Hum Reprod. 2005 Sep 19
Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions.
Laschke MW, Elitzsch A, Vollmar B, Vajkoczy P, Menger MD.
Institute for Clinical & Experimental Surgery, University of Saarland, 66421 Homburg/Saar.
BACKGROUND: Angiogenesis represents the crucial step in the pathogenesis of endometriosis, because endometri-otic lesions require neovascularization to establish, proliferate and invade inside the peritoneal cavity. To elucidate the role of angiogenic factors, we investigated in vivo whether blockade of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) affects angiogenesis of ectopic endometrium. METHODS: Mechanically isolated endometrial fragments were transplanted into the dorsal skinfold chamber of hormonally synchronized hamsters. Subsequently, we analysed the effect of the VEGF inhibitor SU5416 and the combined VEGF, FGF and PDGF inhibitor SU6668 on angiogenesis of the ectopic endometrium over a time-period of 14 days using intravital fluorescence microscopy. RESULTS: Selective blockade of VEGF resulted in a slight reduction of microvessel density when compared to control animals. In contrast, combined inhibition of all three growth factors significantly suppressed angiogenesis of endometrial grafts, as indicated by a reduced size of the microvascular network and a decreased microvessel density. This was caused by an inhibition of blood vessel maturation. CONCLUSIONS: Vascularization of endometriotic lesions is not solely driven by VEGF, but depends on the cross-talk between VEGF, FGF and PDGF. Thus, the combined inhibition of these growth factors may represent a novel therapeutic strategy in the treatment of endometriosis.

Hum Reprod Update. 2005 Sep 19
Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications.
Fauconnier A, Chapron C.
Unite Inserm 149, Recherches Epidemiologiques en Sante Perinatale et Sante des Femmes, Port-Royal; Service de Gynecologie, Obstetrique et Medecine de la Reproduction CHI Poissy-St-Germain, Saint-Germain-En-Laye, Paris, France.
The relationship between chronic pelvic pain symptoms and endometriosis is unclear because painful symptoms are frequent in women without this pathology, and because asymptomatic forms of endometriosis exist. Our comprehensive review attempts to clarify the links between the characteristics of lesions and the semiology of chronic pelvic pain symptoms. Based on randomized trials against placebo, endometriosis appears to be responsible for chronic pelvic pain symptoms in more than half of confirmed cases. A causal association between severe dysmenorrhoea and endometriosis is very probable. This association is independent of the macroscopic type of the lesions or their anatomical locations and may be related to recurrent cyclic micro-bleeding in the implants. Endometriosis-related adhesions may also cause severe dysmenorrhoea. There are histological and physiopathological arguments for the responsibility of deeply infiltrating endometriosis (DIE) in severe chronic pelvic pain symptoms. DIE-related pain may be in relation with compression or infiltration of nerves in the sub-peritoneal pelvic space by the implants. The painful symptoms caused by DIE present particular characteristics, being specific to involvement of precise anatomical locations (severe deep dyspareunia, painful defecation) or organs (functional urinary tract signs, bowel signs). They can thus be described as location indicating pain. A precise semiological analysis of the chronic pelvic pain symptoms characteristics is useful for the diagnosis and therapeutic management of endometriosis in a context of pain.

Hum Reprod Update. 2005 Sep 19
Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis.
Vigano P, Somigliana E, Chiodo I, Abbiati A, Vercellini P.
Department of Obstetrics, Gynecology and Neonatology, Fondazione ‘Policlinico-Mangiagalli-Regina Elena’, Milan, Italy.
Although population-based studies have unequivocally reported an increased risk of ovarian cancer in women with endometriosis, the biological evidence supporting the idea of endometriosis as a preneoplastic condition is scanty and not well substantiated. The fundamental features of human neoplasms (monoclonal growth, genetic changes, mutations in tumour suppressor genes and replicative advantage) have been evaluated in endometriotic lesions but results obtained are discordant. It is plausible that ectopic glands may expand monoclonally but the entity of this phenomenon is debated. According to some allelotyping studies, from one-third to one-half of endometriosis lesions would harbour somatic genetic changes in chromosomal regions supposed to contain genes involved in ovarian tumourigenesis, especially for the endometrioid histotype. These findings would be consistent with the progression model for carcino-genesis from the benign precursor to ovarian cancer but they could not be unequivocally replicated. Gene mutational studies are rare in this context. A single group has found missense mutations and deletions of PTEN gene in about 20% of ovarian endometriotic cysts. Moreover, in a model of genetically engineered mice harbouring an oncogenic allele of K-ras resulting in benign lesions reminiscent of endometriosis, a conditional deletion of PTEN caused the progression towards the endometrioid tumour. Based on these data, the causal link between endometriosis and ovarian endometrioid/clear cell carcinomas remains to be defined both in terms of entity of association and of undelying molecular mechanisms.

Fertil Steril. 2005 Sep;84(3):774-7.
Estrogen receptor dinucleotide repeat polymorphism is associated with minimal or mild endometriosis.
Kim SH, Choi YM, Jun JK, Kim SH, Kim JG, Moon SY.
Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, South Korea.
The present study was designed to explore the association between estrogen receptor-alpha gene polymorphism and the risk of endometriosis by investigating the frequency of PvuII, XbaI, and thymine-adenine (TA) repeat polymorphisms in patients with and without endometriosis in a Korean population. Although there was no significant difference in the allele distribution and frequency of either PvuII or XbaI polymorphisms between endometriosis patients and control subjects, patients with stage I/II endometriosis showed a higher incidence of alleles with fewer (TA)n repeats (12-15 repeats) compared with controls.

