PMID: 15294376 [PubMed – in process]

23: Eur J Obstet Gynecol Reprod Biol. 2004 Sep 10;116(1):89-99.

Genomic alterations in the endometrium may be a proximate cause for endometriosis.
Guo SW, Wu Y, Strawn E, Basir Z, Wang Y, Halverson G, Montgomery K, Kajdacsy-Balla A.
Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, MS 756, Milwaukee, WI 53226-0509, USA.
Objective: To test the hypothesis that endometriosis may originate from genomic alterations in the endometrium by genomic analysis of endometrial tissues in patients with endometriosis and compare them with those from normal controls. Methods: Endometrial tissue samples were taken from five women with endometriosis. For controls, we used endometrial tissue samples from four women who underwent elective abortions and one sample from placenta. Using array-based comparative genomic hybridization (CGH), we determined the normal range of variation in CGH signals using normal controls. CGH results were further confirmed by real-time quantitative PCR and loss of heterozygosity analysis. Results: We identified several regions of genomic alterations in all five patients. Some of these regions were the same regions identified previously in endometriotic lesions. For select markers, the genomic alterations were confirmed by real-time PCR and LOH analyses. Conclusions: There is evidence that the endometrium in women with endometriosis has genomic alterations. This is consistent with numerous reports that the endometrium of women with endometriosis differ from those of women without. Our finding suggests that genomic alterations in the endometrium may be a proximate cause for endometriosis.
PMID: 15294375 [PubMed – in process]

24: Eur J Obstet Gynecol Reprod Biol. 2004 Sep 10;116(1):85-8.
Use of CA125 fluctuation during the menstrual cycle as a tool in the clinical diagnosis of endometriosis; a preliminary report.
Kafali H, Artuc H, Demir N.
Department of Obstetrics and Gynecology, Faculty of Medicine, Harran University , 63100 Sanliurfa , Turkey .
Objective: To elucidate whether endometriosis can be diagnosed clinically by assessing the differences between serum CA125 levels during menstruation and during the rest of the menstrual cycle. Methods: The study was performed in 28 patients who underwent laparoscopy to check for pelvic causes of infertility. Patients with endometriosis were selected as the study group, and patients with normal laparoscopic findings functioned as the control group. Blood specimens were taken for CA125 determination during menstruation and during the rest of the menstrual cycle. Mean serum CA125 concentrations were compared by the two-sample t-test for between-group comparisons and the paired t-test for within-group comparisons. The receiver operating characteristic curve was applied to assess the usefulness of CA125 level changes during the menstrual cycle in the clinical diagnosis of endometriosis. Results: The mean CA125 concentrations of healthy women during menstruation and during the rest of the menstrual cycle were 12.2 and 10Uml(-1), respectively. In this group, the mean CA125 concentration was an average of 22% higher during menstruation than during the rest of the menstrual cycle ( [Formula: see text] ). The patients with endometriosis showed a similar pattern to that of normal women, but the levels differed by 198.3% in these patients ( [Formula: see text] ). Mean CA125 concentrations of these patients during menstruation and in the rest of the cycle were 35.8 and 12Uml(-1), respectively. The mean CA125 concentration during menstruation was significantly higher in patients with endometriosis than in normal women ( [Formula: see text] ), but CA125 concentrations at other points in the menstrual cycle were found to be similar in both groups ( [Formula: see text] ). ROC curve analyses set a cutoff of 83% (percentage increment of CA125 level during menstruation compared with that on days without menstrual bleeding), which gives a sensitivity of 93% and specificity of 92%, with a corresponding likelihood ratio of 11.3. Conclusions: It may be possible to diagnose endometriosis clinically by assessment of the differences in CA125 level during menstruation as against the remainder of the menstrual cycle.
PMID: 15294374 [PubMed – in process]

