Minerva Ginecol. 2007 Feb;59(1):27-34.
[Fertility after surgery for rAFS stage III and IV endometriosis][Article in Italian]
Clinica Ostetrica e Ginecologica, Istituto di Scienze Biomediche San Gerardo, Via Solferino 16, 20052 Monza, Milan, Italy.
AIM: The aim of this paper was to assess the impact on fertility of surgery to eradicate endometriosis. METHODS: One-hundred and twenty-six patients aged between 20 and 40 were observed. All wished to have offspring after the operation and were subjected to conservative surgery for stage III and IV endometriosis (rAFS score > 16) in the period 1992-2002. The type of surgical approach was chosen in consideration of the patient’s clinical condition and on the basis of the experience of the surgeon, with the aim of radically removing the disease and, where necessary, restoring fertility. RESULTS: Fifty-six of 126 patients (44.4%) conceived after the operation; 55 spontaneously and 1 with assisted fecundation. Of the patients observed who became pregnant, about 1/3 (32%) conceived within 6 months of the operation and 1/3 (31%) after 12 months. Forty-four (78.5%) pregnancies reached term with a positive outcome, 7 (12.5%) were in progress at the moment of follow-up, 4 (7.1%) suffered a miscarriage and 1 (1.7%) was extrauterine; 48.2% (27/56 patients) of the pregnancies were stage III, 40% (28/70 patients) were stage IV. CONCLUSIONS: It emerges clearly from the data extrapolated from our series that surgery to eradicate endometriosis increases the fertility of the patients affected, without being resolutive: more than half the patients in fact remained sterile in spite of the operation.
Minerva Ginecol. 2007 Feb;59(1):19-25.
The laparoscopic treatment of bladder endometriosis. A retrospective analysis of 21 cases.[Article in English, Italian]
Obstetrics Gynecology Unit, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. email@example.com
AIM: Endometriosis is the presence of endometrial tissue, including endometrial glands and stroma, outside the uterine cavity. The incidence of endometriosis in the general population is almost unknown, because it varies between 1% and 50%, depending on the paper considered. In any case, the incidence of bladder endometriosis is generally considered about 1% or less of endometriotic patients. The aim of this study is to evaluate the effectiveness of preoperative exams and the effectiveness of laparoscopic treatment. METHODS: We enrolled 21 patients operated laparoscopically for a severe stage of endometriosis, including at least a bladder localization of 10 mL; in 60% of cases a bowel surgery was associated in the cause of a digestive endometriosis. A complete preoperative and follow-up evaluation was carried out for all patients. RESULTS: The preoperative investigation, especially abdominal sonography, predicted endometriotic bladder invasion in only 38% of cases. Urinary symptomatology was present in only 61.9% of cases. The postoperative follow-up showed the remarkable effectiveness of laparoscopic treatment for the cancellation of pain and to improve the quality of life for patients. CONCLUSIONS: Finally, the treatment of severe endometriosis is possible and effective by laparoscopy even in the cases where there is a bladder localization and when, in the absence of specific symptomatology, it isn’t diagnosed preoperatively.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 1;852(1-2):605-10. Epub 2007 Feb 28.
Quantification of NC100692, a new tracer for 99mTc-imaging of angiogenesis, in human plasma using reversed-phase liquid chromatography coupled with electrospray ionization ion-trap mass spectrometry.
Research and Development, GE Healthcare, Nycoveien 2, N-0401 Oslo, Norway.
NC100692 is under development as a diagnostic radiopharmaceutical for targeting angiogenesis associated with diseases, such as cancer and endometriosis. NC100692 consists of a cyclic RGD-containing peptide with an ethylene glycol chain linked to the C-terminal amino acid and a (99m)Tc-binding chelator linked to the N-terminal amino acid. The present report describes a method for quantification of NC100692 in human citrated plasma. The method is based on solid-phase extraction followed by reversed-phase liquid chromatography using a gradient of water and acetonitrile with 0.1% formic acid. The chromatographic system was coupled on-line with an electrospray mass spectrometer. The analyses were performed by selective ion monitoring of the [M+2H](2+) and the [M+3H](3+) ions of NC100692 and the internal standard, which was identical to NC100692 except for containing twice the length of the ethyleneglycol chain. The limit of quantification of the method was 0.5 ng NC100692/ml plasma. The calibration curve ranged from 0.5 to 250 ng NC100692/ml plasma and was fitted to a quadratic equation with a weighing factor of 1/y and found to be highly reproducible. The total precision of the method, expressed as the relative standard error of the mean, was 11.1, 10.8 and 9.7% for the low, medium and high control samples, respectively. The accuracy of the method was 103.4, 111.1 and 107.5% for the low, medium and high control samples, respectively. NC100692 was stable in human plasma during at least 3 freeze/thaw cycles, during 48 h on dry ice and at least 8 weeks when stored in a -20 degrees C freezer.
Mol Hum Reprod. 2007 May;13(5):323-32. Epub 2007 Mar 9.
Altered expression of HOXA10 in endometriosis: potential role in decidualization.
Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA. firstname.lastname@example.org
Endometriosis is a poorly understood gynaecologic disorder that is associated with infertility. In this study, we examined the expression of HOXA10 in the eutopic endometrium of baboons with induced endometriosis. A decrease in HOXA10 mRNA was observed after 3, 6, 12 and 16 months of disease, which reached statistical significance at 12 and 16 months. HOXA10 protein levels were decreased in both the epithelial and stromal cells of the endometrium. Furthermore, expression of beta3 integrin (ITGB3), which is upregulated by HOXA10, was decreased, whereas EMX2, a gene that is inhibited by HOXA10, was increased. Next, methylation patterns of the HOXA10 gene were analysed in the diseased and control animals. The F1 region on the promoter was found to be the most significantly methylated in the endometriosis animals and this may account for the decrease in HOXA10 expression. Finally, we demonstrate that stromal cells from the eutopic endometrium of baboons with endometriosis expressed significantly higher levels of insulin-like growth factor binding protein-1 (IGFBP1) mRNA than disease-free animals in response to estradiol, medroxyprogesterone acetate and dibutyryl cAMP (H + dbcAMP). The functional role of HOXA10 in IGFBP1 expression was further explored using human endometrial stromal cells (HSC). Overexpression of HOXA10 in HSC resulted in a decrease of IGFBP1 mRNA, whereas silencing HOXA10 caused an increase of IGFBP1 mRNA, even in the presence of H + dbcAMP. These data demonstrate that HOXA10 negatively influences IGFBP1 expression in decidualizing cells. Thus, the decrease in HOXA10 levels may in part be involved with the altered uterine environment associated with endometriosis.
Gynecol Obstet Fertil. 2007 Apr;35(4):330-8. Epub 2007 Mar 12.
