Bibliografia 2009 – Pagina 5

Fertil Steril. 2009 Jul 22. [Epub ahead of print]

Comparison of the clinical value of CA 19-9 versus CA 125 for the diagnosis of endometriosis.

Kurdoglu Z, Gursoy R, Kurdoglu M, Erdem M, Erdem O, Erdem A.

Yuzuncu Yil University School of Medicine, Department of Obstetrics and Gynecology, Van, Turkey (Formerly, Gazi University School of Medicine, Department of Obstetrics and Gynecology, Ankara, Turkey).

Preoperative blood samples and intraoperative tissue specimens were obtained from 101 patients with endometriosis and 78 patients without endometriosis referred for benign gynecologic operations to investigate the clinical value of serum and tissue CA 19-9 levels in the diagnostic evaluation of endometriosis as compared to CA 125. Our prospective cohort study showed that serum CA 19-9 is a valuable marker in the diagnosis of endometriosis, and it may be used to predict the patients with severe endometriosis when used with CA 125.


Clin Pediatr (Phila). 2009 Jul 23. [Epub ahead of print]

Mullerian Dygenesis, Renal Agenesis, Endometriosis, and Ascites.

Herman TE, Siegel MJ.

Mallinckrodt Institute of Radiology.

Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 May;40(3):422-5.

Expression and significance of ET-1 and its receptors in endometriosis

[Article in Chinese]

Chen ZG, Wang HJ, Zhou Y, Yang Q, Yu X.

Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.

OBJECTIVE: To investigate the expression of endothelin-1 (ET-1) and its receptors (ET(A)R, ET(B)R) in patients with endometriosis and to explore the possible role of them in the pathogenesis of endometriosis. METHODS: The tissues of ectopic and eutopic endometrium were collected from 48 cases of endometriosis (EM), while the control samples were eutopic endometrium from 13 cases of cervical intraepithelial neoplasia (CIN). The expressions and locations of ET-1, ET(A)R, ET(B)R were measured by immunohistochemical staining. RESULTS: The expression levels of ET-1 and ET(A)R of EMs group, either in eutopic or in ectopic endometrium, were higher than those of the control group (All P<0.01). Moreover, the expression levels of ET-1 and ETAR in eutopic endometrium were higher than those in ectopic endometrium. There were significant correlations between the expression of ET-1 and ETAR in EMs group, either for eutopic or for ectopic endometrium (r=0.970, 0.968 respectively, All P<0.05). There was no significant difference in the expression level of ET(B)R among eutopic endometrium of EMs, ectopic endometrium of Ems and eutopic endometrium of control group (All P>0.05). There was no significant difference in the expression level of ET-1, ET(A)R and ET(B)R in proliferative phase and secretory phase in both EMs group and control group (All P>0.05). The expression levels of ET-1, ET(A)R and ET(B)R were not associated with r-AFS staging of endometriosis (All P>0.05). CONCLUSION: By the way of combining ET(A)R, ET-1 may play a important role in the pathogenesis of endometriosis.

Hum Reprod. 2009 Jul 22. [Epub ahead of print]

L-Selectin ligands in human endometrium: comparison of fertile and infertile subjects.

Margarit L, Gonzalez D, Lewis PD, Hopkins L, Davies C, Conlan RS, Joels L, White JO.

Institute of Life Science, School of Medicine, Swansea University, Swansea, Wales SA2 8PP, UK.

BACKGROUND L-selectin ligands, localized to the luminal epithelium at the time of implantation, may support the early stages of blastocyst attachment. We have assessed the expression of two L-selectin ligands, defined by MECA-79 and HECA-452 monoclonal antibodies, and the sulfotransferase GlcNAc6ST-2, involved in generation of L-selectin ligand epitopes, in the secretory phase of the endometrium from fertile and infertile patients. METHODS Endometrial samples were obtained from 33 fertile, 26 PCOS, 25 endometriosis and 33 patients diagnosed with unexplained infertility. L-selectin ligands and GlcNAc6ST-2 expression was assessed by immunohistochemistry and immunoblotting. RESULTS Immunohistochemical staining of uterine epithelium, from fertile and infertile women, demonstrated differential expression of MECA-79 and HECA-452 epitopes. In fertile women in the secretory phase MECA-79 was more strongly expressed, particularly on the lumen, than in infertile women. HECA-452 staining was significantly stronger in the glands in PCOS and endometriosis patients than in fertile women. GlcNAc6ST-2 expression was reduced in infertile patients, correlating with MECA-79 expression. CONCLUSIONS This study demonstrated significant differences in expression of L-selectin ligands between fertile and infertile women in natural cycles, and could contribute to patient assessment prior to initiating fertility treatment.

Hum Reprod. 2009 Jul 22. [Epub ahead of print]

Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis.

Seracchioli R, Mabrouk M, Manuzzi L, Vicenzi C, Frascà C, Elmakky A, Venturoli S.

Minimally Invasive Gynaecological Surgery Unit, Reproductive Medicine Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

BACKGROUND Endometriosis recurrence after conservative surgery is not infrequent. Variable regimens of hormonal therapy have been proposed as adjuvant post-operative measures for prophylaxis against recurrence. Among these, the combined oral contraceptive pills (OCP), represents a valuable option in terms of safety and tolerability for long-term use. The objective of this review is to evaluate the effect of post-operative use of OCP in preventing symptom recurrence, and/or anatomical relapse of endometriosis. METHODS A systematic search of Medline identified seven studies evaluating post-operative OCP treatment on prevention of endometriosis recurrence. RESULTS A reduction in anatomical relapse rate was observed when oral contraceptive therapy was administered for more than 1 year after conservative surgery. Post-operative use of OCP was associated with a reduction in frequency and intensity of dysmenorrhoea recurrence. No association was found between OCP therapy and dyspareunia prevention, although the effect of OCP on chronic pelvic pain was conflicting. CONCLUSION Long-term OCP therapy can be a reliable adjuvant post-operative measure to prevent or reduce frequency/severity of recurrent dysmenorrhoea and anatomical relapse of endometriosis. Since both continuous and cyclic OCP administration regimens seem to have comparable effects, the choice of regimen can be modulated according to patient preferences. The protective effect seems to be related to the duration of treatment.

Hum Reprod. 2009 Sep;24(9):2385. Epub 2009 Jul 22.

Comment on:

Deeply infiltrating endometriosis and transvaginal ultrasonography.

Acién P.

Publication Types:

Rev Med Inst Mex Seguro Soc. 2009 Jan-Feb;47(1):57-60.

Endometriosis. Pathophysiological background for treatment.

[Article in Spanish]

Hernández-Valencia M, Zárate A.

Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Distrito Federal, México, Mexico.

Endometriosis is the third cause of gynecological morbidity and the complications are associated to ectopically endometrial tissue implantation. The interest on this disease is the functional disability and its association with sterility. It has been established that endometrial growth is estrogen-dependent and that progesterone inhibits the cellular proliferation mediated by estrogens, therefore in endometriosis there is not an adequate response to hormonal signals that control the proliferative activity. It has been described that peritoneal fluid in women with endometriosis has high concentrations of cytokines, growth factors and activated macrophages, which have been shown to have adverse effects on fertility. Therefore, these are not the only causes of infertility since it has been described that wonmen with endometriosis seem to have poor ovarian reserve and ovular quality. When there is infertility, the tendency is to treat the endometriosis due to the changes caused by ectopic tissue presented at the immunological level and in the structure of genital organs, which disturbs the conception process. It has been observed that endometriosis recurs after a surgical procedure. For this reason we should be consider all therapeutic possibilities.

Emerg Infect Dis. 2009 Jul;15(7):1137-9.

Varibaculum cambriense infections in Hong Kong, China, 2006.

Chu YW, Wong CH, Chu MY, Cheung CP, Cheung TK, Tse C, Luk WK, Lo JY.

Obstet Gynecol Surv. 2009 Aug;64(8):542-7.

The role of prolactin- and endometriosis-associated infertility.

Wang H, Gorpudolo N, Behr B.

Department of OB/GYN, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

This review will address the current understanding of the relationship between prolactin (PRL) and endometriosis-associated infertility. Although the exact mechanisms of action of hyperprolactinemia in patients with endometriosis-associated infertility have not been clearly established, this report reviews results from relevant studies in the literature. These include serum PRL levels in endometriosis-associated infertility, PRL receptors in ectopic endometriotic tissues, basal PRL levels after TSH and Danazol (isoxazolic derivative of the synthetic steroid 5alpha-ethinyl-testosterone) therapy, peritoneal fluid and nocturnal serum PRL levels in endometriosis, infertility, and luteal phase PRL concentrations in patients with endometriosis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to explain the relationship between prolactin- and endometriosis-associated infertility, relate endometriosis with infertility, and summarize two ways in which prolactin and endometriosis may be linked in the pathophysiology of infertility.


Med Pregl. 2009 Mar-Apr;62(3-4):185-8.

Decidual transformation in adenomyosis during pregnancy as an indication for hysterectomy

[Article in Serbian]

Jovanović B, Petrović A, Petrović B.

Klinika za ginekologiju i akuserstvo, Klinicki centar, Kragujevac.

INTRODUCTION: Incidence of adenomyosis is estimated on 20% in all of extracted uteruses. Clinically, it usually exists asymptomatically, but could be followed with dysmenorrhoea, menorrhagia and pelvic pain. One third of patients with adenomyosis are sterile, however in other two thirds, conception and pregnancy could have normal development, with delivery without complications. One of possible complications related to adenomyosis is rupture of uterus during delivery. CASE REPORT: A pregnant woman at the end of the 10th lunar month of pregnancy, showed minimal labour contractions, following amnion rupture and the delivery was terminated by section ceasar. Subtotal hysterectomy was performed because of concominant profuse bleeding. Myometrium was occupied with decidual cells in trabecular arrangement, among which elongated endometrial glands were placed. Surrounding muscle fascicles showed atrophic, apoptic, and occasionally necrotic changes. Myometrial stroma was edematous, and infiltrated with mesenchymal cells, as well as with adipose cells, which were extending toward serosa. DISCUSSION: The patient had been receiving treatment, for a long period, because of sterility without clear etiological factor. A small number of similar cases ends with complications. Here, it is evident that abundant decidual transformation of stromal cells in adenomiosis leads to atrophy and necrosis of muscle cells. The reduction of uterine muscle mass causes atony and threating rupture, through separation of muscle cells, and therefore the absence of their synchronized contractions. CONCLUSION: Atony of uterine muscle could be caused by decidual transformation in adenomyosal fields, atrophy of muscle fascicles, edema of the stroma, mesenchymal transformation, and fibrosis. This leads to a decrease in myometrial contractions, and prolonged postpartal bleeding.

J Clin Lab Anal. 2009;23(4):244-8.

Cancer antigen 125 levels in inflammatory bowel diseases.

Ataseven H, Oztürk ZA, Arhan M, Yüksel O, Köklü S, Ibiş M, Başar O, Yilmaz FM, Yüksel I.

Department of Gastroenterology, Erzurum Bölge Egitim ve Araştirma Hastanesi, Erzurum, Turkey.

BACKGROUND: Cancer antigen 125 (CA-125) is a tumor marker used for the diagnosis and monitoring of ovarian carcinoma. It can also be elevated in endometriosis, inflammations, and in nongynecological malignancies. Up to date, serum CA-125 levels in inflammatory bowel diseases (IBD) have not been studied before. AIM: To assess the levels of CA-125 in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Serum levels of CA-125 were investigated in 68 cases with UC (male/female: 47/21), 32 CD (male/female: 21/11), and 31 healthy controls (male/female: 16/15). Levels of CA-125 were also compared among UC patients according to lesion location, severity, and activity of CD. RESULTS: Serum CA-125 levels were 17.29+/-24.50 U/ml, 15.56+/-20.74 U/ml, and 8.85+/-2.62 U/ml in patients with UC, CD, and healthy controls, respectively. Serum CA-125 levels were significantly higher in UC compared to control group (P=0.001). Serum CA-125 levels were higher in CD patients compared to control group but there was no significance (P=0.087). Serum CA-125 levels were higher in pancolitis compared to distal type and left-sided UC. CONCLUSIONS: Our data suggest that serum CA-125 levels may be increased in patients with IBDs.

Obstet Gynecol. 2009 Aug;114(2 Pt 2):484-7.

Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

Park AJ, Paraiso MF.

Female Pelvic Medicine & Reconstructive Pelvic Surgery and Minimally Invasive Surgery, Department of Gynecology & Obstetrics, Cleveland Clinic, Cleveland, Ohio 44195, USA.

BACKGROUND: Refractory dyspareunia presents a challenging therapeutic dilemma. CASE: A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. CONCLUSION: Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009 Jun;31(3):374-7.

Magnetic resonance manifestations of endometriosis

[Article in Chinese]

Wang F, Lu JJ, Feng F, Leng JH, Jin ZY.

Department of Radiology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.

OBJECTIVE: To explore the magnetic resonance (MR) characteristics of endometriosis. METHODS: The clinical and MR data of 33 patients with endometriosis were retrospectively analyzed. RESULTS: MR manifestations of endometriosis included endometrioma, peritoneal endometrial implant, adhesion, and other rare features. CONCLUSIONS: MR manifestations of endometriosis vary. Combining the clinical data with imaging data will help more accurate preoperative assessment of endometriosis.

Int J Gynecol Pathol. 2009 May;28(3):262-6.

Clear cell adenocarcinoma arising from adenomyosis.

Hirabayashi K, Yasuda M, Kajiwara H, Nakamura N, Sato S, Nishijima Y, Mikami M, Osamura RY.

Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.

A 73-year-old postmenopausal Japanese woman presented with a complaint of slight fever and weight loss. An elevated level of CA125 in the blood favored a diagnosis of malignant uterine body tumor, but was not confirmed by endometrial cytology and biopsy. Resection of the uterus revealed a solid whitish tumor in the myometrium that was diagnosed as clear cell adenocarcinoma (CCA) arising from adenomyosis. There were transitions between endometrial epithelium of adenomyosis, noninvasive CCA, and invasive CCA. Immunohistochemical expression of hepatocyte nuclear factor-1beta supported the diagnosis of CCA. Only one other English language document pertaining to CCA arising from adenomyosis exists. Malignant tumor arising from adenomyosis should be considered as a differential diagnosis when the serum level of tumor markers such as CA125 is high and when the tumor is intramyometrial.

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Jul;29(7):1479-81.

Expression of fragile histidine triad in endometriosis

[Article in Chinese]

Su GD, Ke Y, Yu YH, Zhang GL.

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

OBJECTIVE: To detect the expression of fragile histidine triad in endometriosis and investigate the pathogenesis of endometriosis. ETHODS: munohistochemistry was used to examine the expression of Fhit in the eutopic and ectopic endometria of 58 patients with endometriosis and in the endometria in 15 patients with hysteromyoma. RESULTS: The intensity of Fhit expression decreased in the order of normal endometrium, eutopic endometrium in endometriosis group, and ectopic endometrium. In patients with endometriosis, Fhit expression in the eutopic and ectopic endometria in proliferative phase showed no significant difference from that in secretory phase (P>0.05). Fhit expression in the ectopic endometrium showed significant difference between different r-AFS stages. MOD of ectopic endometrium in stages I-II was significantly higher than that in stages III-IV (P<0.05), but Fhit expression in the eutopic endometrium showed no significant difference (P>0.05). MOD of ovarian endometriosis showed no difference with that of adenomyosis. CONCLUSIONS: Fhit may play an important role in the development of endometriosis.

Thromb Res. 2009 Sep;124(4):393-6. Epub 2009 Jul 19.

Tissue factor and the endometrium: from physiology to pathology.

Krikun G, Lockwood CJ, Paidas MJ.

Department of Ob/Gyn, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.

Tissue factor (TF), is a transmembrane protein whose role was first identified as that of the initiator of hemostasis via a series of complicated protein cascades. It is now known however, that TF participates in angiogenesis as well as several processes that contribute to disease progression. Over the last 20 years, our laboratory has studied the expression and function of this molecule in both the pregnant and non-pregnant human endometrium. We demonstrated that TF is particularly upregulated at the time of implantation making it a critical factor to protect against excessive bleeding during trophoblast invasion. We have subsequently demonstrated the altered expression of this factor after long term contraception as well as in endometriosis. We proposed that any changes in this well regulated process can result in various pathologies of the endometrium including, infertility, bleeding, endometriosis, preeclampsia, preterm labor or thrombosis. Below we describe the latest findings of the expression and function of TF as well as its specific role in physiologic or pathologic conditions of the human endometrium.

Int J Epidemiol. 2009 Aug;38(4):1154-5. Epub 2009 Jul 17.

Comment on:

Commentary: Endometriosis–epidemiologic considerations for a potentially ‘high-risk’ population.

Missmer SA.

Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.

Urology. 2009 Jul 16. [Epub ahead of print]

Ectopic Decidual Reaction in the Urinary Bladder Presenting as a Vesical Tumor.

Szopiński TR, Sudoł-Szopińska I, Dzik T, Borówka A.

Department of Urology, Postgraduate Medical Educational Center, Warsaw, Poland.

A urinary bladder tumor in young pregnant women is a very rare finding. It may bring diagnostic problems despite use of advanced imaging techniques. We report on a case of an exceedingly rare occurrence of a decidual reaction in the urinary bladder of a pregnant young woman. To the best of our knowledge, it is the first such case reported in published medical data. The final diagnosis was possible only after histopathologic assessment of a specimen obtained during diagnostic cystoscopy, which showed typical decidual changes within detrusor muscle, without ectopic endometrium, which could suggest more frequent vesical endometriosis.

Histol Histopathol. 2009 Sep;24(9):1181-92.

Involvement of resistance to apoptosis in the pathogenesis of endometriosis.

Nasu K, Yuge A, Tsuno A, Nishida M, Narahara H.

Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan.

Endometriosis, a disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue. Increasingly, endometriosis is also becoming recognized as a condition in which ectopic endometrial cells exhibit abnormal proliferative and apoptotic regulation in response to appropriate stimuli. Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that, in healthy women, endometrial cells expelled during menstruation do not survive in ectopic locations because of programmed cell death, while decreased apoptosis may lead to the ectopic survival and implantation of these cells, resulting in the development of endometriosis. Both the inability of endometrial cells to transmit a ‘death’ signal and the ability of endometrial cells to avoid cell death have been associated with increased expression of anti-apoptotic factors and decreased expression of pre-apoptotic factors. This paper is a review of the recent literature focused on the differential expression of apoptosis-associated molecules in the normal endometria of women without endometriosis, and in the eutopic and ectopic endometria of women with endometriosis. The role of apoptosis in the pathogenesis of endometriosis and the basic and clinical research on the current medical treatment for endometriosis from the view of apoptosis will be discussed.

Am J Pathol. 2009 Aug;175(2):479-88. Epub 2009 Jul 16.

Increased immunoreactivity to SLIT/ROBO1 in ovarian endometriomas: a likely constituent biomarker for recurrence.

Shen F, Liu X, Geng JG, Guo SW.

Institute of Obstetric and Gynecologic Research, Shanghai Jiao Tong University School of Medicine, Renji Hospital, 145 Shandong Zhong Road, Shanghai 200001, China.

While surgery is currently the treatment of choice for endometriosis, recurrence remains a serious problem, and its prevention is an unmet clinical need. SLIT, a secreted protein that functions through the Roundabout (ROBO) receptor as a repellent for axon guidance and neuronal migration, has been recently found to induce tumor angiogenesis. We investigated the potential role of SLIT/ROBO1 in ovarian endometriomas and examined their predictive value in recurrence based on tissue samples from 43 patients with recurrence and 45 without recurrence. Microvascular density counts were evaluated by CD34 immunohistochemistry, and statistical analyses were performed to evaluate the effect of SLIT/Robo1 on recurrence risk after adjustment for other risk factors. We found that SLIT expression was positively correlated with microvascular density in ectopic endometrium and that its expression was higher in ectopic endometrium than control endometrium. Both SLIT and Robo1 expression were higher in recurrent cases than in non-recurrent cases. Higher immunoreactivity to SLIT, along with the presence of adhesion, PR-B, and nuclear factor-kappaB, was identified to be a risk factor for recurrence, with a sensitivity of 86% and a specificity of 87%. Therefore, increased SLIT immunoreactivity is likely an important constituent factor for recurrence of ovarian endometriomas, possibly through promoting angiogenesis in ectopic endometrium. Thus, the SLIT/ROBO1 system may be a potential target for reducing the risk of recurrence.

J Minim Invasive Gynecol. 2009 Jul 14. [Epub ahead of print]

Aromatase Inhibitors: Potential Reproductive Implications.

Bedaiwy MA, Mousa NA, Casper RF.

University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital and the University of Toronto, Toronto, Ontario M5G 1X5, Canada (all authors).

MEDLINE, EMBASE, Scopus, and Web of Science databases literature search from inception to March 2009 was performed to identify published clinical trials and cohort, observational, and in vitro studies that evaluated the use of aromatase inhibitors in reproductive medicine for indications other than ovulation induction. Aromatase inhibitors are currently being investigated for breast cancer prevention in women at high risk. Aromatase inhibitors may be used for treatment of symptomatic myomas and endometriosis as an alternative to surgical intervention. Current evidence does not support the routine use of aromatase inhibitors for these conditions without prospective controlled trials. Aromatase inhibitor cotreatment can be used to prevent the initial estrogen flare effect of gonadotropin-releasing hormone agonist treatment to offer flexibility in initiating this therapy.

Eur J Obstet Gynecol Reprod Biol. 2009 Oct;146(2):219-21. Epub 2009 Jul 15.

Plasminogen activator inhibitor-1 4G/5G polymorphism and susceptibility to endometriosis in the Italian population.

Gentilini D, Vigano P, Castaldi D, Mari D, Busacca M, Vercellini P, Somigliana E, di Blasio AM.

Molecular Biology Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy.

OBJECTIVES: Some controversy exists for the potential association of the plasminogen activator inhibitor-1 (PAI-1) gene polymorphism 4G/5G and susceptibility to endometriosis. To clarify this issue, we have examined the prevalence of this polymorphism in a case-control study in the Italian population. STUDY DESIGN: The PAI-1 4G/5G polymorphism was evaluated in n=368 reproductive year aged Caucasian women who underwent gynaecological laparoscopy for chronic pelvic pain, infertility, ovarian cysts and myomas. A second group of controls included n=329 normal subjects. RESULTS: The 697 women enrolled were divided as follows: the endometriosis group (n=204), the gynaecological control group (n=164) and the general population control group (n=329). No statistical significant differences emerged between endometriosis patients and gynaecological controls with regard to the allele frequencies and co-dominant and dominant models of genotype distribution. A borderline statistical difference was only observed for the recessive model of inheritance in which, contrary to previous findings, the PAI-1 4G/4G genotype seems to be less linked to the disease development. CONCLUSION: The findings reported herein do not support the previously reported data indicating a greater susceptibility to endometriosis in patients harbouring the PAI-1 4G/5G and 4G/4G genotypes and exclude a significant role of polymorphism in endometriosis development.

Fertil Steril. 2009 Jul 15. [Epub ahead of print]

Experimental endometriosis in immunocompromised mice after adoptive transfer of human leukocytes.

Bruner-Tran KL, Carvalho-Macedo AC, Duleba AJ, Crispens MA, Osteen KG.

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

OBJECTIVE: To develop a chimeric human/mouse model of experimental endometriosis for the examination of the role of human immune cells in this disease. DESIGN: Laboratory-based study. SETTING: University-affiliated medical center. PATIENT(S): Healthy women undergoing volunteer endometrial biopsies and blood donation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): In vivo analysis of the impact of the adoptive transfer of human immune cells into immunocompromised mice receiving autologous human endometrium. RESULT(S): Similar to our previous data using nude mice, human endometrial tissue fragments injected intraperitoneally into rag2gamma(c) mice readily established experimental disease. However, in this study, we found a statistically significant reduction in the severity of peritoneal disease in rag2gamma(c) mice which also received adoptive transfer of human immune cells compared with mice that did not receive immune cells. Our studies indicate that human immune cells readily track into the ectopic lesions established in mice. CONCLUSION(S): The ability of immune cells from disease-free women to limit intraperitoneal disease in mice suggests that a robust immune system is protective against the development of endometriosis.

J Pathol. 2009 Oct;219(2):232-41.

Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis.

Chuang PC, Wu MH, Shoji Y, Tsai SJ.

Department of Physiology, National Cheng Kung University Medical College, Taiwan, Republic of China.

Endometriosis, defined as the growth of endometrial tissues outside of the uterine cavity, is a severe and complex disease affecting more than 10% of women. The aetiology of endometriosis is unclear but immune dysfunction might be an important factor for its development. The natural function of the immune system is to detect and destroy aberrant or abnormal cells. Failure of the immune system to eradicate these aberrant cells often results in disease pathogenesis. We report here that the phagocytic ability of macrophages is reduced in peritoneal macrophages isolated from women with endometriosis. In-depth investigation revealed that the level of CD36, a class B scavenger receptor, in peritoneal macrophages derived from women with endometriosis was lower than that in normal macrophages. Blockage of CD36 function by neutralized antibody or knocking down CD36 using siRNA impaired the phagocytic ability of normal macrophages. In contrast, forced expression of CD36 in macrophages isolated from women with endometriosis restored phagocytic ability. Taken together, we identified that the scavenger receptor CD36 is reduced in the peritoneal macrophages of women with endometriosis, which leads to a decrease of the phagocytic ability of macrophages. These findings revealed a potential mechanism of immune dysfunction during endometriosis development. 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Curr Opin Obstet Gynecol. 2009 Aug;21(4):318-24.

Clinical utility of progesterone receptor modulators and their effect on the endometrium.

Spitz IM.

Institute of Hormone Research and Ben Gurion University of the Negev, Jerusalem, Israel.

PURPOSE OF REVIEW: In view of the spate of recent publications related to mifepristone and some second generation progesterone receptor modulators (PRMs), this appears to be an opportune time to view the clinical status of these compounds. RECENT FINDINGS: Randomized double-blind placebo-controlled trials have been conducted with mifepristone, CDB-4124 (Proellex), CDB-2914 (VA 2914, Ulipristal) and asoprisnil (J867). All these PRMs are effective in the treatment of uterine fibroids where they are associated with a reduction in pain, bleeding and improvement in quality of life and decrease in fibroid size. CDB-4124 is also efficacious in endometriosis. Long-term treatment with PRMs may be associated with endometrial thickening on ultrasound and there have been reports of endometrial hyperplasia. Several reassuring recent publications have done much to explain the mechanism underlying these endometrial changes. The most common histological finding is cystic glandular dilatation often associated with both admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histology has not been previously encountered in clinical practice and should not be confused with endometrial hyperplasia. The endometrial thickness is related to this cystic glandular dilatation. SUMMARY: At this stage of development, PRMs cannot be administered for longer than 3 or 4 months. Even over this time, there is improvement of symptoms associated with fibroids and endometriosis. Clinicians and pathologists need to be aware that the endometrial thickening and histological appearance do not represent endometrial hyperplasia.

Hum Reprod. 2009 Oct;24(10):2596-9. Epub 2009 Jul 14.

Interleukin-2 receptor beta gene C627T polymorphism in Korean women with endometriosis: a case-control study.

Lee GH, Choi YM, Kim SH, Hong MA, Ku SY, Kim SH, Kim JG, Moon SY.

Department of Obstetrics and Gynecology, Seoul Medical Center, Seoul, Republic of Korea.

BACKGROUND: The purpose of this study was to investigate the potential association of the C627T polymorphism in the interleukin-2 receptor beta gene (IL-2R beta) with the risk of endometriosis in Korean women. METHODS: Two hundred and thirty-seven women with surgically or histologically diagnosed endometriosis of stages III and IV were recruited for this study, and 164 patients with no evidence of endometriosis diagnosed by laparoscopy or laparotomy served as controls. The C627T polymorphism of the IL-2R beta was assessed using the TaqMan allelic discrimination assay. Chi2 analysis was used to examine any differences in genotype distributions and allele frequencies of the IL-2R beta C627T polymorphism between the endometriosis cases and the controls. RESULTS: There was no statistically significant difference in the frequency of the IL-2R beta C627T polymorphism between the endometriosis patients and the controls (28.7% C/C, 48.1% C/T and 23.2% T/T versus 29.3, 44.5 and 26.2%, respectively, P = 0.72) or in the T allele frequencies (47.3 versus 48.5%, respectively, P = 0.73). Even when the endometriosis cases were subdivided into stages III and IV, no statistically significant differences in genotype distributions or allele frequencies were observed among the three groups. CONCLUSIONS: Contrary to the recent data reported in a Taiwanese population, our results suggest that the C627T polymorphism of the IL-2R beta gene may not be associated with the risk of endometriosis in the Korean population.

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


Histologic classification of specimens from women affected by superficial endometriosis, deeply infiltrating endometriosis, and ovarian endometriomas.

Kamergorodsky G, Ayroza Ribeiro PA, Longo Galvão MA, Abrão MS, Donadio N, Luiz de Barros Moreira Lemos N, Aoki T.

Department of Obstetrics and Gynecology, Santa Casa Medical School, São Paulo, Brazil, Santa Casa Medical School, São Paulo, Brazil.