Eur J Obstet Gynecol Reprod Biol. 2005 Sep 14;
Efficacy of laparoscopic excision of visually diagnosed peritoneal endometriosis in the treatment of chronic pelvic pain.
Wykes CB, Clark TJ, Chakravati S, Mann CH, Gupta JK.
Academic Department of Obstetrics & Gynaecology, Birmingham Women’s Hospital, Birmingham B15 2TG, UK.
OBJECTIVE:: To determine the efficacy of laparoscopic excision of visually diagnosed endometriosis in the treatment of chronic pelvic pain. STUDY DESIGN:: Sixty-two women with chronic pelvic pain and who underwent laparoscopic excision of visually diagnosed peritoneal lesions suggestive of endometriosis returned postal questionnaires. The main outcomes measures were change in pelvic pain symptoms measured on a continuous and ordinal scale and patient satisfaction following treatment. Secondary outcomes were quality of life, time off work and use of health service resources. RESULTS:: 42/62 (68%) women with an average follow up time of 13 months (range 6-38 months) returned completed outcome questionnaires. The mean amount of pelvic pain was reduced following surgery compared to immediately prior to treatment, regardless of the nature of the pain (P<0.05). Overall, 67% (95% CI 50-80%) of women reported improvement in pain symptoms and 71% (95% CI 55-84%) were satisfied with the results of treatment. Satisfaction with treatment was comparable whether the visual diagnosis of peritoneal endometriosis was confirmed histologically or not (62% versus 64%, P=1.0). CONCLUSION:: Laparoscopic excision of visually diagnosed endometriosis appears to be efficacious in the treatment of women with chronic pelvic pain. The launch of a long-term randomised controlled trial to confirm these provisional results is now required.

Minerva Ginecol. 2005 Jun;57(3):257-67.
Endometriosis and subfertility treatment: a review.
De Hondt A, Peeraer K, Meuleman C, Meeuwis L, De Loecker P, D’Hooghe TM.
Leuven University Fertility Centre, Department of Obstetrics and Gynaecology University Hospital Gasthuisberg, Leuven, Belgium.
The aim of this article is to present a review on the influence of endometriosis on assisted reproductive techniques (ART), as well as on the influence of ART on endometriosis. Based on recent literature, this article will try to answer the following questions: 1) Does endometriosis change the success rate of ovulation induction (OI), intrauterine insemination (IUI) and in vitro fertilisation (IVF) and does previous chirurgical treatment of endometriosis change the success rate of OI, IUI and IVF? 2) Do ART alter the course of the disease? In order to answer these questions, we based ourselves on the following recent guidelines and reviews by reknown experts on endometriosis: the ESHRE Guideline for the Diagnosis and Treatment of Endometriosis, The Practice Committee of the American Society for Reproductive Medicine: Endometriosis and Fertility; a recent review paper on the relationship between endometriosis and subfertility and a recent meta-analysis on the relationship between endometriosis and ART. This review was then completed using more recent papers, published on PubMed as well as background articles, important references and own research papers presented at international meetings. The pregnancy rate after OI, IUI and IVF is decreased in women with endometriosis when compared to controls. The effect of previous surgery for endometriosis is unclear, due to great lack of standardised studies using well defined operation techniques and patient groups. The effect of ART on the spontaneous evolution and recurrence rate of endometriosis has hardly been studied. The presence of endometriosis has a negative effect on the pregnancy rate after ART. It is unclear if surgical treatment prior to ART may increase the pregnancy rate after ART. It is also unclear if ART is a risk factor for recurrence/progression of endometriosis.

Minerva Ginecol. 2005 Jun;57(3):249-55.
Medical treatment of endometriosis.
Garcia-Velasco JA, Quea G.
Instituto Valenciano de Infertilidad, IVI-Madrid and Rey Juan Carlos University Madrid, Spain.
The medical treatment of endometriosis is a critical aspect of the therapeutic approach to this disease. This review will present an overview of current literature about the medical treatment of endometriosis, without referring to the surgical treatment or a combination of both. The main purpose of the current medical treatment of endometriosis is to create an amenorrheic state, in other words, to create a hypoestrogenic environment by suppressing estrogen secretion of the ovary. Current research has focused upon medications designed to attack specific aspects of the development and maintenance of endometriosis. This includes progesterone receptor modulators, gonadotropin releasing hormone (GnRH) analogs, aromatase inhibitors and, tumor necrosis factor alfa (TNFalfa) inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors and estrogen receptor beta agonists like inmunomodulators. These drugs show decreased spreading of lesions and reduced disease related symptoms. Medical treatment is moderately effective in reducing pain but ineffective in improving fertility; a combination of medical treatment with assisted reproductive technology may be beneficial in improving fetility.

Minerva Ginecol. 2005 Jun;57(3):237-48.
Immunology of endometriosis.
Ulukus M, Arici A.
Department of Obstetrics and Gynecology, Ege University School of Medicine, Bornova, Izmir, Turkey.
Endometriosis is classically described as the presence of both endometrial glandular and stromal cells outside the uterine cavity, mainly in the pelvis. The pathogenesis of this enigmatic disorder still remains controversial despite extensive research. Although multiple theories have been put forth to explain the pathophysiology and pathogenesis of endometriosis, the retrograde menstruation theory of Sampson is the most widely accepted. However, since retrograde menstruation occurs in most of the reproductive age women, it is clear that there must be other factors which may contribute to the implantation of endometrial cells and their subsequent development into endometriotic disease. There is substantial evidence to support that the alterations in both cell-mediated and humoral immunity contribute to the pathogenesis of endometriosis. Increased number and activation of peritoneal macrophages, decreased T cell and natural killer (NK) cell cytotoxicities are the alterations in cellular immunity and result in inadequate removal of ectopic endometrial cells from the peritoneal cavity. Moreover, increased levels of several cytokines and growth factors which are secreted by either immune and endometrial cells seem to promote implantation and growth of ectopic endometrium by inducing proliferation and angiogenesis. In addition to the impaired capacity of the immune cells to mediate endometrial cell removal, inherent resistance of the ectopic endometrial cells against immune cells is another interesting concept in the pathogenesis of endometriosis. Endo-metriosis has also been considered to be an autoimmune disease, since it is often associated with the presence of autoantibodies, other autoimmune diseases, and possibly with recurrent immune-mediated abortion.

