometriosis are discussed.

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Fertil Steril. 2009 May;91(5):1775-9. Epub 2008 Apr 3.

The use and effectiveness of in vitro fertilization in women with endometriosis: the surgeon’s perspective.

Somigliana E, Daguati R, Vercellini P, Barbara G, Benaglia L, Crosignani PG.

Department of Obstetrics and Gynecology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy. dadosomigliana@yahoo.it

OBJECTIVE: To assess the use and effectiveness of IVF in a cohort of women undergoing surgery for endometriosis. DESIGN: Cohort study. SETTING: University hospital. PATIENT(S): Four hundred thirty-eight patients who attempted to become pregnant after conservative surgery for endometriosis. INTERVENTION(S): Interview. MAIN OUTCOME MEASURE(S): Pregnancy and IVF use. RESULT(S): One hundred ninety-four women conceived in vivo (44%). One hundred twenty-four women did not undergo IVF despite their infertility status (51% of the group of women who failed to conceive in vivo). One hundred thirty-nine women underwent at least one IVF attempt. The cumulative rate of IVF use at 36 months of infertility was 33%. The live-birth/ongoing pregnancy rate per started cycle and per patient was 10% and 20%, respectively. CONCLUSION(S): In a large tertiary care and referral center, IVF played only a minor role in the treatment of endometriosis-associated infertility.

Fertil Steril. 2009 Feb;91(2):335-42. Epub 2008 Apr 18.

Periodontal disease and endometriosis: analysis of the National Health and Nutrition Examination Survey.

Kavoussi SK, West BT, Taylor GW, Lebovic DI.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Michigan Endometriosis Center, Ann Arbor, Michigan 48109, USA.

OBJECTIVE: To investigate whether an association exists between endometriosis and periodontal disease, because endometriosis and periodontal disease are chronic, inflammatory processes more common in patients with systemic autoimmune disorders and because each disease alters immune modulators. DESIGN: Cross-sectional study. SETTING: University health system and statistical center. PATIENT(S): Data for 4136 women, ages 18-50, in the National Health and Nutrition Examination Survey, 1999-2004. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Periodontitis and gingivitis among those patients with and without self-reported endometriosis. RESULT(S): Multinomial logistic regression showed that women with self-reported endometriosis had significantly (57%) higher odds of having both gingivitis and periodontitis relative to not having periodontal disease, compared with women without self-reported endometriosis (adjusted odds ratio, 1.57; 95% confidence interval, 1.06, 2.33), when controlling for other relevant factors. CONCLUSION(S): The results of this study suggest a possible association between endometriosis and periodontal disease. Although it is conceivable that the multifactorial development of endometriosis may be augmented by an immune response to an infectious agent, the potential underlying link between endometriosis and periodontal disease may be a generalized, global immune dysregulation.

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Fertil Steril. 2009 May;91(5 Suppl):2079-86. Epub 2008 Apr 18.

L-carnitine supplementation reduces oocyte cytoskeleton damage and embryo apoptosis induced by incubation in peritoneal fluid from patients with endometriosis.

Mansour G, Abdelrazik H, Sharma RK, Radwan E, Falcone T, Agarwal A.

Reproductive Research Center, Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, Ohio, USA.

OBJECTIVE: To investigate the protective effect of L-carnitine (LC) against deleterious substances present in the peritoneal fluid (PF) of patients with endometriosis, which may affect the oocyte cytoskeleton and embryogenesis. DESIGN: Experimental study. SETTING: Research embryology laboratory at an academic hospital. PATIENT(S): Frozen metaphase II mouse oocytes and embryos. INTERVENTION(S): One hundred metaphase II mouse oocytes were divided into five groups and incubated: PF from endometriosis patients; PF from endometriosis patients + LC; PF from tubal ligation patients (patient control); LC only; and human tubal fluid (HTF) alone. A total of 180 eight-cell mouse embryos were divided into: endometriosis only; tubal ligation only; endometriosis + LC; LC alone; and HTF alone. MAIN OUTCOME MEASURE(S): Protective effect of LC on oocytes and embryos. RESULT(S): Incubation of the oocytes and the embryos with PF from patients with endometriosis statistically significantly damaged the oocyte microtubules and chromosomes and increased embryo apoptosis compared with controls. Incubation with LC (0.6 mg/mL) statistically significantly improved microtubule and chromosome structure and decreased the level of embryo apoptosis. CONCLUSION(S): We propose the use of LC as a supplement in patients with endometriosis, a novel approach that may help improve in vitro fertilization outcome in these patients.