In this retrospective observational study involving 176 patients and 271 biopsies, the histologic differentiation in superficial endometriosis, deeply infiltrating endometriosis, and ovarian endometriomas was evaluated according to a previously proposed classification system. Results showed a predominance of the undifferentiated glandular pattern (33.5%) and mixed glandular pattern (46.9%) in deeply infiltrating endometriosis lesions, whereas the well-differentiated glandular pattern (41.8%) was most frequently seen in superficial endometriosis lesions, and in ovarian endometriomas a predominance of both the undifferentiated (40.5%) and mixed patterns (37.8%) was observed.

Fertil Steril. 2009 Sep;92(3):1170.e1-4. Epub 2009 Jul 9.

Aromatase inhibitor for treatment of a recurrent abdominal wall endometrioma in a postmenopausal woman.

Sasson IE, Taylor HS.

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.

OBJECTIVE: Treat an abdominal wall endometrioma in a post-menopausal patient. DESIGN: Case report. SETTING: Academic medical center. PATIENT(S): A post-menopausal women with a large recurrent abdominal wall endometrioma. INTERVENTION(S): The patient was managed with the combination of an aromatase inhibitor, a progestin, and serial cyst aspiration. MAIN OUTCOME MEASURE(S): Serum and cyst estradiol levels as well as sonographic demonstration of resolution. RESULT(S): Serum and cyst estradiol levels were significantly diminished and the cyst diminished in size. CONCLUSION(S): Taken together, this case demonstrates a novel approach for managing and monitoring medical therapy for unusual clinical presentations of endometriosis. Furthermore, it illustrates that endometriotic implants can be a source of circulating estrogen in postmenopausal women, and that this source of estrogen is generated by increased aromatase activity.

Hernia. 2009 Jul 10. [Epub ahead of print]

Endometriosis of the groin hernia sac: report of a case and review of the literature.

Kiyak G, Ergul E, Sarıkaya SM, Yazgan A.

General Surgery Department, Ankara Ataturk Teaching and Research Hospital, Askaabat Cad. Eser Sitesi B3 Blok Daire:11, TR-06490, Bahçelievler, Ankara, Turkey.

Endometriosis is characterized by the presence of histological normal endometrial tissue outside the uterine cavity. It occurs in up to 15% of menstruating women and often goes undetected. Some cases of soft-tissue involvement have been reported, particularly in the skin and subjacent tissues of surgical scars. However, we came cross a 42-year-old female patient with millimetric focal lesions in a groin hernia sac. A case report and a review of the literature are presented. Although definitive diagnosis still requires biopsy, the patient’s cyclic symptoms and history of previous uterine surgery should suggest the correct diagnosis.

J Gynecol Oncol. 2009 Jun;20(2):122-5. Epub 2009 Jun 29.

A case of multiple metastatic low-grade endometrial stromal sarcoma arising from an ovarian endometriotic lesion.

Kim JY, Hong SY, Sung HJ, Oh HK, Koh SB.

Department of Obstetrics and Gynecology, School of Medicine, Catholic University of Daegu, Daegu, Korea.

The development of endometrial stromal sarcomas (ESSs) in foci of endometriosis is extremely rare, and few cases have been reported in the literature to date, particularly with regard to multiple extrauterine ESS. Here we report a case of endometrial stromal sarcoma with multiple metastasis that arose from an ovarian endometriotic lesion. The literature is also briefly reviewed.

Endocrinology. 2009 Oct;150(10):4701-12. Epub 2009 Jul 9.

Increased mitogen-activated protein kinase kinase/extracellularly regulated kinase activity in human endometrial stromal fibroblasts of women with endometriosis reduces 3′,5′-cyclic adenosine 5′-monophosphate inhibition of cyclin D1.

Velarde MC, Aghajanova L, Nezhat CR, Giudice LC.

Department of Obstetrics, Center for Reproductive Sciences, University of California San Francisco, San Francisco, California 94143-0132, USA.

Endometriosis is characterized by endometrial tissue growth outside the uterus, due primarily to survival, proliferation, and neoangiogenesis of eutopic endometrial cells and fragments refluxed into the peritoneal cavity during menses. Although various signaling molecules, including cAMP, regulate endometrial proliferation, survival, and embryonic receptivity in endometrium of women without endometriosis, the exact molecular signaling pathways in endometrium of women with disease remain unclear. Given the persistence of a proliferative profile and differential expression of genes associated with the MAPK signaling cascade in early secretory endometrium of women with endometriosis, we hypothesized that ERK1/2 activity influences cAMP regulation of the cell cycle. Here, we demonstrate that 8-Br-cAMP inhibits bromodeoxyuridine incorporation and cyclin D1 (CCND1) expression in cultured human endometrial stromal fibroblasts (hESF) from women without but not with endometriosis. Incubation with serum-containing or serum-free medium resulted in higher phospho-ERK1/2 levels in hESF of women with vs. without disease, independent of 8-Br-cAMP treatment. The MAPK kinase-1/2 inhibitor, U0126, fully restored cAMP down-regulation of CCND1, but not cAMP up-regulation of IGFBP1, in hESF of women with vs. without endometriosis. Immunohistochemistry demonstrated the highest phospho-ERK1/2 in the late-secretory epithelial and stromal cells in women without disease, in contrast to intense immunostaining in early-secretory epithelial and stromal cells in those with disease. These findings suggest that increased activation of ERK1/2 in endometrial cells from women with endometriosis may be responsible for persistent proliferative changes in secretory-phase endometrium.


J Pediatr Adolesc Gynecol. 2009 Jul 7. [Epub ahead of print]

Endometriosis in a Patient with Mayer-Rokitansky-Küster-Hauser Syndrome and Complete Uterine Agenesis: Evidence to Support the Theory of Coelomic Metaplasia.

Mok-Lin EY, Wolfberg A, Hollinquist H, Laufer MR.

Division of Gynecology, Department of Surgery, Children’s Hospital Boston, Boston, Massachusetts; Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, Massachusetts; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston Massachusetts.

BACKGROUND: There are many hypotheses regarding the pathogenesis of endometriosis. Most theories, including retrograde menstruation, require the existence of a uterine structure and endometrial tissue. We report endometriosis with the absence of a uterus. This finding supports the theory of coelomic metaplasia. CASE: A 20-year-old with Mayer-Rokitansky-Küster-Hauser syndrome presented with increasing pelvic pain and underwent laparoscopy. Uterine, cervical, vaginal, and tubal agenesis was confirmed. Stage I endometriosis was visualized in the posterior cul-de-sac and destroyed. She received medical therapy for 5 years until she represented with pain and underwent another laparoscopy, at which endometriosis was again identified and destroyed. SUMMARY AND CONCLUSION: This case of endometriosis in a patient with complete uterine agenesis supports the theory of coelomic metaplasia.

J Pediatr Adolesc Gynecol. 2009 Oct;22(5):e146-7. Epub 2009 Jul 8.

Adenomyosis in the adolescent population: a case report and review of the literature.

Itam SP 2nd, Ayensu-Coker L, Sanchez J, Zurawin RK, Dietrich JE.

Department of Obstetrics and Gynecology, Division of Pediatric and Adolescent Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.

BACKGROUND: This report presents a rare cause of dysmenorrhea in the adolescent female and the usefulness of magnetic resonance imaging (MRI) with T2 weighted sequence in the identification of adenomyosis. CASE: Two adolescents who presented with persistent pelvic pain in the absence of outflow tract obstruction or biopsy confirmed endometriosis had MRI-findings consistent with adenomyosis. SUMMARY AND CONCLUSION: In the adolescent female presenting with persistent dysmenorrhea, a diagnosis of adenomyosis is rare but should remain a possibility as one considers the differential diagnosis.


J Gynecol Obstet Biol Reprod (Paris). 2009 Sep;38(5):404-10. Epub 2009 Jul 8.

Linguistic adaptation of the endometriosis health profile 5: EHP 5

[Article in French]

Renouvel F, Fauconnier A, Pilkington H, Panel P.

Service de gynécologie-obstétrique, hôpital André-Mignot, 177, rue de Versailles, 78157 Le-Chesnay, France.

OBJECTIVES: The aim of this work was to develop a French version of an English quality of life questionnaire specific of endometriosis: endometriosis health profile 5. MATERIALS AND METHODS: After many translations and reverse translations, we got a first French version of EHP 5. This scale was then distributed in two centres: Poissy and Versailles. This questionnaire was completed by women with endometriosis proven and chronic pain. We studied acceptability and feasibility. RESULTS: Eighteen patients were included. All items have been completed satisfactorily. Our version was described as understandable and easy to complete. CONCLUSION: Our work consisted in developing a French version of EHP 5 which was very well received by the patient. However, the psychometric and clinical validation remains to be done.

Fukuoka Igaku Zasshi. 2009 May;100(5):141-55.

Toxic effects of PCB/PCDF to human observed in Yusho and other poisonings

[Article in Japanese]

Masuda Y.

Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511.

Yusho PCB poisoning occurred in 1968, when the human environment had been polluted with PCBs and related compounds. The causal rice oil was contaminated with large amounts of PCBs and PCDFs by accidental leakage at the rice oil producing Kanemi Company on February 7-15, 1968. Much less concentrations of PCBs were identified in the rice oil produced and shipped from the Company before and after the critical days. Concentration trend of PCBs and TEQ in human body were examined for 40 years from 1968 to present. Concentrations in the blood of heavily exposed Yusho patients and normal Japanese were PCBs : 80 and 1.5 microg/g-fat, and TEQ : 60 and 0.1 ng/g-fat, respectively, in 1969, and decreased to PCBs : 1 and 0.2 microg/g-fat, and TEQ : 0.5 and 0.02 ng/g-fat, respectively, in 2007. PCBs and PCDFs have been persistently retained in human body for 40 years. Serious cases of Yusho and Yucheng having very high PCB, PCDF concentrations in blood have suffered from severe chloracne, pigmentation, eye discharge and others at the first stage and recovered very slowly with a lapse of several years. However, their hormone mediated signs and symptoms, such as high triglyceride and thyroxin levels in serum, disorder of immunoglobulin, goiter, decrease of sperm mobility, disorder of teeth and joints conditions, decrease of IQ score in children, headache and numbness, etc, are persisting for more than 30 years. The residents in East Slovakia who have been exposed to PCBs wasted from a PCB factory and have about 3 times higher blood PCB concentrations than the controls, have suffered from disorder of FT4 and T3 levels in serum, disorder of thyroid grand and thymus, dental defects in enamel developmental, hearing impairment at low frequency tone, tendency to diabetes and others. Residents in the Great Lakes area, USA, whose blood PCB levels are estimated to be higher than other places, have shown disorder of thyroid, T4, TSH levels, endometriosis, joint disorder, and low IQ score in children. The levels of PCBs and PCDFs in the blood of Yusho patients and Controls are compared to the normal levels of estradiol, testosterone and thyroxin. In the blood of Yusho patients, concentrations of single congeners of PCB118, PCB153, PCB156 and PentaCDF are high enough to disturb the hormonal effects. Blood PCB concentrations in normal Japanese are higher than the FT3 and FT4 levels, indicating hormonal disturbance will be easily produced. PCBs are metabolized to produce HO-PCBs, which bind to TTR and retain in blood medium. Blood HO-PCB concentrations in Yusho patients and normal persons are higher than the FT3, FT4 levels in serum. Therefore, the hormonal effects of thyroxin will be disturbed in Yusho and normal persons. As HO-PCB will be easily transferred to fetus through placenta, fetus development will be possible to be disturbed. In Yusho and other cases, PCBs and TEQ (PentaCDF, PCB118 etc) were ingested together and the strong enzyme inducers of PentaCDF and others have metabolized PCBs to HO-PCBs, which have retained in the blood. Complex reactions of PCDFs, PCBs and HO-PCBs have disturbed the hormonal effects and the induced symptoms and diseases would have been caused.

Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007677.

Pentoxifylline versus medical therapies for subfertile women with endometriosis.

Lv D, Song H, Li Y, Clarke J, Shi G.

West China Second University Hospital, Sichuan University, No. 21, Third Part of Ren Min Nan Road, Chengdu, Sichuan, China, 610041.

BACKGROUND: Endometriosis is a chronic, recurring condition that occurs during the reproductive years. It is characterized by endometrial tissue developing outside the uterine cavity. This endometrial tissue development is dependent on estrogen produced primarily by the ovaries and, therefore, traditional management has focused on ovarian suppression. In this review we considered the role of modulation of the immune system as an alternative approach. OBJECTIVES: To determine the effectiveness and safety of pentoxifylline, which has anti-inflammatory effects, in the management of endometriosis in subfertile, premenopausal women. SEARCH STRATEGY: We searched the following databases (from inception to December 2008) for trials: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and PsycINFO. In addition, all reference lists of included trials were searched and experts in the field were contacted in an attempt to locate trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no treatment, medical treatment, or surgery in subfertile, premenopausal women were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data using data extraction forms. We contacted study authors for additional information and data. The domains assessed for risk of bias were sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting. Odds ratios (OR) were used for reporting dichotomous data with 95% confidence intervals (CI), whilst mean differences (MD) were expressed for continuous data. Statistical heterogeneity was assessed using the I(2) statistic. MAIN RESULTS: Four trials involving 334 participants were included. Results showed pentoxifylline had no significant effect on reduction in pain (one RCT, MD -1.60, 95% CI -3.32 to 0.12). There was no evidence of an increase in clinical pregnancy events in the pentoxifylline group compared with placebo (three RCTs, OR 1.54, 95% CI 0.89 to 266). For recurrence of endometriosis, one RCT reported an OR of 0.88 (95% CI 0.27 to 2.84). No trials reported the effects of pentoxifylline on the odds of live birth rate per woman, improvement of endometriosis-related symptoms, or adverse events. AUTHORS’ CONCLUSIONS: There is not enough evidence to support the use of pentoxifylline in the management of premenopausal women with endometriosis in terms of subfertility and relief of pain outcomes.

Cochrane Database Syst Rev. 2009 Jul 8;(3):CD006568.

Chinese herbal medicine for endometriosis.

Flower A, Liu JP, Chen S, Lewith G, Little P.

Complementary Medicine Research Unit , Dept Primary Medical Care, Southampton University, Norlington Gate Farmhouse, Norlington Lane, Ringmer, Sussex, UK, BN8 5SG.

BACKGROUND: Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse. In China, treatment of endometriosis using Chinese herbal medicine (CHM) is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place. OBJECTIVES: To review the effectiveness and safety of CHM in alleviating endometriosis-related pain and infertility. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following English language electronic databases (from their inception to the present): MEDLINE, EMBASE, AMED, CINAHL, NLH on the 30/04/09.We also searched Chinese language electronic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents (CMCC). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving CHM versus placebo, biomedical treatment, another CHM intervention, or CHM plus biomedical treatment versus biomedical treatment were selected. Only trials with confirmed randomisation procedures and laparoscopic diagnosis of endometriosis were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment, and data extraction and analysis were performed independently by three review authors. Data were combined for meta-analysis using relative risk (RR) for dichotomous data. A fixed-effect statistical model was used, where appropriate. Data not suitable for meta-analysis are presented as descriptive data. MAIN RESULTS: Two Chinese RCTs involving 158 women were included in this review. Both these trials described adequate methodology. Neither trial compared CHM with placebo treatment.There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively).Overall, 100% of women in all the groups showed some improvement in their symptoms.Oral plus enema administration of CHM showed a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25; P < 0.01).Combined oral and enema administration of CHM showed a greater improvement, measured as the disappearance or shrinkage of adnexal masses, than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference either between CHM and danazol. AUTHORS’ CONCLUSIONS: Post-surgical administration of CHM may have comparable benefits to gestrinone but with fewer side effects. Oral CHM may have a better overall treatment effect than danazol; it may be more effective in relieving dysmenorrhea and shrinking adnexal masses when used in conjunction with a CHM enema. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis. 


Bibliografia 2009 – Pagina 4

J Thorac Cardiovasc Surg. 2009 Jun 22. [Epub ahead of print]

Endometriosis-related pneumothorax after in vitro fertilization embryo transfer procedure: A case report.

Baisi A, Raveglia F, De Simone M, Calati AM, Leporati A, Cioffi U.

Thoracic Surgery Unit, Ospedale San Paolo, University of Milan, Milano, Italy.

JSLS. 2009 Apr-Jun;13(2):224-5.

Laparoscopic hysterectomy and ileocecal resection for treatment of endometriosis.

Pickron TB, Cooper J.

Colorectal Surgical Associates, Houston, Texas 77054, USA.

Surgical therapy remains the mainstay for the treatment of endometriosis. In this case report, we review the surgical management of a patient who presented with a cecal implant of endometriosis. She was successfully treated with combined laparoscopic hysterectomy and ileocecal resection. The laparoscopic ileocecal resection was completed with an intracorporeal anastomosis and retrieval of the specimen through the vaginal cuff. This presentation demonstrates the feasibility of combined colon resection and hysterectomy as well as vaginal colon specimen extraction. The vagina as a colon specimen retrieval site has significant implications for the future of natural orifice colorectal surgery.

JSLS. 2009 Apr-Jun;13(2):129-34.

Laparoscopic supracervical hysterectomy: a retrospective analysis of 1000 cases.

Bojahr B, Tchartchian G, Ohlinger R.

Klinik für MIC, Minimally Invasive Center, Berlin, Germany.

OBJECTIVE: Laparoscopic supracervical hysterectomy (LASH) was analyzed with regard to surgical indications and outcomes. METHODS: This is a retrospective analysis of the first 1,000 consecutive laparoscopic supracervical hysterectomies performed by one gynecologist from September 1, 2002 to April 30, 2006. The objective of the study was to find out to what extent the indication and the outcome of surgery changed with the increase in experience of the surgeon and whether a learning curve could be established based on the results. The demographic patient data, indication for surgery, patient history with regard to previous surgery, duration of surgery, intraoperative complications, uterus weight, and length of in-patient stay were collected from the medical records. RESULTS: The main indication in 80.4% of cases was uterus myomatosis. The median duration of surgery was 70.9+/-26.3 minutes (95% CI, 69.2 to 72.5) with an average uterus weight of 212.5+/-177.0g (95% CI, 201 to 223.6). This was reduced from 85.4+/-25.9 minutes (95% CI, 78.5 to 92.3) in 2002 to 72.4+/-30.1 minutes (95% CI, 66.7 to 78.2) in 2006, in conjunction with an increase in average uterus weight from 192.3+/-145.4g (95% CI, 153.8 to 230.9) to 228.7+/-160.3g (95% CI, 198.1 to 259.3). Overall, one intraoperative lesion of the bladder (0.1%) occurred, and in 4 cases the surgeon had to convert to laparotomy instead, due to the size and immobility of the uterus. Sixty-eight patients had a uterus weight of more than 500 g. In 67% of the cases, surgery was performed on patients with at least one previous laparotomy, and 51.4% of the patients required further interventions. CONCLUSION: An experienced surgeon can rapidly learn the technique of laparoscopic supracervical hysterectomy and can safely perform it. In patients with symptomatic uterine myomatosis, previous laparotomy and/or with a uterine weight of more than 500g, laparoscopic supracervical hysterectomy is a useful alternative to total hysterectomy. There are few complications if preservation of the cervix is not contraindicated.

Acta Obstet Gynecol Scand. 2009;88(9):968-75.

Endometriosis-associated nerve fibers and pain.

Medina MG, Lebovic DI.

Department of Obstetrics and Gynecology, University of Michigan, 600 Highland Avenue, Ann Arbor, MI 57392, USA.

The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently, investigators have revealed specific nerve fibers present in endometriotic tissue, with existing parallels between density and pain severity. The aim of this review is to compile a comprehensive review of existing literature on endometriosis-related nerve fiber detection, and the effects of medical therapy on these neural fibers. We performed a systematic literature-based review using Medline and PubMed of nerve fibers detected in eutopic endometrium, endometriotic lesions, and the peritoneum. Various arrangements of significant medical terms and phrases consisting of endometriosis, pelvic pain, nerve fiber detection/density in endometriosis, and diagnoses methodology, including treatment and detection were applied in the search. Subsequent references used were cross-matched with existing sources to compile all additional similar reports. Similar nerve fibers were detected within lesions, endometrium, and myometrium, though at varying degrees of density. Hormonal therapy is widely used to treat endometriosis and was shown to be related to a reduction in fiber density. A direct result of specific nerve fiber detection within eutopic endometrial layers points to the use of a minimally invasive endometrial biopsy technique in reducing delay in diagnosis and subsequent possible preservation of fertility.

Virchows Arch. 2009 Sep;455(3):261-70. Epub 2009 Aug 5.

An allelotype analysis indicating the presence of two distinct ovarian clear-cell carcinogenic pathways: endometriosis-associated pathway vs. clear-cell adenofibroma-associated pathway.

Yamamoto S, Tsuda H, Suzuki K, Takano M, Tamai S, Matsubara O.

Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Patterns of allele loss (loss of heterozygosity (LOH)) were studied to identify the genetic backgrounds underlying the two putative carcinogenic pathways of ovarian clear-cell adenocarcinoma: carcinomas thought to arise in endometriosis (endometriosis-associated carcinomas, 20 cases) and carcinomas thought to be derived from clear-cell adenofibroma ((CCAF)-associated carcinomas, 14 cases). Each tumor was assessed for LOH at 24 polymorphic loci located on 12 chromosomal arms: 1p, 3p, 5q, 8p, 9p, 10q, 11q, 13q, 17p, 17q, 19p, and 22q. For all informative loci, the frequency of LOH was not statistically different between the two carcinoma groups: 38% (66/172 loci) in the endometriosis-associated carcinomas and 35% (40/113 loci) in the CCAF-associated carcinomas. In the endometriosis-associated carcinomas, LOH was detected at high frequencies (>50%) at 3p, 5q, and 11q and at low frequencies (<20%) at 8p, 13q, and 17p. In the CCAF-associated carcinomas, LOH was detected at high frequencies at 1p, 10q, and 13q and at low frequencies at 3p, 9p, 11q, and 17q. The frequencies of LOH at chromosomes 3p, 5q, and 11q were significantly higher in the endometriosis-associated carcinomas than in the CCAF-associated carcinomas (P = 0.026, 0.007, and 0.011, respectively). Immunohistochemical analysis demonstrated a close association between the allelic status of the 3p25-26 locus and levels of von Hippel-Lindau (VHL) protein expression (P = 0.0026). These data further support the presence of two distinct carcinogenic pathways to ovarian clear-cell adenocarcinoma; the allelic status of the 3p, 5q, and 11q loci may provide a means to identify the precursor lesions of these carcinomas.

J Korean Med Sci. 2009 Aug;24(4):767-71. Epub 2009 Jul 30.

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix: a case report.

Park HM, Lee SS, Eom DW, Kang GH, Yi SW, Sohn WS.

Department of Obstetrics and Gynecology, Gangneung Asan Hospital, University of Ulsan, Gangneung, Korea.

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix is rare in premenopausal woman. We describe here a patient with this condition and review the clinical and pathological features of these tumors. A 48-yr-old woman complaining of severe dysmenorrhea was referred for investigation of a pelvic mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological examination revealed an endometrioid adenocarcinoma directly adjacent to the endometriosis at the uterine cervix, with a transition observed between endometriosis and endometrioid adenocarcinoma. The patient was diagnosed as having endometrioid adenocarcinoma arising from endometriosis of the uterine cervix and underwent postoperative chemotherapy. Gynecologists and pathologists should be aware of the difficulties associated with a delay in diagnosis of endometrioid adenocarcinoma arising from endometriosis when the tumor presents as a benign looking endometrioma.

Environ Health Perspect. 2009 Jul;117(7):1070-5. Epub 2009 Mar 31.

Endometriosis and organochlorinated environmental pollutants: a case-control study on Italian women of reproductive age.

Porpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, Ferro A, Ingelido AM, Maggi A, Panici PB, De Felip E.

Department of Gynaecology and Obstetrics, Sapienza University of Rome, Rome, Italy.

BACKGROUND: Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. OBJECTIVE: We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. METHODS: We conducted a case-control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p’-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. RESULTS: We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61-8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60-8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01-11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41-8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25-14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. CONCLUSIONS: The results of this study show that an association exists between increased PCB and p,p’-DDE serum concentrations and the risk of endometriosis.

N Z Med J. 2009 Jun 5;122(1296):69-72.

Medical image. An unusual case of inguinal pain.

Sakowska MM, Short J, Eglinton T.

Department of Surgery, Christchurch Hospital, Christchurch, New Zealand.

Mol Hum Reprod. 2009 Oct;15(10):587-607. Epub 2009 Aug 3.

Epigenetics of endometriosis.

Guo SW.

Institute of Obstetric and Gynecologic Research, and Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.

Endometriosis is a common gynecologic disorder with an enigmatic etiopathogenesis. Although it has been proposed that endometriosis is a hormonal disease, an autoimmune disease, a genetic disease, and a disease caused by exposure to environmental toxins, our understanding of its etiopathogenesis is still inadequate, as reflected by recent apparent setbacks in clinical trials on endometriosis. In the last 5 years, evidence has emerged that endometriosis may be an epigenetic disease. In this article, the evidence in support of this hypothesis is reviewed, and its diagnostic, therapeutic and prognostic implications discussed. Publications, up to the end of June 2009, pertaining to epigenetic aberration in endometriosis were identified through PubMed. In addition, publications on related studies were also retrieved and reviewed. Epigenetics appears to be a common denominator for hormonal and immunological aberrations in endometriosis. Epigenetics also appears to have a better explanatory power than genetics. There is accumulating evidence that various epigenetic aberrations exist in endometriosis. In vitro studies show that histone deacetylase inhibitors may be promising therapeutics for treating endometriosis. In conclusion, several lines of evidence suggest that epigenetics plays a definite role in the pathogenesis and pathophysiology of endometriosis. As such, endometriosis is possibly treatable by rectifying epigenetic aberrations through pharmacological means. DNA methylation markers may also be useful for diagnostic and prognostic purposes. It is also possible that the delineation of the epigenetic changes accompanied by the genesis and progression of endometriosis could lead to interventions that reduce the risk of developing endometriosis.

Rev Port Pneumol. 2009 Sep-Oct;15(5):937-41.

Spontaneous hemothorax in a neurofibromatosis type I patient – a case report

[Article in Portuguese]

Bento A, Gonçalves AP.

Unidade de Saúde Local EPE, Guarda, Serviço de Pneumologia, 6300 Guarda.

Spontaneous hemothorax is a rare and potentially lethal neurofibromatosis’ complication. Several pathological mechanisms may explain the associated vasculopathy: a) direct vascular invasion from adjacent tumors such as Shwannoma, neurofibroma or neurofibrosarcoma; b) vascular dysplasia with stenotic or aneurysm formation. Other mechanisms involved may include pleuropulmonar pathologies (necrotizing infections, pulmonary embolism, endometriosis, neoplasms) and blood dyscrasias. The authors describe a case of a 33 years old female, who went to the ER Service complaining with right persistent hemithoracic pain, extending to the ipsilateral shoulder and shoulder blade, without aggravation or relieving factors, since the last 8 days.

Fertil Steril. 2009 Oct;92(4):1496.e5-8. Epub 2009 Jul 31.

Endometriosis in two sisters with Glanzmann’s thrombasthenia.

Alatas E, Oztekin O, Hacioglu SK.

Department of Obstetrics and Gynecology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.

OBJECTIVE: To present two cases of endometriosis in patients with Glanzmann’s thrombasthenia (GT) and discuss the underlying pathophysiology of endometriosis. DESIGN: Case report. SETTING: Gynecology practice in a university teaching hospital. PATIENT(S): Two sisters, aged 24 and 28 years, previously diagnosed as having GT. INTERVENTION(S): Surgical exploration. MAIN OUTCOME MEASURE(S): Pathologic examination of surgical specimens was performed. RESULT(S): A diagnosis of endometriosis was confirmed pathologically for two sisters previously diagnosed as having GT. CONCLUSION(S): Women with GT seem to represent an important human model of endometriosis from which important data on the pathophysiology of endometriosis can be acquired.

Fertil Steril. 2009 Jul 30. [Epub ahead of print]

Lipopolysaccharide promoted proliferation and invasion of endometriotic stromal cells via induction of cyclooxygenase-2 expression.

Takenaka Y, Taniguchi F, Miyakoda H, Takai E, Terakawa N, Harada T.

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

Lipopolysaccharide-enhanced cyclooxygenase 2 (COX-2) expression and prostaglandin E2 (PGE2) production were compared in endometriotic stromal cells (ESCs) and eutopic endometrial stromal cells. Lipopolysaccharide promotes the proliferation and invasion of ESCs via up-regulation of COX-2 and PGE2 expression, suggesting that pelvic inflammation may promote the progression of endometriosis.

J Pediatr Adolesc Gynecol. 2009 Aug;22(4):257-63.

The effect of combined surgical-medical intervention on the progression of endometriosis in an adolescent and young adult population.

Doyle JO, Missmer SA, Laufer MR.

Division of Gynecology, Children’s Hospital Boston, Boston, Massachusetts, USA.