25: Clin Mol Allergy. 2004 Aug 2;2(1):10.
Autoimmune progesterone dermatitis in a patient with endometriosis: case report and review of the literature.
Baptist AP, Baldwin JL.
Division of Allergy/Immunology, Department of Internal Medicine, University of Michigan, 3918 Taubman Center, #0380, 1500 E Medical Center Drive, Ann Arbor, MI 48109-0380, USA. abaptist@umich.edu
Autoimmune progesterone dermatitis (APD) is a condition in which the menstrual cycle is associated with a number of skin findings such as urticaria, eczema, angioedema, and others. In affected women, it occurs 3-10 days prior to the onset of menstrual flow, and resolves 2 days into menses. Women with irregular menses may not have this clear correlation, and therefore may be missed. We present a case of APD in a woman with irregular menses and urticaria/angioedema for over 20 years, who had not been diagnosed or correctly treated due to the variable timing of skin manifestations and menses. In addition, we review the medical literature in regards to clinical features, pathogenesis, diagnosis, and treatment options.
PMID: 15287986 [PubMed – as supplied by publisher]

26: Ultrasound Obstet Gynecol. 2004 Aug;24(2):180-5.
Diagnostic accuracy of transvaginal sonography for deep pelvic endometriosis.
Bazot M, Thomassin I, Hourani R, Cortez A, Darai E.
Department of Radiology, Hopital Tenon, Paris, France. marc.bazot@tnn.ap-hop-paris.fr
OBJECTIVE: To determine the accuracy of transvaginal sonography (TVS) for the diagnosis of deep pelvic endometriosis. METHODS: In a prospective study, 142 women with clinical signs of endometriosis underwent TVS followed by surgical and histopathological investigations. The presence and extent of endometriosis involving the uterosacral ligaments, vagina, rectovaginal septum, intestines, bladder and ovaries shown by TVS were compared with surgical and histological findings. The sensitivity, specificity, predictive values and accuracy of TVS for predicting deep pelvic endometriosis were assessed. RESULTS: Ovarian and deep pelvic endometriosis were found by surgery and histology in respectively 83 (58.5%) and 79 (55.6%) of the 142 patients. The sensitivity, specificity, and positive and negative predictive values of TVS for the diagnosis of deep pelvic endometriosis were 78.5%, 95.2%, 95.4% and 77.9%, respectively. The sensitivity and specificity of TVS for endometriotic involvement of the uterosacral ligaments, vagina, rectovaginal septum and intestines were 70.6% and 95.9%, 29.4% and 100%, 28.6% and 99.3%, and 87.2% and 96.8%, respectively. The sensitivity and specificity of TVS for bladder involvement were 71.4% and 100%, respectively. CONCLUSION: TVS accurately diagnoses intestinal and bladder endometriosis, but is less accurate for uterosacral, vaginal and rectovaginal septum involvement. Copyright 2004 ISUOG
PMID: 15287057 [PubMed – in process]

27: Ultrasound Obstet Gynecol. 2004 Aug;24(2):175-9.
Accuracy of rectal endoscopic ultrasonography and magnetic resonance imaging in the diagnosis of rectal involvement for patients presenting with deeply infiltrating endometriosis.
Chapron C, Vieira M, Chopin N, Balleyguier C, Barakat H, Dumontier I, Roseau G, Fauconnier A, Foulot H, Dousset B.
Hopitaux de Paris (AP-HP), Service de Gynecologie Obstetrique II, Unite de Chirurgie, Clinique Universitaire Baudelocque, Paris , France . charles.chapron@cch-ap-hop-paris.fr
OBJECTIVE: To compare the accuracy of rectal endoscopic ultrasonography (REU) and magnetic resonance imaging (MRI) for predicting rectal wall involvement in patients presenting histologically proven deeply infiltrating endometriosis (DIE). METHODS: This was a retrospective study of a continuous series of 81 patients presenting histologically proven DIE who underwent preoperative investigations using both REU and MRI. The sonographer and the radiologist, who were unaware of the clinical findings and patient history, but knew that DIE was suspected, were asked whether there was involvement of the digestive wall. RESULTS: Rectal DIE was confirmed histologically in 34 of the 81 (42%) patients. For the diagnosis of rectal involvement, sensitivity, specificity and positive and negative predictive value for REU were 97.1%, 89.4%, 86.8% and 97.7% and for MRI they were 76.5%, 97.9%, 96.3% and 85.2%. CONCLUSION: The sensitivity and negative predictive value of REU were higher than those of MRI suggesting that REU performs better than MRI in the diagnosis of rectal involvement for patients presenting with DIE. Prospective studies with a large number of patients are needed in order to validate these preliminary results. Copyright 2004 ISUOG
PMID: 15287056 [PubMed – in process]