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Fertil Steril. 2009 Apr;91(4 Suppl):1314-5. Epub 2008 Apr 2.

Excision of the posterior vaginal fornix is necessary to ensure complete resection of rectovaginal endometriotic nodules of more than 2 cm in size.

Matsuzaki S, Houlle C, Botchorishvili R, Pouly JL, Mage G, Canis M.

CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétriqueet Médecine de la Reproduction, Clermont-Ferrand, France. sachikoma@aol.com

The minimum distance between the vaginal mucosal epithelium and the endometriotic glands was <1,000 microm in 30 patients (49.2%), <2,000 microm in 44 patients (72.1%), and <5,000 microm in 60 patients (98.4%). Our findings provided histologic evidence that excision of the posterior vaginal fornix was necessary to completely remove large rectovaginal endometriotic nodules.

Fertil Steril. 2009 Feb;91(2):325-30. Epub 2008 Apr 1.

Preterm birth, ovarian endometriomata, and assisted reproduction technologies.

Fernando S, Breheny S, Jaques AM, Halliday JL, Baker G, Healy D.

Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.

OBJECTIVE: To report preterm birth and small for gestational age (SGA) rates from assisted reproduction technologies (ART) patients with ovarian endometriomata compared with control groups. DESIGN: Retrospective cohort study. SETTING: Tertiary university affiliated ART center and Perinatal Data Collection Unit (PDCU). PATIENT(S): Every woman who had an ART singleton baby born between 1991 and 2004 had her database record assessed (N = 4382). Control groups included 1201 singleton babies from ART patients without endometriosis and 2400 randomly selected women from the PDCU database of 850,000 births. INTERVENTION(S): There were 95 singleton ART babies from patients with ovarian endometriomata and 535 ART singleton babies from patients who had endometriosis but no ovarian endometriomata. MAIN OUTCOME MEASURE(S): Preterm birth rates and SGA birth rates. RESULT(S): Preterm birth rate increased only in the ovarian endometriomata group when compared with community birth records (n = 850,000). Furthermore, ART patients with ovarian endometriomata had a statistically significantly increased likelihood of having a SGA baby when compared with other forms of endometriosis. CONCLUSION(S): Rates of preterm birth and SGA babies doubled in infertility patients with ovarian endometriomata who required ART.

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Fertil Steril. 2009 May;91(5):1692-9. Epub 2008 Apr 2.

Altered expression of claudin-3 and claudin-4 in ectopic endometrium of women with endometriosis.

Pan XY, Li X, Weng ZP, Wang B.

Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, People’s Republic of China. changpanxiaoyu@163.com

OBJECTIVE: To investigate the expression of claudin-3 and claudin-4 in the eutopic and ectopic endometrium of women with endometriosis and to evaluate the role of claudin-3 and claudin-4 in the pathogenesis of endometriosis. DESIGN: Cross-sectional measurement of gene expression levels of claudin-3 and claudin-4 on endometriotic tissue. SETTING: Academic. PATIENT(S): Thirty-five patients with endometriosis and 35 healthy women who were free of endometriosis were recruited for the study. INTERVENTION(S): Expression of claudin-3 and claudin-4 were investigated with immunohistochemical analysis, Western blot, and real-time polymerase chain reaction. Morphologic change of tight junction was also observed in different kinds of endometria. MAIN OUTCOME MEASURE(S): The expression levels of claudin-3 and claudin-4 in epithelial cells from 35 ectopic endometrial tissues, 27 eutopic endometrial tissues from women with endometriosis, and 35 normal endometrial tissues from women without endometriosis. RESULT(S): Expression of claudin-3 and claudin-4 was significantly lower in the ectopic endometriotic tissue than in the eutopic endometrium from women with endometriosis and normal controls at both the messenger RNA and protein levels. No significant difference was found between eutopic endometrium from women with endometriosis and normal endometrium from women without endometriosis. CONCLUSION(S): Down-regulated expression of claudin-3 and claudin-4 in ectopic endometrium suggests that claudin-3 and claudin-4 might play a pathogenic role in the formation of endometriosis.

Fertil Steril. 2009 Jan;91(1):40-5. Epub 2008 Apr 18.

Impact of GnRH agonist treatment on recurrence of ovarian endometriomas after conservative laparoscopic surgery.