Minerva Ginecol. 2005 Jun;57(3):225-36.
Genetics of endometriosis.
Di Blasio AM, Di Francesco S, Abbiati A, Vigano P.
Molecular Biology Laboratory, Istituto Auxologico Italiano, Cusano Milanino, Milan, Italy.
Endometriosis is a multifactorial disease that can affect up to 10-15% of women in their reproductive age. Epidemiological studies indicate that it is a polygenic disorder with recurrence risks in first-degree relatives of about 5-7%. Thus, the present aim of different research groups is to identify genetic variations in obvious candidate gene that could be associated with an increased susceptibility to endometrio-sis. The great advancement in molecular biology techniques make this task certainly possible, although particular attention needs to be paid to the study design in order to achieve reliable RESULTS: The data obtained by such studies will allow to expand our knowledge on the pathogenesis of the disease and, more importantly, to develop individualized therapies and prevention strategies to apply at high-risk populations.

J Reprod Immunol. 2005 Sep 12
FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis.
Hayrabedyan S, Kyurkchiev S, Kehayov I.
Molecular Immunology Department, Institute of Biology and Immunology of Reproduction "Akad. K. Bratanov", Bulgarian Academy of Sciences, Sofia 1113, 73, Tsarigrdasko shosse blvd., Bulgaria.
Endometriosis is referred often as an angiogenic disease. The pivotal role of angiogenesis in the pathophysiology of this disease has been confirmed by many studies. This process has several steps, and VEGF is probably the most important in its initiation. There are others involved in its continuation and maintenance of the tight balance between a quiescent and activated blood vessel state. In the process of formation of new blood capillaries and arterioles, many different factors are involved in sometimes distinct pathways. Such factors are TGF-beta and endoglin-the latter being one of the main modulators of the TGF-beta signaling pathway. Endoglin is now not only established as a marker of active neo-angiogenesis and activated endothelium, but also turns to be an active player in the very process of endometriotic angiogenesis. Its signaling pathway of hypoxic activation is tightly interconnected with that of VEGF, and also some of the FGFs. FGF-1 and S100A13 are members of two distinct families of proteins – the FGFs, growth and angiogenic factors, and that of the S100 proteins, – Ca(2+)-binding proteins involved in cell function regulation, motility and signaling. These two particular members are quite unique in having no signal peptide sequence and being involved in common export pathway. Our hypothesis is that these two factors are involved in vascular remodeling in endometriotic angiogenesis, playing a role in vascular wall formation and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). We believe also that endoglin is tightly involved in the new arteriolar formation in endometriosis, being expressed in VSMCs but not on the ECs of the middle-sized vessels.

Pol Merkuriusz Lek. 2005 May;18(107):585-9.
Gonadotropin-releasing hormone analogs
[Article in Polish] Krysiak R, Okopien B, Herman ZS.
Zaklad Farmakologii Klinicznej Slaskiej Akademii Medycznej, Katowice. r.krysiak@pharmanet.com.pl
Pituitary-gonadal axis activity depends on pulsative hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Two groups of GnRH analogs, agonists and antagonists, are presently used for the treatment of clinical conditions in which modulation or interference with sex hormone production is beneficial. They are administered in assisted reproductive technologies to prevent premature luteinizing hormone surges during controlled ovarian stimulation. Due to an inhibitory effect on the growth of hormone-dependent tumors, GnRH analogs are used in the treatment of some cancers. In the present study we discuss in details both these applications. Moreover, we review the potential role of these agents in pharmacotherapy of endometriosis, uterine myomas and central precocious puberty. Based on the available literature we try to show their exact place in the medical therapy of gynecological disorders.

Zhongguo Zhong Yao Za Zhi. 2005 Jul;30(14):1108-10.
Effects of Xianggui pill on cytokine in endometriosis model rat

Tang YJ, Chen Y, Yu HY.
Women’s Hospital, Zhejiang University, School of Medicine, Hangzhou 310006, China. yjk.hf@mail.hz.zj.cn
OBJECTIVE: To study the adjustment of Xianggui pill on the cytokine of endometriosis model rat, and investigate the mechanism of Xianggui pill on the treatment of endometriosis. METHOD: To set up endometriosis model by rat self-endometria transplantation, drench sodium chloride, Xianggui pill elixation or Danazol after grouping, and to detect the contents of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) by ELISA. RESULT: The contents of IL-8, TNF-alpha in the peripheral blood and peritoneal fluid of model group were higher than that of the blank group; The quality of allotopia growth intima tissue, the quantity of macrophage in peritoneal fluid and the contents of IL-8, TNF-alpha in the Xianggui pill group and Danazol group were all lower than those of the model group; but there was no significant difference of each target between the Xianggui pill group and Danazol group. CONCLUSION: Xianggui pill can restrain significantly the growth of allotopia intima tissue, and has apparently adjustment to the cytokine.

J Clin Endocrinol Metab. 2005 Sep 13
Sulindac suppresses NF (nuclear factor)-KappaB activation, RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.
Wieser F, Vigne JL, Ryan I, Hornung D, Djalali S, Taylor RN.
Division of Gynecological Endocrinology and Reproductive Medicine, University of Vienna, Vienna, Austria, Department of Obstetrics and Gynecology, Center for Reproductive Sciences, University of California San Francisco, San Francisco, California, 94143-0556, Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Context: The nuclear factor-kappaB (NF-kappaB) pathway is a critical mediator of RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) regulation and therefore represents a potential target for therapy of endometriosis-associated symptoms. Objective: The objective of this study was to investigate the effects of the anti-inflammatory drug sulindac on NF-kappaB activation, NF-kappaB mediated gene expression, RANTES gene and protein expression in endometrial stromal cells isolated from women with endometriosis and unaffected controls. Design: Clinical experimental study Setting: University Hospital Results: The inflammatory response in endometriosis is augmented as shown by a 5-fold increased TNF-alpha induced RANTES secretion from ectopic endometriotic stromal cells compared with normal endometrial stromal cells (P < 0.05). Western blot analysis revealed basal activation of NF-kappaB in endometriotic cells, which could be suppressed by sulindac. Electromobility shift assays showed that sulindac dramatically decreased NF-kappaB activation and diminished TNF-alpha and interleukin (IL)-1beta induced NF-kappaB DNA binding activity. Sulindac pretreatment resulted in a significant decrease in TNF-alpha-induced luciferase activity of NF-kappaB response element and -477 bp RANTES promoter constructs in normal and endometriotic stromal cells. The addition of sulindac to IL-1beta and TNF-alpha treated endometriotic stromal cells also resulted in a 4-fold inhibition of RANTES protein secretion (P < 0.05). Conclusions: We have demonstrated that the sulindac exerts strong anti-inflammatory effects by suppression of NF-kappaB translocation, inhibition of NF-kappaB mediated gene transcription, RANTES gene expression and protein secretion in normal and endometriotic stromal cells. These results suggest that drugs targeting the NF-kappaB pathway may be beneficial in the treatment of endometriosis-associated symptoms.