28: Am J Obstet Gynecol. 2004 Jun;190(6):1788-95; discussion 1795-6.
Human endometriotic xenografts in immunodeficient RAG-2/gamma(c)KO mice.
Greenberg LH, Slayden OD.
Department of Obstetrics and Gynecology, Providence St. Vincent Hospital , Portland , OR , USA .
OBJECTIVE: The purpose of this study was to create a novel animal model for studies of endometriosis. STUDY DESIGN: To facilitate the study of the transplantation of endometriosis into immunodeficient RAG-2/gamma(c)KO mice, endometriosis biopsy specimens were collected from 19 women by laparoscopic surgery and grafted subcutaneously into the mice, which were treated subsequently with estradiol and progesterone to create 28-day artificial cycles. The grafts were collected during the first, second, and fourth cycles and were evaluated histologically for evidence of bleeding and immunocytochemically for estrogen receptor and progesterone receptor. RESULTS: Biopsy specimens that contained endometrium-like glands were well accepted (>90% success). These grafts maintained glandular morphologic condition, estrogen receptor, and progesterone receptor; bled after progesterone withdrawal; and formed chocolate cysts. However, biopsy specimens that lacked glands or that consisted of peritoneal adhesions and stroma were accepted poorly <5% success) and failed to show evidence of estrogen receptor, progesterone receptor, or cyclic bleeding. CONCLUSION: Human endometriosis transplanted into RAG-2/gamma(c)KO mice can provide a model for endometriotic bleeding.
PMID: 15284801 [PubMed – indexed for MEDLINE]

29: Ann Ital Chir. 2004 Jan-Feb;75(1):29-34; discussion 34.
[The endometriosis of the abdominal wall (personal experience)] [Article in Italian] Donati M, Gandolfo L, Cavallaro G, Ciancio F, Brancato G.
Universita degli Studi di Catania, Policlinico Universitario, Unita Operativa di Chirurgia Generale I.
Endometriosis is a very common gynaecological disease, although the abdominal wall localization is a rare clinical problem in the everyday practise and this explains the incomplete reports in literature and the difficulty of a standard treatment. Authors report four abdominal wall endometriosis cases, underlining how the surgical therapy represents the gold and decisive treatment, thanks also to prosthetic reconstruction techniques who allow more radical demolitions. On the contrary, the medical treatment should be reserved to selected cases such as especially the less symptomatic umbilical primitive diseases.
PMID: 15283384 [PubMed – in process]

30: J Reprod Med. 2004 Jun;49(6):468-72.
T allele for VEGF gene-460 polymorphism at the 5′-untranslated region: association with a higher susceptibility to endometriosis.
Hsieh YY, Chang CC, Tsai FJ, Yeh LS, Lin CC, Peng CT.
Department of Obstetrics and Gynecology, China Medical University Hospital , Taichung , Taiwan .
OBJECTIVE: To investigate whether vascular endothelial growth factor (VEGF) gene 5′-UTR-460 polymorphism could be used as a marker of susceptibility to endometriosis. STUDY DESIGN: Women were divided into 2 groups, endometriosis (n = 122) and nonendometriosis (n = 131). Polymorphisms for VEGF were detected by polymerase chain reaction and BstUI (New England Biolabs, Beverly , Massachusetts ) restriction enzyme analysis. Genotypes and allelic frequencies between the groups were compared. RESULTS: Proportions of different VEGF polymorphisms in the groups were significantly different. Proportions of cuttable (C) homozygote/heterozygote/ uncuttable (T) homozygotefor VEGF in the groups were 0/44.3/55.7% and 0/63.4/36.6%, respectively. A higher percentage of T/F homozygote and T allele was present in the endometriosis population. The proportions of C/T alleles in the groups were 22.1/77.9% and 31.7/68.3%, respectively. CONCLUSION: T/T homozygotes and the T allele of the VEGF-460 gene are associated with a higher risk of endometriosis. Heterozygotes and C allele are related to the lower risk of endometriosis formation. VEGF polymorphism likely contributes to the pathogenesis of endometriosis and may become a useful markerfor predicting endometriosis susceptibility.
PMID: 15283056 [PubMed – in process]