Jee BC, Lee JY, Suh CS, Kim SH, Choi YM, Moon SY.

Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, South Korea.

OBJECTIVE: To analyze the influence of postoperative GnRH agonist treatment on disease recurrence after conservative laparoscopic surgery for ovarian endometriomas according to duration of the treatment. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): One hundred nine consecutive premenopausal women who underwent conservative laparoscopic surgery for ovarian endometriomas (endometriosis stage III/IV) were enrolled in the study. The patients were divided into four treatment groups: expectant management (n = 37) and GnRH agonist therapy for 3 (n = 28), 4 (n = 21), and 6 months (n = 23). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): An ultrasound confirmed recurrence of ovarian endometriomas. RESULT(S): The overall crude recurrence rate was 16.5% after follow-up for an average of 20.1 months. The crude recurrence and the cumulative probabilities of disease recurrence at 24/36 months tended to be lower in patients who received a GnRH agonist for 6 months (4.3%, 5.3%/5.3%) compared with those who received it for 3 months (17.9%, 12.5%/25.0%) and 4 months (28.6%, 18.9%/39.2%) and patients with expectant management (16.2%, 22.4%/37.9%). However, the differences did not reach statistical significance. CONCLUSION(S): Treatment with GnRH agonist for six months had a beneficial impact on the recurrence rate after conservative laparoscopic surgery for ovarian endometriomas.

Fertil Steril. 2009 Apr;91(4 Suppl):1303-6. Epub 2008 Mar 25.

Cyclooxygenase-2 overexpression in ovarian endometriomas is associated with higher risk of recurrence.

Yuan L, Shen F, Lu Y, Liu X, Guo SW.

Department of Gynecology, Shanghai Obstetrics and Gynecology Hospital, Shanghai Medical School, Fudan University, Shanghai, China.

Cyclooxegenase-2 expression was evaluated by immunohistochemistry in endometrioma tissue samples taken from 109 patients, of whom 53 had recurrence by 30 months after surgery and 56 did not. Cyclooxegenase-2 overexpression, along with previous medical treatment of endometriosis and the presence of adhesion, is predictive of recurrence of ovarian endometrioma within 30 months after surgery, with a resultant sensitivity of 72.5% and a specificity of 72.4%, suggesting that there are intrinsic and identifiable biomarkers that confer recurrence risk.

Fertil Steril. 2009 Jan;91(1):32-9. Epub 2008 Mar 25.

Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis.

Greene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N.

Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1871, USA.

OBJECTIVE: To determine whether first physician seen and symptoms beginning in adolescence have an impact on the diagnostic experience of endometriosis. DESIGN: Cross-sectional study of self-reported survey data. SETTING: Academic research. PATIENT(S): Four thousand three hundred thirty-four Endometriosis Association Survey respondents reporting surgical diagnosis of endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Specialty of first physician seen, timing of onset of symptoms, time to seeking medical care and to diagnosis, number of physicians seen, and satisfaction with care. RESULT(S): Almost all respondents reported pelvic pain. Fifty percent first saw a gynecologist and 45% saw a generalist for symptoms related to endometriosis. Two thirds reported symptoms beginning during adolescence; they waited longer to seek medical care than adults did. Those seeing a generalist first took longest to get diagnosed; those seeing a gynecologist first saw fewer physicians. Sometime before diagnosis, 63% were told nothing was wrong with them. CONCLUSION(S): Women and girls who reported seeing a gynecologist first for symptoms related to endometriosis were more likely to have a shorter time to diagnosis, to see fewer physicians, and to report a better experience overall with their physicians. The majority reported symptoms beginning during adolescence, also reporting a longer time and worse experience while obtaining a diagnosis.

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Fertil Steril. 2009 Apr;91(4):979-87. Epub 2008 Mar 18.

High expression levels of cyclin B1 and Polo-like kinase 1 in ectopic endometrial cells associated with abnormal cell cycle regulation of endometriosis.

Tang L, Wang TT, Wu YT, Zhou CY, Huang HF.

Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China.