Eur J Obstet Gynecol Reprod Biol. 2005 Sep 9
Aromatase inhibitors and cyclooxygenase-2 (COX-2) inhibitors in endometriosis: New questions-old answers?
Ebert AD, Bartley J, David M.
Charite Endometriosis Research Center Berlin, Department of Gynecology, Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies for endometriosis-associated pain or recurrent disease are primarily aimed at downregulating ovarian function or antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is providing important results for the development of new, specific treatment modalities. Aromatase overexpression has recently been detected in endometriotic tissue. Aromatase (p450arom) is responsible for converting C19 androgens into estrogen in several types of human tissue. Aromatase activity causes local estrogen biosynthesis, which, in turn, stimulates prostaglandin E(2) production by upregulating cyclooxygenase-2 (COX-2). Thus, a positive feedback cycle develops between the two systems. Another abnormality in endometriosis, the deficient 17beta-hydroxysteroiddehydrogenase type II (17beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations increase the amount of local estradiol and prostaglandin E(2) in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance and even invasiveness. Consequently, aromatase and COX-2 are thought to be promising new therapeutic targets. Thus, specific aromatase inhibitors (e.g. Letrozol/Femara((R)), Anastrozol/Arimidex((R)) or Exemestan/Aromasin((R))) or selective COX-2 inhibitors (e.g. Celecoxib/Celebrex((c)), Rofecoxib/Vioxx((c)), Valdecoxib/Bextra((c))) are of great interest and should be studied in clinical trials in premenopausal woman with endometriosis to expand the spectrum of currently available treatment options.

Eur Radiol. 2005 Sep 10
Diagnosis of endometriosis with imaging: a review.
Kinkel K, Frei KA, Balleyguier C, Chapron C.
Institut de Radiologie, Clinique et fondation des Grangettes, 7, chemin des Grangettes, 1224, Chene-Bougeries/Geneva, Switzerland, Karen.Kinkel@grangettes.ch.
Endometriosis corresponds to ectopic endometrial glands and stroma outside the uterine cavity. Clinical symptoms include dysmenorrhoea, dyspareunia, infertility, painful defecation or cyclic urinary symptoms. Pelvic ultrasound is the primary imaging modality to identify and differentiate locations to the ovary (endometriomas) and the bladder wall. Characteristic sonographic features of endometriomas are diffuse low-level internal echos, multilocularity and hyperchoic foci in the wall. Differential diagnoses include corpus luteum, teratoma, cystadenoma, fibroma, tubo-ovarian abscess and carcinoma. Repeated ultrasound is highly recommended for unilocular cysts with low-level internal echoes to differentiate functional corpus luteum from endometriomas. Posterior locations of endometriosis include utero-sacral ligaments, torus uterinus, vagina and recto-sigmoid. Sonographic and MRI features are discussed for each location. Although ultrasound is able to diagnose most locations, its limited sensitivity for posterior lesions does not allow management decision in all patients. MRI has shown high accuracies for both anterior and posterior endometriosis and enables complete lesion mapping before surgery. Posterior locations demonstrate abnormal T2-hypointense, nodules with occasional T1-hyperintense spots and are easier to identify when peristaltic inhibitors and intravenous contrast media are used. Anterior locations benefit from the possibility of MRI urography sequences within the same examination. Rare locations and possible transformation into malignancy are discussed.

Hum Reprod Update. 2005 Sep 9
Should endometriomas be treated before IVF–ICSI cycles?
Somigliana E, Vercellini P, Vigano’ P, Ragni G, Giorgio Crosignani P.
Department of Obstetrics, Gynecology and Neonatology, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
The laparoscopic excision of ovarian endometriomas appears to increase the chances of spontaneous conception, but the value of this treatment in women selected for IVF-ICSI cycles is debated. Studies recruiting women with unilateral disease and comparing ovarian responsiveness in the affected and contralateral intact gonads indicate that excision of endometriomas is associated with a quantitative damage to ovarian reserve. There are no randomized trials comparing laparoscopic excision to expectant management before IVF-ICSI cycles. The idea that surgery increases IVF pregnancy rates is not supported by the available evidence. However, the chance of conception is not the only issue that has to be considered. Some potential drawbacks are associated with both therapeutical strategies. Specifically, costs and hazard of surgical complications support expectant management whereas oocyte retrieval risks, the possibility of missing occult malignancy and endometriosis progression due to ovarian stimulation would favour surgical treatment. Alternative therapeutical options include medical treatment and ultrasound-guided aspiration. Whereas prolonged GnRH agonist down-regulation may be beneficial, data on ultrasound aspiration are more controversial.