31: Diagn Cytopathol. 2004 Aug;31(2):123-5.
Eosinophilic metaplastic atypia in exfoliated cells of ovarian endometriosis: a potential cytodiagnostic pitfall in peritoneal fluids.
Slade AJ, Dieterich M, Sturgis CD.
Evanston Northwestern Healthcare Research Institute, Evanston , Illinois 60201 , USA .
Endometriosis is a protean clinical condition that is defined pathologically by the presence of endometrial glands and stroma with associated evidence of bleeding occurring outside of the usual anatomy of the endometrium/uterine cavity. It is one of the most common benign gynecologic disorders, affecting approximately 5% of all women. The prevalence of the condition may increase to as high as 30% in infertile premenopausal women. Despite extensive study, the etiology of this condition remains an enigma. Cytopathologists may encounter abnormal cells arising from endometriosis in cervicovaginal cytology samples, nongynecologic exfoliative cytology cases, needle aspiration biopsy slides, and in histologic materials and cell blocks. We report a case of eosinophilic epithelial metaplasia present in cytospins made from a peritoneal washing taken from a perimemopausal woman. This patient was concomitantly histologically documented to have ovarian surface endometriosis with similar metaplastic alteration. The case highlights the potential for misdiagnosis of such processes as being potentially malignant and stresses the need for cytohistologic correlation whenever possible. Copyright 2004 Wiley-Liss, Inc.
PMID: 15282727 [PubMed – in process]

32: Reprod Toxicol. 2004 Jul-Aug;18(6):793-801.

Histomorphometric alteration and cell-type specific modulation of arylhydrocarbon receptor and estrogen receptor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin and 17beta-estradiol in mouse experimental model of endometriosis.
Kitajima M, Khan KN, Fujishita A, Masuzaki H, Ishimaru T.
Department of Obstetrics & Gynecology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8102, Japan .
Our purpose was to examine the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), either singly (10microg/kg) or with 17beta-estradiol (E(2), 100microg/kg), on the growth of endometriosis in a mouse endometriosis model by employing histo-morphometrical analysis as well as expression of arylhydrocarbon receptor (AhR) and estrogen receptor (ER). Epithelial height, stromal thickness, and proliferative activity of the endometriotic lesions were significantly increased by E(2) in ovariectomized mice, whereas co-administered TCDD significantly reduced these effects. TCDD alone did not affect the proliferative activity but rather reduced the epithelial height and stromal thickness. ER expression in the luminal epithelium was decreased by E(2) compared with ovariectomy alone, while TCDD significantly increased it. On the other hand, stromal ER expression was significantly increased by ovariectomy and decreased by E(2), though TCDD did not further enhance this expression. These results indicate that a short-term exposure to TCDD failed to increase the growth of endometriotic lesion and the direct effect of TCDD probably depends on a cell-specific interaction with ovarian steroids mediated by their own receptors. These initial findings in intact tissue of mouse endometriosis may suggest critical roles of steroid hormones in the pathogenesis of endometriosis in relation to endocrine disruptors.
PMID: 15279877 [PubMed – in process]

33: Eur Radiol. 2004 Jul 24 [Epub ahead of print] Rectal endometriosis: MRI study with rectal coil.
Puglielli E, Di Cesare E, Masciocchi C.
Department of Radiology, University of L’Aquila, Ospedale S. Salvatore-Coppito, 67100, L’Aquila, Italy.
PMID: 15278407 [PubMed – as supplied by publisher]

34: Lancet. 2004 Jul 24;364(9431):368.
Caesarean scar endometrioma.
Gaunt A, Heard G, McKain ES, Stephenson BM.
Department of Surgery, Royal Gwent Hospital , Newport , South Wales , NP20 2UB, UK .
Publication Types:
Case Reports
PMID: 15276397 [PubMed – indexed for MEDLINE]