STUDY OBJECTIVE: To evaluate the effect of combined surgical-medical treatment on endometriosis progression in adolescents as measured by disease stage. DESIGN: Retrospective chart review. SETTING: Two academic medical centers. PARTICIPANTS: Sequential cases of young women identified on chart review with chronic pelvic pain unresponsive to dysmenorrheal treatment who underwent initial laparoscopy for diagnosis and surgical destruction of endometriosis. All patients were then treated with standard continuous medical therapy. Patients with exacerbation of pain on anti-endometriosis medical therapy who elected a subsequent laparoscopic procedure were eligible for this study. INTERVENTION: Retrospective chart review MAIN OUTCOME MEASURES: Endometriosis stage and adhesions at subsequent laparoscopy as compared to the initial surgical procedure. RESULTS: 90 patients met inclusion criteria. Eligible patients were 12 to 24 years of age at the time of the initial laparoscopy. The median endometriosis stage at first and second laparoscopy was I. No stage change was observed in 70% of patients, 19% improved by one stage, 1% improved by two stages, and 10% worsened by one stage. Regardless of initial stage, a trend toward disease progression was not observed. There was a significant likelihood for stage improvement at second laparoscopy, with those initially diagnosed as stage II or III most likely to exhibit improvement. CONCLUSIONS: Based on the concept that endometriosis can be progressive, these data suggest that combined surgical-medical management retards disease progression in adolescents and young adults.

Fertil Steril. 2009 Aug;92(2):e21-2; author reply e23.

Comment on:

Fertil Steril. 2009 Jul;92(1):75-87.

Endometrioma and IVF outcome-how little we really know.

Nicopoullos JD, Nikolaou D, Richardson R.


J Obstet Gynaecol Can. 2009 Jun;31(6):538-41.

Malignant chest wall endometriosis: a case report and literature review.

Agrawal A, Nation J, Ghatage P, Chu P, Ross S, Magliocco A.

Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, University of Calgary, Calgary AB.

BACKGROUND: Endometriosis usually affects women in their reproductive years. Most commonly, the pelvic organs are involved. Involvement of the chest wall after hysterectomy is rare. The incidence of malignant transformation is less than 1% for ovarian endometriosis, but is unknown for extraovarian endometriosis. CASE: A 47-year-old woman who had undergone hysterectomy and bilateral salpingo-oophorectomy for endometriosis presented four years after surgery with a well-differentiated endometrioid adenocarcinoma arising in the background of endometriosis in the right chest wall. The tumour was resected, and the patient received six courses of adjuvant chemotherapy. CONCLUSION: Women with endometriosis-associated cancer require individualized management options, depending upon the histopathology and stage of the cancer.

Arch Gynecol Obstet. 2009 Oct;280(4):529-38. Epub 2009 Jul 31.

The pathophysiology of endometriosis and adenomyosis: tissue injury and repair.

Leyendecker G, Wildt L, Mall G.

Kinderwunschzentrum (Fertility Center) Darmstadt, Bratustrasse 9, 64295, Darmstadt, Germany.

INTRODUCTION: This study presents a unifying concept of the pathophysiology of endometriosis and adenomyosis. In particular, a physiological model is proposed that provides a comprehensive explanation of the local production of estrogen at the level of ectopic endometrial lesions and the endometrium of women affected with the disease. METHODS: In women suffering from endometriosis and adenomyosis and in normal controls, a critical analysis of uterine morphology and function was performed using immunohistochemistry, MRI, hysterosalpingoscintigraphy, videohysterosonography, molecular biology as well as clinical aspects. The relevant molecular biologic aspects were compared to those of tissue injury and repair (TIAR) mechanisms reported in literature. RESULTS AND CONCLUSIONS: Circumstantial evidence suggests that endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatizations with the activation of the mechanism of ’tissue injury and repair’ (TIAR). This results in the local production of estrogen. With ongoing peristaltic activity, such sites might increase and the increasingly produced estrogens interfere in a paracrine fashion with the ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt auto-traumatization of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis. In late premenopausal adenomyosis, such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life leads to the same extent of microtraumatization. With the activation of the TIAR mechanism followed by infiltrative growth and chronic inflammation, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principle the same pathophysiology. In conclusion, endometriosis and adenomyosis result from the physiological mechanism of ’tissue injury and repair’ (TIAR) involving local estrogen production in an estrogen-sensitive environment normally controlled by the ovary.

J Ultrasound Med. 2009 Aug;28(8):1061-6.

Three-dimensional sonographic characteristics of deep endometriosis.

Guerriero S, Alcázar JL, Ajossa S, Pilloni M, Melis GB.

Department of Obstetrics and Gynecology, University of Cagliari, Ospedale San Giovanni di Dio, Via Ospedale 46, 09124 Cagliari, Italy.

OBJECTIVE: The purpose of this presentation is to investigate the potential role of 3-dimensional (3D) sonography in the assessment of deep endometriosis. METHODS: Cases of deep endometriosis are presented to illustrate the spectrum of appearances obtained with 3D sonography. In addition, we evaluate the possible role of other functions included in 3D equipment, such as the niche mode and tomographic ultrasound imaging (TUI). RESULTS: Three-dimensional image rendering could allow a good analysis of the endometriotic nodule; in fact, in all presented cases, this reconstruction seems to clearly show the irregular shapes and borders of the lesions. This technique allows unrestricted access to an infinite number of viewing planes, which can be very useful for correctly locating lesions within the pelvis and evaluating the relationship with other organs. The stored 3D volumes can be reassessed and compared by the same or different examiners over time. This characteristic may be relevant for monitoring the effect of medical therapies over time. In the niche mode, sonographic imaging is represented as a “cut-open” view of the internal aspect of the nodule and its surrounding tissue. This additional function, which is associated with TUI, could be particularly useful for evaluation of the extension of a nodule in the rectovaginal septum, the depth of infiltration, and the relationship with the rectosigmoid junction or ureter. CONCLUSIONS: In the near future, 3D sonography in deep infiltrating endometriosis could be an interesting mode of research with positive effects in everyday clinical practice.

Fertil Steril. 2009 Jul 29. [Epub ahead of print]

The molecular signature of endometriosis-associated endometrioid ovarian cancer differs significantly from endometriosis-independent endometrioid ovarian cancer.

Banz C, Ungethuem U, Kuban RJ, Diedrich K, Lengyel E, Hornung D.

Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

OBJECTIVE: To determine whether endometriosis-associated endometrioid cancer (EAOC) is a specific entity compared with endometrioid cancer not associated with endometriosis (OC). DESIGN: Case-control study. SETTING: University hospital research laboratory. PATIENT(S): Seven patients with endometriosis-associated ovarian cancer EAOC and five patients each with OC, ovarian endometriosis, and benign ovaries. INTERVENTION(S): Ovarian tissue samples were collected from surgical procedures. MAIN OUTCOME MEASURE(S): We hybridized cRNA samples to the Affymetrix HG-U133A microarray chip. Representative genes were validated by real time polymerase chain reaction. RESULT(S): We identified two main groups of genes: The first group contained the genes SICA2, CCL14, and TDGF1. These genes were equally regulated in endometriosis and EAOC but not in OC and benign ovaries. The second group contained the genes StAR, SPINT1, Keratin 8, FoxM1B, FOLR1, CRABP1, and Claudin 7. They were equally regulated in EAOC and OC but not in ovarian endometriosis and benign ovaries. CONCLUSION(S): That the first group is composed of the cytokines SICA2 and CCL14 and the growth factor TDGF1 indicates that the regulation of the autoimmune system and of inflammatory cytokines may be very important in the etiology of endometriosis and EAOC. That the second group is composed of genes that play a central role in cell-cell interaction, differentiation, and cell proliferation indicates that they may be important in the development of ovarian cancer in women with endometriosis.

Fertil Steril. 2009 Jul 29. [Epub ahead of print]

Understanding adenomyosis: a case control study.

Taran FA, Weaver AL, Coddington CC, Stewart EA.

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota.

OBJECTIVE: To elucidate the clinical profile of adenomyosis by comparison with uterine leiomyomas. DESIGN: Retrospective case-control study. SETTING: Academic medical center. PATIENT(S): The study comprised 76 women undergoing hysterectomy with adenomyosis and 152 women with uterine leiomyomas but no adenomyosis. INTERVENTION(S): Retrospective medical record review of hospital and ambulatory records. MAIN OUTCOME MEASURE(S): Comparison of women undergoing hysterectomy with a sole pathologic finding of adenomyosis and women with leiomyomas alone. RESULT(S): Adenomyosis was independently associated with younger age (41.1 years vs. 44.3 years), history of depression (57.1% vs. 24.7%), dysmenorrhea (65.7% vs. 42.3%), and pelvic pain (52.9% vs. 21.1%) in a multivariable unconditional logistic regression analysis compared with women with leiomyomas, where women from both groups had gynecologic symptoms. Furthermore, in a second multivariate model where all subjects had uteri weighing >150 g, women with adenomyosis were more likely to have a history of depression (52.6% vs. 22.2%) and endometriosis (26.3% vs. 2.8%) compared with women with leiomyomas. CONCLUSION(S): Women undergoing hysterectomy with a histologic diagnosis of adenomyosis have a distinct symptomatology and medical history compared with women with leiomyomas. Better understanding of this disease is required to improve diagnosis and management.


Fertil Steril. 2009 Jul 29. [Epub ahead of print]

Simvastatin inhibits the proliferation and the contractility of human endometriotic stromal cells: a promising agent for the treatment of endometriosis.

Nasu K, Yuge A, Tsuno A, Narahara H.

Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan.

Simvastatin significantly inhibited the proliferation of endometriotic stromal cells, attenuated the collagen gel contraction mediated by these cells, and suppressed endometriotic stromal cell attachment to collagen fibers. Simvastatin is considered to be a promising agent for the treatment of endometriosis-associated fibrosis, which is among the major pathologies caused by endometriosis.


Ginekol Pol. 2009 Jun;80(6):453-5.

Tumour in the ureter stump 13 years after nephrectomy–a rare case of endometriosis

[Article in Polish]

Bortnowski L, Zabkowski T, Syryło T, Piotrowicz G, Zieliński H.

Klinika Urologii Wojskowego Instytutu Medycznego w Warszawie.

Endometriosis is found in the urinary tract in 1-2% of women suffering from this disease. The most common site is urinary bladder (81%). In the ureter it is found in only 15% of cases and it mainly involves the pelvic part. The authors present a case of 49-year old woman who was diagnosed with an endometriotic tumour in the stump of the ureter, 13 years after left nephrectomy performed for hydronephrosis and lack of the kidney’s function confirmed in renal scintigraphy. After laser ablation and hormonal therapy the tumour burden was diminished and symptoms resolved.

Ginekol Pol. 2009 Jun;80(6):419-23.

Concetration of anticardiolipin antybodies in peritonel fluid and in fluid from lymphocytes culture in women with endometriosis

[Article in Polish]

Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z, Switała J, Jaśniok E.

Katedra i Zakład Immunologii i Serologii, Slaski Uniwersytet Medyczny w Katowicach.

AIM: The aim of our work was to study both the concentration of anticardiolipin antibodies (aCL) in peritoneal fluid in women with endometriosis and to examine peritoneal lymphocyte ability to produce anticardiolipin antibodies. MATERIAL AND METHODS: Study group included 30 women with endometriosis. The clinical stages of the disease were assessed by the revised American Fertility Society (rAFS) classification. Reference group included fifteen healthy women, with excluded endometriosis and other pathological disorders within the pelvis. The concentration of aCL in the peritoneal fluid and in fluid from lymphocyte culture was measured by enzyme-linked immunosorbent ELISA assay. RESULTS: Statistical analysis showed significantly increased mean concentration of aCL in peritoneal fluid in women with endometriosis compared to women from the reference group (p<0.0001). The concentration of aCL in fluid from lymphocyte culture was also significantly higher in samples from women with endometriosis than from the reference group (p<0.0001). The highest mean levels of aCL in peritoneal fluid and in fluid from lymphocyte culture were observed in samples from women with stage I of the disease. CONCLUSIONS: An increased level of anticardiolipin antibodies in peritoneal fluid in women with endometriosis and increased antibodies production by lymphocytes may suggest an impairment of humoral immunity and its intensification in the early stages of the disease.

Ginekol Pol. 2009 Jun;80(6):414-8.

Lack of varied endometrial expression of proprotein convertase 6 in infertile women with minimal grade endometriosis and idiopathic infertility.

Mikołajczyk M, Wirstlein P, Skrzypczak J.

Department of Obstetrics, Gynecology and Gynecological Oncology, Division of Reproduction, K. Marcinkowski Medical University, Poznan, Poland.

OBJECTIVE: Proprotein convertase 6 (PC6) is known to be the key enzyme involved in the transformation of many hormones, cytokines and their receptors into their active forms. Experimental in vitro studies have also proven that lack of PC6 in the endometrium prevents decidualisation. Therefore in our study we have aimed at determining whether infertility in some patients might be attributable to decreased expression of PC6. MATERIAL AND METHODS: With the use of RealTime PCR we have studied the expression level of PC6 in receptive phase endometria from 36 idiopathic infertile patients, 26 infertile patients with minimal grade endometriosis and compared those results with fertile, age-matched controls. The endometria were collected 7-9 days after ovulation. RESULTS: There were no statistically significant differences regarding the expression of PC6 in endometria from patients with idiopathic infertility, infertile patients with endometriosis and controls. CONCLUSIONS: Since there is no detectable difference in PC6 expression, the decreased expression of PC6 is unlikely to cause infertility.


Ceska Gynekol. 2009 Jun;74(3):236-9.

Rectal duplication cyst–case report

[Article in Czech]

Turyna R, Horák L, Kucera E, Hejda V, Krofta L, Feyereisl J.

Ustav pro péci o matku a díte, Praha.

OBJECTIVE: The authors demonstrate a rare case of duplication anomaly of the rectum. DESIGN: Case report. SETTING: Institute for the Care of Mother and Child, Prague. SUBJECT AND METHOD: We present a rare case of cystic rectal duplication in adult, completely removed and histologically confirmed. A literature review was summarized. CONCLUSION: The case was complicated by delay in diagnosis, multiple operations, and by the association with endometriosis, as well. Mentioned anomaly is published in the Czech literature for the very first time.

Ceska Gynekol. 2009 Jun;74(3):188-92.

IgG antibodies against laminin-1 in serum and in peritoneal fluid in patients with decreased fertility

[Article in Czech]

Cervená R, Bibková K, Micanová Z, Sedivá B, Ulcová-Gallová Z.

Gynekologicko-porodnická klinika LF UK a FN Plze.

OBJECTIVE: To study of IgG antibodies against laminin-1 (IgG-a-Ln-1) in patients with decreased fertility, especially with endometriosis and with diagnosis of polycystic ovaries. DESIGN: Prospective study. SETTING: Special Consultation for Immunology of Reproduction and Research Laboratories for Reproductive Immunology, Department of Gynaecology and Obstetrics, Medical School of Charles University and Faculty Hospital, Pilsen. METHODS: Commercial ELISA kits for detection of IgG antibodies against laminin-1 in serum (S) and peritoneal fluid (PF) in 120 patients after diagnostic laparoscopy, and in serum in 277 patients after 2-3 in vitro fertilizations and with diagnosed endometriosis. RESULTS: Only 16 positive results in IgG-a-Ln-1 antibodies (more than 15 IU/ml) were detected in sera and peritoneal fluids in the group of 120 women after laparoscopy. We have not detected any serum IgG-a-Ln-1 positivity in the group of 277 patients after 2-3 unsuccesfull IVF and with anamnestical date about endometriosis together. CONCLUSION: Increased levels of IgG-a-Ln are in particular found in endometriosis II-III and in diagnosis of polycystic ovaries, in female diseases also related to autoimmune process.

Gynecol Obstet Invest. 2009;68(3):167-70. Epub 2009 Jul 30.

Thiazolidinediones as therapy for endometriosis: a case series.

Moravek MB, Ward EA, Lebovic DI.

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

BACKGROUND: Current medical therapies for endometriosis result in delayed conception and have not been shown to provide any fertile benefit subsequent to treatment. Thiazolidinediones (TZDs) do not impede conception and have been shown to reduce endometriotic lesions in animal models; however, no studies have been performed in humans. The aim of this study was to provide preliminary data about the effectiveness of a TZD in treating endometriosis-related pain. METHODS: Case series of women with endometriosis recruited from the University of Michigan as part of an open-label prospective phase 2a clinical trial. Participants were given rosiglitazone, 4 mg daily, for 6 months. Subjective endometriosis symptoms were assessed using a modified Biberoglu and Behrman symptom severity scale and the McGill pain questionnaire. RESULTS: Two of the 3 patients exhibited improvement in severity of symptoms and pain levels with a concurrent decrease in pain medication, while 1 experienced no change. Rosiglitazone was well tolerated by all patients. CONCLUSIONS: Combined with data gathered from studies in rats and nonhuman primates, the results from this study offer positive justification for using TZDs as a well-tolerated treatment for endometriosis that can address pain without impeding ovulation and without the need for add-back therapy.

J Reprod Med. 2009 Jun;54(6):407-10.

Laparoscopic ureteroneocystostomy and vesicopsoas hitch with double ureter for infiltrative endometriosis: a case report.

Nezhat C, Rottenberg H.

Atlanta Center for Minimally Invasive Surgery and Reproductive Medicine, 5555 Peachtree Dunwoody Road, Suite 276, Atlanta, GA 30342, USA.

BACKGROUND: The incidence of congenital anomalies of the ureter is very low, as is the incidence of endometriosis of the ureter. The presence of the 2 conditions together is extremely rare. To our knowledge, this is the first description in the medical literature of a laparoscopic ureteroneocystostomy and vesicopsoas hitch in the setting of a double ureter for the treatment of infiltrative endometriosis. CASE: A 31-year-old multigravid woman with a history of severe endometriosis involving the urogenital tract and complete duplication of the right renal collecting system, as well as a right ureterovaginal fistula, presented for evaluation and surgical consult. The patient underwent laparoscopic ureteroneocystostomy and vesicopsoas hitch for the treatment of infiltrative endometriosis with a double ureter. CONCLUSION: In skilled operative hands, a minimally invasive approach, applying the principles of laparotomy, in the setting of a duplicated renal collecting system is feasible.

J Reprod Med. 2009 Jun;54(6):366-72.

Uterine adenomyosis in persistence of dysmenorrhea after surgical excision of pelvic endometriosis and colorectal resection.

Ferrero S, Camerini G, Menada MV, Biscaldi E, Ragni N, Remorgida V.

Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1, 16132 Genoa, Italy.

OBJECTIVE: To determine whether the presence of uterine adenomyosis may impair the amelioration of pain symptoms after laparoscopic excision of pelvic endometriosis combined with colorectal resection. STUDY DESIGN: This prospective study included 50 women with bowel endometriosis with or without uterine adenomyosis. Presence of uterine adenomyosis was investigated by magnetic resonance imaging. Patients underwent excision of pelvic endometriosis and colorectal resection; some patients with focal adenomyosis underwent uterine surgery. Pain symptoms and gastrointestinal complaints were evaluated before surgery and at 6, 12 and 18 months’ follow-up. RESULTS: At 6-month follow-up, dysmenorrhea significantly improved in women without uterine adenomyosis and in those with adenomyosis that was excised at surgery; this improvement persisted at 18 months’ followup. No significant improvement in dysmenorrhea was observed in women with adenomyosis not excised at surgery. Deep dyspareunia and chronic pelvic pain significantly improved at follow-up in all study groups. Most of gastrointestinal symptoms improved or disappeared at 6 months’ follow-up; the improvement in gastrointestinal function persisted at 18 months’ follow-up. CONCLUSION: Excision of pelvic endometriosis combined with bowel resection significantly improves chronic pelvic pain, dyspareunia and gastrointestinal symptoms; however, the presence of uterine adenomyosis may determine persistence of dysmenorrhea.

J Reprod Med. 2009 Jun;54(6):353-60.

Serum and peritoneal fluid antiendometrial antibodies in assisted reproduction.

Randall GW, Bush S 2nd, Gantt PA.

West Virginia University Physicians of Charleston, Charleston, West Virginia 25302, USA.

OBJECTIVE: To study the impact of surgically verified endometriosis and serum and peritoneal fluid antiendometrial antibodies (AEA) on pregnancy outcomes in gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT) and in vitro fertilization (IVF) patients using assisted reproductive technologies (ART). STUDY DESIGN: Surgical evaluation of endometriosis and collection of serum and peritoneal fluid was performed at the time of laparoscopy. For patients who did not undergo laparoscopy, only serum samples were obtained. Sera and peritoneal fluid were tested by indirect immunofluorescence for AEA. RESULTS: There was no correlation between surgically verified endometriosis, serum or peritoneal fluid AEA and clinical pregnancy in patients undergoing ART. There was no significant difference in surgically verified endometriosis in patients who delivered and those who miscarried (p < 0.0594), whereas serum (p < 0.0223) and peritoneal fluid (p < 0.0032) AEA showed differences. In the total group of 352 ART patients, positive serum AEA was statistically significant in those who miscarried vs. those who delivered (p < 0.0000). CONCLUSION: Endometriosis does not significantly impair the pregnancy potential of ART patients, but it may be associated with miscarriage. The presence of serum and peritoneal fluid AEA correlate better with miscarriage than surgically verified endometriosis.

Gynecol Endocrinol. 2009 Jul 28:1-4. [Epub ahead of print]

Anti muellerian hormone serum levels in women with endometriosis: A case-control study.

Shebl O, Ebner T, Sommergruber M, Sir A, Tews G.


Department of Obstetrics and Gynecology, IVF-Unit, Landesfrauen- und Kinderklinik, Linz, Austria.

Objective. To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis. Design. A case-control study Setting. Women’s General Hospital, Linz, Austria. Patient(s). Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male factor (control group). Interventions. None. Main outcome measures. AMH serum level. Results. Mean AMH serum level was significantly lower in the study than in the control group (2.75 +/- 2.0 ng/ml vs. 3.46 +/- 2.30 ng/ml, p < 0.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group (3.28 +/- 1.93 ng/ml vs. 3.44 +/- 2.06 ng/ml; p = 0.61). A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group (2.38 +/- 1.83 ng/ml vs. 3.58 +/- 2.46 ng/ml; p < 0.0001). Conclusion. Lower AMH serum levels and an association with the severity were found in women with endometriosis. Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation (COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH, especially in women with severe endometriosis.

Gynecol Endocrinol. 2009 Jul 28:1-5. [Epub ahead of print]

Endometriosis and in vitro fertilisation: A review.

Dechaud H, Dechanet C, Brunet C, Reyftmann L, Hamamah S, Hedon B.

Department of OB/GYN and Reproductive Medicine, Faculty of Medicine, University Hospital Arnaud de Villeneuve, France.

This review aims to evaluate whether severe endometriosis has an impact on the outcome of in vitro fertilisation (IVF), whether IVF is associated with specific complications in this context, whether a specific ovarian stimulation protocol is most appropriate, whether the endometrial condition progresses following ovarian stimulation, and whether endometrial cysts pose a specific problem for IVF. In patients with severe endometriosis, IVF represents an effective treatment option for infertility, as a complement to surgery. The prognostic parameters of IVF are identical to those of other patients. However, the risks related to the severity of endometriosis, particularly the risk of ovarian deficiency, need to be considered. Because of this issue, to which endometriosis-related pain often adds, IVF treatment should be initiated as early as possible, using appropriate protocols and after having fully informed the patient about the specific oocytes retrieval-related risks.

Gynecol Endocrinol. 2009 Jul 28:1-7. [Epub ahead of print]

Endometriosis in Italy: From cost estimates to new medical treatment.

Luisi S, Lazzeri L, Ciani V, Petraglia F.

Division of Obstetrics and Gynecology, Department of Pediatrics, Siena, Italy.

Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induced a chronic inflammatory reaction. The data collected from Italy showed that around 3 million women are affected by endoemtriosis and the condition was predominantly found in women of reproductive age (50% of women were in the 29-39 age range), only 25% of women were asymptomatic. The associated symptoms can create an impact in general physical, mental, and social well-being. Endometriosis is associated with severe dysmenorrhea, deep dyspareunia, chronic pelvic pain, ovulation pain, cyclical, or perimenstrual symptoms, with or without abnormal bleeding, infertility, and chronic fatigue. The annual cost for hospital admission can be estimated to be in a total around 54 million euros. The average time for right diagnosis is around 9 years still today and it follows a long and expensive diagnostic search. Therapies can be useful to relieve and sometimes solve the symptoms, encourage fertility, eliminate endometrial lesions, and restore the anatomy of the pelvis. For medical therapy, several different preparations (oral contraceptives, progestogenics, gestrinone, danazol, and GnRHa) and new options (GnRH antagonists, aromatase inhibitors, estrogen receptor beta agoinist, progesterone receptor modulators, angiogenesis inhibitors, and COX-2 selective inhibitors) are available.

Gynecol Endocrinol. 2009 Jul 23:1-6. [Epub ahead of print]

Effect of peritoneal fluid from endometriosis patients on neuroblastoma cells in culture.

Bersinger NA, Brodbeck MH, Jahns B, Mueller MD.

Departments of Obstetrics/Gynaecology and Clinical Research, University of Berne, Berne, Switzerland.

Aim. Endometriosis is often associated with lower abdominal pain, dysmenorrhea, dyspareunia, and chronic pelvic pain. There is no correlation between the extent of endometriosis and the intensity of pain. The mechanism of pain in endometriosis is unknown. The aim of our study was to investigate the influence of peritoneal fluid (PF) from endometriosis patients on cultured neural cells that are the morphological basis of nociception, and to determine whether there was a relationship between the rAFS staging and an elevation of TGF-beta1 production by these cells. Methods. Different human neuroblastoma cell lines were grown to 3/4 confluence and then cultured in presence of PF pooled according to the presence of no, mild, or severe endometriosis. After 6 and 24 h of incubation, the morphological changes were assessed and the metabolic activity was determined. Results. The different cell lines showed strongly varying proliferation and aggregation patterns. The metabolic activity was also varying between cell lines, but no consistently increased cell turnover in the PF when compared with the control medium nor associated to a particular, endometriosis-derived PF pool could be shown. In this experimental setting, we have observed that the cell proliferation in the presence of PF was inhibited, and not enhanced as it might have been expected. Measurement of TGF-beta1 showed higher production rates for this cytokine under exposure to PF than in controls for some but not all tested cell lines, but there was no association with the stage (rAFS) of the disease. Conclusion. The neuronal cell culture model may become a useful tool to investigate the endometriosis-derived pain, but different endpoints and cell lines may have to be introduced.

Gynecol Endocrinol. 2009 Jul 23:1-6. [Epub ahead of print]

Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis.

Scholl B, Bersinger NA, Kuhn A, Mueller MD.

Department of Obstetrics/Gynaecology.

Endometriosis affects 10-20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-alpha (TNF-alpha), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-alpha and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-alpha and glycodelin when compared with the other patients (no or moderate pain). TNF-alpha and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.

Gynecol Endocrinol. 2009 Jul 23:1-4. [Epub ahead of print]

Impact of endometriosis on quality of life: A pilot study.

Oehmke F, Weyand J, Hackethal A, Konrad L, Omwandho C, Tinneberg HR.

Department of Obstetrics and Gynecology, Justus Liebig University of Giessen, Giessen, Germany.

Endometriosis affects 6-10% of women in reproductive age, 35-50% of whom experience pain, infertility or both. Mild cases are managed medically but surgery provides relief to women in pain. However, symptoms recur in 75% of cases within 2 years. We investigated the impact of endometriosis on quality of life among 65 women aged 18-60 years working at a city supermarket in Giessen, Germany. Of the 65 women, 12 had undergone surgeries, 22 had dysmenorrhoea, 24 dyspareunia and 3 were infertile. Of the 22 women with dysmenorrhoea, 10 had difficulties performing gardening, housework, sports and leisure activities. Five of these 10 women experienced social isolation, 6 professional setbacks; 6 declined efficiency at work and 3 had taken time off work. Of the 24 women with dyspareunia, 7 experienced minimal, 12 light and 5 moderate to strong pain. Only 16 of these 24 women discussed the problem with their partners. This study demonstrates that pain is a major cause of physical, psycho-social, emotional and professional or work related impairment among women with endometriosis. Because endometriosis is likely to impose emotional and financial burdens, we suggest that future studies should be extended to include interviews with family members.

Histopathology. 2009 Jun;54(7):907-12.

Immunohistochemical localization of tyrosine receptor kinases A and B in endometriosis-associated ovarian cancer.

Foster WG, Elias R, Faghih M, Dominguez MA, Elit L, Boutross-Tadross O.

Anal Quant Cytol Histol. 2009 Jun;31(3):170-6.

Endometriosis and other benign and malignant müllerian lesions in pelvic and extrapelvic organs.

Lambrinoudaki I, Augoulea A, Creatsa M, Vlachos N, Christodoulakos G, Papadias C.

Second Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece.

OBJECTIVE: To conduct a retrospective study on case reports found in literature across the world on benign müllerian lesions of the urogenital tract and on cases of malignant transformation from müllerian duct remnants in order to better understand these rare anatomopathologic entities and to avoid overdiagnosis and overtreatment. STUDY DESIGN: We reviewed a number of case reports on benign and malignant müllerian lesions and compared the developments associated with endometriosis, endosalpingiosis and endocervicosis. RESULTS: Our sampling of case reports confirm the suggestion that both malignant neoplasms and benign müllerian lesions can arise in foci of endometriosis in both pelvic and extrapelvic sites. CONCLUSION: The development of malignant tumors is a well-known complication of endometriosis and endosalpingiosis, but data about endocervicosis are unclear.