[Prolegomena before any psychoanalytical approach to endometriosis][Article in French]
Cabinet médical, 74, rue Dunipos, 75013 Paris, France. email@example.com
Endometriosis is a disease, which requires medication or surgery to be treated. However, it can be considered as a symptom psychoanalytically speaking. Before going further into the question from this point of view, let us examine some prolegomena–preliminary principles. The scientistic ideology of a La Mettrie’s “Human Machine”, the unconscious subject promoted by psychoanalysts for more than a century, the Anglo-American notion of post-traumatic stress disorder, and womanhood and the mental structure customarily called hysteria stand for the main prolegomena. English and French speaking psychopathological literature is reviewed to introduce our personal experience of women with endometriosis. Finally, a public consultation is considered to confirm or invalidate scientific data stemmed from psychoanalytical experience.
Mol Cell Endocrinol. 2007 Apr 15;269(1-2):65-80. Epub 2007 Feb 6.
The gonadotropins: tissue-specific angiogenic factors?
Department of Obstetrics and Gynecology, University of Giessen, Klinikstrasse 32, 35385 Giessen, Germany.
The gonadotropins, whose members are human chorionic gonadotropin (hCG), lutenizing hormone (LH) and follicle-stimulating hormone (FSH) are a well characterized hormone family known to regulate reproductive functions in both females and males. Recent studies indicate that they can modulate the vascular system of reproductive organs. It was shown that gonadotropins not only influence the expression of vascular endothelial growth factor (VEGF) and both its receptors VEGFR-1 and -2, but also modulate other ubiquitously expressed angiogenic factors like the angiopoietins and their receptor Tie-2, basic fibroblast growth factor or placental-derived growth factor. Some recent data indicates a possible direct action of gonadotropins on endothelial cells. Thus, the gonadotropins act as tissue-specific angiogenic factors providing an optimal vascular supply during the menstrual cycle and early pregnancy in the female reproductive tract as well as in testis. In pathological conditions (e.g. preeclampsia, intrauterine growth restriction, ovarian hyperstimulation or endometriosis), these tightly regulated interactions between the gonadotropins and the ubiquitous angiogenic factors appear to be disturbed. The intent of this short manuscript is to review the current knowledge of the regulatory role of the gonadotropins in vasculo- and angiogenesis. We also review angiogenic actions of thyroid-stimulating hormone (TSH), a glycoprotein closely related to gonadotropins, which display strong gonodal actions.
Fertil Steril. 2007 Dec;88(6):1568-72. Epub 2007 Mar 8.
Women with advanced-stage endometriosis and previous surgery respond less well to gonadotropin stimulation, but have similar IVF implantation and delivery rates compared with women with tubal factor infertility.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA. firstname.lastname@example.org
OBJECTIVE: To investigate the response to controlled ovarian hyperstimulation and ART outcomes in women with advanced-stage endometriosis and previous surgeries at the Yale IVF program between 1996 and 2002. DESIGN: Retrospective case control study. SETTING: Academic medical center. PATIENT(S): The study group consisted of 68 women who previously undergone laparoscopic surgery for advanced-stage endometriosis. The control group included 106 women with tubal-factor infertility. The women with endometriosis underwent 133 IVF-ET cycles and the control group 208 cycles. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET. MAIN OUTCOME MEASURE(S): Response to gonadotropins, fertilization, cleavage, implantation, pregnancy, miscarriage, and live birth rates. RESULT(S): Lower peak E(2) levels, higher total gonadotropin requirements, lower oocyte yield, and higher cancellation rates were found in women with endometriosis compared with tubal-factor control subjects. However, no differences were found in fertilization, cleavage, implantation, pregnancy, miscarriage, and delivery rates between the endometriosis and tubal-factor groups. CONCLUSION(S): Women with advanced-stage endometriosis who have undergone previous surgery respond less well to gonadotropins than women with tubal-factor infertility. However, implantation, pregnancy, and delivery rates are similar, suggesting that embryo quality and uterine receptivity remains unaffected despite diminished ovarian reserve in women with endometriosis.
Ann Diagn Pathol. 2007 Apr;11(2):117-21.
Xanthogranulomatous salpingitis associated with fallopian tube mucosal endometriosis: a clue to the pathogenesis.
The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai Medical Center, New York, NY 10029-6574, USA.
Xanthogranulomatous salpingitis is an unusual inflammatory lesion of the fallopian tube, characterized by accumulation of foamy macrophages in the wall of the fallopian tube along with other chronic inflammatory cells. Only a few cases of xanthogranulomatous salpingitis have been reported in the English medical literature, some under different nomenclature. An association, most commonly with pelvic inflammatory disease and endometriosis, has been suggested. A 41-year-old woman with prior history of breast carcinoma underwent bilateral salpingoophorectomy because of hematosalpinx. The histology revealed xanthogranulomatous salpingitis in the setting of extensive fallopian tube mucosal endometriosis, endometritis, and presence of an intrauterine contraceptive device. Multiple etiologies have been linked to the xanthogranulomatous process at this location in previously reported cases. A whole spectrum of changes may exist in this lesion and probably represent a specialized form of tissue reaction secondary to multiple etiologies. Although it has been associated with pelvic endometriosis, it has never been demonstrated through progressive changes, beginning with mucosal endometriosis to the full-blown xanthogranulomatous inflammation. To the best of our knowledge, this is the first reported case that demonstrates different stages in the pathogenesis of this lesion and provides an insight into the histogenesis of this entity.
Hum Reprod Update. 2007 Jul-Aug;13(4):331-42. Epub 2007 Mar 8.
In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis.
Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Germany. email@example.com
Endometriosis represents one of the most common gynaecological disorders. According to the implantation theory, angiogenesis is a major prerequisite for the initiation and progression of the disease. Thus, during the last decade, many studies have focused on the mechanisms regulating angiogenesis in endometriotic lesions. For this purpose, sophisticated in vitro and in vivo approaches have been established, which are highlighted in this review. Enzyme-linked immunosorbent assays demonstrate the imbalance of pro- and anti-angiogenic growth factors in isolated peritoneal fluid from endometriosis patients. Histological, immunohistochemical and gene expression analyses of endometriotic tissue provide detailed information on the angio-architecture of endometriotic lesions and the different growth factor expression by various cell populations. Moreover, cell culture systems are useful tools for the identification of hormonal and immunological factors involved in the angiogenic process. Finally, sophisticated in vivo models, such as rodent models of peritoneal endometriosis as well as the chorioallantoic membrane assay and the dorsal skinfold chamber, allow for the detailed analysis of blood vessel development in ectopic endometrium and the efficacy of angiogenesis inhibitors. The findings resulting from all these approaches will help to provide better insights into the pathophysiology of endometriosis and to establish new anti-angiogenic treatment strategies for the future.
J Obstet Gynaecol Can. 2007 Mar;29(3):247-9.
Removal of a non-communicating horn may not affect persistence or recurrence of endometriosis: a case report.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver BC.