OBJECTIVE: To investigate the possible roles of cyclin B1/cyclin-dependent kinase (cdc2) and Polo-like kinase 1 (Plk1) in the pathogenesis of endometriosis. DESIGN: A case-control study. SETTING: University hospital. PATIENT(S): Patients with or without endometriosis were diagnosed by pathological examination or laparoscopy. The patients with the following criteria within the past 6 months were excluded: endocrine or inflammatory diseases, pregnancy or lactation, hormonal therapy, and neoplasm in the uterine cavity. INTERVENTION(S): Eutopic and ectopic endometria were obtained at the time of surgery. Blood was collected on the same day as surgery. MAIN OUTCOME MEASURE(S): The mRNA/protein expression and localization of cyclin B1, cdc2, and Plk1 in endometrium, and serum levels of E(2) and P. RESULT(S): The expression levels of cyclin B1 and Plk1, but not cdc2, in ectopic endometria were significantly higher than in eutopic endometria. The immunohistochemical staining of cyclin B1 and Plk1 was detected in the nuclei of ectopic and eutopic endometrial cells. Furthermore, ectopic endometrial expression levels of cyclin B1 or Plk1 were positively correlated with serum E(2) levels. CONCLUSION(S): Cyclin B1 and Plk1 may play important roles in the pathogenesis of endometriosis by mediating ectopic endometrial cell proliferation under regulation of ovarian hormones.

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Fertil Steril. 2009 Apr;91(4):975-8. Epub 2008 Mar 18.

Arguments for a left lateral predisposition of endometrioma.

Matalliotakis IM, Cakmak H, Koumantakis EE, Margariti A, Neonaki M, Goumenou AG.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Yale University School of Medicine, New Haven, Connecticut, USA. matakgr@yahoo.com

OBJECTIVE: To analyze a hypothesis regarding the pathogenesis of endometriosis. DESIGN: Retrospective study. SETTING: Two academic endometriosis referral centers. PATIENT(S): We evaluated operative and pathologic reports of 251 women who underwent laparoscopic or laparotomy treatment of endometrioma from August 1996 to February of 2002 at Yale University School of Medicine and at the University of Crete Department of Obstetrics and Gynecology. INTERVENTION(S): Laparascopic examination. MAIN OUTCOME MEASURE(S): Statistical methods included chi(2) and Mann-Whitney U tests measuring incidence of right- vs. left-sided endometria. RESULT(S): One hundred seventy patients from Yale University and 81 Greek patients participated in this study. Endometrioma was significantly more frequent in the left ovary (139 of 206 [67.4%]) than in the right ovary (67 of 206 [32.6%]; odds ratio [OR] = 4.3; 95% confidence interval [CI) 2.9-6.5; chi(2) = 48.9) and significantly different from the expected proportion of 50% (chi(2) = 25.2). When bilateral endometriomas were included, 62.1% (184 of 296) were left-sided and 37.15 (112 of 296) were right-sided (OR = 17.5; 95% CI 1.9-3.8; chi(2) = 34.1). Dilated ovarian veins in were found in 22 (68.7%) of 32 Greek cases with endometrioma. All 20 women with left endometrioma had left ovarian vein dilated. CONCLUSION(S): We suggest a new mechanical theory of implication, the female varicocele theory, which could play an important role in the development of ovarian endometriosis or endometriomas.

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Fertil Steril. 2009 Mar;91(3):682-6. Epub 2008 Mar 5.

P27Kip1 is down-regulated in the endometrium of women with endometriosis.

Schor E, da Silva ID, Sato H, Baracat EC, Girão MJ, de Freitas V.

Pelvic Pain and Endometriosis Unit, Gynecology Department, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil. eduschor@uol.com.br

OBJECTIVE: To evaluate p27 protein expression in the endometrium of women with endometriosis. DESIGN: Transversal case-control study. SETTING: Endometriosis Unit, Federal University of São Paulo, Brazil. PATIENT(S): Thirteen patients with stage I/II endometriosis, five with stage III/IV endometriosis, and 11 control subjects. INTERVENTION(S): Endometrial biopsies were obtained from patients with proven endometriosis and women without disease at laparoscopy. P27 protein was immunolocalized in the biopsy tissues and quantified by light microscopy. MAIN OUTCOME MEASURE(S): Immunostaining scores of glandular and stromal cells in endometrial biopsies obtained from patients with confirmed endometriosis compared with those of healthy control women with normal pelvis at laparoscopy. The staining scores of stage I/II and stage III/IV patients and of both patient groups and the control group were compared. RESULT(S): The level of p27 protein expression observed in the control group, both in the stroma and in the endometrial glands, was significantly different from that observed in the endometriosis patient groups. Significant differences in p27 protein expression levels in the glandular epithelium and stroma were not observed among groups of patients with endometriosis. CONCLUSION(S): The decreased level of p27 protein in the endometrium of women with endometriosis suggests that cell cycle alterations in the endometrial mucosa may be involved in the pathogenesis of this disease.