Vet Rec. 2009 Jul 25;165(4):102-6.

Effects of the administration of ketoprofen at parturition on the milk yield and fertility of Holstein-Friesian cattle.

Richards BD, Black DH, Christley RM, Royal MD, Smith RF, Dobson H.

Paragon Veterinary Group, Townhead Road, Dalston, Cumbria.

A total of 220 cows and heifers were treated with 3 mg/kg ketoprofen immediately after calving and 24 hours later, and 227 were left untreated as controls. The treated animals tended to have a lower incidence of retained fetal membranes and were 1.7 times less likely to develop the condition than the untreated animals. The treatment did not affect the incidence of milk fever, the endometritis score or the presence of a corpus luteum by 20 to 25 days after calving, and did not affect the cows’ early lactation milk yield. There was no particular level of dystocia or periparturient conditions other than retained fetal membranes for which there might be a reproductive or productive advantage following the use of ketoprofen. The intervals from calving to first insemination or to pregnancy, the numbers of inseminations per pregnancy and the pregnancy rate to first insemination were also unaffected by ketoprofen treatment.


Mol Hum Reprod. 2009 Oct;15(10):577-86. Epub 2009 Jul 24.

The non-human primate model of endometriosis: research and implications for fecundity.

Braundmeier AG, Fazleabas AT.

Department of Obstetrics and Gynecology (MC808), College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

The development of an animal model of endometriosis is crucial for the investigation of disease pathogenesis and therapeutic intervention. These models will enhance our ability to evaluate the causes for the subfertility associated with disease and provide a first-line validation of treatment modulators. Currently rodents and non-human primate models have been developed, but each model has their limitations. The aim of this manuscript is to summarize the current findings and theories on the development of endometriosis and disease progression and the effectiveness of therapeutic targets using the experimental induced model of endometriosis in the baboon (Papio anubis). 


Bibliografia 2009 – Pagina 3

Fertil Steril. 2009 Oct;92(4):1497.e9-12. Epub 2009 Aug 22.

Patient with pelvic pains: retroperitoneal fibrosis or pelvic endometriosis? A case report and review of literature.

Pezzuto A, Pomini P, Steinkasserer M, Nardelli GB, Minelli L.

Center for Reproductive Medicine, Department of Obstetrics, Gynecology, and Neonatology, University of Parma, Parma, Italy.

OBJECTIVE: To describe how a hydronephrosis can lead to a difficult differential diagnosis between endometriosis and retroperitoneal fibrosis. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Sacro Cuore Don Calabria General Hospital, Negrar, Verona, Italy. PATIENT(S): The history of a 34-year-old woman revealed the appearance of hydroureteronephrosis on the right side at the 35th week of pregnancy. She had an magnetic resonance imaging scan and was diagnosed with a spread retroperitoneal fibrosis. After 2 months, the patient reported the occurrence of pelvic pain, dyspareunia and dysmenorrhea. She was treated with corticosteroids and tamoxifen with no results. INTERVENTION(S): Laparoscopic surgery. A complete retroperitoneal extirpation was done of an endometriotic nodule of the right broad ligament, near the right ureter (without stenosis). MAIN OUTCOME MEASURE(S): Reduction of pelvic pain. RESULT(S): She noticed an important decrease of pain. CONCLUSION(S): The cause of hydronephrosis could be a physiologic hydroureteronephrosis, which is the most common cause of dilatation of the urinary tract in pregnancy. The pain symptoms of the patients seemed to be linked to endometriosis and not to retroperitoneal fibrosis. Magnetic resonance imaging sometimes does not enable a correct diagnosis between these two pathologies. Fertile women with suspected fibrosis should undergo a diagnostic laparoscopy by an expert surgeon in retroperitoneal surgery.


Med Hypotheses. 2009 Aug 20. [Epub ahead of print]

Induction of a local pseudo-pregnancy for the treatment of endometriosis.

Yuan P, Huang Y, Cheng B, Zhang J, Xin X.

Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi’an, Shaan’xi 710032, China.

As a common cause of chronic pelvic pain, endometriosis affects 10% of women of reproductive age. The most popular strategy for treating endometriosis is pseudo-pregnancy therapy. However, the efficacy of common systemic pseudo-pregnancy therapy is significantly attenuated by poor compliance because of so many side effects. While levonorgestrel-releasing intrauterine systems (LNG-IUS) successfully localize the effect of pseudo-pregnancy to the genital tract in treating endometriosis, it seemed to be insufficient to suppress the ovarian and extragenital endometriosis. We postulate that induction of a local pseudo-pregnancy via progestogen-loaded microsphere in the lesions of endometriosis may provide a more effective treatment with fewer side effects.

Soc Sci Med. 2009 Oct;69(8):1220-7. Epub 2009 Aug 21.

The etiquette of endometriosis: stigmatisation, menstrual concealment and the diagnostic delay.

Seear K.

Monash University, Sociology, School of Political and Social Inquiry, Victoria 3800, Australia.

Endometriosis is a chronic gynaecological condition of uncertain aetiology characterised by menstrual irregularities. Several studies have previously identified a lengthy delay experienced by patients between the first onset of symptoms and eventual diagnosis. Various explanations have been advanced for the diagnostic delay, with both doctors and women being implicated. Such explanations include that doctors normalise women’s menstrual pain and that women might delay in seeking medical advice because they have difficulty distinguishing between ‘normal’ and ‘abnormal’ menstruation. It has been suggested that the diagnostic delay could be reduced if women were trained in how to distinguish between ‘normal’ and ‘abnormal’ menstrual cycles. In this paper I argue that whilst these may be factors in the diagnostic delay, women’s reluctance to disclose problems associated with their menstrual cycle may be a more significant and hitherto neglected factor. I argue women are reluctant to disclose menstrual irregularities because menstruation is a ‘discrediting attribute’ (Goffman, 1963) and disclosure renders women vulnerable to stigmatisation. Women actively conceal their menstrual irregularities through practices of the ‘menstrual etiquette’ (Laws, 1990) which involves the strategic concealment of menstrual problems. This argument is supported through an analysis of the experiences of 20 Australian women diagnosed with endometriosis. The ramifications of this analysis for chronic pain conditions more generally and for practical strategies designed to address the endometriosis diagnostic delay are considered.

Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):415-8.

Bowel resection for severe endometriosis: an Australian series of 177 cases.

Wills HJ, Reid GD, Cooper MJ, Tsaltas J, Morgan M, Woods RJ.

Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

BACKGROUND: Colorectal resection for severe endometriosis has been increasingly described in the literature over the last 20 years. AIMS: To describe the experiences of three gynaecological surgeons who perform radical surgery for colorectal endometriosis. METHODS: The records of three surgeons were reviewed. Relevant information was extracted and complied into a database. RESULTS: One hundred and seventy-seven women were identified as having undergone surgery between February 1997 and October 2007. The primary reason for presentation was pain in the majority of women (79%). Eighty-one segmental resections were performed, 71 disc excisions, ten appendicectomies and multiple procedures in ten women. The majority of procedures (81.4%) were performed laparoscopically. Histology confirmed the presence of disease in 98.3% of cases. A further 124 procedures to remove other sites of endometriosis were conducted, along with an additional 44 procedures not primarily for endometriosis. A total of 16 unintended events occurred. CONCLUSIONS: Our study adds to the growing body of literature describing colorectal resection for severe endometriosis. Overall, the surgery appeared to be well tolerated, demonstrating the role for this surgery.

Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):411-4.

Relevance of gastrointestinal symptoms in endometriosis.

Maroun P, Cooper MJ, Reid GD, Keirse MJ.

Department of Endogynaecology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

BACKGROUND: Endometriosis commonly presents with a range of symptoms none of which are particularly specific for the condition, often resulting in misdiagnosis or delay in diagnosis. AIM: To investigate gastrointestinal symptoms in women with endometriosis and compare their frequency with that of the classical gynaecological symptoms. METHODS: Systematic exploration of symptoms in a consecutive series of 355 women undergoing operative laparoscopy for suspected endometriosis. RESULTS: Endometriosis was confirmed by histology in 290 women (84.5%). Bowel lesions were present in only 7.6%. Ninety per cent of women had gastrointestinal symptoms, of which bloating was the most common (82.8%), but 71.3% also had other bowel symptoms. All gastrointestinal symptoms were similarly predictive of histologically confirmed endometriosis. Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed. CONCLUSION: Gastrointestinal symptoms are nearly as common as gynaecological symptoms in women with endometriosis and do not necessarily reflect bowel involvement.

Am J Reprod Immunol. 2009 Sep;62(3):187-95.

Plasma C3a-des-Arg levels in women with and without endometriosis.

Fassbender A, D’Hooghe T, Mihalyi A, Kyama C, Simsa P, Lessey BA.

Leuven University Fertility Centre, Department of Obstetrics & Gynecology, University Hospital Gasthuisberg, Leuven, Belgium.

PROBLEM: The lack of a reliable method for early non-invasive detection of endometriosis often results in delayed diagnosis. The aim of this study was to test the hypothesis that the plasma concentration of complement factor C3a (anaphylatoxin) can be used as a non-invasive test in the diagnosis of endometriosis. METHOD OF STUDY: The C3a concentration was analyzed using ELISA in 160 patients with (n = 109) or without (n = 51) endometriosis during menstruation (n = 49), follicular phase (n = 55), and luteal (n = 56) phase. RESULTS: Plasma C3a concentration was comparable between patients with [102 (27-2213) ng/mL] and without [105 (32-2340) ng/mL] (P = 0.84) endometriosis, also when assessed separately during menstruation, follicular phase, and luteal phase. CONCLUSION: We found no difference in C3a levels between women with and without endometriosis and did not confirm our hypothesis that plasma C3a levels can be used as diagnostic test for endometriosis.

Am J Reprod Immunol. 2009 Sep;62(3):128-38.

Effects of peritoneal fluid from endometriosis patients on interferon-gamma-induced protein-10 (CXCL10) and interleukin-8 (CXCL8) released by neutrophils and CD4+ T cells.

Kim JY, Lee DH, Joo JK, Jin JO, Wang JW, Hong YS, Kwak JY, Lee KS.

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

PROBLEM: Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-gamma-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4(+) T cells, and monocytes. METHOD OF STUDY: Neutrophils, CD4(+) T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. RESULTS: The addition of ePF to cultures of CD4(+) T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4(+) T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P < 0.001), CD4(+) T cells (R = 0.93, P < 0.001), and monocytes (R = 0.70, P = 0.01). Moreover, the addition of ePF significantly enhanced the interferon-gamma-induced release of IP-10 by nuetrophils and CD4(+) T cells. CONCLUSION: These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients.

Mol Hum Reprod. 2009 Oct;15(10):625-31. Epub 2009 Aug 19.

MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis.

Burney RO, Hamilton AE, Aghajanova L, Vo KC, Nezhat CN, Lessey BA, Giudice LC.

Division of Reproductive Endocrinology and Infertility, Madigan Army Medical Center, Tacoma, WA, USA.

Endometriosis is a common gynecologic disorder characterized by pain and infertility. In addition to estrogen dependence, progesterone resistance is an emerging feature of this disorder. Specifically, a delayed transition from the proliferative to secretory phase as evidenced by dysregulation of progesterone target genes and maintenance of a proliferative molecular fingerprint in the early secretory endometrium (ESE) has been reported. MicroRNAs (miRNAs) are small noncoding RNAs that collectively represent a novel class of regulators of gene expression. In an effort to investigate further the observed progesterone resistance in the ESE of women with endometriosis, we conducted array-based, global miRNA profiling. We report distinct miRNA expression profiles in the ESE of women with versus without endometriosis in a subset of samples previously used in global gene expression analysis. Specifically, the miR-9 and miR-34 miRNA families evidenced dysregulation. Integration of the miRNA and gene expression profiles provides unique insights into the molecular basis of this enigmatic disorder and, possibly, the regulation of the proliferative phenotype during the early secretory phase of the menstrual cycle in affected women.


Mol Med. 2009 Aug 17. [Epub ahead of print]

Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues.

Forte A, Schettino MT, Finicelli M, Cipollaro M, Colacurci N, Cobellis L, Galderisi U.

Departments of Experimental Medicine.

Endometriosis is a chronic disease characterized by the presence of ectopic endometrial tissue outside of the uterus and with mixed traits of benign and malignant pathology.This study aimed at analysing in endometrial and endometriotic tissues the differential expression of a panel of genes involved in preservation of stemness status and consequently considered as markers of stem cell presence.The expression profiles of a panel of 13 genes (SOX2, SOX15, ERAS, SALL4, OCT4, NANOG, UTF1, DPPA2, BMI1, GDF3, ZFP42, KLF4, TCL1) were analysed by RT-PCR in human endometriotic (n=12) and endometrial samples (n=14). The expression of SALL4 and OCT4 was further analysed by immunohistochemistry.Genes UTF1, TCL1 and ZFP42 showed a trend for higher frequency of expression in endometriosis than in endometrium (p<0.05 for UTF1), while GDF3 showed an higher frequency of expression in endometrial samples. Immunohistochemical analysis revealed that SALL4 was expressed in endometriotic samples but not in endometrium, despite the expression of the corresponding mRNA in both the sample groups.This study highlights a differential expression of stemness-related genes in ectopic and eutopic endometrium and suggests a possible role of SALL4-positive cells in the pathogenesis of endometriosis.

Hum Reprod. 2009 Aug 18. [Epub ahead of print]

Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study.

Al-Jefout M, Dezarnaulds G, Cooper M, Tokushige N, Luscombe GM, Markham R, Fraser IS.

Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, NSW 2006, Australia.

BACKGROUND Diagnosis of endometriosis currently requires a laparoscopy and this need probably contributes to the considerable average delay in diagnosis. We have reported the presence of nerve fibres in the functional layer of endometrium in women with endometriosis, which could be used as a diagnostic test. Our aim was to assess efficacy of nerve fibre detection in endometrial biopsy for making a diagnosis of endometriosis in a double-blind comparison with expert diagnostic laparoscopy. METHODS Endometrial biopsies, with immunohistochemical nerve fibre detection using protein gene product 9.5 as marker, taken from 99 consecutive women presenting with pelvic pain and/or infertility undergoing diagnostic laparoscopy by experienced gynaecologic laparoscopists, were compared with surgical diagnosis. RESULTS In women with laparoscopic diagnosis of endometriosis (n = 64) the mean nerve fibre density in the functional layer of the endometrial biopsy was 2.7 nerve fibres per mm(2) (+/-3.5 SD). Only one woman with endometriosis had no detectable nerve fibres. Six women had endometrial nerve fibres but no active endometriosis seen at laparoscopy. The specificity and sensitivity were 83 and 98%, respectively, positive predictive value was 91% and negative predictive value was 96%. Nerve fibre density did not differ between different menstrual cycle phases. Women with endometriosis and pain symptoms had significantly higher nerve fibre density in comparison with women with infertility but no pain (2.3 and 0.8 nerve fibre per mm(2), respectively, P = 0.005). CONCLUSIONS Endometrial biopsy, with detection of nerve fibres, provided a reliability of diagnosis of endometriosis which is close to the accuracy of laparoscopic assessment by experienced gynaecological laparoscopists. This study was registered with the Australian Clinical Trials Registry (ACTR) 00082242 (registered: 12/12/2007). The study was approved by the Ethics Review Committee (RPAH Zone) of the Sydney South West Area Health Service (Protocol number X05-0345) and The University of Sydney Human Research Ethics Committee (Ref. No. 10761) and all women gave their informed consent for participation.

Hum Reprod. 2009 Aug 18. [Epub ahead of print]

Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis.

Bokor A, Kyama CM, Vercruysse L, Fassbender A, Gevaert O, Vodolazkaia A, De Moor B, Fülöp V, D’Hooghe T.

Experimental Laboratory for Gynaecology, Department of Obstetrics and Gynaecology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.

BACKGROUND The aim of our study was to test the hypothesis that multiple-sensory small-diameter nerve fibres are present in a higher density in endometrium from patients with endometriosis when compared with women with a normal pelvis, enabling the development of a semi-invasive diagnostic test for minimal-mild endometriosis. METHODS Secretory phase endometrium samples (n = 40), obtained from women with laparoscopically/histologically confirmed minimal-mild endometriosis (n = 20) and from women with a normal pelvis (n = 20) were selected from the biobank at the Leuven University Fertility Centre. Immunohistochemistry was performed to localize neural markers for sensory C, Adelta, adrenergic and cholinergic nerve fibres in the functional layer of the endometrium. Sections were immunostained with anti-human protein gene product 9.5 (PGP9.5), anti-neurofilament protein, anti-substance P (SP), anti-vasoactive intestinal peptide (VIP), anti-neuropeptide Y and anti-calcitonine gene-related polypeptide. Statistical analysis was done using the Mann-Whitney U-test, receiver operator characteristic analysis, stepwise logistic regression and least-squares support vector machines. RESULTS The density of small nerve fibres was approximately 14 times higher in endometrium from patients with minimal-mild endometriosis (1.96 +/- 2.73) when compared with women with a normal pelvis (0.14 +/- 0.46, P < 0.0001). CONCLUSIONS The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal-mild endometriosis with 95% sensitivity, 100% specificity and 97.5% accuracy. To confirm our findings, prospective studies are required.


Aust N Z J Public Health. 2009 Aug;33(4):358-64.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women’s Health.

Herbert DL, Lucke JC, Dobson AJ.

School of Population Health, The University of Queensland.

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women’s Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Clin Exp Obstet Gynecol. 2009;36(2):123-5.

Successful long-term management of adenomyosis associated with deep thrombosis by low-dose gonadotropin-releasing hormone agonist therapy.

Akira S, Iwasaki N, Ichikawa M, Mine K, Kuwabara Y, Takeshita T, Tajima H.

Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.

We report the case of a patient with adenomyosis complicated by deep vein thrombosis in whom low-dose gonadotropin-releasing hormone agonist (GnRHa) therapy was useful as a uterus-conserving therapeutic option. The patient was a 34-year-old nulliparous woman who presented with edema and pain in the left lower leg. The patient had been treated with four cycles of GnRHa therapy for adenomyosis and repeatedly experienced chronic pelvic pain, dysmenorrhea and anemia due to hypermenorrhea. Leg venography confirmed deep vein thrombosis, and thrombolytic therapy was performed to eliminate symptoms. Because the patient strongly wanted to conserve the uterus, low-dose GnRHa therapy was initiated. The patient is currently taking 450 microg/day buserelin acetate nasally (regular dose: 900 microg/day), and estradiol levels have been maintained at 24-50 pg/ml. Anemia, leg numbness and chronic pelvic pain have dissipated, and the patient has not experienced estrogen deficiency symptoms for more than two years.

Hum Reprod. 2009 Aug 17. [Epub ahead of print]

Combating endometriosis by blocking proteasome and nuclear factor-{kappa}B pathways.

Cvek B.

Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Olomouc, Czech Republic.


Mol Hum Reprod. 2009 Oct;15(10):653-63. Epub 2009 Aug 14.

Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro.

Zhang H, Li M, Zheng X, Sun Y, Wen Z, Zhao X.

Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, People’s Republic of China.

In normal endometrium, stromal factors regulate the growth of epithelial cells. However, epithelial cells in endometriotic lesions display increased proliferation and decreased apoptosis. This work tested the hypothesis that in endometriosis stromal cells lose the ability to regulate survival signaling and cell growth in epithelial cells. Primary normal, endometriotic eutopic and ectopic epithelial cells were cultured in the presence of medium conditioned by normal, eutopic and ectopic endometriotic endometrial stromal cells. Endometriotic epithelial cells showed higher Survivin expression than normal epithelial cells. Conditioned medium (CM) from normal or eutopic endometriotic stromal cells significantly inhibited the Survivin expression and AKt phosphorylation in normal or eutopic endometriotic epithelial cells. However, CM from ectopic endometriotic stromal cells did not have an inhibitory effect on normal or ectopic endometriotic epithelial cells. Inhibition of AKt phosphorylation and Survivin expression in normal or eutopic endometriotic epithelial cells in the presence of stromal factors from normal or eutopic endometriotic stromal cells was enhanced by progesterone, whereas progesterone had little effect in the presence of stromal factors from ectopic endometriotic stromal cells. The inability of ectopic endometriotic stromal cells to regulated PI3K/AKt/Survivin signaling and mediate the progesterone response in endometriotic epithelial cells may facilitate epithelial cell proliferation in endometriosis and promote the survival of endometriotic lesions.

Hum Reprod. 2009 Aug 14. [Epub ahead of print]

The epidemiology of infertility in the North East of Scotland.

Bhattacharya S, Porter M, Amalraj E, Templeton A, Hamilton M, Lee AJ, Kurinczuk JJ.

Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Foresterhill, Aberdeen AB25 2ZD, UK.

BACKGROUND There is a perception that the prevalence of infertility is on the rise. This study aimed to determine the current prevalence of infertility in a defined geographical population, ascertain changes in self-reported infertility over time and identify risk factors associated with infertility. METHODS A postal questionnaire survey of a random population-based sample of women aged 31-50 years was performed in the Grampian region of Scotland. Questions addressed the following areas: pregnancy history, length of time taken to become pregnant each time, whether medical advice had been sought and self-reported exposure to factors associated with infertility. RESULTS Among 4466 women who responded, 400 (9.0%) [95% CI 8.1, 9.8] had chosen not to have children. Of the remaining 4066 women, 3283 (80.7%) [95% CI 79.5, 82.0] reported no difficulties in having children and the remaining 783 (19.3%) [95% CI 18.1, 20.5] had experienced infertility, defined as having difficulty in becoming pregnant for more than 12 months and/or seeking medical advice. In total 398 (9.8%) [95% CI 8.9, 10.7] women had primary infertility, 285 (7.0%) [95% CI 6.2, 7.8] had secondary infertility, 100 (2.5%) [95% CI 2.0, 2.9] had primary as well as secondary infertility. A total of 342 (68.7%) and 208 (73.0%) women with primary and secondary infertility, respectively, sought medical advice and 202 (59.1%) and 118 (56.7%) women in each group subsequently conceived. History of pelvic surgery, Chlamydial infection, endometriosis, chemotherapy, long-term health problems and obesity were associated with infertility. In comparison with a similar survey of women aged 46-50 from the same geographical area, the prevalence of both primary infertility (>24 months) [70/1081, (6.5%) versus 68/710 (9.6%) P = 0.02] and secondary infertility [29/1081 (2.7%) versus 40/710 (5.6%) P = 0.002] were significantly lower. CONCLUSIONS Nearly one in five women attempting conception sampled in this study experienced infertility, although over half of them eventually conceived. Fertility problems were associated with endometriosis, Chlamydia trachomatis infection and pelvic surgery, as well as obesity, chemotherapy and some long-term chronic medical conditions. There is no evidence of an increase in the prevalence of infertility in this population over the past 20 years.

Fertil Steril. 2009 Aug 13. [Epub ahead of print]

PPAR-gamma expression in peritoneal endometriotic lesions correlates with pain experienced by patients.

McKinnon B, Bersinger NA, Huber AW, Kuhn A, Mueller MD.

Department of Obstetrics and Gynecology, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland.

Endometriosis is a significant gynecologic condition that can cause both pain and infertility and affects up to 15% of women during their reproductive years. In peritoneal endometriotic lesions, the expression of peroxisome proliferation-activated receptor gamma, a nuclear receptor with antiinflammatory and neuroprotective roles, is positively correlated with the pain reported by patients.

Zhongguo Zhong Yao Za Zhi. 2009 May;34(10):1285-9.

Inhibitory effect of Sanlengwan on expression of adhesion molecules ICAM-1, CD44 in rats of endometriosis

[Article in Chinese]

Li Z, Li A, Chen G, He Y, Wang J, Xu X.

Pharmaceutical Sciences College of Chongqing University of Medical Science, Chongqing 400016, China.

OBJECTIVE: To explore the effect of Sanlengwan (SLW) on adhesion molecules expression and the accretion in ectopic endometrium of rats. METHOD: Endometriosis was established by surgical implant of endometrial tissue which belong to its body. Forty EMS model rats were randomly divided into five groups: model control group, three dose of SLW groups and anastrozole group. Meanwhile, eight normal rats were used as the normal group. All the rats were treated for 4 weeks respectively, and the volume of grafts were measured by vernier caliper, morphological changes were measured by HE stain, and the adhesion molecules, ICAM-1 and CD44 protein, were also measured by immunohistochemical test before and after treatment of SLW. RESULT: SLW markedly reduced the volume of grafts, improve the morphological characters and decreased the expression of ICAM-1 and CD44 in ectopic endometrial tissue. CONCLUSION: SLW can inhibit the accretion of ectopic endometrium tissue of rats, and its mechanism might be associated with inhibiting the expression of ICAM-1 and CD44 protein.

Gynecol Endocrinol. 2009 Aug 11:1-7. [Epub ahead of print]

Expression of the human endogenous retroviruse-W envelope gene syncytin in endometriosis lesions.

Oppelt P, Strick R, Strissel PL, Winzierl K, Beckmann MW, Renner SP.

Department of Gynecology and Obstetrics, University of Erlangen, Erlangen, Germany.

Background. None of the existing theories provides a satisfactory explanation of the development of endometriosis. One hypothesis that may lead to further clarification is that the expression of specific proteins of human endogenous retroviruses (HERVs) might influence the development of endometriosis lesions. Such endogenous retroviral proteins include syncytin, coded by HERV-W, which is associated with the physiological development of the placenta during pregnancy. This study investigated the influence of HERV-W gene expression in endometriosis foci (EM) quantitatively at the RNA level. Materials and methods. Specific RNA expression of syncytin (HERV-W) was investigated in various endometrial tissues from 42 patients (with normal endometrium, postmenopausal endometrium, EM, and endometrial carcinoma). RNA was isolated from the tissue samples and transcribed into DNA using reverse transcriptase polymerase chain reaction. The resulting DNA fragments were analyzed using agarose gel electrophoresis and assessed quantitatively. Results. Normalized syncytin expression was low in EM. In Histologically normal endometrium from endometriosis patients, the expression of normalized syncytin was seven times higher in comparison with the histologically normal endometrium in the control group. Conclusions. HERV-W syncytin expression apparently does not play a role in EM. However, it may possibly influence the development of endometriosis because of increased expression in normal endometrium in endometriosis patients.

Mol Hum Reprod. 2009 Oct;15(10):633-43. Epub 2009 Aug 11.

Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model.

Mönckedieck V, Sannecke C, Husen B, Kumbartski M, Kimmig R, Tötsch M, Winterhager E,

Grümmer R.

Institute of Molecular Biology, University Hospital Essen, 45122 Essen, Germany.

Progestins are successfully used in the treatment of endometriosis; however, the exact mechanisms of their action are still unsolved. We here focused on the effect of different progestins on parameters of extracellular matrix degradation and angiogenesis involved in the establishment and maintenance of ectopic endometrial lesions. Human endometrium was intraperitoneally transplanted into nude mice. After 7 and 28 days of treatment with progesterone, dydrogesterone, or its metabolite dihydrodydrogesterone, respectively, ectopic lesions were evaluated for proliferation and apoptosis. Expression of estrogen receptor alpha, progesterone receptor-AB, the angiogenetic factors, cysteine-rich angiogenic inducer (CYR61), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFA) and the matrix metalloproteinase (MMP)-2, -3, -7 and -9 was investigated. Functional impact on angiogenesis was evaluated by density of microvessels and of vessels stabilized by pericytes within the ectopic lesions. Although dydrogesterone significantly reduced proliferation of endometrial stromal cells after 28 days, suppression of apoptosis was independent from progestins. Expression of MMP-2 was significantly reduced by all progestins and MMP-3 by dydrogesterone. In the grafted endometrial tissue, transcription of bFGF was suppressed by progesterone and dihydrodydrogesterone, and VEGFA and CYR61 by dihydrodydrogesterone and dydrogesterone. In parallel, microvessel density was slightly suppressed by progestins, whereas number of stabilized vessels increased. Thus, progestins regulate factors important for the establishment and maintenance of ectopic endometrial lesions.

J Proteome Res. 2009 Oct;8(10):4622-32.

Comprehensive proteomic analysis of human endometrial fluid aspirate.

Casado-Vela J, Rodriguez-Suarez E, Iloro I, Ametzazurra A, Alkorta N, García-Velasco JA, Matorras R, Prieto B, González S, Nagore D, Simón L, Elortza F.

Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed, Technology Park of Bizkaia, Derio, Spain, Proteomika S.L. Technology Park of Bizkaia, Derio, Spain, Instituto Valenciano de Infertilidad, Madrid, Spain, Hospital de Cruces, Barakaldo, Spain, and Instituto Valenciano de Infertilidad, Bilbao, Spain.