35: Mol Hum Reprod. 2004 Sep;10(9):651-4. Epub 2004 Jul 23.
Analysis of the codon 72 polymorphism of the TP53 gene in patients with endometriosis.
Lattuada D, Vigano P, Somigliana E, Abbiati A, Candiani M, Di Blasio AM.
II Department of Obstetrics and Gynecology, University of Milano, Milano, Italy and Molecular Biology Laboratory, Istituto Auxologico Italiano, Milano, Italy.
Endometriosis is a benign gynaecologic disease that is associated with a certain risk for malignant degeneration. The disease has a genetic background, but the locations of possible genomic aberrations are still poorly clarified. In this context, the proline form of TP53 codon 72 polymorphism has been recently associated with the risk of developing endometriosis. In this case-control study, we aimed to investigate further the potential association between endometriosis and this polymorphism in order to evaluate whether this genetic variant may influence the susceptibility to the disease. Genomic DNA was obtained from a consecutive series of 303 Italian Caucasian women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. Endometriosis was defined according to the criteria of Holt and Weiss [Holt V and Weiss NS (2000) Recommendations for the design of epidemiologic studies of endometriosis. Epidemiol 11,654-659] for the definite disease. Subjects of similar age without laparoscopic evidence of the disease served as control group. Molecular analysis of TP53 codon 72 polymorphism was performed by PCR amplification. Endometriosis was documented in 151 women. We found no statistically significant difference in the distribution of TP53 codon 72 polymorphism genotypes between patients with and without endometriosis. The respective proportions of arginine homozygotes, heterozygotes and proline homozygotes were 55.6, 39.7 and 4.6% in the group with endometriosis and 59.9, 30.9 and 9.2% in the control group. Moreover, no statistically significant association was demonstrated between TP53 codon 72 polymorphism and the various clinical manifestations of the disease, although a non-significant tendency towards an increased frequency of the proline allele was observed in association with specific manifestations of the disease reflecting a more severe form. Our results suggest that the TP53 codon 72 polymorphism does not confer genetic susceptibility to endometriosis in the Italian population. However, a possible susceptibility role of this polymorphism in endometriosis development towards very severe forms cannot be ruled out.
PMID: 15273281 [PubMed – in process]

36: Clin Endocrinol (Oxf). 2004 Aug;61(2):190-4.
Genetics of endometriosis: a role for the progesterone receptor gene polymorphism PROGINS?
Lattuada D, Somigliana E, Vigano P, Candiani M, Pardi G, Di Blasio AM.
Molecular Biology Laboratory, Istituto Auxologico Italiano, University of Milan, Milan, Italy.
OBJECTIVE: Endometriosis is a steroid-dependent disease with a particular genetic background, but the locations of possible genomic aberrations are still poorly clarified. We have investigated the potential association between endometriosis and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor (PR) gene, which has been reported previously to segregate with this disease. DESIGN: In a case-control study, we examined the PROGINS polymorphism of the progesterone receptor gene in 131 Italian women affected by endometriosis diagnosed according to published criteria for the definition of the definite disease. Control subjects were represented by 127 Italian women without laparoscopic evidence of the disease. MEASUREMENTS: Peripheral blood samples, DNA extraction and polymerase chain reaction (PCR) were used to genotype women for the presence of the PROGINS polymorphism. RESULTS: We found a statistically significant difference in the distribution of PROGINS genotypes between patients with and without endometriosis. The frequency of the PROGINS allele T2 was 17.2% and 11%, respectively, in affected women and in controls [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.0-2.8]. This association was stronger in patients with more severe forms of endometriosis, such as an infiltrating disease or a disease characterized by severe pelvic adhesions (OR 2.4, 95% CI 1.2-4.8; and OR 2.7, 95% CI 1.4-5.3, respectively). Combination of the results from an earlier study and the current data indicates that carrying the allele variant T2 is associated with a twofold increase in the risk of developing endometriosis (OR 2.0, 95% CI 1.3-2.9). CONCLUSIONS: Our results further support the idea that the PROGINS polymorphism of the progesterone receptor may be associated with an increased risk of endometriosis.
PMID: 15272913 [PubMed – in process]