BACKGROUND: Retrograde menstruation is thought to initiate and potentiate endometriosis in women with non-communicating uterine anomalies. The effect of removing a non-communicating uterine horn on the persistence or recurrence of endometriosis is unknown. CASE: A 29-year-old woman with a non-communicating uterine horn and endometriosis underwent surgical removal of the non-communicating horn with cautery of the endometriosis. A laparoscopy done two years later showed endometriosis similar in stage to that found at the initial procedure. CONCLUSION: Removal of a non-communicating uterine horn in a woman with endometriosis did not reduce the risk of persistence or recurrence of the disease.
Mymensingh Med J. 2007 Jan;16(1):81-4.
Histopathological analysis of hysterectomy specimens.
Department of Pathology, Mymensingh Medical College, Mymensingh, Bangladesh. firstname.lastname@example.org
The objective of this study was to explore the histopathological findings and the rate of removal of ovaries in hysterectomy specimens. This study took into account 328 hysterectomy specimens examined in the Department of Pathology, Mymensingh Medical College and in one private Pathology Laboratory in Mymensingh town from March to August, 2005. Formalin fixed paraffin embedded tissue sections stained with haematoxylin and eosin were examined under light microscope. Patients’ age, parts of uterus examined and their histopathological findings were retrieved from laboratory records. The common histopathological findings were: chronic cervicitis (87.80%), leiomyoma (17.07%), uterine prolapse (16.72%), adenomyosis (3.96), non-specific endometritis (3.35%), squamous cell carcinoma of cervix (2.44%), endometrial polyp (2.44%), serous cystadenoma of ovary (2.44%) and endometrial hyperplasia (1.83%). Some of the specimens show more than one lesions in the body of uterus, of which coexistence of adenomyosis and leiomyoma was the most common. Neoplastic lesions in cervix were 4.27%, in body 16.92% and in ovaries 5.06%. Malignant neoplasms were found in cervix 71.43%, in uterine corpus 3.03% and in ovaries 25%. Ovaries of both sides were removed in 48.17% of total cases. Their median age was 45 years, lowest age 23 years and maximum age was 82. The rate of removal of both ovaries was found to be increasing with the increase of age. Only one case was found to be subtotal hysterectomy and others were total hysterectomy. The present study revealed that the most common histopathological cause of hysterectomy is chronic cervicitis. Most common neoplastic cause of hysterectomy is leiomyoma. The rationalities and the possible after effect of hysterectomy in sexual functions and other physiological impairment should be followed up.
Ann N Y Acad Sci. 2007 Apr;1101:38-48. Epub 2007 Mar 7.
Utero-tubal sperm transport and its impairment in endometriosis and adenomyosis.
Department Obstetrics and Gynecology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
The uterus is composed of different smooth muscle layers that serve various functions. First, menstrual debris is expulsed at the time of the menses. Second, sperm is transported in the preovulatory phase to maximize fertility, and third, the human embryo is placed in an adequate setting during implantation. Endometriosis is a gynecologic disorder leading to severe pain symptoms such as severe pain during menstruation (dysmenorrhea), chronic pelvic pain, pain during sexual intercourse (dyspareunia), and abnormal uterine bleeding. Besides, endometriosis is often associated with female infertility and exhibits a massive impairment in the physiology of uterine contractility that can be documented by the in vivo examination method of hysterosalpingoscintigraphy (HSSG). In addition, endometriosis is associated in 80-90% of subjects with adenomyosis and our data clearly indicate that sperm transport is disturbed by hyperperistalsis when at least one focus of adenomyosis can be detected via magnetic resonance imaging (MRI) and turns into dysperistalsis (a complete failure in sperm transport capacity) when diffuse adenomyosis affecting all myometrial uterine muscle layers is detected. Hence, dysperistalsis is significantly associated with reduced spontaneous pregnancy rates. We therefore recommend MRI and HSSG in every sterility workup.
Fertil Steril. 2007 May;87(5):1222-4. Epub 2007 Mar 6.
Ureteral suspension facilitates surgery for deep pelvic endometriosis.
Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.
This study describes a technique that facilitates the identification of the ureter during radical excision of endometriosis. After dissection of the ureter, a biocompatible silicone sling is introduced into the pelvis through the trocar; the sling is applied around the ureter and the two ends of the sling are pulled until adequate traction on the ureter is obtained. Ureteral suspension was performed in 126 consecutive women with endometriotic lesions involving the ovarian fossa and/or the uterosacral ligaments. This surgical technique facilitated the identification of the ureter, preventing injuries.
Fertil Steril. 2007 Aug;88(2):462-71. Epub 2007 Mar 7.
Toward gene therapy of endometriosis: adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells.
Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt.
OBJECTIVE: To use dominant negative mutants of estrogen receptor genes delivered to endometriosis cells via an adenovirus vector (Ad-DN-ER) to abrogate estrogen action on these cells. DESIGN: Experimental in vitro study. SETTING: University research laboratory. PATIENT(S): Patients with ovarian endometriomas provided endometriotic cells, and patients with uterine prolapse or subserous leiomyoma provided control endometrial cells. INTERVENTION(S): Transfection of endometriotic cells by dominant negative estrogen receptor genes via adenovirus vector (Ad-DN-ER). MAIN OUTCOME MEASURE(S): The main outcome measures were cellular proliferation, cytokine production, and induction of apoptosis in endometriotic cells. RESULT(S): Coxsackievirus-adenovirus receptor mRNA expression and adenovirus transduction efficiency were significantly higher in endometriotic than normal endometrial cells. Ad-DN-ER-treated endometriotic cells, as compared with control virus-treated cells, showed cell rounding and detachment (cell death), a 72% reduction in the number of viable cells 5 days after transduction, significantly less production of monocyte chemotactic protein-1 (7.8 +/- 0.5 vs. 152.8 +/- 1.9 pg/mL, respectively), vascular endothelial growth factor (356.2 +/- 11.6 vs. 997.3 +/- 16.5 pg/mL, respectively), and interleukin-6 (268.7 +/- 2.6 vs. 414.5 +/- 3.6 pg/mL, respectively), and a significantly higher percentage of apoptotic cells (51.2 +/- 7.8 vs. 23.8 +/- 1.7, respectively). CONCLUSION(S): An adenovirus can effectively transfect endometriotic cells in vitro. The DN-ER delivered to endometriotic cells via an adenovirus decreases cell proliferation, induces apoptosis, and decreases cytokine production. Adenovirus-mediated gene therapy may represent a potential therapeutic option for endometriosis in the future.
Surg Endosc. 2007 Sep;21(9):1572-7. Epub 2007 Mar 7.
Laparoscopic segmental colorectal resection for endometriosis: limits and complications.