Hum Reprod. 2005 Sep 9
Asthma in women with endometriosis.
Ferrero S, Petrera P, Colombo BM, Navaratnarajah R, Parisi M, Anserini P, Remorgida V, Ragni N.
Department of Obstetrics and Gynaecology, University of Genoa, Largo R.Benzi 1, 16132 Genoa, Italy.
INTRODUCTION: This study aimed to investigate asthma prevalence and severity in women with and without endometriosis. METHODS: Before laparoscopy, asthma prevalence was evaluated in 879 women of reproductive age, undergoing surgery because of benign gynaecological conditions. Diagnosis of bronchial asthma was based on the American Thoracic Society criteria; asthma severity was classified in four categories according to the 2002 Global Initiative for Asthma guidelines. Asthmatic patients completed the Living with Asthma Questionnaire (LWAQ). Endometriosis was confirmed histologically and classified according to the revised American Fertility Society criteria. RESULTS: There were no significant differences in age, smoking status, and other demographic and health characteristics between patients with endometriosis (n = 467) and controls (n = 412). Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.1-7.3) and without (22/412, 5.3%; 95% CI, 3.4-8.0; P = 0.781) endometriosis. Asthma severity was similar in women with and without endometriosis, with 12 (52.2%) women with endometriosis and 13 (59.1%) controls being in the intermittent (mildest) degree of severity. No significant difference was observed between women with and without endometriosis in the LWAQ total score. CONCLUSIONS: Women with endometriosis do not have an increased risk of having asthma.

Hum Reprod. 2005 Sep 9
No association between HLA-DRB1 alleles and susceptibility to advanced stage endometriosis in a Korean population.
Hee Whang D, Hoon Kim S, Min Choi Y, Hee Park M, Hyun Noh J, Bong Kim Y.
Department of Laboratory Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul.
BACKGROUND: The aetiological factors of endometriosis still remain poorly understood. While there is growing evidence that genetic and immunological factors play important roles in the pathogenesis of the disease, HLA-DRB1 alleles have been reported to be associated with the risk of endometriosis in Japanese populations. This study was performed to determine whether susceptibility to advanced endometriosis is also associated with HLA-DRB1 alleles in a Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 100 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. HLA-DRB1 genotyping was carried out in two steps. Low to intermediate resolution typing was performed by PCR sequence-specific oligonucle-otide hybridization method, followed by high resolution typing utilizing group-specific amplification and PCR-single strand conformation polymorphism method. Distribution of HLA-DRB1 alleles was compared with that of 800 unrelated ethnically matched individuals as well as 108 healthy female subjects. RESULTS: Genotyping revealed that the distribution of HLA-DRB1 alleles in patients with advanced endometriosis was not different from that in the two control groups. CONCLUSIONS: The findings of the present study suggest that susceptibility of advanced endometriosis is not associated with HLA-DRB1 alleles in a Korean population, which is apparently not the case in the Japanese population.

Eur J Obstet Gynecol Reprod Biol. 2005 Sep 1;122(1):95-103.
Peritoneal fluid cytokines and sICAM-1 in minimal endometriosis: search for discriminating factors between infertility and/or endometriosis.
Skrzypczak J, Szczepanska M, Puk E, Kamieniczna M, Kurpisz M.
Clinic of Reproduction, University Medical School, ul. Polna 33, 60-533 Poznan, Poland.
OBJECTIVE:: To evaluate cytokine levels (IL-1beta, TNF-alpha, IL-6, IL-8), soluble intercellular adhesion molecule-1 (sICAM-1) and number of macrophages in peritoneal fluid (PF) of women with no minimal endometriosis and associated (or not) infertility in order to discriminate between infertility and/or endometriosis. STUDY DESIGN:: Cytokines and sICAM-1 were measured by using quantitative enzyme-linked immunosorbent assay (ELISA) while the macrophages were identified by May-Grunwald-Giemsa and non-specific esterase staining and presented as medians. The measurements were performed in 78 women belonging to four selected subgroups according to their endometriosis and/or infertility status. Statistical analysis was performed using Kruskal-Wallis non-parametric ANOVA test. Additionally, discriminant function analyses were performed. RESULTS:: We have found the most elevated macrophage numbers in the groups of women with endometriosis. IL-1beta did not present any statistically significant values differentiating the analysed subgroups. IL-6 (110.0pg/ml) and TNF-alpha exhibited the highest concentrations (statistically significant) in a group of fertile women with endometriosis. IL-8 clearly differentiated between the subgroups with infertility and sICAM-1 was statistically significantly elevated in the subgroups of infertile women. In the forward discriminant analysis, when subdividing the studied population according to its infertility status (we considered macrophages, IL-8 and IL-6 in order of probability values), we have found striking probability value of 92% for the correct classification into an infertile population. CONCLUSION:: Out of the range of the analysed factors we have found only the sICAM-1 to be singled out between the standard discriminant analysis and the forward one. However, this important flagging molecule might be of considerable value for discrimination between different types of pathology at the level of immune effector function. The increased levels of TNF-alpha and IL-6 signified a group of fertile women with endometriosis; however only IL-6 presented a discriminating value in multifunctional analysis of examined subgroups. The analysed range of factors had a greater tendency to discriminate between infertility status rather than endometriosis.

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2005 Aug;25(8):748-9
Clinical observation of Yu’s neiyi recipe. Combined Chinese herbs enema and external application in treating 36 patients with endometriosis

Song YH, Yu J, Yu CQ.

Am J Obstet Gynecol. 2005 Sep;193(3):878-80.
Incisional hernia on the 5-mm trocar port site and subsequent wall endometriosis on the same site: A case report.
Sirito R, Puppo A, Centurioni MG, Gustavino C.
Department of Obstetrics and Gynaecology, Ospedale Evangelico Internazionale.
A 26-year-old nulliparous woman underwent a laparoscopy to remove a 10-cm endometrial cyst on the left ovary (type II Nezhat). The cyst was extracted from the 10-mm umbilical incision; the other 2 trocars were inserted through 5-mm incisions. One year later, in correspondence to the previous 5-mm incision site, a hernia occurred that contained omentum and was reduced easily with a local anesthetic. After 2 years of good health, an aching nodule occurred on the same trocar site; vaginal ultrasound examination showed another left ovarian cyst. A second laparoscopy was performed; the cyst was very adherent and was removed in fragments. The wall nodule was removed, and the histologic examination classified it as endometriosis.

Reprod Biol Endocrinol. 2005 Sep 8;3(1):45
Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-beta1 and bax genes.
Johnson MC, Torres M, Alves A, Bacallao K, Fuentes A, Vega M.
BACKGROUND: Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes. METHODS: Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants. RESULTS: Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p<0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p<0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p<0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p<0.05). CONCLUSIONS: An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium.