The endometrial fluid is a noninvasive sample which contains numerous secreted proteins representative of endometrial function and reflects the state of the endometrium. In this study, we describe, for the first time, a comprehensive catalogue of proteins of the endometrial fluid during the secretory phase of the menstrual cycle. To achieve this objective, three different but complementary strategies were used: First, in-solution digestion followed by reverse phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS); second, protein separation by denaturing one-dimensional electrophoresis (SDS-PAGE) followed by HPLC-MS/MS analysis. Finally, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) followed by MALDI-TOF/TOF analysis. The combination of the three strategies led to the successful identification of 803 different proteins in the International Protein Index (IPI) human database (v3.48). An extensive description of the endometrial fluid proteome will help provide the basis for a better understanding of a number of diseases and processes, including endometriosis, endometrial cancer and embryo implantation. We believe that the thorough catalogue of proteins presented here can serve as a valuable reference for the study of embryo implantation and for future biomarker discovery involved in pathologic alterations of endometrial function.

Klin Khir. 2009 Mar;(3):39-41.

Catamenial pneumothorax: a rare manifestation of endometriosis

[Article in Ukrainian]

[No authors listed]

Catamenial pneumothorax is an rare disease which arise in women during menses, etiologically related to endometriosis of diaphragm and lung. The five observations and literature review are presented. During 2006-2008 years 45 women with spontaneous pneumothorax were treated at Kyiv Clinical Hospital Number 17. Among them, catamenial pneumothorax was recognized in 5. In 3 women, diagnosis was established based on clinical data and thoracoscopy results, in 2–the cause of recurrent pneumothorax was seen intraoperatively. All the patients were operated on, in 2–videothoracoscopic diaphragm plication was done, in 2–we performed video-assisted resection of the affected part of the diaphragm, in 1–partial resection of the diaphragm was done with lateral thoracotomy. Abrasion of parietal pleura was performed in all patients. Endometrioid implants in the resected parts of diaphragm were confirmed histologically. No recurrences were observed during the average 32 months. The treatment of catamenial pneumothorax is symptomatic, to prevent recurrences and avoid illness every month. Since catamenial pneumothorax is caused by thoracic endometriosis, decisions on treatment should be made with a gynecologist’s opinion.

Gynecol Endocrinol. 2009 Aug 6:1-8. [Epub ahead of print]

Neurokinin 1 receptor gene polymorphism might be correlated with recurrence rates in endometriosis.

Renner SP, Ekici AB, Maihofner C, Oppelt P, Thiel FC, Schrauder M, Uenluehan N, Bani MR, Strissel PL, Strick R, Beckmann MW, Fasching PA.

Department of Gynecology and Obstetrics, University Hospital Erlangen.

Introduction. Dysmenorrhoea is the major symptom in women with endometriosis. Recently, pain modulation through Neurokinin-1-receptor (NK1R) pathways have been investigated in neuropathic pain patients. Aim of this study was, therefore, to examine the effect of a single nucleotide polymorphism (SNP) of the NK1R gene on the susceptibility for endometriosis and the disease free survival (DFS) after surgery for endometriosis. Material and methods. A case-control study was conducted and germline DNA was isolated. Patients were followed up for a recurrence of the disease up to 4 years. Case-control analyses were performed for parameters of the medical history and the genotype of the NK1R-SNP rs881. Furthermore, DFS probabilities were calculated. Results. Concerning the DFS preoperative pain levels and the NK1R genotype were independent predictors for a recurrence with hazard ratios of 2.55 (95% CI: 1.32-4.95) for patients with a high preoperative pain level and 0.44 for patients with a heterozygous or homozygous variant genotype in rs881 (95% CI: 0.21-0.88). Conclusion. The polymorphism rs811 seems to be associated with a lower recurrence risk in endometriosis patients. Thus, there might be a clinical relevant role of the NK1 pathway in the pain perception of endometriosis patients.

Steroids. 2009 Aug 7. [Epub ahead of print]

Estrogen-induced stromal cell-derived factor-1 (SDF-1/Cxcl12) expression is repressed by progesterone and by Selective Estrogen Receptor Modulators via estrogen receptor alpha in rat uterine cells and tissues.

Glace L, Grygielko ET, Boyle R, Wang Q, Laping NJ, Sulpizio AC, Bray JD.

Department of Urogenital Biology, Cardiovascular and Urogenital Center for Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA.

Endometriosis, defined as the presence of endometrial glands and stroma at extra-uterine sites, is a gynecological condition that affects women of reproductive age. Consistent with its uterine origins, endometriotic lesions and resulting symptoms are hormonally responsive. To investigate Progesterone Receptor (PR)-based therapies, we measured physiological endpoints and gene expression in rat models of uterine cell estrogenic activity. Estrogen-induced ELT-3 rat leiomyoma cell proliferation was significantly inhibited by progesterone (P4), while the antiprogestin RU486 or the Selective PR Modulator (SPRM) asoprisnil, did not block proliferation. Stromal cell-derived factor-1 (SDF-1/Cxcl12) gene expression was induced by estrogen, and was repressed by the Selective Estrogen Receptor Modulators (SERMs), the antiestrogen ICI 182,780, and P4, but not by RU486 or the ERbeta-selective ligand ERB-041. In ELT-3 cells, asoprisnil demonstrated partial PR agonism on SDF-1 gene repression. Magnetic Resonance Imaging was used to monitor development of ectopic cysts in a rat surgical model of endometriosis. SERMs and P4 significantly decreased cyst volumes comparably by approximately 60%. However, ERB-041 and asoprisnil had no effect on cyst volume, and RU486 increased cyst volume by 20%. SDF-1 expression was modestly, but significantly, increased in the cyst compared to eutopic uterus, and P4 and raloxifene could repress the expression. We showed that SDF-1 was similarly regulated in human cells. These data suggest that transcriptional regulation of SDF-1 is a surrogate marker of estrogenic activities via ERalpha in rat uterine cells, and that SDF-1 repression by PR agonists can predict the ability to oppose the actions of estrogen in vivo.

Eur J Obstet Gynecol Reprod Biol. 2009 Aug 6. [Epub ahead of print]

Recurrence rate of endometrioma after laparoscopic cystectomy: A comparative randomized trial between post-operative hormonal suppression treatment or dietary therapy vs. placebo.

Sesti F, Capozzolo T, Pietropolli A, Marziali M, Bollea MR, Piccione E.

Endometriosis Center, Section of Gynecology & Obstetrics, Department of Surgery, School of Medicine, Tor Vergata University Hospital, Viale Oxford, 81-00133 Rome, Italy.

OBJECTIVE(S): To assess the recurrence rate of endometrioma after laparoscopic cystectomy plus hormonal suppression treatment or plus dietary therapy compared to post-operative placebo. STUDY DESIGN: A randomized comparative trial was conducted on 259 consecutive women who underwent laparoscopic unilateral/bilateral cystectomy for endometrioma. Seven days after surgery, the patients were randomly allocated on the basis of a computer-generated randomization sequence, to one of four post-operative management arms as follows: placebo (n=65) or gonadotrophin-releasing hormone analogue (tryptorelin or leuprorelin, 3.75mg every 28 days) (n=65) or continuous low-dose monophasic oral contraceptives (ethynilestradiol, 0.03mg plus gestoden, 0.75mg) (n=64) or dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n=65) for 6 months. At 18 months’ follow-up after surgery, all patients were monitored with a clinical gynecologic examination, and a transvaginal ultrasonography for possible evidence of endometrioma recurrence. RESULT(S): At 18 months’ transvaginal ultrasonographic follow-up after surgery, no significant recurrence rate of endometrioma was detected in women who received a postoperative course of hormonal suppression treatment or dietary therapy when compared with placebo (placebo vs. GnRH-a P=0.316, placebo vs. estroprogestin P=0.803, placebo vs. dietary therapy P=0.544). Second-look laparoscopy was performed on a clinical basis and confirmed the ultrasonographic suspicion of recurrence of endometrioma in all cases: 10 (16.6%) in the post-operative placebo group vs. 6 (10.3%) in the post-operative GnRH-a group vs. 9 (15.0%) in the post-operative continuous estroprogestin group vs. 11 (17.8%) in the post-operative dietary therapy group. Of 36 patients with recurrent ovarian endometriosis, 8 had recurrence on the treated ovary, 20 on the contralateral ovary that appeared to be normal at the time of the first-line surgery, and 8 on both the treated and untreated ovaries. Endometrioma recurrences were associated with moderate-to-severe painful symptoms in 14/36 patients (38.8%), while the remaining 22 (61.1%) patients were asymptomatic. CONCLUSION(S): A 6-month course of hormonal suppression treatment or dietary therapy after laparoscopic cystectomy had no significant effect on the recurrence rate of ovarian endometriosis when compared with surgery plus placebo. So, treatment of endometrioma can be carried out exclusively by laparoscopic cystectomy without post-operative therapy, if a complete excision of ovarian endometriosis has been assured.

OMICS. 2009 Oct;13(5):381-96.

Resampling reveals sample-level differential expression in clinical genome-wide studies.

Hiissa J, Elo LL, Huhtinen K, Perheentupa A, Poutanen M, Aittokallio T.

Biomathematics Research Group, Department of Mathematics, University of Turku, Turku, Finland.

Genome-scale molecular profiling of clinical sample material often results in heterogeneous datasets beyond the capability of standard statistical procedures. Statistical tests for differential expression, in particular, rely upon the assumption that the sample groups being compared are relatively homogeneous. Such assumption rarely holds in clinical materials, which leads to detection of secondary findings (false positives) or loss of significant targets (false negatives). Here, we introduce a resampling-based procedure, named ReScore, which aggregates individual changes across all the samples while preserving their clinical classes, and thereby provides multiple sets of markers that can effectively characterize distinct sample subsets. When applied to a public leukemia microarray study, the procedure could accurately reveal hidden subgroup structures associated with underlying genotypic abnormalities. The procedure improved both the sensitivity and specificity of the findings, as well as helped us to identify several disease subtype-specific genes that have remained undetected in the conventional analyses. In our endometriosis study, we were able to accurately distinguish between various sources of systematic variation, linked, for example, to tissue-specificity and disease-related factors, many of which would have been missed with standard approaches. The generic procedure should benefit also other global profiling experiments such as those based on mass spectrometry-based proteomic assays.

Clin Obstet Gynecol. 2009 Sep;52(3):380-9.

Pediatric and adolescent gynecologic laparoscopy.

Broach AN, Mansuria SM, Sanfilippo JS.

Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA, USA.

Minimally invasive techniques to treat children and adolescents requiring surgery have increasingly become standard of care. Similarly, gynecologists frequently use laparoscopy to treat pelvic pathology. We present the necessary equipment and surgical techniques required to perform gynecologic procedures on the pediatric and adolescent population. We will give particular focus to the treatment of adnexal masses, chronic pelvic pain, endometriosis, and ovarian torsion. We will also discuss the role of the incidental appendectomy in children and adolescents.

Clin Obstet Gynecol. 2009 Sep;52(3):351-61.

Laparoscopic surgery for endometriosis.

Catenacci M, Sastry S, Falcone T.

The Cleveland Clinic, Department of Obstetrics and Gynecology, 9500 Euclid Avenue, Cleveland, OH, USA.

Endometriosis is a leading cause of pelvic pain and infertility in women. Laparoscopy can both diagnose and treat this disease. The aim of this review was to examine current literature on treatments for endometriosis for both pain and infertility. Evidence supports removal of severe disease, including ovarian endometriomas, for improved pregnancy outcomes. However, for patients that fail initial surgery, in vitro fertilization may yield superior outcomes over repeat surgery. For pelvic pain, surgery has been shown to improve symptoms although there is a significant placebo effect with surgery. Finally, hysterectomy can be offered to women who fail initial conservative surgery.

Clin Obstet Gynecol. 2009 Sep;52(3):344-50.

Tubal surgery.

Zarei A, Al-Ghafri W, Tulandi T.

Department of Obstetrics and Gynecology, McGill University, Pine Avenue West, Montreal, QC, Canada.

Today, reproductive surgery has a limited place. In selected cases such as young women with a history of pelvic inflammatory disease, pelvic adhesions, and endometriosis, surgery could be considered. Most operations can be performed by laparoscopy; these include tubal anastomosis that yields a high pregnancy rate. On the other hand, women over the age of 37 with a long history of infertility or those who require a laparotomy are better treated with in-vitro fertilization. For women with hydrosalpinx undergoing IVF, salpingectomy is the best treatment option. It increases the chance of pregnancy and live birth rates and decreases the miscarriage rate.

Reproduction. 2009 Aug 6. [Epub ahead of print]

Association between MMP1 and MMP9 activities and ICAM1 cleavage induced by TNF in stromal cell cultures from eutopic endometria of women with endometriosis.

Pino M, Galleguillos C, Torres M, Sovino H, Fuentes A, Boric MA, Johnson MC.

M Pino, Institute of Maternal and Child Research, University of Chile, Santiago, Chile.

Endometriosis is a benign gynecological pathology in which immune system deregulation may play a role in its initiation and progression. In endometriotic lesions, ICAM1 is released from the cell membrane by proteolytic cleavage of its extracellular domain, a process that coincides with increased expression and proteolytic activity of metalloproteinases such as MMP1 and MMP9. The objective of our study was to investigate the association between MMP1 and MMP9 activities and ICAM1 cleavage mediated by TNF in eutopic endometrial stromal cells from women with and without (control) endometriosis during culture. The RNA was evaluated by RT-PCR, and the protein was determined by western blot (ICAM1, MMP1), casein or gelatin zymographies (secreted active MMP1 or MMP9, respectively), ELISA (sICAM1), and fluorescence assay (secreted active MMP1). Under basal conditions, proMMP9 dimer and MMP9 were higher in endometriosis cell cultures. In stromal cultures derived from control women and those with endometriosis, TNF augmented the intracellular proMMP1 (1.2-fold in control stromal cells) and ICAM1 (1.4- and 1.9-fold), greatly increased MMP1 and proMMP9 levels, and the sICAM1 concentration (2.3- and 4.3-fold) in their media compared to basal levels. The combination of TNF and MMP9 increased the sICAM1 concentration by 14-fold in the endometriosis cell media, whereas GM6001 inhibited the stimulatory effect of TNF in both cell cultures. The deregulation of MMP9, and the TNF participation in the MMP1 and proMMP9 secretions, in the MMP9 expression and in the expression and cleavage of ICAM1 may contribute to the pathophysiology of this disease.

Hum Reprod. 2009 Aug 6. [Epub ahead of print]

Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium.

Gomes MK, Rosa-E-Silva JC, Garcia SB, de Sá Rosa-E-Silva AC, Turatti A, Vieira CS, Ferriani RA.

Department of Obstetrics and Gynecology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.

BACKGROUND The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections. METHODS Pre- and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n = 11) or GnRHa (n = 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor alpha (ER-alpha) were analyzed by immunohistochemistry. RESULTS The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P < 0.05). Expression of ER-alpha and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P < 0.05). No difference was detected between groups for any of the markers. CONCLUSIONS LNG-IUS reduced both cell proliferation and the expression of PRA and ER-alpha and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.


Mol Hum Reprod. 2009 Oct;15(10):645-52. Epub 2009 Aug 6.

Connexin expression pattern in the endometrium of baboons is influenced by hormonal changes and the presence of endometriotic lesions.

Winterhager E, Grümmer R, Mavrogianis PA, Jones CJ, Hastings JM, Fazleabas AT.

Institute of Molecular Biology, University of Duisburg-Essen, 45122 Essen, Germany.

Experimentally induced endometriosis in baboons serves as an elegant model to discriminate between endometrial genes which are primarily associated with normal endometrial function and those that are changed by the presence of endometriotic lesions. Since connexin genes are characteristic of the hormonally regulated differentiation of the endometrium, we have examined connexin expression in baboon endometrium to delineate if they are altered in response to the presence of endometriotic lesions. Connexin expression in the endometrium of cycling baboons is similar to that of the human endometrium with Connexin(Cx)43 being primarily seen in the stromal compartment and Cx26 and Cx32 being present predominantly in the epithelium. Although Cx32 is up-regulated during the secretory phase, Cx26 and Cx43 are down-regulated. In the baboon model of induced endometriosis a change in connexin pattern was evident in the presence of endometriotic lesions. In the secretory phase, Cx26 and Cx32 are no longer present in the epithelium but Cx26 is now observed primarily in the stromal cells. Infusion of chorionic gonadotrophin in a manner that mimics blastocyst transit in utero failed to rescue the aberrant stromal expression of Cx26 that is associated with the presence of endometriotic lesions suggesting an impairment of the implantation process. The altered connexin pattern coupled with a loss of the channel protein in the epithelium and a gain of Cx26 in the stromal compartment suggests that the presence of lesions changes the uterine environment and thereby the differentiation programme. This aberrant expression of connexins may be an additional factor that contributes to endometriosis-associated infertility. 


Bibliografia 2009 – Pagina 2

Histol Histopathol. 2009 Nov;24(11):1479-86.

Hepatocyte nuclear factor-1beta(HNF-1beta) in human urogenital organs: its expression and role in embryogenesis and tumorigenesis.
Kato N, Motoyama T.
Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.
Molecules responsible for embryogenesis are often involved in tumorigenesis. Recent exhaustive cDNA microarray analyses in human neoplasms expanded knowledge of such molecules. Hepatocyte nuclear factor-1beta (HNF-1beta) is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF-1alpha. In contrast to HNF-1alpha, HNF-1beta is very weakly expressed in the liver and is commonly expressed in the kidneys. During human embryonic stage, HNF-1beta plays an important role in organogenesis, especially of the urogenital system. In the human fetus, HNF-1beta expression is common in mesonephric duct derivatives and metanephros (permanent kidneys). HNF-1beta germline mutations cause malformations of these structures. Recent microarray analyses have disclosed that HNF-1beta is aberrantly up-regulated in clear cell carcinoma of the ovary, which is a carcinoma of müllerian nature, but which was initially misnamed “mesonephroma”. HNF-1beta is also expressed in ovarian endometriosis, which is a probable origin of clear cell carcinoma. On the other hand, HNF-1beta is down-regulated in renal neoplasms, such as chromophobe cell carcinoma. In this review, we first summarize HNF-1beta expression in the developing urogenital system of the human embryo. Then, we describe the HNF-1beta status in human urogenital neoplasms and discuss its role in tumorigenesis.

J Obstet Gynaecol. 2009 Oct;29(7):590-3.
Endometriosis: the elusive epiphenomenon.
Quinn M.

The denervation-reinnervation view proposes that retrograde menstruation results from loss of normal, fundocervical polarity caused by injuries to uterine nerves. Injuries may be sporadic (following vaginal delivery) or recurrent (after persistent straining during defaecation) creating very different appearances at laparoscopy. Clinical symptoms of pelvic pain, menstrual problems, dyspareunia, and dysmenorrhoea result from aberrant reinnervation that may occur with, or without deposits of pelvic endometriosis. Endometrium, delivered by retrograde menstruation, adheres to any injured tissues in the lower pelvis. Classical ‘endometriosis’ is largely an epiphenomenon to underlying processes of denervation and reinnervation.

Gynecol Endocrinol. 2009 Sep 12:1-6. [Epub ahead of print]

Progestins and medical treatment of endometriosis – Physiology, history and society.

Belaisch J.
Maternite Pinard, Hopital Saint Vincent de Paul, Universite Rene Descartes Paris France.

The transitory effect of hormonal treatment is the alleged main reason to criticize progestins (PGS) and combined pills (OP) in the managment of endometriosis. To the contrary their poor efficacy in the long run is often underlined. As a result, medical treatment is too seldom advised in endometriosis. In this article, we shall focus on the analysis of the reasons of the paucity of the medical interest given to progestins, reasons, which are not of a scientific or objective nature. The ultimate aim of this analysis is to develop arguments in favour of continuous administration of hormones as to obtain not simply an anovulation but a state of prolonged amenorrhea much more efficacious than the simple suppression of ovulation too often advised. And, with an emphasis on the fundamental role of surgery in the treatment of endometriosis, to give the greatest consideration to the specific nature of this disease, which is a chronic disease, justifying the long duration of hormonal administration.

Gynecol Endocrinol. 2009 Sep 15:1. [Epub ahead of print]
Endometriosis – an European perspective.
Schindler AE, Druckmann R.
Mol Biol Rep. 2009 Sep 13. [Epub ahead of print]
Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women.
Attar R, Agachan B, Kucukhuseyin O, Toptas B, Attar E, Isbir T.
Department of Obstetrics and Gynecology, Yeditepe University Hospital, Istanbul, Turkey.

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women didnot have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women.
Radiographics. 2009 Sep-Oct;29(5):1353-70.
Female infertility: a systematic approach to radiologic imaging and diagnosis.
Steinkeler JA, Woodfield CA, Lazarus E, Hillstrom MM.
Department of Diagnostic Imaging, Warren Alpert Medical School of Brown University and Rhode Island Hospital, 593 Eddy St, Providence, RI 02903, USA.

Imaging plays a key role in the diagnostic evaluation of women for infertility. The pelvic causes of female infertility are varied and range from tubal and peritubal abnormalities to uterine, cervical, and ovarian disorders. In most cases, the imaging work-up begins with hysterosalpingography to evaluate fallopian tube patency. Uterine filling defects and contour abnormalities may be discovered at hysterosalpingography but typically require further characterization with hysterographic or pelvic ultrasonography (US) or pelvic magnetic resonance (MR) imaging. Hysterographic US helps differentiate among uterine synechiae, endometrial polyps, and submucosal leiomyomas. Pelvic US and MR imaging help further differentiate among uterine leiomyomas, adenomyosis, and the various müllerian duct anomalies, with MR imaging being the most sensitive modality for detecting endometriosis. The presence of cervical disease may be inferred initially on the basis of difficulty or failure of cervical cannulation at hysterosalpingography. Ovarian abnormalities are usually detected at US. The appropriate selection of imaging modalities and accurate characterization of the various pelvic causes of infertility are essential because the imaging findings help direct subsequent patient care. (c) RSNA, 2009.

Inflamm Allergy Drug Targets. 2009 Sep;8(4):285-91.
Leptin in non-autoimmune inflammation.
Cai C, Hahn BH, Matarese G, La Cava A.
Department of Medicine, University of California Los Angeles, Los Angeles, California 90095-1670, USA.
Leptin is an adipokine that modulates multiple functions including energy homeostasis, thermoregulation, bone metabolism, endocrine and pro-inflammatory immune responses. Several studies have implicated leptin in the pathogenesis of chronic autoimmune inflammatory conditions such as autoimmune encephalomyelitis, intestinal bowel inflammation and type-1 diabetes. This review focuses on the role of leptin in non-autoimmune inflammatory diseases that include renal, liver and lung inflammation, atherosclerosis and metabolic syndrome, Behçet’s disease and endometriosis.
J Obstet Gynaecol Res. 2009 Aug;35(4):753-60.
McGill Pain Questionnaire: A multi-dimensional verbal scale assessing postoperative changes in pain symptoms associated with severe endometriosis.
Fabbri E, Villa G, Mabrouk M, Guerrini M, Montanari G, Paradisi R, Venturoli S,

Seracchioli R.
Centre for Reconstructive Pelvic Endo-Surgery, Reproductive Medicine Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Background: Objective evaluation of pelvic pain symptoms using a standard pain questionnaire is essential to assessing the treatment of endometriosis and related pain. Aim: To evaluate the McGill Pain Questionnaire (MPQ) as a multi-dimensional verbal scale in providing information about chronic pelvic pain associated with endometriosis, before and after laparoscopic surgery. Methods: Fifty-five women undergoing laparoscopy for severe endometriosis were asked to complete the MPQ before surgery and at the 6-month follow up. All patients presented with preoperative pain symptoms of variable severity. We obtained the pain indexes and studied their relation with: patients’ characteristics (age, body mass index, parity, qualification, occupation); operative findings (number, site and size of endometriotic lesions and presence of pelvic adhesions); and postoperative evolution of variable MPQ pain indexes at the 6-month follow up. Results: Median present pain index (PPI) (index of pain intensity), before surgical treatment was 3 (2-4): preoperative PPI was <2 in 25% of patients while 25% of patients had PPI > 4. Overall median PPI after surgical treatment was 1 (0-2): postoperative index of pain intensity was <1 in 50% of patients, >2 in 25% of patients while 25% of patients did not experience postoperative pain. Overall pain intensity significantly decreased after laparoscopic treatment of endometriosis (Wilcoxon test P < 0.0005). None of the patients’ characteristics were found to be significantly correlated with the severity or improvement of preoperative pain at postoperative follow up (P > 0.05), and the intensity of preoperative pain was not correlated to any of the operative variables. There was a significant reduction in all individual MPQ pain indexes; however 18.2% of women did not show improvement of pain symptoms after laparoscopic surgery. An increasing endometrioma diameter was associated with a significant decrease in the difference in evaluative rank score of pain rating index between pain indexes at the 6-month follow up and preoperatively (P = 0.04, Spearman’s rank correlation Rho = -0.277). Conclusions: MPQ appears to be useful as a multi-dimensional scale in describing patients’ pain semiology and evaluating pain evolution after surgical treatment. However, due to the extreme variability of pain experience, MPQ results don’t clarify the relationship between pain intensity and the severity of endometriosis.
Minerva Ginecol. 2009 Aug;61(4):371.
Severe hydroureteronephrosis due to deep infiltrating ureteral endometriosis.
Leanza V, Accardi M, Cavallaro A, Russo ER.
Dipartimento di Ginecologia e Ostetricia, Università di Catania, Catania, Italia

Minerva Ginecol. 2009 Aug;61(4):299-318.
Endometriosis and the role of reproductive medicine.
Bukulmez O.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, USA

Endometriosis is a complex trait with significant environmental and genetic influences that are likely to affect its phenotype. Natural history of the disease varies from one individual to another. The gold standard of surgical diagnosis is limited in accuracy by visibility and recognition of lesions by the attending surgeon. Several lines of evidence suggest that pelvic endometriosis results from the reflux of viable endometrial tissue through the fallopian tubes. Endometriosis is an inflammatory disease that nuclear factor kappa B pathway may play an important role in its pathogenesis. Endometriotic lesions demonstrate increased aromatase expression in association with increased cyclo-oxygenase-2 expression, especially in red lesions which represent earlier stages of inflammation. Estrogen and progesterone receptor expressions vary according to the morphology and the inflammatory status of the endometriotic lesions. Normal endometrial tissue fragments can adhere and implant to peritoneum. Aromatase expression, a possible intrinsic survival factor for endometrial tissue, is inducible in human endometrial fragments by androstenedione at physiological concentrations found in peritoneal fluid. Inflammatory response to ectopic endometrial tissue, which may vary in each individual seems to be important in disease progression. Current therapies for endometriosis include surgical and medical approaches aimed at cytoreduction or hormonal suppression. However, the disease have tendency to recur in many symptomatic women. Although new management approaches are emerging, properly designed clinical trials are desperately needed in treatment of pain and subfertility associated with endometriosis. Future studies should also focus on identifying risk population to develop preventive strategies, since the treatment of endometriosis is costly and challenging.

Minerva Ginecol. 2009 Aug;61(4):285-98.
Endometriosis: a critical appraisal of the advances and the controversies of a challenging health problem.
Bedaiwy MA, Abdel-Aleem MA, Miketa A, Falcone T.
Departments of Obstetric/Gynecology and Women’s Health Institute, Cleveland Clinic, Cleveland, OH, USA
Endometriosis is an enigmatic disorder with obscure pathogenesis. The objective of this review was to critically appraise the recent advances in the etiopathogenesis, diagnosis and clinical management of endometriosis. Several studies support the familial role in the initiation of the disease with key roles of endometriosis-associated polymorphisms in the genes that control fibrinolysis, angiogenesis, steroidogesis, aromatization of androgens, proliferation and cytokine production. Many active substances (cytokines, growth factors, hormones and oxidative stress parameters) have been identified in endometriosis patients at different stages of the disease. In addition to the traditional diagnostic role of ultrasonography and CA 125, evidence is accumulating regarding a potential role sonorectovaginography. Currently the routine use of antiflammatory drugs and birth control pills is not supported by evidence. New protocols of medications incorporation new gonadotrophin releasing hormone agonists with add back therapy, androgenic agents and aromatase inhibitors have been proposed. Prospective randomiazed controlled trials proved that surgical treatment of endometriosis is better than placebo for endometriosis related pain and infertility for patients with stage I and II disease.

Mol Hum Reprod. 2009 Oct;15(10):609-24. Epub 2009 Sep 10.
Reassessing the evidence for the link between dioxin and endometriosis: from molecular biology to clinical epidemiology.
Guo SW, Simsa P, Kyama CM, Mihályi A, Fülöp V, Othman EE, D’Hooghe TM.
Institute of Obstetric and Gynecologic Research, and Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
A 1993 study reporting the link between exposure to dioxin and the risk of developing endometriosis in rhesus monkeys prompted many investigators to look suspiciously at dioxin. Since 1993, many in vitro, animal and epidemiological studies have been published, but the link between dioxin exposure and endometriosis is still unclear. The aim of our review is to present a summary of the biological effects of dioxin and its aryl hydrocarbon receptor, and to reassess the evidence presented in published, in vitro, preclinical and epidemiological studies regarding the association between dioxins and endometriosis. Although in vitro and animal studies provide results in support for a role of dioxins in the pathogenesis of endometriosis, caution should be exercised since these findings are mostly context dependent and since negative findings from these studies are rarely published. On the basis of our review of original epidemiological studies, no significant evidence can be found to support a link between dioxins and endometriosis in women. This observation can be explained by positive publication bias and by significant methodological problems associated with these studies, or by the absence of such a link. In conclusion, it seems that there is insufficient evidence at this moment in support of the hypothesis that dioxin exposure may lead to increased risk of developing endometriosis in women.
Mol Hum Reprod. 2009 Oct;15(10):575. Epub 2009 Sep 10.