37: Hum Reprod. 2004 Sep;19(9):2043-2051. Epub 2004 Jul 22.
The FLUSH Trial– Flushing with Lipiodol for Unexplained (and endometriosis-related) Subfertility by Hysterosalpingography: a randomized trial.
Johnson NP, Farquhar CM, Hadden WE, Suckling J, Yu Y, Sadler L.
University of Auckland Department of Obstetrics and Gynaecology, National Women’s Hospital, Auckland, Fertility Plus, National Women’s Hospital, Auckland, University Specialists, Mercy Specialist Centre, Epsom, Auckland and Auckland Radiology Group, 641 Manukau Road, Royal Oak, Auckland, New Zealand.
BACKGROUND: To assess the effectiveness of flushing with the oil-soluble contrast medium lipiodol in women with unexplained infertility. METHODS: An open randomized controlled trial design in a single centre secondary and tertiary level infertility service setting. A total of 158 women with unexplained infertility were stratified into two populations: 96 women without confirmed endometriosis and 62 women with endometriosis who had normal Fallopian tubes and ovaries. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered envelopes. Lipiodol flushing was tested versus no intervention. The main outcome measures were clinical pregnancy (assessed at 6 months following randomization) and live birth. RESULTS: Lipiodol flushing resulted in a significant increase in pregnancy [48.0 versus 10.8%, relative risk (RR) 4.44, 95% confidence interval (CI) 1.61-12.21] and live birth (40.0 versus 10.8%, RR 3.70, 95% CI 1.30-10.50) rates versus no intervention for women with endometriosis, although there was no significant difference in pregnancy (33.3 versus 20.8%, RR 1.60, 95% CI 0.81-3.16) or live birth (27.1 versus 14.6%, RR 1.86, 95% CI 0.81-4.25) rates for women with unexplained infertility without confirmed endometriosis. CONCLUSIONS: Lipiodol flushing is an effective treatment for couples with unexplained infertility (based on meta-analysis data), but is particularly effective for women with endometriosis who have normal Fallopian tubes and ovaries.
PMID: 15271870 [PubMed – as supplied by publisher]

38: Arch Ital Urol Androl. 2004 Jun;76(2):91-3.
Ureteral endometriosis: an unusual case of a pelvic mass arising in the ureter and involving the rectum and uterine cervix.
Dominici A, Agostini S, Sarti E, Maleci M, Raspollini MR, Mondaini N, Rizzo M, Nesi G.
Clinica Urologica I, Universita di Firenze, Firenze, Italy.
The case of a 41-year-old woman with a pelvic mass arising in the left ureter is reported. The diagnosis of endometriosis was made on transperineal biopsy exclusively. After unsuccessful treatment with LH-RH analogues, the patient underwent ureteral resection and ureteroneocystostomy. At six months’ follow-up, she is asymptomatic with no evidence of hydronephrosis.
PMID: 15270422 [PubMed – in process]

39: Clin Exp Obstet Gynecol. 2004;31(2):107-9.
Correlation of endoscopic interpretation of endometriosis with histological verification.
Schollmeyer T, Pandit K, Schmutzler A, Mettler L.
Department of Gynaecology & Obstetrics, University of Kiel , Michaelisstr , Germany .
INTRODUCTION: In this study we correlate the laparoscopic findings of endometriosis with the histological confirmation of the disease over a period of two years. MATERIALS AND METHODS: One hundred and sixty-four laparoscopies performed at the Department of Gynecology & Obstetrics, University of Kiel , over a two-year period were reviewed for laparoscopic findings and histological confirmation of endometriosis. RESULTS: The majority of patients suspected of endometriosis at laparoscopy were confirmed by histological examination, i.e. 138 out of 164 patients (84.1%). CONCLUSION: Laparoscopy is the easiest diagnostic tool for the diagnosis of endometriosis which can be confirmed by histological examination.
PMID: 15266761 [PubMed – in process]