Service de gynécologie, Obstétrique et médecine de la reproduction, Hôpital Tenon, 4 rue de la chine, 75020, Paris, France. email@example.com
BACKGROUND: Deep pelvic endometriosis with colorectal involvement is a complex disorder often requiring segmental bowel resection. This study investigated the limits and complications of laparoscopic segmental colorectal resection. METHODS: Laparoscopic segmental colorectal resection was performed for 71 women with bowel endometriosis. Intra- and postoperative complications were evaluated, together with symptom outcomes, by means of questionnaires completed before and after surgery. Surgical procedures and complications were compared between the first part of the study (40 cases, previously published) and the second part (31 cases). RESULTS: Of the 71 women, 64 (90%) underwent laparoscopic segmental colorectal resection, with 7 requiring laparoconversion. Major complications occurred in nine cases (12.6%), six with rectovaginal fistulae and three with pelvic abscesses. The mean operating time decreased significantly during the study (p < 0.05). The mean follow-up period after colorectal resection was 24.4 +/- 2.2 months. No differences in the rates of laparoconversion or complications were observed between the two periods, whereas major associated surgical procedures were more frequent during the second period. Dysmenorrhea (p < 0.0001), dyspareunia (p = 0.0001), pain at defecation (p = 0.0004), bowel movement pain or cramping (p < 0.0001), lower back pain (p < 0.0001), and asthenia (p < 0.0001) were improved after the operation, with no difference between the study periods. CONCLUSION: This large series confirms the feasibility and efficacy of laparoscopic segmental colorectal resection. However, women must be informed of the risk for potentially severe complications.
Singapore Med J. 2007 Mar;48(3):217-21.
Urological complications of laparoscopic hysterectomy: a four-year review at KK Women’s and Children’s Hospital, Singapore.
Minimally Invasive Surgery Unit, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899. firstname.lastname@example.org
INTRODUCTION: This review assessed the incidence, predisposing conditions, and key surgical steps, where urological injuries occurred during laparoscopic hysterectomies at the Minimally Invasive Surgery Unit, KK Women’s and Children’s Hospital over a four-year period. METHODS: A retrospective review of 495 cases of laparoscopic assisted vaginal hysterectomies (LAVH) and total laparoscopic hysterectomy (TLH) from January 2001 to December 2004 was conducted. RESULTS: A total of eight urological injuries occurred, all within the initial two years of review. There were seven unintentional bladder injuries occurring at LAVH during dissection of the bladder off the uterovaginal attachment. The associated factors included previous caesarean section and fibroids. All bladder injuries were diagnosed and repaired intraoperatively with no long-term complications. A single case of ureteric injury occurred with TLH. The patient presented on the ninth postoperative day with fever and continuous vaginal discharge. The most likely aetiology was thermal damage from electrocautery used to secure haemostasis of the uterine artery pedicle. Ureteric re-implantation was eventually required in the patient. CONCLUSION: Urological injuries occurred in 1.6 percent of laparoscopic hysterectomies in our hospital. The predisposing factors include previous caesarean surgery, multiple fibroids and severe endometriosis. A definite learning curve exists with laparoscopic hysterectomy with a thorough knowledge of pelvic anatomy being an essential prerequisite for advanced pelvic surgery. Similarly, good exposure of the surgical field, vigilant dissection and judicious use of electro-surgery are important practices to adopt to prevent injuries.
Fertil Steril. 2007 Jul;88(1):32-8. Epub 2007 Mar 6.
Aromatase expression in endometriotic tissues and its relationship to clinical and analytical findings.
Service of Obstetrics and Gynecology, San Juan University Hospital, Alicante, Spain. email@example.com
OBJECTIVE: To study the relationship between aromatase expression in endometriotic tissues and clinical and laboratory findings. DESIGN: Prospective basic and clinical research. SETTING: University hospital. PATIENT(S): Sixty-two women with endometriosis, and 12 without endometriosis. INTERVENTION(S): Conservative surgery, or hysterectomy and adnexectomy, along with an immunohistochemical study of aromatase in endometriotic and nonendometriotic tissues. MAIN OUTCOME MEASURE(S): Symptoms of the disease, ultrasound and surgical findings, values of tumor markers, steroids and immunoglobulins, and recurrences after surgery. RESULT(S): We observed positive immunohistochemical expression for aromatase in endometriotic tissues from 38 patients (61.3%). Aromatase expression was negative in the rest of the tissues studied and in the 12 cases without endometriosis. Aromatase-positive patients had a higher number of endometriomas, more bilaterality, and more moderate-to-severe chronic pelvic pain. Also, infertility and associated leiomyomas were more frequent in these patients, though without significant differences. There were no differences in recurrence of the disease 1 year later. Estradiol and PRL levels were significantly higher, and IgG values lower, than in aromatase-negative patients. High values of blood sedimentation rate were more frequent in aromatase-negative patients. CONCLUSION(S): Molecular alterations such as the presence of aromatase in endometriotic tissues could be involved in the development or maintenance of endometriosis. Our findings suggest major severity, activity, and chronic pelvic pain in patients with aromatase in endometriotic tissue.
Fertil Steril. 2007 Sep;88(3):691-7. Epub 2007 Mar 6.
Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia.
Division of Obstetrics and Gynecology, Department of Clinical Science, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden. firstname.lastname@example.org <email@example.com>
OBJECTIVE: To investigate whether the structure or regulation of the growth of endometrial blood vessels might be abnormal in women with idiopathic menorrhagia (IM). Perturbation of angiogenesis is associated with IM. DESIGN: Prospective, clinical study. SETTING: Department of gynecology at a university hospital. PATIENT(S): Twenty-four patients with IM, and 18 women with eumenorrhea. INTERVENTION(S): Endometrial biopsy samples underwent immunohistochemical staining for CD34, CD31, von Willebrand factor, vascular endothelial growth factor (VEGF)-A, and VEGF receptors 1 and 2. MAIN OUTCOME MEASURE(S): Differences in immunostaining for these markers by computer-assisted stereological analysis. RESULT(S): Endometrial vessels in patients and controls manifested focal discontinuities, or gaps, in endothelial staining for CD34, CD31, and von Willebrand factor. Electron and confocal microscopy revealed that perivascular cells, probably pericytes, covered these gaps in the vessel wall. The relative size of the gaps was significantly greater in patients with IM than in controls. Vessel circumference was also larger, and more vessels were positive for VEGF-A and for VEGF receptors 1 and 2, in patients than in controls. Gap size was significantly correlated with the number of vessels expressing VEGF-A or VEGF receptor 1. CONCLUSION(S): Endometrial blood vessels possess a discrete morphology that is characterized by endothelial gaps, and these gaps  are more pronounced in women with IM,  are related to overexpression of VEGF-A and VEGF receptor 1, and  might contribute to IM, e.g., by destablizing vessels.
Fertil Steril. 2007 Jun;87(6):1287-90. Epub 2007 Mar 6.
Bladder endometriosis: getting closer and closer to the unifying metastatic hypothesis.