Fertil Steril. 2009 Feb;91(2):343-9. Epub 2008 Mar 7.

Human leukocyte antigen-G, a ligand for the natural killer receptor KIR2DL4, is expressed by eutopic endometrium only in the menstrual phase.

Kawashima M, Maeda N, Adachi Y, Takeuchi T, Yamamoto Y, Izumiya C, Hayashi K, Furihata M, Udaka K, Fukaya T.

Department of Obstetrics and Gynecology, Kochi Medical School, Nankoku, Kochi, Japan. km501212km@hotmail.com

OBJECTIVE: To investigate menstrual cycle changes in expression by eutopic endometrium of a nonclassic human leukocyte antigen, HLA-G, which binds to the killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) on natural killer (NK) cells. Such antigens have been linked to endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): We examined 20 Japanese women undergoing hysterectomy for endometriosis and 17 undergoing hysterectomy for myoma. INTERVENTION(S): Immunohistochemical HLA-G staining of eutopic endometrium and peritoneal fluid (PF) cells from women with and without endometriosis. Flow cytometric analysis of PF NK cells from women with and without endometriosis. MAIN OUTCOME MEASURE(S): HLA-G staining in eutopic endometrium was quantified by image analysis. The KIR2DL4-expressing NK cells in PF were investigated by flow cytometry. RESULT(S): The HLA-G was expressed by eutopic endometrium only in the menstrual phase and not in the late proliferative or secretory endometrium. Intensity of HLA-G staining did not differ significantly between women with and without endometriosis. The HLA-G- expressing cells were detected in PF during the menstrual period. These cells are morphologically and flow cytometrically different from mesothelial cells and NK cells. CONCLUSION(S): The HLA-G expression is observed in eutopic endometrium only during the menstrual phase, and no differences were observed between women with and without endometriosis. Epithelial cells bearing HLA-G may enter the peritoneal cavity during retrograde menstruation, allowing the antigen to react locally with KIR2DL4.

Fertil Steril. 2009 Mar;91(3):687-93. Epub 2008 Mar 7.

Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis.

Ulukus M, Ulukus EC, Tavmergen Goker EN, Tavmergen E, Zheng W, Arici A.

Department of Obstetrics & Gynecology, Ege University School of Medicine, Bornova, Izmir, Turkey.

OBJECTIVE: To investigate the expression and localization of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in women with and without endometriosis. DESIGN: Comparative immunohistochemical study. SETTING: Academic medical center. PATIENT(S): Ectopic (n = 24) and homologous eutopic endometrium (n = 24) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of IL-8 and MCP-1. INTERVENTION(S): Tissue sections were immunostained with antihuman IL-8 and MCP-1 antibodies. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and localization of IL-8 and MCP-1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with endometriosis and comparison with normal endometrium. RESULT(S): In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples. Epithelial MCP-1 expression was similar in both proliferative and secretory phases. Proliferative phase samples showed higher epithelial IL-8 and MCP-1 expressions in eutopic endometrium of women with endometriosis compared with that of normal women. Immunoreactivities of both chemokines were significantly increased in the epithelial cells of ectopic endometrial tissues compared with those of normal endometrium. CONCLUSION(S): These findings suggest that IL-8 and MCP-1 may be involved in the pathogenesis of endometriosis.

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Fertil Steril. 2009 Mar;91(3):698-704. Epub 2008 Mar 7.

Defining the proliferative phase endometrial defect.

Bromer JG, Aldad TS, Taylor HS.

Department of Obstetrics, Division of Reproductive Endocrinology and Infertility, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