Endometriosis: science and sense.
Winterhager E, Fazleabas A, Hillier S.

Ethiop Med J. 2009 Jan;47(2):171-4.
Cesarean scar endometriosis–a case report.
Bekele D, Kumbi S.
Department of Gynecology and Obstetrics, Medical Faculty, Hawassa College of Health Sciences, Hawassa University.
Scar endometriosis is a rare event which usually develops after pelvic operations involving the uterus and fallopian tubes. Its diagnosis can sometimes be difficult and may be confused with various other surgical conditions. We present here a case of abdominal wall scar endometriosis in a woman who has undergone cesarean delivery four years prior to her current presentation. The epidemiology, pathogenesis, clinical features, diagnosis, treatment and methods of prevention of this condition will be discussed in brief. This is an interesting case of surgical scar endometriosis and to the best of our knowledge this is the first case report in Ethiopia.
Hum Reprod. 2009 Sep 7. [Epub ahead of print]

HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility.
Matsuzaki S, Canis M, Darcha C, Pouly JL, Mage G
CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction, Boulevard Léon Malfreyt, 63058 Clermont-Ferrand, France.
BACKGROUND The aim of this study was to investigate HOXA-10 expression in endometrium from infertile patients with different forms of endometriosis; with uterine fibromas, or with unexplained infertility and from normal fertile women. METHODS Expression levels of HOXA-10 mRNA and protein in endometrium were measured during the mid-secretory phase. This study utilized laser capture microdissection, real-time RT-PCR and immunohistochemistry. RESULTS HOXA-10 mRNA and protein expression levels in endometrial stromal cells were significantly lower in infertile patients with different types of endometriosis (deep infiltrating endometriosis, ovarian endometriosis and superficial peritoneal endometriosis), with uterine myoma, and unexplained infertility patients as compared with healthy fertile controls. HOXA-10 mRNA expression levels of microdissected glandular epithelial cells were significantly lower than those of microdissected stromal cells, without significant differences among the different groups. No protein expression was detected in glandular epithelial cells. The percentage of patients with altered protein expression of HOXA-10 in stromal cells were significantly higher in patients with only superficial peritoneal endometriosis (100%, 20/20, P < 0.05) compared with the other infertile groups (deep infiltrating endometriosis: 72.7%, 16/22; ovarian endometriosis: 70.0%, 14/20; uterine myoma: 68.8%, 11/16; unexplained infertility: 55.6%, 5/9). CONCLUSION The present findings suggested that altered expression of HOXA-10 in endometrial stromal cells during the window of implantation may be one of the potential molecular mechanisms of infertility in infertile patients, particularly in patients with only superficial peritoneal endometriosis. One of the underlying causes of infertility in patients with only superficial endometriosis may be altered expression of HOXA-10 in endometrial stromal cells.

Reprod Biol Endocrinol. 2009 Sep 8;7:94.

A cross-study gene set enrichment analysis identifies critical pathways in endometriosis.

Zhao H, Wang Q, Bai C, He K, Pan Y.
Shanghai Jiao Tong University, PR China.

BACKGROUND: Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. METHODS: We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. RESULTS: We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. CONCLUSION: The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.

Eur J Obstet Gynecol Reprod Biol. 2009 Sep 4. [Epub ahead of print]
Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests.
Penninx J, Brandes M, de Bruin JP, Schneeberger PM, Hamilton CJ.
Department of Obstetrics and Gynaecology, Jeroen Bosch Ziekenhuis, ‘s-Hertogenbosch, The Netherlands.
OBJECTIVES: Chlamydia antibody test (CAT) has been proposed to predict tubal disease. A correlation between CA-125 and the extent of endometriosis has been found by others. In this study we explored whether a combination of the two tests adds to the predictive value of the individual tests for predicting tubal disease or endometriosis. We also used the combination of tests as a new index test to screen for severe pelvic pathology. STUDY DESIGN: This retrospective study compares the findings of 240 laparoscopies with the serological test results. Findings were classified according to the existing ASRM scoring systems for adnexal adhesions, distal tubal occlusion and endometriosis. Severe pelvic pathology was defined as the presence of ASRM classes III and IV tubal disease or ASRM classes III and IV endometriosis. The predictive value was calculated for both tests separately and for the combined test. The combined test was positive if at least one test result was abnormal (CAT positive and/or CA-125 >/=35IU/ml). RESULTS: 67/240 women had tubal disease, 81/240 had some degree of endometriosis. The odds ratios (ORs) of the CAT and the combined test to diagnose severe tubal disease were 6.6 (2.6-17.0) and 7.3 (2.9-19.3), respectively. The ORs of the CA-125 and the combined test to diagnose severe endometriosis were 15.6 (6.2-40.2) and 3.0 (1.2-8.0), respectively. Severe pelvic pathology was present in 65/240 women (27%). The ORs for severe pelvic pathology of the CAT, CA-125 and the combined test were 2.5 (1.4-5.3), 4.9 (1.9-9.6) and 6.6 (3.3-13.4), respectively. If the combined test was normal 15 out 131 women (11%) were shown to have severe pelvic pathology. CONCLUSIONS: The combined test adds hardly anything to the predictive value of CAT alone to diagnose severe tubal disease. The combined test is better than the CAT to predict severe pelvic pathology, but is not significantly better than the CA-125. If both the CAT and CA-125 are normal one could consider not performing a laparoscopy.

Best Pract Res Clin Obstet Gynaecol. 2009 Sep 2. [Epub ahead of print]
Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer.
Vlahos NF, Economopoulos KP, Fotiou S.
Department of Obstetrics and Gynecology, Aretaieio Hospital, University of Athens, 76 Vas. Sofias Av., 11527, Athens, Greece.
There is evidence that endometriosis as well as drugs used in the process of in vitro fertilisation appear to associate with increased risk for gynaecological cancer. In this review, we attempt to describe this relationship according to the most recent epidemiologic data and to present the possible mechanisms on the molecular level that could potentially explain this correlation. There are data to support that ovarian endometriosis could have the potential for malignant transformation. Epidemiologic and genetic studies support this notion. It seems that endometriosis is associated with specific types of ovarian cancer (endometrioid and clear cell). There is no clear association between endometriosis and breast or endometrial cancer. More studies are needed to establish the risk factors that may lead to malignant transformation of this condition and to identify predisposed individuals who may require closer surveillance. Currently, there is no proven relationship between any type of gynaecological cancer and drugs used for infertility treatment. In principle, infertile women have increased risk for gynaecologic malignancies. Nulligravidas who received treatment are at increased risk for malignancy compared with women who had conceived after treatment. There is limited evidence that clomiphene citrate use for more than six cycles or 900mg or treatment of women over the age of 40 could increase their risk for ovarian and breast cancer. More studies with the appropriate statistical power and follow-up time are required to evaluate accurately the long-term effects of these drugs and procedures.
Fertil Steril. 2009 Sep 2. [Epub ahead of print]

Ovarian steroid hormones differentially regulate thrombospondin-1 expression in cultured endometrial stromal cells: implications for endometriosis.
Tan XJ, Lang JH, Zheng WM, Leng JH, Zhu L.
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.
Thrombospondin-1 messenger RNA and protein levels in cultured human endometrial stromal cells (ESCs) treated with 17-beta estradiol (10 nM) were reduced by 47.6% (+/-6.5% SD; P < 0.05) and 49.0% (+/-8.6%; P < 0.05) compared with untreated cells, whereas thrombospondin-1mRNA and protein levels in ESCs treated with progesterone (10 muM) were 2.1-fold (+/-0.4 SD; P < 0.05) and 2.3-fold (+/-0.6; P < 0.05) higher than those in untreated cells. These findings not only provide evidence for the estrogen dependence of endometriosis, but also partly explain the mechanisms by which progestins exert their therapeutic activities in endometriosis.

Gynecol Obstet Invest. 2009 Sep 2;68(4):217-223. [Epub ahead of print]
Apoptosis in Endometriosis.
Agic A, Djalali S, Diedrich K, Hornung D.
Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Apoptosis is a physiologic process that eradicates undesired cells without inducing an inflammatory reaction. It is an important regulator of eutopic endometrial function and evidence suggests that apoptosis aids in maintaining cellular homeostasis during the menstrual cycle by eliminating aging cells from the functional layer of the uterine endometrium. Endometriosis, which is characterized by the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. Eutopic endometrium from women with endometriosis has several differences compared with normal endometrium of women without endometriosis. These differences may contribute to the survival of regurgitated endometrial cells into the peritoneal cavity and thus to the development of endometriosis. In this article, we will summarize recent literature concerning apoptosis-related genes such as Bcl-2 and Fas, outline the molecular basis of apoptosis and review the literature focused on the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis. Copyright © 2009 S. Karger AG, Basel.
Dis Markers. 2009;26(4):149-54.
Estrogen receptor-alpha gene (T/C) Pvu II polymorphism in endometriosis and uterine fibroids.
Govindan S, Shaik NA, Vedicherla B, Kodati V, Rao KP, Hasan Q.
Department of Genetics, Vasavi Medical and Research Centre, Khairtabad, Hyderabad-500 004, Andhra Pradesh, India.
Endometriosis and fibroids are estrogen-dependent benign pathologies of the uterus, which account for infertility and pelvic pain along with dysmenorrhea in women. Suppression of the disease and recurrence after discontinuing hormone therapy strongly suggests that these are responsive to hormones, especially estrogen, which acts via its receptor. A T/C SNP in intron 1 and exon 2 boundary of estrogen receptor (ER) alpha gene recognized by PvuII enzyme has been associated with several female pathologies like breast cancer, osteoporosis, endometriosis and fibroids in various ethnic groups. The aim of the present study was to assess this ER alpha T/C polymorphism in endometriosis and fibroid patients from Asian Indian population. Genomic DNA was isolated from 367 women, who included 110 cases of endometriosis, 142 cases of uterine fibroids and 115 healthy age matched women volunteers. PCR was carried out to amplify ER alpha gene followed by restriction digestion with Pvu II. Results indicate a significant association of C allele with both endometriosis [OR=2.6667, 95% CI=1.4166 to 5.0199; p < 0.05] and fibroids [2.0833, 95% CI=1.1327 to 3.8319; p < 0.05]. Further studies are needed in larger population to establish ERalpha C allele as a risk marker for endometriosis and fibroids in Asian Indian women. Ethnicity, race, diet etc may play a role in susceptibility to endometriosis and fibroids and further studies are warranted in this area.

Hum Reprod. 2009 Sep 3. [Epub ahead of print]
The role of survivin in the resistance of endometriotic stromal cells to drug-induced apoptosis.
Watanabe A, Taniguchi F, Izawa M, Suou K, Uegaki T, Takai E, Terakawa N, Harada T.
Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, 36-1, Nishimachi, Yonago 683-8504, Japan.
BACKGROUND Decreased susceptibility of endometrial tissue to apoptosis may contribute to the pathogenesis of endometriosis. We investigate the role of survivin in the pathophysiology of endometriosis through the ability of ectopic and eutopic endometrial stromal cells (ESCs) to resist apoptosis. METHODS Ectopic ESCs were obtained from ovarian chocolate cysts in patients undergoing laparoscopic surgery (n = 22). Eutopic ESCs were isolated from endometrial tissue of cyclic premenopausal women undergoing hysterectomy for fibroids (n = 22). Purified stromal cells were studied in vitro. The number of surviving cells and activation of caspases were assessed by WST-8 assay and immunoblotting. Expression of inhibitor of apoptosis proteins (IAP) family members: cIAP1 (birc2), cIAP2 (birc3), XIAP (birc4), survivin (birc5) were examined using cDNA array and real-time RT-PCR. Effects of gene silencing by small inhibitor RNAs (siRNA) were examined by WST-8-assay, Annexin-V staining and immunoblotting. RESULTS After staurosporine (SS) treatment, 55% of eutopic ESCs survived versus 70% of ectopic ESCs. Procaspase-3 or -7 was more intensely activated by SS treatment in eutopic than in ectopic ESCs (P < 0.01). mRNAs for IAP-family genes, such as cIAP-1, XIAP and survivin, were highly expressed in ectopic ESCs before SS treatment. The fold induction of survivin expression after SS treatment was higher in ectopic than eutopic ESCs (2.8 +/- 0.27 versus 0.69 +/- 0.07, respectively). Survivin gene silencing in SS-treated ectopic ESCs led to an increase of apoptotic cells (P < 0.05, versus control siRNA). CONCLUSIONS We demonstrated that survivin plays a critical role in susceptibility of ESCs to apoptosis. Our results indicate that a survivin inhibitor may be effective as a novel treatment for endometriosis.

Hum Reprod. 2009 Sep 2. [Epub ahead of print]
Letrozole combined with norethisterone acetate compared with norethisterone acetate alone in the treatment of pain symptoms caused by endometriosis.
Ferrero S, Camerini G, Seracchioli R, Ragni N, Venturini PL, Remorgida V.
Department of Obstetrics and Gynaecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1 16132, Genoa, Italy.
BACKGROUND The available data on effectiveness of aromatase inhibitors in treating pain symptoms related to endometriosis is limited. We compared the efficacy and tolerability of the aromatase inhibitor letrozole combined with norethisterone acetate versus norethisterone acetate alone in treating pain symptoms. METHODS This prospective, open-label, non-randomized trial included 82 women with pain symptoms caused by rectovaginal endometriosis. Patients received either a combination of letrozole and norethisterone acetate (group L) or norethisterone acetate alone (group N) for 6 months. Changes in pain symptoms during treatment and in the 12 months of follow-up were evaluated. Side effects of each treatment protocol were recorded. RESULTS Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (P < 0.001 versus baseline by 3 months) in both study groups. At both 3- and 6-month assessment, the intensity of chronic pelvic pain (P < 0.001, P = 0.002, respectively) and deep dyspareunia (P < 0.001, P = 0.005, respectively) was significantly lower in group L than group N. At completion of treatment, 63.4% of women in group N were satisfied with treatment compared with 56.1% in group L (P = 0.49). Pain symptoms recurred after the completion of treatment; at 6-month follow-up no difference was observed in the intensity of pain symptoms between the groups. Adverse effects were more frequent in group L than in group N (P = 0.02). CONCLUSIONS The combination drug regimen was more effective in reducing pain and deep dyspareunia than norethisterone acetate; however, letrozole caused a higher incidence of adverse effects, cost more and did not improve patients’ satisfaction or influence recurrence of pain.
JAMA. 2009 Sep 2;302(9):955-61.
Laparoscopic uterosacral nerve ablation for alleviating chronic pelvic pain: a randomized controlled trial.
Daniels J, Gray R, Hills RK, Latthe P, Buckley L, Gupta J, Selman T, Adey E, Xiong T, Champaneria R, Lilford R, Khan KS; LUNA Trial Collaboration.Collaborators (56)

Latthe P, Selman T, Daniels J, Adey E, Hills R, Hiller L, Buckley L, Xiong T, Champaneria R, Gair R, Powell R, Lynch L, Goodsell S, Hilken N, Tyler E, Wilcockson A, Khan KS, Latthe P, Selman T, Gupta JK, Mann C, Clark TJ, Newton J, Chien P, Macleod M, Thornton J, Rose E, Connor M, Baxter A, Farrell T, Bonner C, Kay V, Crystal W, Pheely M, Irani S, Dwarakanath L, Hollingworth J, Honest H, Chin K, Kabukoba J, Samra JS, Cox CW, Fender GR, Ismail KM, Keay S, Awadzi G, Shaxted EJ, Hitchcock R, Smith J, Zakaria M, Beecham N, Phillips WD, Brocklehurst P, Jordan J, Braunholtz P, Sandercock J.

Department of Obstetrics and Gynecology, Birmingham Women’s Hospital, University of Birmingham, Metchley Park Road, Edgbaston, Birmingham, B15 2TG UK.
CONTEXT: Chronic pelvic pain is a common condition with a major effect on health-related quality of life, work productivity, and health care use. Operative interruption of nerve trunks in the uterosacral ligaments by laparoscopic uterosacral nerve ablation (LUNA) is a treatment option for patients with chronic pelvic pain. OBJECTIVE: To assess the effectiveness of LUNA in patients with chronic pelvic pain. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 487 women with chronic pelvic pain lasting longer than 6 months without or with minimal endometriosis, adhesions, or pelvic inflammatory disease, who were recruited to the study by consultant gynecological surgeons from 18 UK hospitals between February 1998 and December 2005. Follow-up was conducted by questionnaires mailed at 3 and 6 months and at 1, 2, 3, and 5 years. INTERVENTION: Bilateral LUNA or laparoscopy without pelvic denervation (no LUNA); participants were blinded to the treatment allocation. MAIN OUTCOME MEASURES: The primary outcome was pain, which was assessed by a visual analogue scale. Data concerning the 3 types of pain (noncyclical pain, dysmenorrhea, and dyspareunia) were analyzed separately as was the worst pain level experienced from any of these 3 types of pain. The secondary outcome was health-related quality of life, which was measured using a generic instrument (EuroQoL EQ-5D and EQ-VAS). RESULTS: After a median follow-up of 69 months, there were no significant differences reported on the visual analogue pain scales for the worst pain (mean difference between the LUNA group and the no LUNA group, -0.04 cm [95% confidence interval {CI}, -0.33 to 0.25 cm]; P = .80), noncyclical pain (-0.11 cm [95% CI, -0.50 to 0.29 cm]; P = .60), dysmenorrhea (-0.09 cm [95% CI, -0.49 to 0.30 cm]; P = .60), or dyspareunia (0.18 cm [95% CI, -0.22 to 0.62 cm]; P = .40). No differences were observed between the LUNA group and the no LUNA group for quality of life. CONCLUSION: Among women with chronic pelvic pain, LUNA did not result in improvements in pain, dysmenorrhea, dyspareunia, or quality of life compared with laparoscopy without pelvic denervation. TRIAL REGISTRATION: Identifier: ISRCTN41196151.
Gynecol Endocrinol. 2009 Aug 28:1-6. [Epub ahead of print]
Preoperative pain and recurrence risk in patients with peritoneal endometriosis.
Renner SP, Rix S, Boosz A, Lermann JH, Strissel PL, Thiel FC, Oppelt P, Beckmann MW, Fasching PA.
Department of Gynaecology and Obstetrics, Erlangen University Hospital, Erlangen, Germany.
Objective. Pain symptoms in endometriosis patients do not necessarily correlate with the extent of the disease, and there is little evidence regarding the recurrence risk. Aim of this study was to assess the risk factors for the recurrence of endometriosis, with regard to preoperative and postoperative pain. Design. Retrospective observational study. Setting. Single institution study. Population. A total of 150 patients were followed up for recurrence after surgical treatment for endometriosis. Methods. The patients were interviewed retrospectively to obtain information about pain levels during the course of the disease. Main outcome measures. Disease free survival. Results. High preoperative pain levels were associated with a higher risk of recurrence after 4 years of follow-up. The hazards ratio was 2.30 (95% CI, 1.22-4.31; p = 0.009). None of the other parameters assessed for medical history, reproductive history, or lifestyle was associated with the recurrence risk. Conclusions. The risk for recurrence after surgery for endometriosis may be substantially influenced by the patients’ perception of pain. Risk classifications for the recurrence risk in endometriosis are nonexistent. Developing these is imperatively needed soon to improve further treatment and/or prophylaxis for patients after surgery. A classification might be improved by adding sensory testing before surgery.
Gynecol Endocrinol. 2009 Aug 28:1-7. [Epub ahead of print]
Endometriosis and ovarian cancer: A review.
Vlahos NF, Kalampokas T, Fotiou S.
Division of Reproductive Endocrinology, Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Objectives. To describe the relationship between endometriosis and ovarian cancer. Search strategy. Review of the relevant clinical, epidemiologic, and molecular biology literature. Selection criteria. Studies published in the English language using the MEDLINE database. Data collection and analysis. Relevant studies were reviewed by the three authors and those that seem to be of significant scientific value, based on the methodology and statistical power, were included. Main results. Endometriosis and ovarian cancer share many common predisposing factors. Both conditions demonstrate similar patterns regarding local invasion and distal spread they respond similarly to estrogen-induced growth signaling, they express resistance to apoptotic mechanisms and they are characterized by genomic instability. Endometrioid and clear-cell are the most frequent types of ovarian cancer associated with endometriosis. Tubal ligation, in women with endometriosis, seems to prevent retrograde menstruation but it has also been shown to be protective from these types of ovarian cancer. Conclusion. There is evidence to support that endometriosis (by definition a benign process), could simultaneously have the potential for malignant transformation. More studies are needed to establish risk factors that may lead to malignant transformation of this condition and to identify predisposed individuals who may require closer surveillance.
Int J Gynaecol Obstet. 2009 Aug 27. [Epub ahead of print]
A surgical window to access the obliterated posterior cul-de-sac at vaginal hysterectomy.

Sheth SS.
Breach Candy Hospital, Sir Hurkisondas Nurrotamdas Hospital, and Sheth Gynaecological Nursing Home, Mumbai, Maharashtra, India.
OBJECTIVE: To perform vaginal hysterectomy and adnexectomy without laparoscopic assistance in women with ovarian endometriosis by accessing the posterior cul-de-sac via the posterior uterocervical-broad ligament space. METHOD: The author identified the posterior uterocervical-broad ligament space as a surgical window while reviewing his experience at accessing the pouch of Douglas in 40 women in whom vaginal hysterectomy without laparoscopic assistance was performed for ovarian endometriosis. He then used this window in 102 women to remove the adnexa vaginally during vaginal hysterectomy, also without laparoscopy. RESULTS: This new technique was successful in 98 women, with no major complications, but 4 of the first 50 required laparotomy to complete the surgery. CONCLUSION: This new approach allows experienced surgeons to treat women with endometrial ovarian cysts by removing the adnexa vaginally during vaginal hysterectomy without laparoscopy, and complete the surgery abdominally or laparoscopically when necessary.
Tohoku J Exp Med. 2009 Sep;219(1):39-42.
Benefit of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography findings.
Tsuji I, Ami K, Miyazaki A, Hujinami N, Hoshiai H.
Department of Obstetrics and Gynecology, Kinki University of Medicine, Osaka, Japan.
Patients with unexplained infertility following standard infertility screening tests usually undergo timing therapy that coordinates the time of ovulation and coitus, controlled ovarian hyperstimulation, or intrauterine insemination. If the treatment is unsuccessful, diagnostic laparoscopy is performed. However, with recent improvements in the assisted reproductive technology (ART), there has been a growing tendency that bypasses diagnostic laparoscopy and proceeds directly to ART. Therefore, the value of diagnostic laparoscopy in current fertility practice is under debate. In the present study, we evaluated the usefulness of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography (HSG) findings. Between January 1997 and December 2006, 57 infertile patients with normal HSG findings underwent diagnostic laparoscopy at Kinki University Hospital. In 46 (80.7%) of these patients, diagnostic laparoscopy revealed pathologic abnormalities. Specifically, endometriosis and peritubal and/or perifimbrial adhesions were found in 36 (63.2%) and 5 (8.8%) of the patients, respectively. In 8 patients (14.0%), the management plan was switched to ART because of severe tubal diseases. Among the 57 patients, 29 pregnancies (50.9%) were achieved, including 6 ART-mediated pregnancies. We conclude that diagnostic laparoscopy is beneficial for patients with unexplained infertility and normal HSG findings. Indeed, by diagnostic laparoscopy, we are able to detect the cause(s) of infertility in the pelvic cavity and to design a suitable management plan, which could lead to postoperative pregnancy. Therefore, because of the potential diagnostic and therapeutic benefits, patients with unexplained infertility and normal HSG findings should undergo diagnostic laparoscopy prior to ART.
Gynecol Oncol. 2009 Aug 26. [Epub ahead of print]
Extragenital adenosarcoma: A case report, review of the literature, and management discussion.
Huang GS, Arend RC, Sakaris A, Hebert TM, Goldberg GL.
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Women’s Health, Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Albert Einstein Cancer Center, 1695 Eastchester Road, Suite 601, Bronx, NY 10461, USA.
BACKGROUND: Müllerian adenosarcoma is a rare mixed epithelial-mesenchymal tumor. An extragenital site of origin and sarcomatous overgrowth are associated with aggressive clinical behavior. CASE: We present a rare case of extragenital adenosarcoma with sarcomatous overgrowth and coexistent endometriosis. She was treated with initial cytoreductive surgery and chemotherapy. She underwent a second surgery for management of a high-grade bowel obstruction, due to pathologically confirmed recurrent intraperitoneal adenosarcoma. A complete clinical response was achieved with liposomal doxorubicin, and the patient remains disease-free eighteen months after completion of chemotherapy. CONCLUSION: Liposomal doxorubicin appears to be an active agent for the treatment of adenosarcoma with sarcomatous overgrowth. In addition, we conclude from our review of all reported cases of extragenital adenosarcoma that concurrent endometriosis may represent a favorable prognostic factor.
Obstet Gynecol. 2009 Aug;114(2 Pt 2):425-6.
Endometriosis mimicking ovarian cancer in the setting of acquired immune deficiency syndrome.
Haeri S, Cosin JA.
Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7516, USA.
BACKGROUND: With rising rates of human immunodeficiency virus (HIV) among women and resultant immunosuppression, clinicians face varying presentations of gynecologic pathologies. We report a case of endometriosis in a patient with acquired immunodeficiency syndrome (AIDS) presenting with a Sister Mary Joseph’s nodule and mimicking carcinomatosis. CASE: A woman with AIDS and 2-month history of abdominal pain, distention, and weight loss was found to have periumbilical and pelvic masses, ascites, lymphadenopathy, and an elevated CA 125 level. Operative findings included chocolate-colored ascites and peritoneal seeding involving the ovaries, uterus, appendix, bowel, umbilicus, and omentum. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and resection of all gross disease. Pathologic diagnosis was endometriosis and AIDS-associated adenopathy. COMMENT: Immunodeficiency from AIDS can affect the progression of endometriosis to the point of mimicking ovarian malignancy.
Acta Obstet Gynecol Scand. 2009 Aug 25:1-9. [Epub ahead of print]
The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: A systematic review.
Vercellini P, Somigliana E, Vigano P, De Matteis S, Barbara G, Fedele L.
Department of Obstetrics and Gynecology, University of Milan, Milan, Italy.
Estimates of endometriosis recurrence after primary surgery are around 10% per annum during the first postoperative quinquennium. The aim of this study was to define the effect of reoperation in women seeking conception. A MEDLINE and PubMed search was conducted to identify English language studies published in the last 30 years evaluating reproductive performance after second-line surgery. Repeat surgery for recurrent endometriosis and identification of women seeking pregnancy were selected. Two authors abstracted data on standardized forms. The initial literature screening yielded 41 citations, but 19 were excluded because no data on reoperation were described, seven as no original figures were included, three because analyses were performed on the same cohort, and one because extremely skewed data were reported. A total of 313 patients who sought pregnancy after repetitive surgery for recurrent endometriosis were found, 139 in six non-comparative studies, and 174 in five retrospective comparative studies. Overall, pregnancy was achieved in 81 women (26%; 95% confidence interval (CI), 21-31%), without significant difference between the laparotomy (27%) and laparoscopy (25%) approach. Three studies compared pregnancy rate after second-line (28/124; 23%) and primary surgery (236/577; 41%; common odds ratio (OR), 0.44; 95% CI, 0.28-0.68%), and two compared the probability of conception after in-vitro fertilization (IVF) (14/27; 30%) and repetitive surgery (10/50; 20%; common OR, 1.51; 95% CI, 0.58-3.91%). Conclusions. The probability of conception after repeat surgery for recurrent endometriosis appeared limited and reduced compared with that after primary surgery. The results of IVF were not inferior to those of reoperation.
Ther Clin Risk Manag. 2009 Jun;5(3):561-74. Epub 2009 Aug 3.
The levonorgestrel-releasing intrauterine system: Safety, efficacy, and patient acceptability.

Beatty MN, Blumenthal PD.
Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy. Overall, the system is very well tolerated and patient satisfaction is quite high when proper education regarding possible side effects is provided. However, despite all of the obvious benefits of the LNG-IUS, utilization rates remain quite low in the developed countries, especially in the United States. This is thought to be largely secondary to the persistent negative impressions from the Dalkon Shield intrauterine experience in the 1970s. This history continues to negatively influence the opinions of both patients and health care providers with regards to intrauterine devices. Providers should resolve to educate themselves and their patients on the current indications and uses for this device, as it, and intrauterine contraception in general, remains a largely underutilized approach to a variety of women’s health issues.