Department of Obstetrics and Gynecology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy. firstname.lastname@example.org <email@example.com>
OBJECTIVE: It has been hypothesized that bladder endometriotic nodules are an independent form of endometriosis that should be considered a distinct clinical entity. If this is true, the frequency of nonvesical endometriotic lesions in affected patients should be similar to the prevalence of the disease in the general population (about 10%). The aim of the study was to evaluate the presence of other forms of endometriosis in patients with bladder endometriotic nodules. DESIGN: Case series. SETTING: Two gynecologic surgical units. PATIENT(S): Fifty-eight women with large bladder endometriotic nodules. INTERVENTION(S): To evaluate the concomitant presence of other forms of endometriosis. MAIN OUTCOME MEASURE(S): Presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis. RESULT(S): The presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis was observed in 58.6% (95% confidence interval [CI]: 45.2-71.2), 44.8% (95% CI: 32.2-58.2), 81.0% (95% CI: 68.4-89.6), and 27.6% (95% CI: 16.7-40.8) of cases, respectively. The presence of at least one of them was documented in 87.9% of cases (95% CI: 76.7-94.3). CONCLUSION(S): Endometriotic nodules of the bladder are frequently associated with other forms of pelvic endometriosis. This result does not support the vision that bladder endometriotic nodules should be considered an independent form of the disease.
Fertil Steril. 2007 Jun;87(6):1271-6. Epub 2007 Mar 6.
Ovarian endometrioma vascularization in women with pelvic pain.
Department of Obstetrics and Gynecology, Clínica Universitaria de Navarra, School of Medicine, University of Navarra, Pamplona, Spain. firstname.lastname@example.org <email@example.com>
OBJECTIVE: To assess whether a correlation exists between angiogenesis in ovarian endometrioma with the presence of pelvic pain. DESIGN: Prospective study. SETTING: Tertiary-care university hospital. PATIENT(S): Sixty-five patients (mean age, 33.3 years; range, 20-49 years) were diagnosed as having suspected cystic ovarian endometriosis, and were scheduled for surgery. Patients were classified into two groups according to clinical complaints: group A, asymptomatic patients or patients presenting mild dysmenorrhea; and group B, severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia. INTERVENTION(S): Transvaginal power-Doppler ultrasonography and immunohistochemical staining for CD-34 in histological specimens. MAIN OUTCOME MEASURE(S): The amount of blood flow, lowest pulsatility and resistance indexes, and microvessel density (MVD). RESULT(S): Five patients were excluded after surgery because no ovarian endometriosis was found in histological analysis. Thirty women were included in each group. Ovarian endometriomas were more frequently vascularized in group B (87%) than in group A (60%). The lowest pulsatility and resistance indexes were significantly lower, and MVD was significantly higher, in group B compared with group A. There was a correlation between the degree of vascularization detected by power-Doppler ultrasound and MVD. CONCLUSION(S): We conclude that vascularization of ovarian endometriomas evaluated by transvaginal color Doppler and MVD is higher in patients who present with pelvic pain than in asymptomatic patients. This could be an indicator of the activity of endometriosis.
Fertil Steril. 2007 Oct;88(4):785-8. Epub 2007 Mar 6.
Estrogen receptor beta gene +1730 G/A polymorphism in women with endometriosis.
Department of Obstetrics and Gynecology, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
OBJECTIVE: To investigate whether the +1730 G/A polymorphism of the estrogen receptor beta (ER-beta) gene is associated with the risk of endometriosis in a Korean population. DESIGN: Case-control study. SETTING: University Department of Obstetrics and Gynecology. PATIENT(S): Women with (n = 239) or without (n = 287) endometriosis. INTERVENTION(S): The +1730 G/A polymorphism of 3′-UTR of exon 8 in the ER-beta gene was assessed by polymerase chain reaction-restriction fragment-length polymorphism analysis utilizing digestion with AluI restriction enzyme. MAIN OUTCOME MEASURE(S): Genotype distribution and allele frequency of the +1730 G/A polymorphism in the ER-beta gene. RESULTS: The genotype distribution of the +1730 G/A polymorphism in the ER-beta gene was not different between the endometriosis patients and the controls (G/G of 74.9% vs. 72.5%, G/A of 25.1% vs. 26.1%, and A/A of 0.0% vs. 1.4%, respectively). There was also no difference in the G and A allele frequencies between the two groups (87.4% vs. 85.5%, and 12.6% vs. 14.5%, respectively). Even when the endometriosis cases were subdivided into American Society for Reproductive Medicine stage I-II, III, IV, and III-IV, no differences were found at all in the genotype distribution or allele frequencies between the two groups. CONCLUSION(S): Our results suggest that the +1730 G/A polymorphism of the ER-beta gene may not be associated with the risk of endometriosis in the Korean population, which was not the case in the Japanese population.
Pediatr Pulmonol. 2007 Apr;42(4):386-8.
Catamenial hemoptysis from endobronchial endometriosis in a child with type 1 von Willebrand disease.
Dipartimento di Biomedicina dell’Età Evolutiva, University of Bari, Bari, Italy.
Catamenial hemoptysis is a rare condition characterized by cyclic pulmonary hemorrhage, synchronous with menses and associated with the presence of intrapulmonary or endobronchial endometrial tissue. Because of the paucity of cases reported in the literature, information regarding the natural history is limited and also the optimal diagnostic workup and management of these patients are not well defined. In this report, we present a case of endobronchial endometriosis in a 12-year-old female diagnosed by bronchoscopy and immunocytochemical assay, associated with type 1 von Willebrand disease. (c) 2007 Wiley-Liss, Inc.
J Assist Reprod Genet. 2007 Jun;24(6):249-58. Epub 2007 Mar 1.
Comparison of c-DNA microarray analysis of gene expression between eutopic endometrium and ectopic endometrium (endometriosis).
Department of Obstetrics & Gynaecology, University Hospitals Schleswig-Holstein, Campus Kiel, Michaelisstr. 16, 24105, Kiel, Germany.
PROBLEM: As recent studies have suggested abnormalities in the regulation of specific genes in the development of endometriosis, we investigated differentially expressed genes in endometriosis compared to endometrium. METHOD OF STUDY: Gene expression profiles using the Atlas microarray were performed in endometriotic tissue and endometrium. Nine of the 13 genes of endometriotic tissue showed an up-regulation in relation to endometrium and four of the 13 genes a down-regulation. RESULTS: Of the 1176 genes on the Atlas Human 1,2 array, only 13 differentially expressed identical genes were detected after repeating the gene analysis three times. CONCLUSION: According to our c-DNA analysis some differentially expressed genes may be involved in the pathogenesis of endometriosis. An imbalance in the genes responsible for the reproductive process may lead to a decrease in embryo implantation in patients with endometriosis.
Arch Gynecol Obstet. 2007 Sep;276(3):285-9. Epub 2007 Feb 28.
HPV induced ovarian squamous cell carcinoma: case report and review of the literature.