OBJECTIVE: To evaluate proliferative phase endometrial development in a heterogeneous infertility population. DESIGN: Retrospective study. SETTING: University-based infertility practice. PATIENT(S): Two hundred forty-six treatment cycles. INTERVENTION(S): Clomiphene citrate or FSH ovarian stimulation, followed by IUI or IVF. MAIN OUTCOME MEASURE(S): Endometrial thickness according to transvaginal ultrasonography; clinical pregnancy rate. RESULT(S): Endometrial growth began from a nadir of approximately 4.5 mm on cycle day 4 and increased linearly to a plateau of approximately 10 mm on cycle day 9. This same pattern was observed in all cycles, regardless of pregnancy, drug, or underlying diagnosis. Follicle-stimulating hormone-stimulated cycles showed a significantly increased endometrial thickness compared with clomiphene citrate cycles (10.1 vs. 8.3 mm). Maximum endometrial thickness achieved showed a correlation with age, body mass index, and maximum E(2) level. Subjects who carried a primary diagnosis of polycystic ovary syndrome, endometriosis, or recurrent pregnancy loss all achieved a significantly lower peak endometrial thickness than control subjects. There was a trend toward increased endometrial thickness in cycles resulting in pregnancy compared with those not (10.1 vs. 9.6 mm, respectively). CONCLUSION(S): Endometrial development follows a predictable pattern, with a plateau in growth at cycle day 9. Diseases associated with infertility manifest a proliferative phase defect that can be recognized clinically.

Fertil Steril. 2009 Feb;91(2):350-8. Epub 2008 Mar 7.

Elevated levels of gremlin-1 in eutopic endometrium and peripheral serum in patients with endometriosis.

Sha G, Zhang Y, Zhang C, Wan Y, Zhao Z, Li C, Lang J.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China.

OBJECTIVE: To examine the expression of gremlin-1 (GREM1) on the levels of messenger RNA (mRNA) and protein in eutopic endometrium and its serum level in patients with endometriosis. DESIGN: Prospective, experimental study using reverse-transcription polymerase chain reaction, Western blot, immunofluorescence, and ELISA. SETTING: Gynecological oncology laboratory in a department of obstetrics and gynecology in a medical college in China. PATIENT(S): Thirty-five patients with endometriosis and 23 healthy control women. INTERVENTION(S): During surgery, the eutopic endometria and peripheral serum were obtained from the patients with endometriosis and the control women. MAIN OUTCOME MEASURE(S): The cellular compartment location of GREM1 expression was examined by using immunofluorescent double staining. The expression levels of mRNA and protein for GREM1 were determined by reverse-transcription polymerase chain reaction and Western blot, respectively. The serum level of GREM1 was measured by indirect ELISA. RESULT(S): The expression of GREM1 was defined within endometrial blood vessel endothelium exclusively, with the concomitant expressions of GREM1 and CD146. The expression of GREM1 on the levels of mRNA and protein was significantly higher in eutopic endometria of patients with endometriosis than in those from healthy control women. According to the ELISA established in our laboratory, the concentration of GREM1 in peripheral serum that was collected during the follicular menstrual phase of patients with endometriosis was significantly higher than that in serum from healthy control women. CONCLUSION(S): Gremlin-1 plays a role to some extent in the aberrant angiogenesis of eutopic endometrium in patients with endometriosis. It is possible that the peripheral serum level of GREM1 is a prospective serum biomarker of endometriosis.

Fertil Steril. 2009 Feb;91(2):320-4. Epub 2008 Mar 4.

Interleukin-12 but not interleukin-18 is associated with severe endometriosis.

Fairbanks F, Abrão MS, Podgaec S, Dias JA Jr, de Oliveira RM, Rizzo LV.

Endometriosis Unit, Gynecological Clinic, São Paulo University School of Medicine, São Paulo, SP, Brazil.

OBJECTIVE: To evaluate interleukin (IL)-12 and IL-18 levels in the serum and peritoneal fluid of women with and without endometriosis. DESIGN: Cross-sectional survey. SETTING: University hospital. PATIENTS: Interleukin-12 and IL-18 levels were compared in 105 patients submitted to laparoscopy because of symptoms suggestive of endometriosis (pain and/or infertility). The disease was confirmed in 72 patients (study group), while in 33 patients findings were not compatible with endometriosis (control group). INTEVENTION(S): Blood sample and peritoneal fluid were obtained from patients during videolaparoscopy. MAIN OUTCOME MEASURE(S): The levels of IL-12 and IL-18 in peripheral blood and peritoneal fluid were determined and compared with the stage and site of the disease and histologic classification. RESULT(S): IL-12 levels measured in peritoneal fluid were higher in patients with endometriosis compared with the control group. A significant increase in IL-12 levels was found when the more advanced stages of the disease were compared with the initial stages. No statistically significant differences were found in IL-18 levels, either in serum or in peritoneal fluid samples. CONCLUSION(S): Patients with severe endometriosis have higher IL-12 levels irrespective of IL-18 levels, suggesting that in this disease an alternative pathway is involved in induction of the Th1 immune response.