Regul Pept. 2009 Aug 23. [Epub ahead of print]
Effects of the LHRH antagonist Cetrorelix on affective and cognitive functions in rats.
Telegdy G, Adamik A, Tanaka M, Schally AV.
Department of Pathophysiology, University of Szeged, Hungary.
The decapeptide LHRH antagonist, Cetrorelix, inhibits gonadotropin and sex-steroid secretion. Cetrorelix is used for IVF-ET procedures and for the treatment of benign prostatic hyperplasia, endometriosis and leiomyomas. However little is known about the effects of Cetrorelix on brain functions. Previously we have tested Cetrorelix in mice on the impairment of the consolidation of a passive avoidance behavior caused by beta-amyloid 25-35, anxiolytic action in the plus-maze, antidepressive action in a forced swimming test, tail suspension and open-field behavior following its administration into the lateral brain ventricle. In the present study we repeated and extended the experiments in rats in order to determine whether there are species differences in the action of Cetrorelix between mice and rats. The effects of Cetrorelix evaluated included the methods used in mice without tail suspension test and extended by measuring core temperature. Cetrorelix fully blocked the impairment of the consolidation of passive avoidance learning when given icv 30 min following administration of beta-amyloid 25-35. If beta-amyloid 25-35 and Cetrorelix were given simultaneously, Cetrorelix was ineffective. Cetrorelix elicited slight anxiogenic and stronger anxiolytic action in the plus-maze, depending on the dose used. In the forced swimming tests, Cetrorelix showed antidepressive-like action. In open-field behavior tests Cetrorelix displayed a U-type action on locomotion with 0.5 and 2 microg increasing locomotion, and increase rearing but and had no effect on grooming at 0.5-2 microg. Cetrorelix had no action on core temperature. Our findings demonstrate that Cetrorelix is able to correct the impairment of the memory consolidation caused by beta-amyloid 25-35. Cetrorelix elicits anxiolytic and antidepressive action, slightly increases locomotion and rearing in open field, but it does not influence the core temperature. The results obtained in rats are similar to those reported previously by us in mice. Collectively our findings confirm the effects of Cetrorelix on brain function in two species and suggest the possible merit of a clinical trial with Cetrorelix in patients with anxiety, depression and Alzheimer’s disease.

J Sex Res. 2009 Aug 24:1-15. [Epub ahead of print]


Sexual Functioning Following Elective Hysterectomy: The Role of Surgical and Psychosocial Variables.
Peterson ZD, Rothenberg JM, Bilbrey S, Heiman JR.
Department of Psychology and Institute for Women and Gender Studies, University of Missouri-St. Louis.
In this article, two studies were conducted to investigate the surgical and psychosocial correlates of women’s post-hysterectomy sexual functioning. In Study 1, sexual functioning was measured in an online convenience sample of 65 women who had undergone elective hysterectomy. Results suggested that most women experienced improved sexual functioning after their hysterectomy. Women who underwent hysterectomy to treat endometriosis reported less improvement in sexual functioning as compared to women who had hysterectomies for other indications, and women who had abdominal hysterectomies reported less improvement in sexual functioning as compared to women who had vaginal hysterectomies. Sexual functioning post-hysterectomy was associated with psychosocial variables, particularly body esteem and relationship quality. In Study 2, sexual functioning was investigated at two time points three to five months apart in a sample of 14 women who reported developing sexual problems following their elective hysterectomies. Results suggested that, among women suffering from post-hysterectomy sexual dysfunction, sexual pain and difficulty with orgasm increased over time.
Gynecol Endocrinol. 2009 Aug 20:1-5. [Epub ahead of print]

Immunohistochemical expression of YKL-40 in peritoneal endometriosis.
Kim PJ, Hong DG, Park JY, Cho YL, Park IS, Lee YS.
Department of Obstetrics and Gynecology.
Aims. To evaluate the relationship between the immunohistochemical expression of YKL-40 and peritoneal endometriosis by using paraffinized peritoneal tissue blocks. Methods and materials. We retrospectively collected data from 27 patients whose pathologic reports indicated invasion of the peritoneum by endometriosis. A conventional peroxidase staining technique was performed using rabbit polyclonal antibody (Quidel(R) corporation, Santa Clara, CA) on peritoneal tissue blocks; their histology was then reviewed by a pathologist, and data were analyzed by nonparametric and Mann-Whitney tests. Results. YKL-40 was detected immunohistochemically in 17 (63%) of 27 cases. The number of biopsies which were invaded by endometriosis (P = 0.015), with a score based on the revised classification of endometriosis (American Society for Reproductive Medicine) had statistical significance (P = 0.001). The obstetric history, age, body mass index, severity, and occurrence of dysmenorrhea, menstrual phase, preoperative CA 125, erythrocyte sedimentation rate, and white blood cell count had no statistical significance. YKL-40 immunoreactivity was recognized as brown staining, localized to the cytoplasm of epithelial cells of endometrial gland in peritoneal endometriosis. There was no positive staining on endometrial stromal cells or smooth muscle cells. Conclusions. YKL-40 is related to severity of peritoneal endometriosis. However why a different expression level of immunohistochemical staining should occur is not known and needs further investigation.
Fertil Steril. 2009 Aug 21. [Epub ahead of print]
Voiding dysfunction in women undergoing laparoscopic treatment for moderate to severe endometriosis.
Vashisht A, Gulumser C, Pandis G, Saridogan E, Cutner A.
Department of Obstetrics and Gynaecology, University College Hospital, London, United Kingdom.
We conducted a prospective study to evaluate the incidence and the surgical factors determining the development of postoperative voiding dysfunction following this surgery. The presence of rectovaginal dissection was significantly associated with the development of voiding dysfunction, and we suggest vigilance among practitioners about the possibility of the development of voiding dysfunction in this group of women. 


Bibliografia 2009 – Pagina 1

Colorectal Dis. 2009 Oct 13. [Epub ahead of print]

Irritable bowel syndrome and chronic constipation in patients with endometriosis.

Meurs-Szojda MM, Mijatovic V, Felt-Bersma RJ, Hompes PG.

Endometriosis Centre VUmc: Dep. of Gastroenterology and Hepatology, VU University Medical Centre, P.O.Box 7057, 1007 MB Amsterdam, The Netherlands.

Abstract Aim: To evaluate how many patients with endometriosis had concomitant irritable bowel syndrome (IBS) and/or constipation according to the Rome III criteria. Furthermore, the value of an additional gastroenterological consultation with therapeutic advice was evaluated. Method: Patients with proven endometriosis were included in a prospective, single-centre study. A questionnaire was undertaken regarding IBS and chronic constipation. Patients who complied with Rome III criteria were referred to our gastroenterological outpatient clinic. Results: In total 101 patients where included. Endometriosis was diagnosed surgically in 97%, and visually in the vagina in 3%. Fifteen percent of them had additional IBS and 14% had functional constipation without IBS. Of the 22 patients finally presenting to the gastroenterologist, five had a significant stenotic rectosigmoid lesion and were treated surgically. The remaining 17 patients were treated conservatively. Defecation symptoms improved in 82% and pain was reduced in 53%. Conclusion: In patients with endometriosis, 30% also had IBS or constipation. Referral to a gastorenterologist resulted in improvement of defaecation in 86% and 64% had pain reduction.


Zhejiang Da Xue Xue Bao Yi Xue Ban. 2009 Sep;38(5):531-4.


Diagnosis and management of 57 cases with rectovaginal endometriosis.

[Article in Chinese]


Wang WX, Peng ZL.

Department of Obsterics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

OBJECTIVE: To study the diagnosis and therapy of the rectovaginal endometriosis. METHODS: Clinical data of 57 women with rectovaginal endometriosis admitted to the West China Second University Hospital of Sichuan University in last two years,were retrospectively reviewed. RESULT: The average age of patients was 40.1 years. The main clinical manifestations were dysmenorrheal, changes of menorrhea and digestive stimulation. The diameter of deep endometriosis nodules was between 1-6 cm, and 77% were found to have more than one nodules. Seven of these patients had positive results in transvaginal ultrasonography; 61%(11/18) patients had elevated CA125 levels. Thirteen patients were given preoperational medical treatment, but had no effect. All patients, except one accepted laparotomic therapy of complete excision of endometriosis nodules; 23 cases underwent drug therapy after operation. No patients had recurrence in recto-vaginal septum after complete excision; only one recurred in right ovary. Patients who failed to remove the total lesion showed improvement in pain. CONCLUSION: Diagnosis of the rectovaginal endometriosis is based on symptoms, vaginal and rectal examination, and auxiliary examination. Complete excision of endometriosis nodules is the main therapeutic method.


Ultrasound Obstet Gynecol. 2009 Oct 14. [Epub ahead of print]


Diagnostic accuracy and potential limitations of transvaginal sonography for bladder endometriosis.

Savelli L, Manuzzi L, Pollastri P, Mabrouk M, Seracchioli R, Venturoli S.

Gynecology and Reproductive Medicine Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

OBJECTIVES: To evaluate the accuracy and the potential limitations of transvaginal sonography (TVS) in the preoperative evaluation of women with clinically suspected bladder endometriosis and to describe the sonographic features of the pathological condition in cases in which it was confirmed. METHODS: In the period between 2001 and 2006, we operated on 490 patients with clinically/sonographically suspected endometriosis. In 41 cases, bladder endometriosis was diagnosed at surgery and confirmed at histopathological examination. All patients underwent TVS in a standardized manner not more than 1 month before surgery. Findings at preoperative TVS were described and compared with those at laparoscopy in order to evaluate the sensitivity, specificity, and positive and negative predictive values of TVS. RESULTS: Bladder endometriosis was correctly identified at TVS in 18/41 cases (43.9%) while 23/41 (56.1%) patients had a negative preoperative sonogram. The sensitivity, specificity and positive and negative predictive values of TVS for bladder endometriosis were 44% (18/41), 100% (449/449), 100% (18/18) and 95% (449/472), respectively, and the total accuracy was 95% (467/490). The detection rate was strongly related to mean lesion diameter as measured by the pathologist (mean +/- SD, 42.5 +/- 22.1 mm in the nodules detected vs. 28.9 +/- 14.8 mm in the nodules missed; P = 0.029) and to a history of previous surgery for endometriosis (70.6% vs. 25.0%; P = 0.005). At TVS, the nodule was hypoechogenic, its morphology was either elongated (‘comma-shaped’: 12/18, 66.7%) or spherical (6/18, 33.3%), and the site involved was the dome (11/18, 61.1%) or the base (7/18, 38.9%) of the bladder. Small anechogenic cystic areas within the nodule were seen in five of the 18 patients (27.8%) and a bright hyperechogenic rim was seen in 10 (55.6%). CONCLUSIONS: The detection rate of bladder endometriosis by TVS depends on the size of the endometriotic nodules, with detected nodules being larger than those that were missed. A history of previous surgery for endometriosis increases the likelihood of bladder endometriosis being detected on ultrasound examination. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.


J Med Case Reports. 2009 Jul 22;3:8387.

Cornual pregnancy as a complicaton of the use of a levonorgestrel intrauterine device: a case report.

Beltman J, de Groot C.

Medisch Centrum Haaglanden, Department of Obstetrics and Gynaecology Lijnbaan 32, 2501 CK, The Hague The Netherlands.

INTRODUCTION: Complications of copper load intrauterine devices, including ectopic pregnancies are well reported. Rates of ectopic pregnancy are 0.6 to 1.1% per year. However, the levonorgestrel intrauterine device has been described as more protective against ectopic pregnancies due to the addition of the hormone levonorgestrel. The hormone released from the intrauterine device causes some systemic effects, but local effects such as glandular atrophy and stromal decidualization, in addition to foreign body reaction, are dominant. Few case reports have described ampullary ectopic pregnancies. However, we report, for the first time, a major complication of levonorgestrel intrauterine device: a cornual pregnancy. CASE PRESENTATION: A 36-year-old Caucasian nulliparous woman presented with complaints of progressive nausea, abdominal pain and irregular vaginal bleeding for 2 months. For 3 years, she had been using a levonorgestrel intrauterine device. A two-dimensional transvaginal sonogram noted a sac situated external to the endometrial cavity in the right cornua of the uterus with an empty uterus. She was successfully treated with chemotherapy. CONCLUSION: Many complications have been described, including ectopic pregnancies, using copper intrauterine devices. The levonorgestrel-releasing intrauterine system is a particularly good choice for adolescents because of associated non-contraceptive benefits such as decreased menstrual bleeding, dysmenorrhea and pain associated with endometriosis [1]. Yet a cornual pregnancy following the use of a levonorgestrel intrauterine device is a complication which, to our knowledge, has not been described before. Physicians prescribing this type of intrauterine device should be aware of this rare event.

Kyobu Geka. 2009 Oct;62(11):1015-8.

Catamenial pneumothorax with breast cancer treated successfully by goserelin acetate

[Article in Japanese]

Matsuura M, Fujiwara T, Kataoka K, Itoh M, Ohtani S, Higaki K, Senoo N.

Department of Thoracic Surgery, Hiroshima City Hospital, Hiroshima, Japan.

A 47-year-old woman with 4 episodes of right pneumothorax related to onset of menstruation was reported. A month ago, she was undergone breast conserving resection for breast cancer. She had recurrent right pneumothorax a month later and operation was performed. Thoracoscopy revealed the presence of multiple fenestrations in the right diaphragm. Thoracoscopic partial resection of the diaphragm was performed. Histopathological findings of the lesion showed spindle cells with hemosiderosis. Immunohistochemistry showed that spindle cells were estrogen receptor (ER) positive and progesterone receptor (PgR) positive, compatible with endometriosis. She was treated by tamoxifen and goserelin acetate for breast cancer and endometriosis. Two years later, gonadotropin releasing hormone (GnRH) analogue was converted from goserelin acetate to leuprorelin acetate. She was diagnosed as having recurrence of right pneumothorax 17 months later and was treated with a chest tube. Additionally, GnRH analogue was re-converted to goserelin acetate. Since then, she has been asymptomatic free for 18 months. A catamenial pneumothorax is rare disease with difficulty of diagnosis and treatment We herein report a case of the disease that was treated successfully by goserelin acetate.

Rev Obstet Gynecol. 2009 Summer;2(3):176-85.

Is surgical repair of the fallopian tubes ever appropriate?

Sotrel G.

Brigham and Women’s Hospital and Harvard Medical School Boston, MA.

The overall median prevalence of infertility, defined as no conception after more than 12 months of unprotected intercourse with the husband or cohabiting partner in women aged 15 to 44 years, is approximately 9%. About 25% to 33% of female infertility is the result of tubal disease and endometriosis. In view of very successful alternative treatment of tubal factor infertility, the surgical repair of the fallopian tubes is all but obsolete and has been replaced with assisted reproductive technology.

This article reviews situations in which surgical repair of the fallopian tubes may facilitate conception.


J Obstet Gynaecol. 2009 Nov;29(8):729-31.

Can high histological confirmation rates be achieved for pelvic endometriosis?

Stavroulis AI, Saridogan E, Benjamin E, Cutner AS.

Elizabeth Garrett Anderson and Obstetric Hospital, The University College London Hospitals NHS Foundation Trust.

This paper aims to determine the correlation between the diagnosis of endometriosis on the basis of the visualisation at laparoscopy and the histological diagnosis. Histological confirmation rates vary in the current literature. We retrospectively reviewed 160 patients over 2 years, who had laparoscopy for pelvic pain or suspected endometriosis. Our results showed higher histological confirmation rate compared with other studies. In addition, the use of CD10 IHC may increase detection rates further when the diagnosis is suspected but not confirmed by routine histology. Diagnosis of endometriosis is essential as it can influence patients’ management.

Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001300.

Laparoscopic surgery for pelvic pain associated with endometriosis.

Jacobson TZ, Duffy JM, Barlow D, Koninckx PR, Garry R.

Department of Obstetrics and Gynaecology, South Auckland Clinical School, Middlemore Hospital, Private Bag 93311, Auckland, New Zealand.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions and relieve painful symptoms. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. SEARCH STRATEGY: For the update in July 2009 we searched the Cochrane Menstrual Disorders and Subfertility Group’s specialised register of trials (searched July 2009), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 July 2009), EMBASE (1980 July 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials were selected comparing the effectiveness of laparoscopic surgery used to treat pelvic pain associated with endometriosis, with other treatment modalities or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and extraction of relevant data was performed independently by two reviewers. MAIN RESULTS: Five studies were included in the meta-analysis, including three full papers and two conference reports. All the randomised controlled trials with the exception of Lalchandani 2003 compared different laparoscopic surgical techniques with diagnotic laparoscopy only. Lalchandani 2003 compared laparoscopic coagulation therapy with diagnostic laparoscopy and medical treatment. Three studies (Abbott 2004; Sutton 1994; Tutunaru 2006) reported the pain scores six months post operatively. Meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 5.72 95%Cl 3.09 to 10.60 ; 171 participants, three trials, Analysis 1.1). A single study (Tutunaru 2006) reported pain scores twelve months after the procedure. Analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 7.72 95%Cl 2.97 to 20.06 ; 33 participants, one trial, Analysis 1.1). AUTHORS’ CONCLUSIONS: Laparoscopic surgery results in improved pain outcomes when compared to diagnostic laparoscopy alone. There were few women diagnosed with severe endometriosis included in the meta-analysis and therefore any conclusions from this meta-analysis regarding treatment of severe endometriosis should be made with caution. It is not possible to draw conclusions from the meta-analysis which specific laparoscopic surgical intervention is most effective.

J Huazhong Univ Sci Technolog Med Sci. 2009 Oct;29(5):637-41. Epub 2009 Oct 11.


Elevated vascular endothelia growth factor-A in the serum and peritoneal fluid of patients with endometriosis.

Wang H, Gorpudolo N, Li Y, Feng D, Wang Z, Zhang Y.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China,

There has been emergence of evidence suggesting that specific variants of the vascular endothelia growth factor (VEGF) family, based on their ability to regulate angiogenesis, would be pivotal in the pathogenesis of endometriosis. This study was aimed at determining whether high levels of VEGF-A could be found in the serum and peritoneal fluid (PF) of patients with endometriosis. VEGF-A levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum and PF from 46 patients with surgically confirmed endometriosis, and 40 controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. The results showed the mean VEGF-A levels were significantly higher in the serum and PF of patients with endometriosis than in the controls. The VEGF-A levels in the serum and PF of patients with severe endometriosis (stages III-IV) were significantly higher than in those with minimal endometriosis (P<0.001). It was concluded that endometriosis was associated with significant modulation in the levels of circulating VEGF-A.


Hum Reprod. 2009 Oct 10. [Epub ahead of print]

Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study.

Ferrero S, Camerini G, Ragni N, Venturini PL, Biscaldi E, Remorgida V.

Department of Obstetrics and Gynaecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1, 16132 Genoa, Italy.

BACKGROUND This pilot study evaluates the efficacy of norethisterone acetate in treating pain and gastrointestinal symptoms of women with colorectal endometriosis. METHODS This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded. RESULTS Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle. CONCLUSIONS In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Gynecol Obstet Fertil. 2009 Oct 9. [Epub ahead of print]

Ovarian gonadotropic inhibition and endometriosis. About fighting false dogmas…

[Article in French]


Belaisch J.

36, rue de Tocqueville, 75017 Paris, France.

Ovarian gonadotropic inhibition is today an efficacious tool in the treatment of endometriosis mainly when associated with surgery and sometimes by itself. However, to be useful, this inhibition must be stable – without any cyclical looseness – of long duration, sometimes during years and sufficiently powerful. Depending on the severity of symptoms and that of the disease, the choice will be among GnRH agonists, gestagens and combined OCs. The recent development of continuous oral contraception with protracted amenorrhoea makes treatment by continuous hormonal administration easier for the patients with endometriosis.

Pain. 2009 Oct 9. [Epub ahead of print]

Endometriosis-induced vaginal hyperalgesia in the rat: Role of the ectopic growths and their innervation.

McAllister SL, McGinty KA, Resuehr D, Berkley KJ.

Program in Neuroscience, Florida State University, Tallahassee, FL 32306-4301, USA.

Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. We tested the hypothesis that the cysts are necessary to maintain vaginal hyperalgesia by assessing the effect of surgically removing them. Complete-cyst-removal eliminated ENDO-induced vaginal hyperalgesia up to 4months post-operatively. Sham-cyst-removal in ENDO rats, in which cysts were not removed, or partial cyst-removal increased the ENDO-induced hyperalgesia. The decreases and increases both took 3-6weeks to develop. Changes in ENDO-induced hyperalgesia did not occur in a control group of ENDO rats who had no surgery after ENDO. In a double-surgery control group, neither shamENDO surgery nor a subsequent sham surgery that mimicked “removal” of non-existent cysts influenced vaginal nociception. In a no-surgery control group, vaginal nociception remained stable for >6months. The increases in ENDO-induced hyperalgesia produced by the sham-cyst-removal surgery were smaller in proestrus than in other estrous stages. During the other stages (but not during proestrus), sympathetic innervation of the cysts increased. These results suggest that maintenance of ENDO-induced vaginal hyperalgesia requires continued presence of at least some ectopic endometrial tissue, and that surgical treatment that fails to remove ectopic endometrial tissue can exacerbate the hyperalgesia, possibly due in part to an increase in the cysts’ sympathetic innervation.

Int J Gynaecol Obstet. 2009 Oct 9. [Epub ahead of print]

A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis.

Köhler G, Faustmann TA, Gerlinger C, Seitz C, Mueck AO.

Department of Gynecology and Obstetrics, University of Greifswald, Greifswald, Germany.

OBJECTIVES: To compare the efficacy and safety of dienogest at doses of 1, 2, and 4mg/day orally in the treatment of endometriosis. METHODS: An open-label, randomized, multicenter, 24-week comparative trial in women with histologically confirmed endometriosis. Efficacy was assessed by second-look laparoscopy and patient-reported symptoms. Statistical tests included chi(2) and Wilcoxon signed rank tests. RESULTS: Dienogest reduced mean revised American Fertility Society scores from 11.4 to 3.6 (n=29; P<0.001) in the 2-mg group and from 9.7 to 3.9 (n=35; P<0.001) in the 4-mg group. Dienogest at 2 and 4mg/day was associated with symptom improvements in substantial proportions of women. Both dienogest doses were generally well tolerated, with low rates of treatment discontinuation due to adverse events. The 1-mg dose arm was discontinued owing to insufficient bleeding control. CONCLUSION: Dienogest at 2mg once a day is recommended as the optimal dose in future studies of endometriosis.

Fertil Steril. 2009 Oct 9. [Epub ahead of print]

Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis.

Matsuzaki S, Schubert B.

CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction, Clermont-Ferrand.

Expression levels of 8-hydroxydeoxyguanosine, a sensitive indicator of DNA damage resulting from oxidative stress, were significantly higher in samples of normal ovarian cortex surrounding endometriotic cysts when compared with ovarian cortex surrounding dermoid and serous ovarian cysts. These findings suggest that the normal ovarian cortex surrounding endometriotic tissues is more severely affected by oxidative stress than ovarian cortex adjacent to other benign ovarian cysts.

Fertil Steril. 2009 Oct 9. [Epub ahead of print]

Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis.

Bilotas M, Meresman G, Stella I, Sueldo C, Barañao RI.

Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.

OBJECTIVE: To evaluate the effect of aromatase inhibitors on ectopic endometrial growth and on the release of proangiogenic and proinflammatory factors in peritoneal fluid (PF). DESIGN: Prospective experimental study. SETTING: Animal research and laboratory facility. ANIMAL(S): Female Balb/c mice 2 months of age. INTERVENTION(S): Mice had surgery performed to induce endometriosis-like lesions. Treatment with anastrozole or letrozole was started on either postoperative day 1 or 28 and continued for 4 weeks. MAIN OUTCOME MEASURE(S): Endometriotic lesions were counted and measured and aromatase expression, cell proliferation, and apoptosis were assessed. Vascular endothelial growth factor (VEGF) and prostaglandin E (PGE) levels were evaluated in the PF. RESULT(S): Endometriosis-like lesions express aromatase P-450. Treatment with either anastrozole or letrozole did not prevent lesion establishment; however, it significantly decreased the size of the endometriotic lesion. When treatment was initiated on postoperative day 1, letrozole and anastrozole decreased cell proliferation and increased apoptosis. When treatment was started on postoperative day 28, both aromatase inhibitors decreased cell proliferation, but only anastrozole augmented apoptosis levels. In addition, letrozole reduced VEGF and PGE levels in PF. Anastrozole diminished VEGF content but did not cause any significant change in PGE levels. CONCLUSION(S): These findings support the further investigation of aromatase inhibition as a treatment option for endometriosis.


Reprod Biol Endocrinol. 2009 Oct 12;7(1):109. [Epub ahead of print]

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis.

Camanni M, Bonino L, Delpiano EM, Berchialla P, Migliaretti G, Revelli A, Deltetto F.

ABSTRACT: BACKGROUND: this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis. Methods: Eighty cases of histologically confirmed endometriosis affecting the ureter, 10 of which with bladder involvement were prospectively studied. In detail, patients were 13 women with ureteral stenosis (7 with hydronephrosis), 32 with circular lesions totally encasing the ureter, and 35 with endometriotic foci on the ureteral wall, but not completely encasing it. They were submitted to laparoscopic ureterolysis with or without partial cystectomy, ureteroneocistostomy. The rate of surgical complications, the recurrence rate, the patients’ satisfaction rate was assessed during 22 months (median) follow-up. Results: Laparoscopic ureterolysis was employed for all patients and set free the ureter from the disease in 95 % of cases, whereas ureteroneocystostomy was necessary for 4 patients showing severe stenosis with hydronephrosis, among which 2 had intrinsic endometriosis of the ureteral muscularis. Three post-surgery ureteral fistulae occurred in cases with ureteral involvement longer than 4 cm: two cases were successfully treated placing double J catheter, the third needed ureteroneocistostomy. During follow-up, ureteral endometriosis recurred in 2 patients who consequently underwent ureteroneocystostomy. Most patients expressed high satisfaction rate throughout the whole follow-up period. Conclusions: laparoscopic ureterolysis is effective and well tolerated in most cases of ureteral endometriosis. Ureteroneocystostomy is a better strategy for patients with extended (more than 4 cm) ureteral involvement or with severe stenosis with or without hydronephrosis.

Sci Total Environ. 2009 Oct 5. [Epub ahead of print]

Urinary phthalate monoesters and endometriosis in infertile Japanese women.

Itoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Phthalates may act as an estrogen and are a potential risk factor for estrogen-related diseases such as endometriosis. We assessed the association between phthalate exposure and endometriosis in 166 consecutive women who presented at a university hospital for consultation regarding infertility. The subjects were interviewed and provided a urine specimen prior to a laparoscopic diagnosis of endometriosis. They were then categorized by the severity of endometriosis as controls (stages 0-I) and cases (stages II-IV). Urinary concentrations of the phthalate metabolites monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate were measured in 57 cases and 80 controls using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Adjusted odds ratios for endometriosis in relation to dichotomized individual phthalate metabolites (standardized for creatinine) were calculated. No significant association between endometriosis and any urinary creatinine-adjusted phthalate monoester was seen. Adjusted odds ratio (95% confidence interval) for higher dichotomized MEHP by endometriosis was 1.57 (0.74-3.30). No monotonic trend was seen in urinary creatinine-adjusted concentration of phthalate metabolites by endometriosis stage (p=0.23-0.90). Our results do not support the hypothesis that higher urinary concentrations of phthalate metabolites are associated with the risk of endometriosis in infertile Japanese women.

Reprod Sci. 2009 Oct 2. [Epub ahead of print]

Haptoglobin Expression in Endometrioid Adenocarcinoma of the Uterus.

Nabli H, Tuller E, Sharpe-Timms KL.

Objective: Elevated serum haptoglobin (Hp) concentrations have been reported in patients with malignant diseases. We have shown that Hp is produced by and localizes only in the stroma and not the epithelium of endometriotic lesions, which share many characteristics of carcinoma. Furthermore, Hp mRNA and protein are found exclusively in the stroma of eutopic endometrium from women with endometriosis and not those without endometriosis. We hypothesized that characteristic patterns of Hp gene expression and protein localization in endometrioid adenocarcinoma of the uterus may provide insight into the clinical utility of Hp as a tumor marker or alternative therapeutic approach. Methods: Biopsies of endometrioid adenocarcinoma tumors of the uterus and their adjacent nonaffected endometrium were collected. Normal endometrium was collected from healthy women. Haptoglobin messenger RNA (mRNA) levels were quantified by quantitative polymerase chain reaction (Q-PCR). Haptoglobin protein cell-specific localization was identified by immunohistochemistry. Results: Haptoglobin mRNA levels were significantly greater (P < .005) in endometrioid adenocarcinoma and adjacent nonaffected endometrial tissues than normal endometrium. No correlation was found between Hp levels and cancer stage (P = .673) or grade (P = .739). Haptoglobin protein localized in both stromal and glandular epithelial cells of endometrioid adenocarcinoma and their adjacent nonaffected tissue but not in control endometrium. Conclusions: Our results have identified, for the first time, unique patterns of Hp mRNA expression and protein localization in the stromal and glandular epithelial cells of endometrioid adenocarcinoma of the uterus. We propose that this unique pattern of endometrioid adenocarcinoma Hp expression may be developed as a novel diagnostic marker. Modulation of Hp, with its immunomodulatory and angiogenic properties, may generate novel methods of prevention or treatment for endometrial cancer.