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. firstname.lastname@example.org
BACKGROUND: Ovarian squamous cell carcinoma is usually derived from a teratoma, a Brenner tumour or endometriosis. Association with an HPV infection is rare. CASE: A fourth case of ovarian squamous cell cancer associated with HR-HPV is presented. Debulking for stage IIIc ovarian squamous cell cancer was performed and she received adjuvant combination chemotherapy. She developed bone metastases and received radiotherapy. The Progression of these metastases and the newly developed metastases did not respond to an oral tyrosine kinase inhibitor (gefitinib). CONCLUSION: The development of bone metastases in association with an ovarian squamous cell carcinoma is a rare finding, and it did not respond to treatment with a tyrosine kinase. A review of literature is presented.
Fertil Steril. 2007 Sep;88(3):724-6. Epub 2007 Feb 28.
Letrozole and norethisterone acetate in rectovaginal endometriosis.
Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.
This open-label prospective study evaluated the efficacy of letrozole (2.5 mg/day) combined with norethisterone acetate (2.5 mg/day) in the treatment of pain symptoms related to the presence of rectovaginal endometriosis. The treatment significantly and quickly decreased the intensity of symptoms, but pain recurred at 3-month follow-up; five women underwent surgery during the follow-up, and histologic examination of rectovaginal nodules revealed the presence of active endometriotic lesions.
Zhonghua Fu Chan Ke Za Zhi. 2007 Jan;42(1):43-7.
[The chick embryo chorioallantioc membrane as a model for in vivo research on anti-angiogenesis in endometriosis][Article in Chinese]
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
OBJECTIVE: To establish the chick embryo chorioallantioc membrane (CAM) as a model for in vivo research on endometriosis. The model was used to investigate the mechanism of anti-vascular endothelial growth factor (VEGF) antibody for treatment of endometriosis. METHODS: Human endometrial fragments were explanted onto the CAM. Then anti-VEGF antibody was used for the endometriosis-like lesions after transplantation of human endometrial fragments. The CAM models were treated respectively as control groups and experimental groups. The terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were used in vivo for analysis of anti-angiogenesis. RESULTS: The apoptosis intensity of anti-VEGF antibody treated groups (6.7 +/- 0.9, 6.9 +/- 0.8) was significantly higher than that of the control groups (5.0 +/- 0.9, 5.4 +/- 1.1; P < 0.05). The proliferation intensity was not different in these groups. Lower MVD was observed in experimental groups [(4.2 +/- 1.1), (4.9 +/- 1.2) vessels] than the control groups [(6.9 +/- 1.6), (9.1 +/- 3.0) vessels; P < 0.05]. CONCLUSIONS: CAM is an extraembryonic membrane that is commonly used in vivo for the study of angiogenesis and anti-angiogenesis. Anti-VEGF antibody can be used to accelerate apoptosis of the endometrial cells and vascular endothelium cells, but it has no effect on the proliferation of these cells.
Neurosurgery. 2007 Mar;60(3):E582; author reply E582.
Intramedullary endometriosis of the conus medullaris: case report.
Hum Reprod. 2007 May;22(5):1464-73. Epub 2007 Feb 26.
Imbalance in the expression of the activating type I and the inhibitory type II interleukin 1 receptors in endometriosis.
Unité d’Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d’Assise, Centre Hospitalier Universitaire de Québec, Canada. email@example.com
BACKGROUND: The ectopic establishment and progression of endometrial tissue is dependent upon its interaction with and responsiveness to the stimuli present in its new environment. Immune cell-derived cytokines, such as interleukin 1 (IL1), may alone or in concert with estrogens enhance the capability of ectopic endometrial cells to implant and develop into the host tissue. The objective of this study was to further evaluate the expression and significance of IL1 receptor type I (IL1R1), the signalling receptor that mediates cell activation by IL1, and IL1 receptor type II (IL1R2), a potent and specific down-regulator of IL1 action, in normal compared to endometriotic/endometrial tissues. METHODS: Techniques included immunohistochemistry, immunofluorescent staining, ELISA, western blotting and endometriotic cell culture transfection. RESULTS: Our study showed an imbalance in the expression of IL1R1 and IL1R2 in eutopic, and particularly in ectopic, endometrial tissues of women with endometriosis. Actually, a decreased IL1R2 expression is predominant in the eutopic and ectopic endometrium of women with endometriosis when compared with normal women, whereas a concomitant increase in IL1R1 expression occurs in ectopic endometrial tissue in comparison to eutopic endometrial tissue of normal or endometriotic women, particularly in the initial and most active implants. Transfection of endometriotic cells with a cDNA coding for IL1R2 resulted in a significant decrease in IL1-induced secretion of vascular endothelial cell growth factor and monocyte chemotactic protein 1. CONCLUSIONS: IL1R1/IL1R2 imbalance may amplify endometrial cell responsiveness to IL1 and represent a key mechanism underlying the ability of these cells to implant and develop into host tissues.
Fertil Steril. 2007 Sep;88(3):588-93. Epub 2007 Feb 22.
Bias versus causality: interpreting recent evidence of association between endometriosis and ovarian cancer.
Department of Obstetrics and Gynecology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
OBJECTIVE: To establish whether causality versus biases may explain the association of endometriosis and ovarian cancer. DESIGN: We employ the nine criteria proposed by Austin Bradford Hill, which still stand as foundation milestones for causal inference. SETTING: University-based clinic. PATIENT(S): None. INTERVENTION(S): Search strategies included online searching of the MEDLINE database and hand searching of relevant publications and reviews. Additional reports were collected by systematically reviewing all references from retrieved papers. MAIN OUTCOME MEASURE(S): Examination of the causal relationship between endometriosis and ovarian cancer. RESULT(S): Based on the present analysis, the criterion of strength has not been fulfilled. There were insufficient or mixed data for four criteria (biological gradient, biological plausibility, analogy, coherence), and four criteria were fulfilled (consistency, temporality, specificity, experimental evidence in animal model). CONCLUSION(S): A causal relationship between endometriosis and specific histotypes of ovarian cancer should be recognized, but the low magnitude of the risk observed is consistent with the view that ectopic endometrium undergoes malignant transformation with a frequency similar to its eutopic counterpart.
Fertil Steril. 2007 Oct;88(4 Suppl):1029-38. Epub 2007 Feb 20.
Expression and regulation of estrogen-converting enzymes in ectopic human endometrial tissue.
Institute of Anatomy, University Hospital Essen, Universität Duisburg-Essen, Essen, Germany.