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Fertil Steril. 2009 Feb;91(2):331-4. Epub 2008 Feb 20.

Low serum and peritoneal fluid concentration of interferon-gamma-induced protein-10 (CXCL10) in women with endometriosis.

Galleri L, Luisi S, Rotondi M, Romagnani P, Cobellis L, Serio M, Petraglia F.

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

OBJECTIVE: To evaluate serum and peritoneal fluid concentrations of interferon-gamma-inducible protein-10 (CXCL10), a chemokine involved in local immune function, in women with endometriosis. DESIGN: Prospective study. SETTING: Division of Obstetrics and Gynecology, University of Siena. PATIENT(S): A total of 147 women were divided in two groups: women with (n = 77) and without (n = 70) endometriosis. INTERVENTION(S): Serum and peritoneal fluid were collected from all patients undergoing laparoscopy. MAIN OUTCOME MEASURE(S): CXCL10 concentrations were measured by a specific ELISA. RESULT(S): Serum CXCL10 concentrations in women with endometriosis were significantly lower than in those without endometriosis. No statistically significant difference between women with early endometriosis and those with advanced endometriosis was found. CXCL10 concentrations in peritoneal fluid of women with advanced endometriosis were significantly lower than in that of women with an early stage of, or without, endometriosis. CONCLUSION(S): The decreased concentrations of CXCL10 in serum and peritoneal fluid of women with endometriosis indicate an impaired immune activity in women with endometriosis.

Eur J Radiol. 2009 Apr;70(1):128-32. Epub 2008 Feb 15.

Uterine artery embolisation for symptomatic adenomyosis–mid-term results.

Bratby MJ, Walker WJ.

Radiology Department, Royal Surrey County Hospital, Egerton Road, Guildford, Surrey GU2 7XX, United Kingdom.

PURPOSE: To evaluate the role of uterine artery embolisation (UAE) in the treatment of adenomyosis. MATERIALS AND METHODS: 27 women with symptomatic adenomyosis diagnosed on magnetic resonance imaging (MRI) underwent UAE between 1998 and 2004. Clinical evaluation using a standardised questionnaire was made at regular intervals after embolisation to assess patient outcome. RESULTS: The diagnosis of adenomyosis was confirmed histologically by transvaginal biopsy in 5 women. There were 14 women with associated uterine fibroids. Diffuse adenomyosis was identified in 18 women. A focal adenomyoma was present in another 8 women. In 1 patient adenomyosis was not classified. All patients except one underwent bilateral uterine artery embolisation. There was an initial favourable clinical response, with improvement of menorrhagia in 79% (13/16) of patients at 12 months. Follow-up data was available on a total of 14 patients at 2 and 3 years after embolisation. 45.5% (5/11) reported a deterioration in menorrhagia symptoms at 2 years. CONCLUSION: UAE for symptomatic adenomyosis is effective in the short-term but there is a high rate of recurrence of clinical symptoms 2 year following treatment.

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Fertil Steril. 2009 Jan;91(1):201-6. Epub 2008 Feb 20.

Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Women’s Health Across the Nation (SWAN).

Weiss G, Maseelall P, Schott LL, Brockwell SE, Schocken M, Johnston JM.

Department of Obstetrics, Gynecology, and Women’s Health, New Jersey Medical School, Newark, New Jersey 07103, USA. weissge@umdnj.edu

OBJECTIVE: Our study evaluates the symptoms commonly attributed to adenomyosis in women undergoing the menopausal transition. We hypothesized that adenomyosis is more commonly seen in women with fibroids, pelvic pain, abnormal uterine bleeding, and in the presence of endometriosis. DESIGN: Retrospective cohort. SETTING: Multisite community-based study. PATIENT(S): Enrollees in the Study of Women’s Health Across the Nation who had hysterectomies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relationship of adenomyosis to presenting symptoms and other patient characteristics. RESULT(S): Adenomyosis was found in 48% of 137 patients. Frequencies of presenting symptoms were similar in those with and without evidence of adenomyosis. The same prevalence of fibroids was seen in the presence or absence of adenomyosis: 37% versus 43%, endometriosis, 3% versus 5%, abnormal bleeding, 27% versus 33%, or chronic pelvic pain in the presence of fibroids 12% versus 17%. CONCLUSION(S): Adenomyosis is a common diagnosis seen in hysterectomized specimens from women undergoing the perimenopausal transition. Adenomyosis is equally common in women who also have fibroids, endometriosis, pelvic pain, or abnormal uterine bleeding, and women who do not. Therefore, adenomyosis is an incidental finding, not the source of the symptomatology. It appears not to be a “disease” per se but rather a normal variant.