Eur J Obstet Gynecol Reprod Biol. 2009 Sep 30. [Epub ahead of print]

The impact of IVF procedures on endometriosis recurrence.

Benaglia L, Somigliana E, Vercellini P, Benedetti F, Iemmello R, Vighi V, Santi G, Ragni G.

Infertility Unit, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy; Università degli Studi di Milano, Milan, Italy.

OBJECTIVE: In infertile women with endometriosis requiring an in vitro fertilization (IVF) procedure, the potential risk of an IVF-related progression of the disease remains a matter of debate. Thus, since available data on this issue are scanty and controversial, an observational study has been herein conducted in order to clarify this issue. STUDY DESIGN: We recruited 233 women with endometriosis who underwent IVF cycles in our unit. Patients were contacted to assess whether they experienced recurrences of the disease after IVF. The main outcome was to evaluate the impact of the number of IVF cycles and the responsiveness to ovarian hyperstimulation on the likelihood of recurrence. Clinical characteristics of women who did and did not have a recurrence were compared. RESULTS: One hundred and eighty-nine women were included, 41 of whom (22%) had a diagnosis of endometriosis recurrence. The 36 months cumulative recurrence rate was 20%. The number of IVF cycles and the responsiveness to ovarian hyperstimulation were not associated with the risk of disease recurrence. The adjusted OR for recurrences according to the number of started cycles was 0.92 (95% CI: 0.77-1.10) per cycle (p=0.35). The adjusted OR for recurrences in women with intact versus compromised ovarian reserve was 0.80 (95% CI: 0.40-1.58) (p=0.52). CONCLUSIONS: IVF procedures do not seem to influence the likelihood of endometriosis recurrence.

Fertil Steril. 2009 Sep 30. [Epub ahead of print]

Malignant transformation of residual endometriosis after hysterectomy: a case series.

Karanjgaokar VC, Murphy DJ, Samra JS, Mann CH.

Department of Gynaeoncology, New Cross Hospital, Wolverhampton, West Midlands, United Kingdom.

OBJECTIVE: To explore the role of long-standing hormone replacement therapy (HRT) in the malignant transformation of endometriosis. DESIGN: Short case series. Three cases of women with pelvic clearance receiving long-standing HRT studied in detail. SETTING: Teaching hospital in the United Kingdom (Gynaecological Cancer Centre) (Institutional Review Board approval was not obtained as it was not deemed necessary, this being a case series). PATIENT(S): Women with a history of pelvic clearance for endometriosis and longstanding HRT. INTERVENTION(S): HRT. MAIN OUTCOME MEASURE(S): Malignant transformation of endometriosis. RESULT(S): Long-standing HRT in all three women with pelvic clearance for endometriosis resulted in malignant transformation of residual endometriosis many years after the initial surgery. All cases presented with a new pelvic lesion. CONCLUSION(S): The diagnosis of malignant transformation needs to be considered in women with a history of endometriosis and with long-term HRT use in whom a new pelvic lesion is detected. The risk of malignant transformation in women with endometriosis after pelvic clearance receiving HRT needs to be explored further. Surveillance with CA-125 and imaging in such cases to predict recurrence or malignant transformation needs to be studied further in a research setting.

Acta Cytol. 2009 Sep-Oct;53(5):587-90.

Peritoneal washing cytology of disseminated low grade endometrial stromal sarcoma: a case report.

Lim BJ, Choi SY, Kang DY, Suh KS.

Department of Pathology, Chungnam National University College of Medicine, Chung-go, Daejeon, Korea.

BACKGROUND: Low grade endometrial stromal sarcoma (LESS) with dissemination is rare, and its cytomorphology has not been well described. Recently, we experienced a case of LESS with peritoneal dissemination that was confirmed by peritoneal washing cytology and histology. CASE: A 51-year-old woman was admitted for evaluation of vaginal bleeding. Uterine ultrasonography revealed a diffisely thickened endomyometrium with a vaguely circumscribed nodular mass-like lesion measuring 7.4 cm in the largest dimension. Under the impression of adenomyosis, an exploratory laparotomy was performed. On examination of the abdominal cavity, multiple tiny, grayish nodular excrescences firmly attached to the peritoneal wall and the serosal surface of the small bowel and uterus were noted. A total hysterectomy with bilateral salpingo-oophorectomy and peritoneal fluid sampling were performed. The peritoneal fluid smear demonstrated several loosely packed clusters of monotonous cells showing round to oval nuclei, rare small nucleoli and scanty cytoplasm. CD10 immunostaining revealed cytoplasmic positivity in these cells, but reactive mesothelial cells showed a negative reaction. Histologic examination of the uterus revealed the typical histologic findings of LESS. CONCLUSION: Cytopathologic diagnosis of disseminated LESS is not always easy. Immunocytochemical staining for CD10 can be helpful.

Taiwan J Obstet Gynecol. 2009 Sep;48(3):232-8.

Adenomyosis and its variance: adenomyoma and female fertility.

Wang PH, Su WH, Sheu BC, Liu WM.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, National Yang-Ming University Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan.

Extensive adenomyosis (adenomyosis) or its variance, localized adenomyosis (adenomyoma) of the uterus, is often described as scattered, widely-distributed endometrial glands or stromal tissue found throughout the myometrium layer of the uterus. By definition, adenomyosis consists of epithelial as well as stromal elements, and is situated at least 2.5 mm below the endometrialmyometrial junction. However, the diagnosis and clinical significance of uterine adenomyosis and/or adenomyoma remain somewhat enigmatic. The relationship between infertility and uterine adenomyosis and/or adenomyoma is still uncertain, but severe endometriosis impairs the chances of successful pregnancy when using artificial reproductive techniques. To date, there is no uniform agreement on the most appropriate therapeutic methods for managing women with uterine adenomyosis and/or adenomyoma who want to preserve their fertility. Fertility has been restored after successful treatment of adenomyosis using multiple modalities, including hormonal therapy and conservative surgical therapy via laparoscopy or exploratory laparotomy, uterine artery embolization, and other methods, including a potential but under-investigated procedure, magnetic resonance-guided focused ultrasound. This review will explore recent publications that have addressed the use of different approaches in the management of subfertile women with uterine adenomyosis and adenomyoma.

Hum Reprod Update. 2009 Sep 30. [Epub ahead of print]

Should the ovaries be removed or retained at the time of hysterectomy for benign disease?

Hickey M, Ambekar M, Hammond I.

School of Women’s and Infants’ Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia.

BACKGROUND Bilateral oophorectomy is commonly performed at the time of hysterectomy for benign disease. Indications for oophorectomy vary, but in most cases relatively little high-quality information is available to inform the surgeon or patient regarding the relative risks and benefits of ovarian conservation or removal. This review will address the common clinical situations when oophorectomy may be performed and will evaluate the evidence for risk and benefit in each of these circumstances. The aim of this review is to bring together the evidence regarding oophorectomy in pre- and post-menopausal women and to highlight the areas needing further study. METHODS We searched the published literature for studies related to outcomes following surgical menopause, risk-reducing surgery for ovarian cancer, surgical treatment for endometriosis, bilateral oophorectomy for benign disease and treatment for premenstrual syndrome/premenstrual dysphoric disorder. RESULTS Rates of oophorectomy at the time of hysterectomy for benign disease appear to be increasing. There is good evidence to support bilateral salpingoophorectomy (BSO) as a risk-reducing surgery for women at high risk of ovarian cancer, but relatively little evidence to support oophorectomy or BSO in other circumstances. There is growing evidence from observational studies that surgical menopause may impact negatively on future cardiovascular, psychosexual, cognitive and mental health. CONCLUSION Clinicians and patients should fully consider the relative risks and benefits of oophorectomy on an individual basis prior to surgery.

JSLS. 2009 Jul-Sep;13(3):376-83.

Incidental appendectomy during endoscopic surgery.

Song JY, Yordan E, Rotman C.

Oak Brook Institute of Endoscopy, Rush Medical College, St. Charles, Illinois, USA.

BACKGROUND AND OBJECTIVES: The first laparoscopic appendectomy was performed over 25 years ago, and yet controversy still exists over the open method vs. the laparoscopic approach, and whether an incidental appendectomy is warranted. This study aimed to evaluate our experience in performing a laparoscopic incidental appendectomy and to address these issues. METHODS: A total of 772 laparoscopic appendectomies were performed and analyzed and statistically evaluated. RESULTS: Mean age of the patients was 30.8+/-7.0 years. Mean operating time for an incidental appendectomy was 12.3+/-4.5 minutes. Most common pathology result was adhesions, and the rarest was endometriosis. Of patients with confirmed appendicitis, 75.8% did not have an initial preoperative diagnosis of appendicitis. When warranted, 103 (13.3%) patients underwent a second-look laparoscopy: 75.5% had no adhesions, 23.5% had mild adhesions, 2% had moderate adhesions. Backward elimination logistic regression revealed that endometriosis (P=0.016), endometrioma (P=0.039), pelvic or abdominal adhesions (P=0.015) were associated with a reduced likelihood of encountering appendicitis on pathology examination. The complication rate was 0.13%. Anesthesia cost was lower for an incidental appendectomy compared with an urgent one. CONCLUSION: Laparoscopic incidental appendectomy is safe and quick to perform. Due to the complex nature of confirming the diagnosis of pelvic and abdominal pain, this study supports the routine performance of an incidental appendectomy in the female patient.


JSLS. 2009 Jul-Sep;13(3):350-7.

Early identification of interstitial cystitis may avoid unnecessary hysterectomy.

Chung MK, Jarnagin B.

Midwest Regional Center for Chronic Pelvic Pain, Lima, Ohio 45805, USA.

BACKGROUND: Interstitial cystitis is a clinical syndrome characterized by symptoms of pelvic pain, urinary urgency and frequency, and nocturia. It can be difficult to accurately identify interstitial cystitis because the symptoms overlap many other common gynecologic and urologic conditions. Patients with undiagnosed interstitial cystitis may undergo unnecessary procedures, including hysterectomy. METHODS: A PubMed literature search for articles dating back to 1990 was conducted on the topics of interstitial cystitis and hysterectomy. Further references were identified by cross-referencing the bibliographies in articles of interest. RESULTS: The literature review found that hysterectomy is performed more often in patients with undiagnosed interstitial cystitis than in patients with a confirmed diagnosis. Interstitial cystitis often coexists with conditions like endometriosis, for which hysterectomy is indicated. Many patients subsequently diagnosed with interstitial cystitis continue to experience persistent pelvic pain despite having had a hysterectomy for chronic pelvic pain. Careful history and physical examination can identify the majority of interstitial cystitis cases. CONCLUSION: Interstitial cystitis should be considered prior to hysterectomy in women who present with pelvic pain or who experience pelvic pain after a hysterectomy. If interstitial cystitis is diagnosed, appropriate therapy may eliminate the need for hysterectomy.


Thorax. 2009 Oct;64(10):919-20.

Thoracic endometriosis: rare presentation as a solitary pulmonary nodule with eccentric cavitations.

Lee CH, Huang YC, Huang SF, Wu YK, Kuo KT.

Department of Surgery, Buddhist Tzu Chi General Hospital, Taipei Branch, Xiandian City, Taipei County 23142, Taiwan.

Expert Opin Ther Pat. 2009 Sep 28. [Epub ahead of print]

Recent patent trends in the field of progesterone receptor agonists and modulators.

Schmees N, Weinmann H.

Bayer Schering Pharma, Medicinal Chemistry, Muellerstrasse 178, 13353 Berlin, Germany +49 30 468 12972 ; +49 30 468 92972;

Background: Progesterone receptor agonists are used in female contraception, hormone replacement therapy or some gynecological conditions like endometriosis. The interest for antagonists or selective progesterone receptor modulators (SPRMs) is growing. Recent reports on this class of compounds indicate that they could become the next generation of therapeutics in gynecological treatments. Objective: This overview summarizes the work on progesterone receptor agonists, SPRMs and antagonists reported in the patent literature in the past 4 years. Methods: The focus of the article is the examination of patents, primarily published as WO, EU or US patents since 2005. In some cases, additional data from the public literature is included into the discussion. These data are of substantial interest as the available biological data disclosed in patents are usually limited for new compound classes. Results/conclusion: Some highly active clusters of compounds have been disclosed in the past 4 years. The current research seems to focus on SPRMs and progesterone receptor antagonists.

Acta Dermatovenerol Alp Panonica Adriat. 2009 Sep;18(3):126-30.

Spontaneous endometriosis in an umbilical skin lesion.

Chatzikokkinou P, Thorfinn J, Angelidis IK, Papa G, Trevisan G.

Department of Dermatology and Venereology, University of Trieste, Ospedale Maggiore, Via Stuparich 1, I-34100 Trieste, Italy.

Cutaneous endometriosis of the umbilicus is an unusual condition with unclear pathogenetic mechanisms that might be mistaken for a malignant condition. A 46-year-old woman presented with a cutaneous black mass in the umbilicus. The lesion was removed surgically and histological analyses revealed that it consisted of endometrial tissue. There was no recurrence at 18-month follow-up. Endometriosis of the umbilicus is a rare condition and the pathogenesis is not completely elucidated. According to one theory, intraperitoneal endometrial tissue is translocated during endoscopic surgery or other surgical procedures that involve the umbilicus. However, in this case there was no history of abdominal wall surgery. We conclude that endometriosis is important to consider in cases of unclear skin lesions of the umbilicus, even in cases with no previous abdominal surgery. Moreover, umbilical endometriosis of the skin can have different appearances that resemble malignant tumors, and radical surgery with histology is therefore indicated.


Int J Gynaecol Obstet. 2009 Sep 25. [Epub ahead of print]

Primary squamous cell carcinoma of the ovary associated with endometriosis.

Acién P, Abad M, Mayol MJ, Garcia S, Garde J.

Department of Obstetrics and Gynecology, San Juan University Hospital, Alicante, Spain; Department of Gynecology, Miguel Hernandez University, Campus of San Juan, Alicante, Spain.

OBJECTIVE: To analyze the clinical, therapeutic, and pathologic features of published cases presenting primary squamous cell carcinoma (SCC) of the ovary associated with endometriosis. METHODS: A case report, 15 cases of infiltrating SCC of the ovary associated with or arising from endometriosis, and 1 case of synchronous carcinoma in situ in the cervix and ovary from a review of the literature were studied. RESULTS: Young age, advanced stage of the disease, and hypogastric pain were frequent at the time of diagnosis. There was no ascites, but infiltration of neighboring organs was common. The tumor was associated with 80% patient mortality in the first few months. Adjuvant chemotherapy with paclitaxel and carboplatin or cisplatin appeared to improve the results. CONCLUSION: Primary SCC of the ovary associated with endometriosis is extremely rare and has a poor prognosis. The best therapeutic results are obtained with paclitaxel and carboplatin or cisplatin after radical surgery.

Chin Med J (Engl). 2009 Sep 5;122(17):2079-80.

A gastric duplication cyst at the splenic hilum mimicking endometriosis clinically in a female adult.

Hsu HT, Hsing MT, Chen ML, Chen CJ.

Department of Surgical Pathology, Changhua Christian Hospital, Changhua, 500 Taiwan, China.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;34(9):926-32.


Effect of GnRH-II on VEGF secreted by stromal cells from endometrium of endometriosis.]

[Article in Chinese]

Liu Q, Huang F, Wang H, Zou Y.

Department of Gyneology and Obstetrics, Second Xiangya Hospital, Central South University, Changsha 410011, China

Objective To inspect the effect of gonadotropin-releasing hormonelII (GnRH-II)on the secretion of VEGF by eutopic and ectopic endometrial stromal cells cultured in vitro.Methods Eutopic and ectopic stromal cells cultured in vitro were treated with different concentrations (1*10(-10)~1*10(-6) mol/L)of GnRH-II,and the control group was not treated by GnRH-II.Enzyme-linked immunosorbent assay (ELISA) was used to measure the VEGF protein in the medium of the above 2 groups.Results There was no difference between the VEGF protein expressed by eutopic and ectopic stromal cells in the medium after culturing in vitro for 48 hours (P>0.05). The 1*10(-10)~1*10(-6) mol/L GnRH-II could dose-dependently reduce VEGF protein secreted by endometrial stromal cells(P<0.01),and the inhibition to ectopic endometrial stromal cells was stronger than that to eutopic endometrial stromal cells (P<0.01).Conclusion Ectopic stromal cells cultured in vitro can secrete VEGF,and so can eutopic stromal cells.This may play an important role in the formation and development of endometriosis. GnRH-II can reduce VEGF protein secreted by ectopic endometrial stromal cells cultured in vitro,and its inhibition is stronger than that of eutopic endometrial stromal cells.


Conn Med. 2009 Sep;73(8):453-6.

Thoracic endometriosis: an unusual cause of hemothorax.

El Ghazal R, Fabian T, Ahmed ZA, Moritz ED.

Department of Medicine, Hospital of Saint Raphael, New Haven, USA.

In this report we describe the clinical presentation, diagnosis, treatment and outcome of a 45-year-old woman with thoracic endometriosis. Four clinical presentations have been described. The majority have presented with catamenial pneumothorax, followed by hemothorax, hemoptysis and lung nodules. Our patient presented with right-sided hemothorax and lung nodules. Video-assisted thoracoscopic aurgery confirmed the presence of endometrial tissue embedded in the diaphragmatic pleura. Talc pleurodesis alongwith atotal abdominal hysterectomy and bilateral salpingo-oophorectomy led to a clinical and radiological resolution.

Urologe A. 2009 Oct;48(10):1193-4,1196-8.

Chronic pelvic pain in women from a gynecologic viewpoint.

[Article in German]

Siedentopf F.

Frauenklinik, DRK-Kliniken Westend, Berlin.

Chronic pelvic pain in women is a difficult subject that challenges the gynecologist in practice. Possible gynecological causes are endometriosis, adhesions/PID, pelvic varicosis and ovarian retention syndrome/ovarian remnant syndrome. Other somatic causes are irritable bowel syndrome, bladder pain syndrome and fibromyalgia.Confirmed psychosocial factors contributing to chronic pelvic pain are comorbidity with anxiety disorders, substance abuse or depression, but the influence of social factors is less certain. The connection to physical and sexual abuse also remains unclear. Important diagnostic steps are studying the patient’s history, a gynecological examination and laparoscopy. Multidisciplinary therapeutic approaches are helpful. Basic psychosomatic care and psychotherapy should be integrated into the therapeutic concept at an early stage of the disease.

Gynecol Obstet Invest. 2009 Sep 24;68(4):262-268. [Epub ahead of print]

Evaluation of Estrogen Treatment in an Immunodeficient Mouse Endometriosis Model.

Colette S, Defrère S, Lousse JC, Van Langendonckt A, Loumaye E, Donnez J.

Université Catholique de Louvain, Faculty of Medicine, Gynecology Unit, Brussels, Belgium.

Background/Aims: Endometriosis is known to be an estrogen-dependent disease. However, only a few studies have analyzed the effect of estrogen treatment in mice xenotransplanted with human endometrium. The objective of this study was to adapt a previously developed heterologous murine model to the study of estrogens and test the impact of estrone treatment on endometriosis development. Methods: Human proliferative endometrium was xenotransplanted into the peritoneal cavity of castrated immunodeficient mice. These mice were treated with estrogens by means of subcutaneous estrone-releasing pellets. The effect of estrone on estradiol level, uterine histology and endometriosis development was evaluated after 21 days. Results: Bioactivity of estrone pellets and their metabolization into estradiol were demonstrated. However, there was no impact on endometriosis development (no difference in lesion number, weight, size or fluorescence). This lack of response was not due to absence of estrogen receptor expression, since strong expression was found in all lesions harvested. Surprisingly, castrated nontreated mice presented with lesions showing high proliferative activity, similar to lesions found in treated mice (around 30%). Conclusion: The high proliferation observed in lesions recovered from ovariectomized nontreated mice questions the utility of using estrogens in heterologous murine models. Copyright © 2009 S. Karger AG, Basel.

J Clin Lab Anal. 2009;23(5):331-5.

The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass.

Montagnana M, Lippi G, Ruzzenente O, Bresciani V, Danese E, Scevarolli S, Salvagno GL, Giudici S, Franchi M, Guidi GC.

Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi di Verona, Verona, Italy.

AIM: Although CA125 is the most widely used cancer marker in the diagnostic approach of pelvic masses in women, its clinical usefulness is limited because it lacks expression of the antigen in the early stages of disease. The human epididymis protein 4 (HE4) is frequently over-expressed in ovarian cancer, whereas its expression in normal tissues, including the ovary, is low. The aim of this study was to assess the concentration of both HE4 and CA125 in patients with different forms of benign and malign pelvic masses. METHODS: The study population included 99 patients with gynecological cancer (46 ovarian, 39 endometrial, 14 cervical) and 40 affected by benign disease (22 endometriosis and 18 benign ovarian mass). Twelve control subjects were also included in the study. In all the patients, serum samples were collected on the day before scheduled surgery. RESULTS: The median CA125 and HE4 serum levels were significantly higher among ovarian cancer patients as compared with healthy subjects and with those with benign mass, cervical, and endometrial tumors. The receiver operating characteristics curve analysis on healthy controls and patients with ovarian cancers revealed that HE4 had a significantly higher area under the curve when compared with CA125 (0.99 vs. 0.91), with a sensibility and specificity of 98 and 100%, respectively. CONCLUSIONS: HE4 seems to be a promising ovarian cancer marker, and its measurement might improve the diagnostic approach to patients with pelvic masses.

Hum Reprod Update. 2009 Sep 22. [Epub ahead of print]

The role of microRNAs in endometriosis and associated reproductive conditions.

Ohlsson Teague EM, Print CG, Hull ML.

School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, The Robinson Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.

BACKGROUND microRNAs (miRNAs) are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Recent research has shown that miRNAs and their target mRNAs are differentially expressed in endometriosis and other disorders of the female reproductive system. Since miRNAs control a broad spectrum of normal and pathological cellular functions, they may play pivotal roles in the pathogenesis of these disorders. METHODS A systematic review was undertaken of the published literature on; (i) the expression and functions of miRNAs in mammalian female reproductive tissues with a focus on endometriosis and the malignancies and fertility disorders related to this disease; and (ii) the potential roles played by validated mRNA targets of endometriosis-associated miRNAs. The current understanding of the biology of miRNAs is overviewed and the potential diagnostic and therapeutic potential of miRNAs in endometriosis is highlighted. RESULTS The differential expression of miRNAs in endometriosis, and the putative molecular pathways constituted by their targets, suggests that miRNAs may play an important role in endometriotic lesion development. Models for miRNA regulatory functions in endometriosis are presented, including those associated with hypoxia, inflammation, tissue repair, TGFbeta-regulated pathways, cell growth, cell proliferation, apoptosis, extracellular matrix remodelling and angiogenesis. In addition, specific miRNAs which may be associated with malignant progression and subfertility in endometriosis are discussed. CONCLUSIONS miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic tools in endometriosis.

Gynecol Obstet Fertil. 2009 Oct;37(10):771-2. Epub 2009 Sep 17.

Postoperative long-term amenorrhea avoids endometriosis recurrences: That is ultimately proven!

[Article in French]

Roman H.

Clinique gynécologique et obstétricale, CHU Charles-Nicolle, 1, rue de Germont, 76031 Rouen cedex, France.

Methods Mol Biol. 2009;590:295-306.

Use of laser capture microdissection in studying hormone-dependent diseases: endometriosis.

Matsuzaki S, Canis M, Mage G.

CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction, Clermont-Ferrand Cédex, France.

Endometriosis, a common gynecological disorder responsible for infertility and pelvic pain, is defined as the presence of endometrial glands and stroma within extra-uterine sites. Gene expression studies performed on endometriotic tissue homogenates have yielded results reflecting mRNA abundance in a mixture of cell types (including epithelial cells, stromal cells, fibrotic tissue, and muscle tissue). Therefore, a method for quantifying gene expression separately in individual cell populations is essential for identifying genetic markers. Laser capture microdissection is a technique for obtaining pure populations of cells from heterogeneous tissues. This chapter provides methods to obtain high-quality RNA suitable for a variety of different down stream applications from frozen endometrial and endometriotic tissues for laser capture microdissection, using the Arcturus PixCell II system.

Eur J Gynaecol Oncol. 2009;30(4):437-9.

Synchronous endometrioid carcinoma of the uterine corpus and ovary. A case report and review of the literature.

Grammatoglou X, Skafida E, Glava C, Katsamagkou E, Delliou E, Vasilakaki T.

Department of Pathology, Tzaneion General Hospital, Piraeus, Greece.

Synchronous endometrioid carcinoma of the uterine corpus and ovary is an uncommon but well recognized event. Diagnosis as either a separate independent primary or as a metastatic tumor requires careful consideration of a number of gross and histological features. These features illustrate the criteria helpful in distinguishing independent primaries from metastatic carcinomas which have a different therapeutic implication. The possible link between fertility drugs and carcinogenesis still remains controversial. We report a case of a 52-year-old woman who came to our hospital with a cystic left ovarian mass (8 cm). Hysterectomy and bilateral salpingo-oophorecromy were carried out. Histological examinations showed well differentiated endometrioid ovarian cancer and well differentiated endometrioid endometrial cancer. The endometrial tumor was intramucosal without myometrial or vascular invasion and was associated with atypical complex hyperplasia. The woman had not been previously treated with ovulation induction drugs. She was free of recurrence two years after surgery. Patients with synchronous endometrioid tumors of the endometrium and ovary are generally younger than reported for either endometrial adenocarcinomas or ovarian adenocarcinomas. They tend to be low grade and early stage and are frequently associated with endometriosis. The prognosis of endometrioid type carcinomas is better than other histological types of carcinoma.

Eur J Gynaecol Oncol. 2009;30(4):402-7.

The contribution of laparoscopy to the diagnosis of adnexal masses in young and premenopausal women.

Liberis V, Tsikouras P, Zografos Ch, Ammari A, Dislian V, Iatrou Ch, Maroulis G.

Department of Obstetrics and Gynecology, Democritus University of Thrace, Greece.

The purpose of this retrospective study was to investigate the contribution of laparoscopy to the diagnosis of adnexal masses in young and premenopausal women, in whom surgery was deemed necessary, between the years 2002-2008. A total of 130 young and premenopausal women scheduled for surgery for an adnexal mass with a diameter of 5-10 cm underwent transvaginal ultrasound (US) examination prior to surgery. Laparoscopic management was successfully completed for 118 of the 130 patients in this study; however, 12 required conversion of laparoscopy to laparotomy due to endometriosis with extensive bowel adhesions, or suspected ovarian malignancy and peritoneal implants. One hundred and twenty-four patients (95.38%) had benign lesions, four (3.07%) had borderline tumors and two patients had malignant lesions (1.53%). We found a statistically significant association between laparoscopic and histological findings. Laparoscopic diagnosis of adnexal masses suspicious at US may help avoid many laparotomies for the treatment of benign ovarian disorders.

Zhen Ci Yan Jiu. 2009 Jun;34(3):188-92.

Randomized controlled study on ear-electroacupuncture treatment of endometriosis-induced dysmenorrhea in patients

[Article in Chinese]

Jin YB, Sun ZL, Jin HF.

Department of Acu-moxibustion, Zhejiang Hospital of Integrated Chinese and Western Medicine, Hangzhou 310003, China.

OBJECTIVE: To observe the therapeutic effect of ear-electroacupuncture (Ear-EA) on dysmenorrhea in patients with endometriosis and to explore its underlying mechanism. METHODS: A total of 80 endometriosis patients were randomly and equally divided into ear-EA group and body-EA group. EA (50 Hz, 0.5-0.8 mA) was applied to auricular points (Uterus, Subcortex, Shenmen, Endocrine, etc.) and body acupoints [Tianshu (ST 25), Qihai (CV 6), Guanyuan (CV 4), Sanyinjiao (SP 6), Diji (SP 8), Uterus (EX-CA 1), etc.] respectively for 30 min, once every other day for 3 months. Dysmenorrhea severity score (DSS) was assessed and plasma prostaglandin (PGE2) and 6-Keto-PGF1alpha levels detected by radioimmunoassay. RESULTS: Compared with pre-treatment, DSS lowered significantly during the 1st and 2nd menstrual cycle in body-EA group, and during the 1st, 2nd and 3rd menstruation in ear-EA group; and the DSS of ear-EA group during the 3rd menstruation was evidently lower than that of body-EA group (P < 0.05). During the 3rd menstrual onset after the treatment, plasma PGE2 contents in both groups decreased obviously (P < 0.01), and plasma 6-Keto-PGF1alpha, levels increased considerably in comparison with pre-treatment (P < 0.01). Comparison between two groups during the 3rd menstruation showed that plasma PGE2 level of ear-EA group was markedly lower than that of body-EA group, and 6-Keto-PGF1alpha, level of ear-EA group was significantly higher than that of body-EA group (P < 0.05). No significant difference was found between two groups in clinical therapeutic effect (P > 0.05). CONCLUSION: Both ear-EA and body-EA can effectively relieve endometriosis-induced dysmenorrhea, and the former is superior to the later in reducing pain severity, which may be closely related to their effects in reducing plasma PGE2 and raising 6-Keto-PGF1alpha level.