101: Hum Reprod Update. 2004 Jan-Feb;10(1):29-38. Related Articles, Links Apoptosis in human endometrium and endometriosis. Harada T, Kaponis A, Iwabe T, Taniguchi F, Makrydimas G, Sofikitis N, Paschopoulos M, Paraskevaidis E, Terakawa N. Department of Obstetrics and Gynaecology, Tottori University School of Medicine, 36-1 Nishimachi, 683-8504, Yonago, Japan. email@example.com Apoptosis plays a critical ...
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.
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.
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]
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.
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.
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.
Deeply infiltrating endometriosis and transvaginal ultrasonography.
Rev Med Inst Mex Seguro Soc. 2009 Jan-Feb;47(1):57-60.
Endometriosis. Pathophysiological background for treatment.
[Article in Spanish]
Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Distrito Federal, México, Mexico. firstname.lastname@example.org.
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.
Obstet Gynecol Surv. 2009 Aug;64(8):542-7.
The role of prolactin- and endometriosis-associated infertility.
Department of OB/GYN, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. email@example.com
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]
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.
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.
Female Pelvic Medicine & Reconstructive Pelvic Surgery and Minimally Invasive Surgery, Department of Gynecology & Obstetrics, Cleveland Clinic, Cleveland, Ohio 44195, USA. firstname.lastname@example.org
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]
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.
Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan. email@example.com
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]
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. firstname.lastname@example.org
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.
Department of Ob/Gyn, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. email@example.com
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.
Commentary: Endometriosis–epidemiologic considerations for a potentially ‘high-risk’ population.
Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. Stacey.firstname.lastname@example.org
Urology. 2009 Jul 16. [Epub ahead of print]
Ectopic Decidual Reaction in the Urinary Bladder Presenting as a Vesical Tumor.
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.
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan. email@example.com
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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]
Service de gynécologie-obstétrique, hôpital André-Mignot, 177, rue de Versailles, 78157 Le-Chesnay, France. firstname.lastname@example.org
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]
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.
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.
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.