40: Cochrane Database Syst Rev. 2004;(3):CD003678.
Pre and post operative medical therapy for endometriosis surgery .
Yap C, Furness S, Farquhar C.
Department of Obstetrics & Gynaecology, Singapore General Hospital , Outram Road , Singapore , SINGAPORE , 169608.
BACKGROUND: Endometriosis is a common gynaecological condition which affects approximately 10% of women of reproductive age (Askenazi 1997). There is a range of symptoms and most commonly women present with dysmenorrhoea, pelvic pain, infertility or a pelvic mass. Direct visualisation and biopsy during laparoscopy or laparotomy is the gold standard diagnostic test for this condition and enables the gynaecologist to identify the location, extent and severity of the disease. Surgical therapy can be performed concurrently with diagnostic surgery and may include removal (excision) or destruction (ablation) of endometriotic tissue, division of adhesions and removal of endometriotic cysts. Laparoscopic excision or ablation of endometriosis has been shown to be effective in the management of pain in mild-moderate endometriosis. Adjunctive medical treatment pre or post-operatively may prolong the symptom-free interval. OBJECTIVES: To determine the effectiveness of systemic medical therapies used for hormonal suppression before or after surgery for endometriosis, or before and after surgery for endometriosis in the eradication of endometriosis, improvement of symptoms, pregnancy rates and overall tolerability by comparing them with no treatment or placebo. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility group trials register (searched 10 September 2003 ), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2003), MEDLINE (January 1966 to September 2003), EMBASE (January 1985 to September 2003) and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Trials were included if they were randomised controlled trials of the use of systemic medical therapies for hormonal suppression before or after, or before and after surgery for endometriosis. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment was performed independently by using relative risk or weighted mean difference and 95% confidence intervals. MAIN RESULTS: Eleven trials were included in the review. One study comparing pre-surgical medical therapy with surgery alone showed a significant improvement in AFS scores in the medical therapy group (WMD -9.60, 95% CI -11.42 to -7.78) but this may or may not be associated with better outcomes for the patients. Post surgical hormonal suppression of endometriosis compared to surgery alone (either no medical therapy or placebo) showed no benefit for the outcomes of pain or pregnancy rates but a significant improvement in disease recurrence (AFS scores (WMD -2.30, 95% CI -4.02 to -0.58)). There were no trials identified in the search that compared hormonal suppression of endometriosis before and after surgery with surgery alone. There is no significant difference between pre surgery hormonal suppression and post surgery hormonal suppression for the outcome of pain in the one trial identified (RR 1.01, 95% CI 0.49 to 2.07). Info rmation concerning AFS scores and ease of surgery was reported only as a descriptive summary so any difference between the groups can not be quantified from the information in the report of this trial. REVIEWERS’ CONCLUSIONS: There is insufficient evidence from the studies identified to conclude that hormonal suppression in association with surgery for endometriosis is associated with a significant benefit with regard to any of the outcomes identified. There may be a benefit of improvement in AFS scores with the pre-surgical use of medical therapy. The possible benefit should be weighed in the context of the adverse effects and costs of these therapies.
PMID: 15266496 [PubMed – in process]

41: Am J Physiol Endocrinol Metab. 2004 Jul 20 [Epub ahead of print] Gonadotropin Releasing Hormone and TGF-Beta Activate MAP Kinase and Differentially Regulate Fibronectin Expression in Endometrial Epithelial and Stromal Cells.
Luo X, Ding L, Chegini N.
Department of OB/GYN, University of Florida , Gainesville , FL , USA .
Gonadotropin releasing hormone analogue (GnRHa) is used for medical management of endometriosis and premature luteinizing hormone surge during controlled ovarian stimulation. Human endometrium expresses GnRH receptors and GnRHa alters the expression of transforming growth factor beta (TGF-beta) and receptors in endometrial cells. Since the diverse biological action of GnRHa and TGF-beta are mediated in part through mitogen-activated protein kinase (MAPK) pathway, we determined whether utilization of MAPK/ERK and transcriptional activation of immediate early genes, c-fos and c-jun, result in differential regulation of fibronectin, known as key regulator of embryo implantation and endometriosis progression. Using endometrial stromal cells (ESC) and endometrial epithelial cell line (HES) we demonstrated that GnRHa and TGF-beta1 in a dose-, time- and cell-dependent manner increased the level of phosphorylated ERK1/2 (pERK1/2). GnRH antagonist, antide also increased pERK1/2 induction in ESC and HES, while pretreatment reduced GnRHa-induced pERK2 in ESC, but not in HES. Co-treatments with GnRHa + TGF-beta1 did not have an additive or an inhibitory effect on pERK1/2 induction compared to GnRHa or TGF-beta1 action alone. TGF-beta1 and GnRHa increased ERK1/2 nuclear accumulation and inversely regulated the expression of c-fos and c-jun, and that of fibronectin in a cell specific manner. Pretreatment with U0126, a MEK1/2 inhibitor, blocked basal, as well as GnRHa- and TGF-beta1-induced pERK1/2, however it differentially affected c-fos, c-jun, and fibronectin expression. In conclusion, the results indicate that GnRHa and TGF-beta signaling through MAPK/ERK results in differential regulation of fibronectin expression in endometrial cells, a molecular mechanism where short- and long-term GnRHa therapy and locally expressed TGF-beta could influence embryo implantation and endometriosis implants, respectively.
PMID: 15265761 [PubMed – as supplied by publisher]