J Obstet Gynaecol. 2005 Apr;25(3):275-8.
An audit of patients investigated by Hysterosalpingo-Contrast-Sonography (HyCoSy) for infertility.
Shahid N, Ahluwalia A, Briggs S, Gupta S.
South Manchester Unversity Hospitals, UK. shahidnaw@hotmail.com
We reviewed 171 case notes of patients investigated by HyCoSy for sub-fertility in South Manchester University Hospital to assess HyCoSy as a screening test for tubal occlusion, in low risk infertile women and to evaluate the performance of HyCoSy in our unit by confirming its results with the results of laparoscopy & dye test in those patients who had both procedures. We also assessed the prognostic significance of HyCoSy, for fertility outcome over a follow-up period ranging from 12 to 63 months. An audit proforma was designed to collect data on maternal age, type of infertility (primary or secondary), duration of infertility and parity. History suggestive of ovulatory factors (PCO), pelvic inflammatory disease and endometriosis was noted. Findings of standard trans-vaginal scan, hysterosalpingography and HyCoSy were recorded. In total 333 tubes were examined in 171 patients. There were 121/171 diagnoses of bilateral patent tubes, 24/171 bilateral blocked tubes and 26/171 findings of one patent tube. In 15 (8.8%) women, laparoscopy and dye test was performed after HyCoSy and 19 patients had laparoscopy and dye test before HyCoSy. The findings in both investigations were similar. 70 additional uterine and adnexal pathologies were detected. Out of 171 40.9% (n=70) women conceived, 62 of these women had both tubes patent and 8 had one patent tube. In conclusion we have found that HyCoSy is a valuable cost effective screening test for low risk couples. Its results in our hands are as good as demonstrated by other studies. HyCoSy can be offered as a screening test for low risk infertile women as it is an effective alternative for laparoscopy and dye test.

J Obstet Gynaecol. 2005 Jan;25(1):52-4.
Safety of the Helica Thermal Coagulator in treatment of early stage endometriosis.
Hill NC, El-Toukhy T, Chandakas S, Grigoriades T, Erian J.
Minimal Access Unit, Department of Obstetrics and Gynaecology, The Princess Royal University Hospital, Orpington, Kent, UK. denise.Dalton@bromleyhospitals.nhs.uk
The objective of this prospective study was to assess the safety and short-term outcome of the Helica Thermal Coagulator in the laparoscopic treatment of early stage endometriosis. Two hundred and fifty consecutive women with chronic pelvic pain and stage I and II endometriosis (r-AFS classification) were treated laparoscopically with the Helica Thermal Coagulator. No bladder, ureteric or bowel injuries occurred. None of the procedures was converted to laparotomy and there were no major peri-operative complications. The only complication was a vaginal perforation during dissection of the cul-de-sac in a patient with a vaginal vault endometriotic nodule. We conclude that the Helica Thermal Coagulator is a safe alternative for the treatment of mild to moderate endometriosis. Long-term efficacy studies are required to better assess the role of the device in laparoscopic management of endometriosis.

Expert Opin Investig Drugs. 2005 Sep;14(9):1085-97.
New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists.
Schultze-Mosgau A, Griesinger G, Altgassen C, von Otte S, Hornung D, Diedrich K.
Department of Obstetrics and Gynecology, Medical University of Schleswig-Holstein, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany. A.Schultze-Mosgau@web.de
Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer.

Biochem Genet. 2005 Jun;43(5-6):203-10.
Polymorphism for transforming growth factor beta 1-509 (TGF-B1-509): association with endometriosis.
Hsieh YY, Chang CC, Tsai FJ, Peng CT, Yeh LS, Lin CC.
Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
Transforming growth factor beta (TGF-B) family members are multi-functional cytokines that play a key role in cellular growth, proliferation, and differentiation. The aim of the study was to investigate whether the TGF-B1-509 gene polymorphism could be used as a marker of susceptibility in endometriosis. Women were divided into two groups: endometriosis (n = 150) and non-endometriosis (n = 159). Polymorphisms for TGF-B 1-509 genes were amplified by polymerase chain reaction and detected after restriction enzyme digestion. Genotypes and allelic frequencies in both groups were compared. Genotype proportions and allele frequencies of TGF-B1 gene polymorphisms differed significantly in both groups. Proportions of C homozygote, heterozygote, and T homozygote for TGF-B1 gene polymorphisms were 9.3/61.3/29.4% in the endometriosis group and 41.3158.510% in the non-endometriosis group. Alleles C and T for TGF-B1 gene polymorphism were 40/60% (endometriosis) and 70.8/29.2% (non-endometriosis). Association of endometriosis with TGF-B 1-509 gene polymorphism exists. T homozygote and T allele for TGF-B1 are associated with higher susceptibility to endometriosis.

J Gynecol Obstet Biol Reprod (Paris). 2005 Sep;34(5):501-3.
Malignant tumors arising in extra-ovarian endometriosis: a case report