OBJECTIVE: To investigate the regulation of estrogen-converting enzymes in human ectopic endometrial tissue. DESIGN: Animal study. SETTING: Academic medical center. ANIMAL(S): Sixty female nude mice with implanted human endometrial tissue. PATIENT(S): Twenty-two premenopausal women undergoing endometrial biopsy or hysterectomy. INTERVENTION(S): Human endometrial tissue was implanted into the peritoneal cavity of nude mice, and the effect of therapeutic drugs on transcription of steroid receptors and estrogen-converting enzymes was analyzed. MAIN OUTCOME MEASURE(S): Transcript levels of steroid hormone receptors, 17beta-hydroxysteroid dehydrogenase type 1 and 2, aromatase, and steroid sulfatase as well as proliferation rate were analyzed in the human ectopic endometrial tissue. RESULT(S): Steroid receptors and estrogen-converting enzymes were expressed in the ectopic human endometrial fragments. Application of medroxyprogesterone acetate, dydrogesterone, danazol, and the aromatase inhibitor finrozole significantly inhibited aromatase transcription. In addition, danazol caused a significant decrease in transcription of steroid sulfatase, and finrozole, of 17beta-hydroxysteroid dehydrogenase type 1 in parallel to a decrease in proliferation rate in the ectopic human endometrial tissue. CONCLUSION(S): Pharmacological regulation of transcription of estrogen-converting enzymes in human endometrium cultured in nude mice may help to develop new therapeutic concepts based on local regulation of estrogen metabolism in endometriosis.
Surgeon. 2007 Feb;5(1):62; author reply 62.
BMJ. 2007 Feb 17;334(7589):328.
Infertility set in context.
Hum Reprod. 2007 May;22(5):1457-63. Epub 2007 Feb 15.
Accuracy of magnetic resonance imaging and rectal endoscopic sonography for the prediction of location of deep pelvic endometriosis.
Services de Radiologie, Hôpital Tenon, Paris, APHP, France. firstname.lastname@example.org
BACKGROUND: We compared the accuracy of magnetic resonance imaging (MRI) and rectal endoscopic sonography (RES) for the diagnosis of deep pelvic endometriosis (DPE), with respect to surgical and histological findings. METHODS: Longitudinal study of 88 consecutive patients referred for surgical management of DPE, who underwent both MRI and RES pre operatively. The diagnostic criteria were identical for MRI and RES and were based on visualization of hypointense/hypoechoic areas in specific locations. DPE was diagnosed when at least one site was involved. We calculated the sensitivity, specificity, predictive values, accuracy and 95% confidence interval of MRI and RES for DPE. RESULTS: DPE and endometriomas were present in 97.7 and 39.7% of women, respectively. The sensitivity, specificity and positive and negative predictive values of MRI and RES, respectively, were 84.8 and 45.6%, 88.8 and 40%, 98.5 and 87.8% and 40 and 8.5% for uterosacral endometriosis; 77.7 and 7.4%, 70% and 100, 85.3 and 100% and 89.7 and 70.9% for vaginal endometriosis and 88.3 and 90%, 92.8 and 89.3%, 96.4 and 94.7% and 78.8 and 80.6% for colorectal endometriosis. CONCLUSIONS: MRI is more accurate than RES for the diagnosis of uterosacral and vaginal endometriosis, whereas the two methods are similarly accurate for colorectal endometriosis.
Ugeskr Laeger. 2007 Feb 5;169(6):523-4.
[Hymen imperforatus with atypical symptom presentation][Article in Danish]
Sønderborg Sygehus, Røntgenafdelingen. email@example.com
One in every 2,000 girls has hymen imperforatus. A few are recognized at birth because of mucocolpos. The rest are not detected before puberty. Typical symptoms are abdominal pain and distension of the lower abdomen, and half of the girls present with acute urinary retention. A case is presented where the symptoms started after a minor trauma. Diagnosis and treatment are easy. Complications can be infertility, endometriosis and adhesions.
Clin Endocrinol (Oxf). 2007 Mar;66(3):309-21.
Thyroid disease and female reproduction.
Department of Endocrinology, Vrije Universiteit Brussel (AZ-VUB), Brussels, Belgium. firstname.lastname@example.org
The menstrual pattern is influenced by thyroid hormones directly through impact on the ovaries and indirectly through impact on SHBG, PRL and GnRH secretion and coagulation factors. Treating thyroid dysfunction can reverse menstrual abnormalities and thus improve fertility. In infertile women, the prevalence of autoimmune thyroid disease (AITD) is significantly higher compared to parous age-matched women. This is especially the case in women with endometriosis and polycystic ovarian syndrome (PCOS). AITD does not interfere with normal foetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without AITD. During the first trimester, however, pregnant women with AITD carry a significantly increased risk for miscarriage compared to women without AITD, even when euthyroidism was present before pregnancy. It has also been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with AITD. It is therefore advisable to measure thyroid function and detect AITD in infertile women before ART, and to follow-up these parameters after COH and during pregnancy when AITD was initially present. Women with thyroid dysfunction at early gestation stages should be treated with l-thyroxine to avoid pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with AITD remains controversial. To date, there is a lack of well-designed randomized clinical trials to elucidate this controversy.
Int J Gynecol Cancer. 2007 May-Jun;17(3):709-14. Epub 2007 Feb 9.
Malignant degeneration of perineal endometriosis in episiotomy scar, case report and review of the literature.
Department of Obstetrics, Gynecology and Reproductive Medicine, CHU Polyclinique, Clermont-Ferrand, France. email@example.com
Although malignant degeneration of cutaneous endometriosis is rare at only 0.3-1% in endometriosis surgical scars, diagnosis and management need to be defined. A case of malignant degeneration of perineal endometriosis is reported, with a review of literature. Physiopathology, epidemiological data, diagnostic and therapeutic methods are discussed for malignant degeneration of cutaneous endometriosis. Any scar lesion that evolves in response to the menstrual cycle should be considered endometriosis until proven otherwise, and thus could require surgical resection, with histological analysis. A history of cutaneous endometriosis with frequent recurrences can indicate malignant degeneration. All cases require long-term clinical follow-up because, despite the rarity of this diagnosis, the delay between benign endometriosis and malignant transformation can vary from a few months to over 40 years.
Eur J Obstet Gynecol Reprod Biol. 2007 Nov;135(1):88-93. Epub 2007 Feb 12.
Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells.
Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, MS 756, Milwaukee, WI 53226-0509, USA.
OBJECTIVE: Over-production of cyclooxygenase-2 (COX-2) plays an important role in the positive feedback loop that leads to proliferation and inflammation in endometriosis. Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA suppresses IL-1beta-induced COX-2 expression in endometrial stromal cells. STUDY DESIGN: In vitro study using a recently established immortalized endometrial stromal cell line. The stromal cells were pretreated with TSA before stimulation with IL-1beta, and COX-2 gene and protein expression was measured by real-time quantitative RT-PCR and Western blot analysis, respectively. RESULTS: IL-1beta stimulated COX-2 expression in a concentration-dependent manner in endometrial stromal cells. The induced COX-2 gene and protein expression were suppressed by TSA pretreatment. CONCLUSIONS: TSA suppresses IL-1beta-induced COX-2 gene and protein expression in endometrial stromal cells. This finding, coupled with the findings that TSA and another HDACI, valproic acid, suppress proliferation and induce cell cycle arrest, suggests that HDACIs are a promising class of compound that has therapeutic potential for endometriosis.