42: Clin Chem Lab Med. 2004;42(6):590-4.
Activity of eosinophils and immunoglobulin E concentration in the peritoneal fluid of women with endometriosis.
Eidukaite A, Tamosiunas V.
Department of Molecular Immunology, Institute of Immunology , Vilnius , Lithuania . elza@takas.lt
Autoinflammatory phenomena, including autoantibody production and atopy, have been regarded as associated with endometriosis. The present study investigates the activity of eosinophils and the distribution of immunoglobulin E concentrations in the peritoneal fluid of women with early endometriosis. The study group consisted of 30 patients with laparoscopically diagnosed early endometriosis. The healthy control group consisted of 18 females with no evident changes in the abdominal cavity and no endometrial foci. Concentrations of immunoglobulin E in serum and peritoneal blood were determined by enzyme immunoassay. The activity of eosinophils was estimated according to the expression of the early activation molecule CD69 by the flow cytometry method. The concentrations of immunoglobulin E in the peripheral blood and peritoneal fluid were similar in both groups. However, the count of CD69+ eosinophils was higher in the peritoneal fluid of women with endometriosis. The results indicate that activated eosinophils accumulate in the peritoneal fluid in early endometriosis and can play a significant role in the pathogenesis of the disease.
PMID: 15259373 [PubMed – in process]

43: Minerva Ginecol. 2004 Jun;56(3):259-70.
[Etiopathogenesis of endometriosis related infertility] [Article in Italian] Greco E, Pellicano M, Di Spiezio Sardo A, Scherillo A, Cerrota G, Bramante S, Nappi C.
Dipartimento di Ginecologia, Ostetricia e Fisiopatologia della Riproduzione, Universita degli Studi di Napoli Federico II, Naples, Italy.
In the last years the entire scientific community has devoted remarkable resources to the understanding of endometriosis. In spite of this, endometriosis remains one of the most complex gynecological diseases, in nearly all of its physiopathological aspects and implications. In particular, the association between endometriosis and infertility has proven to be complex and it has been widely discussed. It is generally accepted that moderate/severe endometriosis related sterility is due to mechanical factors, namely to the distortion/subversion of the regular pelvic anatomy. On the contrary, the factors behind infertility/subfertility related to minimal/mild endometriosis are less clear. None of the hypothesized mechanisms exhaustively explained the infertility related to endometriosis, while it is possible that such disease is caused by multiple factors altogether. The aim of this thorough review of the international literature is to analyze the main etiological factors (i.e. alterations in oocyte maturation and/or growth, defects of fertilization, impairments of implantation or aberrant immunological mechanisms) that are potentially involved, as well as the role that each of the above mentioned factors has in determining the endometriosis related infertility/subinfertility.
PMID: 15258537 [PubMed – in process]

44: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11094-8. Epub 2004 Jul 15.
Innervation of ectopic endometrium in a rat model of endometriosis.
Berkley KJ, Dmitrieva N, Curtis KS, Papka RE.
Program in Neuroscience, Florida State University , Tallahassee , 32306-1270, USA . kberkley@psy.fsu.edu
Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimic those in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and A delta fibers), substance P (SP) (sensory C and A delta fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.
PMID: 15256593 [PubMed – indexed for MEDLINE]

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