Paillocher N, Pessaux P, Catala L, Maillard P, Croue A, Arnaud JP, Descamps P.
Service de Gynecologie-Obstetrique, CHU Hotel-Dieu, 4, rue Larrey, 49033 Angers Cedex 01.
We report a case of degenerative extra-ovarian endometriosis. This is a rare complication of endometriosis, the frequency of which is estimated at 0.9%. In more than 50% of the cases, the diagnosis is made following investigation for abdominal pain. If the degeneration is of the same histological type as the endometriosis, it can be said to have arisen from the endometriosis. First-line treatment is surgery, removing as much endometriosis as possible, staging at this point is also necessary. Second-line treatment, with chemotherapy, radiotherapy and even hormonotherapy may be needed. Prognosis for this tumor is variable, from 10 to 100% five-year survival, depending on histological type and localization of the disease.
Endocrinology. 2005 Sep 1
The Development of a Mouse Model of Ovarian Endosalpingiosis.
Bristol-Gould SK, Hutten CG, Sturgis C, Kilen SM, Mayo KE, Woodruff TK.
Department of Neurobiology and Physiology (S.K.B.G., T.K.W.), Northwestern University, Evanston, IL 60208; Evanston Northwestern Hospital (C.S.), Evanston, IL 60208; Department of Medicine (T.K.W.) Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; Robert H. Lurie Comprehensive Cancer Center of Northwestern University (T.K.W.), Chicago, IL 60611; Department of Biochemistry, Molecular Biology and Cell Biology (K.E.M.), Northwestern University, Evanston, IL 60208; and Center for Reproductive Science (C.G.H, S.K., K.E.M., T.K.W.) Northwestern University, Evanston, IL 60208.
Pelvic pain is a common presenting ailment in women often linked to ovulation, endometriosis, early pregnancy, ovarian cancer and cysts. Clear differential diagnosis for each condition caused by these varied etiologies is difficult and may slow the delivery of therapy which, in the case of ovarian cancer, could be fatal. Ovarian endosalpingiosis, a pelvic condition typified by the presence of cystic glandular structures lined by benign tubal/salpingeal epithelium, is also associated with pelvic pain in women. The exact cellular antecedents of these epithelial lined cystic structures are not known, nor is there a known link to ovarian cancer. A mouse model of ovarian endosalpingiosis has been developed by directing a dominant-negative version of the Transforming Growth Factor-beta (TGF-beta) transcription factor, Smad2, to the ovary using the Mullerian Inhibiting Substance promoter (MIS-Smad2-dn). Female mice develop an ovarian endosalpingeal phenotype as early as three months of age. Importantly, cysts continuous with ovarian surface epithelium (OSE) have been identified, indicating that these cyst cells may be derived from the highly plastic OSE cell layer. A second transgenic mouse model that causes loss of activin action (inhibin alpha-subunit transgenic mice) develops similar cystic structures, supporting a TGF-beta/activin/Smad2-dependence in the onset of this disease.

Eur J Obstet Gynecol Reprod Biol. 2005 Sep 1
Serum and follicular fluid levels of soluble Fas and soluble Fas ligand in IVF cycles.
Onalan G, Selam B, Onalan R, Ceyhan T, Cincik M, Pabuccu R.
Centrum Clinic, Nenehatun, No. 59, Ankara, 06520-8063, Turkey.
OBJECTIVE:: To determine follicular fluid (FF) and serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients undergoing IVF cycles. STUDY DESIGN:: A prospective comparative study among patients with endometriosis (n=12), infertility due to male factor (n=12) and poor responders (n=32) undergoing IVF cycles in Centrum IVF Clinic. Individual FF and serum samples were collected from patients during transvaginal ultrasonography-guided follicle aspiration. Patients were classified as poor responder patients undergoing IVF cycles with GnRHa, triptorelin and GnRH antagonist, cetrotide, patients with endometriosis and patients with infertility due to male factor. sFas, sFasL levels in both FF and serum samples and their correlations with clinical outcomes of IVF were measured in each study group. RESULTS:: Serum and FF levels of sFas, sFasL were similar in the poor responder and male factor groups. There were no differences between the serum and FF levels of both sFas and sFasL among poor responder patients receiving either GnRH agonist or antagonist therapies. Serum levels of sFas were significantly lower in the endometriosis group compared to the male factor group. Serum and FF levels of sFas, sFasL were similar among patients with or without clinical pregnancy. CONCLUSION:: sFas and sFasL are detected in both serum and follicular fluid samples from IVF cycles, their levels are similar between poor responder and male factor groups as well as between GnRH agonist and antagonist treatment groups. These soluble apoptotic factors may not be predictive for the outcomes of IVF. Decreased serum levels of sFas, suggests increased apoptosis in endometriosis.

Physiol Behav. 2005 Sep 1
A life of pelvic pain.
Berkley KJ.
Program in Neuroscience, Florida State University, Tallahassee, FL 32306-1270, USA.
Pelvic pain associated with menstruation, i.e., dysmenorrhea, is a chronic pelvic pain that not only interferes with a woman’s wellbeing for a large part of her life but also often co-occurs with other chronic painful conditions such as interstitial cystitis and irritable bowel syndrome and others. Little has been known about mechanisms underlying these chronic pelvic pains. This paper reviews 37 years of research in my laboratory at Florida State University on such mechanisms. Our research, mostly on rats, has contributed to the following findings: (1) Female reproductive organs are innervated in a topographic fashion by afferents in the pelvic (vagina/cervix) and hypogastric (cervix/uterine horn) nerves. (2) The input contributes to uterine and vaginal perceptions (nociception) that are modified by reproductive status. (3) Throughout the CNS, neurons responsive to stimulation of the reproductive tract also respond to stimulation of skin and other internal organs, in a manner modifiable by reproductive status and peripheral pathophysiology. (4) This dynamic physiological convergence may reflect extensive anatomical divergence of and interconnections between pathways entering the CNS via gateways through the spinal cord, dorsal column nuclei, and solitary nucleus. (5) The convergence also indicates the existence of extensive cross-system, viscero-visceral interactions within the CNS, that, while organized for coherent bodily functioning, serves as a substrate by which pathophysiology in one organ can influence physiology and responses to pathophysiology in other organs. (6) Some cross-system effects observed so far include: (a) Bladder inflammation reduces the rate of uterine contractions and the effects of drugs on the uterus. (b) Colon inflammation produces signs of inflammation in the otherwise healthy bladder and uterus. (c) A surgical model of endometriosis produces vaginal hyperalgesia, exacerbates pain behaviors induced by a ureteral stone, and reduces volume voiding thresholds if the bladder. These cross-system effects, which likely involve CNS mechanisms, likely also underlie co-occurrence of painful clinical conditions. Research continues on details of these mechanisms and their relevance for clinical diagnosis and therapy. None of this work could have been done without collegial support of colleagues and technical staff at Florida State University.