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Abdom Imaging. 2009 Mar-Apr;34(2):251-9.

Efficiency of MR imaging to orientate surgical treatment of posterior deep pelvic endometriosis.

Roy C, Balzan C, Thoma V, Sauer B, Wattiez A, Leroy J.

Department of Radiology B, Universitary Hospital of Strasbourg-Civil Hospital, 1, place de l’hopital BP 426, 67091, Strasbourg Cedex, France. catherine.roy@chru-strasbourg.fr

OBJECTIVE: The purpose of this retrospective study was to evaluate the accuracy of MRI using pelvic-phased-array and endocavitary coils in detecting intestinal wall invasion by an endometriotic nodule. MATERIALS AND METHODS: Forty-seven patients (32.1 +/- 4.2 years) who were planned for a surgical cure of deep endometriosis underwent MRI with conventional sequences using both coils. A thin bright layer on T(2)-w with enhancement on post-Gd T(1)-w defined our MR pattern for muscular layer involvement. MR results were correlated with surgical and pathological findings of the removed nodule. RESULTS: MR results for Group 1 (both coils) achieved a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100-63%, 96-92%, 90-70%, 100-85%, and 97-83% for endovaginal coil and phased-array coil, respectively. Group 2 (phased-array coil) had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 73%, 93%, 84%, 88%, and 87% for this coil, respectively. CONCLUSION: Combined pelvic-phased-array and endovaginal coils are better than phased array alone in the detection of intestinal wall invasion. Easy to perform, it has to be considered as a preoperative staging for deep posterior endometriosis to orientate the surgical management.

Fertil Steril. 2009 Jan;91(1):46-50. Epub 2008 Jan 18.

Measurable serum markers of oxidative stress response in women with endometriosis.

Lambrinoudaki IV, Augoulea A, Christodoulakos GE, Economou EV, Kaparos G, Kontoravdis A, Papadias C, Creatsas G.

Second Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece. ilambrinoudaki@hotmail.com

OBJECTIVE: To evaluate the hypothesis of increased systemic oxidative stress in patients with endometriosis. SETTING: Tertiary care university hospital. DESIGN: Cross-sectional study. PATIENT(S): Sixty-six women of reproductive age undergoing laparoscopy. INTERVENTION(S): All women were investigated for endometriotic foci during laparoscopy. Forty-five women had laparoscopically and histologically confirmed endometriosis, and 21 women did not have endometriosis. MAIN OUTCOME MEASURE(S): Four markers of oxidative stress were assessed in the serum of each patient: heat shock protein 70 (HSP70), HSP70b’, thioredoxin (TRX), and ischemia-modified albumin (IMA). RESULT(S): Mean serum HSP 70b’ level was higher in patients with endometriosis compared with controls (0.178 ng/mL, SD 0.103, and 0.135 ng/mL, SD 0.014, respectively). The disease stage did not affect HSP70b’ levels. Heat shock protein 70, IMA, and TRX levels did not differ between patients with endometriosis and controls. Women with a history of arterial hypertension had higher mean IMA levels compared with women with normal blood pressure independently of the presence of endometriosis (106.7 [SD 25.4] U/mL and 85.0 [SD 11.5] U/mL, respectively). CONCLUSION(S): Endometriosis is associated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies.

Fertil Steril. 2009 Jan;91(1):293.e1-3. Epub 2007 Oct 24.

Cryopreservation of oocytes in a young woman with severe and symptomatic endometriosis: a new indication for fertility preservation.

Elizur SE, Chian RC, Holzer HE, Gidoni Y, Tulandi T, Tan SL.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill Reproductive Center, McGill University Health Center, Montreal, Quebec, Canada. shai.elizur@muhc.mcgill.ca

OBJECTIVE: To report a new indication for fertility preservation. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 25-year-old nulliparous woman with severe and symptomatic endometriosis and low antral follicular count. INTERVENTION(S): Oocyte cryopreservation. MAIN OUTCOME MEASURE(S): Number of cryopreserved oocytes. RESULT(S): After three cycles of ovarian stimulation, we cryopreserved 21 oocytes. CONCLUSION(S): We recommend fertility preservation as part of preoperative counseling in young women with severe endometriosis.

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