Fertil Steril. 2007 Jun;87(6):1277-86. Epub 2007 Feb 12.
Treatment utilization for endometriosis symptoms: a cross-sectional survey study of lifetime experience.
Reproductive Biology and Medicine Branch, National Institute of Child and Human Development, National Institutes of Health, Bethesda, Maryland, USA. firstname.lastname@example.org <email@example.com>
OBJECTIVE: To examine the lifetime utilization and perceived benefit of medical treatments and surgical procedures for endometriosis-related symptoms. DESIGN: Cross-sectional study of self-reported survey data. SETTING: Academic research setting. PATIENT(S): Self-reported surgically diagnosed endometriosis by 1,160 women responding to the 1998 Endometriosis Association survey. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Use, perceived helpfulness, and outcomes of medical treatments and surgical procedures. RESULT(S): Ninety-five percent of respondents reported pelvic pain, had endured symptoms on average of 16 years, and were young (mean: 36 years), white, and educated. Many women (46%) had tried three or more medical treatments, and almost 20% took them for 10+ years. Many reported medical treatments as helpful for symptoms (range, 36.4%-61.9%), but some reported stopping because of ineffectiveness (range, 15.6%-26.1%) or side effects (range, 10.0%-43.5%). Danazol or medroxyprogesterone acetate (MPA) was most commonly stopped because of side effects (range, 40.7%-43.5%). Surgical procedures were performed at least three times on 42%. Nearly 20% had a hysterectomy or oophorectomy; these procedures were reported as most successful in improving symptoms (45.9% and 37.8%, respectively). CONCLUSION(S): Despite reporting various treatments as helpful, women used many different types and endured symptoms for an average of almost two decades, indicating the profound effect of endometriosis on women’s health.
Fertil Steril. 2007 Jul;88(1):200-5. Epub 2007 Feb 12.
Deranged expression of follistatin and follistatin-like protein in women with ovarian endometriosis.
Section of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy.
OBJECTIVE: To evaluate the messenger RNA (mRNA) expression and peptide localization of follistatin and follistatin-like protein (FLRG) in ovarian endometriosis, compared to healthy human endometrium. DESIGN: Samples of ovarian endometriotic and healthy endometrial tissues were processed by semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. SETTING: Academic health centers in Siena, Italy, and Belo Horizonte, Brazil. PATIENT(S): Women with endometrioma who underwent laparoscopic excision of ovarian endometriotic cysts (n = 16), and healthy, nonpregnant women (n = 18, control group). MAIN OUTCOME MEASURE(S): Immunostaining and relative quantification of follistatin and FLRG mRNA in ovarian endometriosis and eutopic endometrium. RESULT(S): Both ovarian endometriosis and healthy endometrium expressed and localized follistatin and FLRG. In endometriotic glands, follistatin immunostaining was homogeneously distributed throughout the cytoplasm of the epithelial cells, contrasting with normal eutopic endometrium, where follistatin expression was focal, irregular, and confined to the basal side of the glands. Follistatin-like protein was immunolocalized in the nuclei of both glandular epithelial cells and stromal cells, with less intense staining in endometriotic samples. The relative intensity of follistatin and FLRG immunostaining was significantly higher and lower, respectively, in endometriosis than in controls. The expression of follistatin mRNA was higher, while that of FLRG mRNA was lower, in ovarian endometriosis than in healthy eutopic endometrium. CONCLUSION(S): Ovarian endometriotic lesions show a deranged expression of FLRG and follistatin, which are activin A-binding proteins. This may result in an altered effect of activin A on angiogenesis and/or endometrial differentiation.
Fertil Steril. 2007 Aug;88(2):513-5. Epub 2007 Feb 12.
Vascular endothelial growth factor (VEGF) and ovarian endometriosis: correlation between VEGF serum levels, VEGF cellular expression, and pelvic pain.
Department of Obstetrics and Gynecology, Clínica Universitaria de Navarra, Pamplona, Spain. firstname.lastname@example.org <email@example.com>
Vascular endothelial growth factor (VEGF) serum levels and VEGF and cellular expression were prospectively analyzed in 60 patients (group A consisted of asymptomatic patients or patients presenting mild dysmenorrhea; 30 women comprised group B severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists among VEGF serum levels, VEGF cellular expression, and pelvic pain. No differences were found in VEGF serum levels and VEGF cellular expression between both groups. Therefore, we conclude that pain symptoms in ovarian endometriosis are not correlated with VEGF serum levels and VEGF cellular expression.
Fertil Steril. 2007 Jul;88(1):220-3. Epub 2007 Feb 12.
Differential expression of selected gene products in uterine leiomyomata and adenomyosis.
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
Gene products estrogen receptor alpha, progesterone receptor-A, retinoid X receptor alpha, insulin-like growth factor-II, insulin-like growth factor I receptor beta, platelet-derived growth factor, epithelial growth factor receptor, and BCL-2 were examined by immunohistochemistry with the aid of a tissue microarray from 46 hysterectomies with adenomyosis and leiomyomata. With appropriate internal controls, there were significant differences in gene expression between adenomyosis and leiomyomata.
Am J Reprod Immunol. 2007 Mar;57(3):218-26.
Expression of inducible microsomal prostaglandin E synthase in local lesions of endometriosis patients.
Department of Obstetrics and Gynecology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. firstname.lastname@example.org
PROBLEM: Recently, an inducible microsomal human prostaglandin E synthase (mPGES) was identified. This enzyme converts the cyclooxygenase (COX) product, prostaglandin (PG) H(2), to PGE(2), an eicosanoid linked to carcinogenesis. Although elevated levels of PGE(2) have been observed in many tumor types including colorectal adenomas and cancers, its role in the pathophysiology of endometriosis is unknown. We previously reported increased expression of COX-2 messenger RNA (mRNA) in local lesions of endometriosis. To further elucidate the mechanism responsible for the elevated levels of PGE(2) in endometriosis, we examined the expression levels of mPGES. METHOD OF STUDY: Samples were obtained from 28 patients, fixed in formalin, and embedded in paraffin for immunohistochemical analysis. We examined the expression of mPGES mRNA in seven cases by reverse transcriptase-polymerase chain reaction using total RNA extracted from frozen samples. RESULTS: Immunohistochemistry revealed increased mPGES immunoreactivity in endometriosis samples compared with eutopic endometria. Microsomal PGES immunoreactivity was observed in both epithelial cells and stromal or inflammatory cells of endometriosis. Increased expression of mPGES-1 mRNA was detected in most of the endometriosis samples. CONCLUSION: Our results suggest that expression of mPGES in addition to COX-2 plays a role in increasing PGE(2) production in endometriosis.