Rev Med Inst Mex Seguro Soc. 2005 May-Jun;43(3):237-42.
Endometriosis in delayed scarring of postpartum eutocic episiorrhaphy. Integral aspects and a case report

Hernandez Valencia M, Zarate A, Hernandez Quijano T, Landero Montes de Oca ME, Escamilla Godinez G.
Unidad de Investigacion Medica en Enfermedades Endocrinas, Instituto Mexicano del Seguro Social. mhernandezvalencia@prodigy.net.mx
Endometriosis remains a mystery because it has not yet been shown why these cells are viable in the abdominal cavity, although it has been thought that the immune system plays a role in implantation outside the intrauterine cavity by abasement in the regulatory capacity of natural killer cells, as well as peripheral and peritoneal immunologic cells. Among methods used to recognize this illness are laparoscopy, laparotomy, ultrasound, antibodies, and the histologic study. It has been observed that surgical scars can present cyclical inflammation and pain when affected with this pathology. We present the case of a patient with a second delivery who arrived at the Gynecology Service due to referring intense pain in the episiorrhaphy scar as well as superficial dyspareunia. One year after performance of the surgical procedure, pain did not allow the patient was unable to sit normally; in addition, during the last 3 months the area of the cicatrix augmented in volume during menstruation. Under peridural block and with surgical spindle excision, the abnormal tissue was dissected without complications; the surgery showed brittle tissue and with abundant new vascularity. The histologic diagnosis reported vulvar-tissue endometriosis. Was initiate complementary treatment was initiated with gestrinon once a week for 4 weeks, as well as danazol daily for 2 months to avoid possible persistence of endometrial tissue. The scar at present is minimal and is observed along the borders of the surgical union line, without an increase in size nor discomfort on digital pressure. We consider it necessary to assure cleaning of the episiotomy before initiating surgical suturing to diminish presence of endometriosis, despite the fact that incidence of this disturbance is low (0.03%). Advancement in knowledge of the physiopathology process will permit elimination of the remaining endometrial tissue with new therapeutic strategies, as well as clearing up the mechanism of ectopic implantation of endometrial cells.

J Gynecol Obstet Biol Reprod (Paris). 2005 Jun;34(4):351-9. Related Articles, Links

Endometriosis with massive hemorrhagic ascites: a case report and review of the literature

Ekoukou D, Guilherme R, Desligneres S, Rotten D.
Service de Gynecologie-Obstetrique, Centre Hospitalier Delafontaine, 2, rue Pierre-Delafontaine, BP 279, 93205 Saint-Denis 1.
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. It generally involves the peritoneum, ovaries and rectovaginal septum. Its characteristic symptoms include dysmenorrhea, pelvic pain, deep dyspareunia and infertility. It may also involve the gastrointestinal tract, urinary tract or extra abdominal sites, giving rise to a wide variety of clinical symptoms such as bloody stools, renal haemorrhage, hemoptysis and pleural effusion during menstruation. Recurrent hemorrhagic ascites secondary to endometriosis is an unusual occurrence, 41 cases have been reported since 1954. Here we report an additional case, in order to draw attention to this condition. A 28 years-old black nulligravida woman was seen for the first time in april 2000 with a chief complaint of infertility. Her past medical history was unremarkable. She had regular menses but associated with severe dysmenorrhea. She also recalled abdominal and pelvic pain for several years. She underwent an ovulation induction with gonadotrophin, which resulted in a progressive increase of pelvic pain. A first laparoscopy was performed, revealing voluminous ascites (10 I). Two years later the ascites recurred spontaneously. Ultrasound examination revealed suspect "para uterine masses". A second exploratory laparoscopy showed a voluminous bloody ascites (71), and extensive adhesions. On histologic examination all specimens (peritoneal biopsies) were compatible with endometriosis and ruled out malignancy. Treatment with Gn RH analog was performed and full remission was obtained after 6 months. One year later the ascites recurred again spontaneously, leading to a third laparoscopy in an other medical institution. Histologic examination showed endometrial stromal tissue and fibrous proliferation. Later she became pregnant after in vitro fertilization. In the first trimester of pregnancy, the pelvic ultrasound showed only a small effusion in the pouch of Douglas. Still, the ascites did not progress during pregnancy. The patient was hospitalized from 27 to 33 weeks of gestational age for threatened labor, but she finally had a normal vaginal delivery at 36 weeks of gestational age. Four months later, she had no complaint, but the pelvic ultrasound showed the recurrence of the ascites. She will have a drainage. The future treatement will consists of GnRH analog for about six months, which will be relayed by a long term progestative therapy. A diagnosis of endometriosis should always be considered in middle-age women who presents with bloody ascites. Long follow-up is advisable for patients who undergo conservative treatment because of thehigh risk of recurrence.

Clin Evid. 2005 Jun;(13):2326-39

Endometriosis.
Johnson N.
University of Aukland, Auckland, New Zealand.
Publication Types:
Review

J Bone Miner Metab. 2005;23(5):389-94

Long-term effects on bone mineral density and bone metabolism of 6 months’ treatment with gonadotropin-releasing hormone analogues in Japanese women: comparison of buserelin acetate with leuprolide acetate.
Makita K, Ishitani K, Ohta H, Horiguchi F, Nozawa S.
Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. makita@sc.itc.keio.ac.jp
Our objective was to assess the effects of 6 months’ treatment with two types of gonadotropin-releasing hormone (GnRH) analogues on lumbar bone mineral density (BMD) and bone metabolism. We studied 27 women who had been given a diagnosis of endometriosis or uterine myoma. The subjects received drug therapy for 6 months and were subsequently followed up for 1 year. The BMD of the lumbar spine (L2, L3, L4) was measured by dual energy X-ray absorptiometry four times: at baseline, after 6 months, after 12 months, and after 18 months. The serum concentrations of sex steroids and bone metabolic markers were measured at the same times as BMD. Compared with the baseline value, the mean decrease in the buserelin group L2-4 BMD was 3.7% at 6 months, 1.7% at 12 months, and 0.4% at 18 months. In the leuprolide group, L2-4 BMD decreased respectively by 5.1%, 6.2%, and 4.3%. Serum concentrations of calcium increased significantly after 6 months of treatment (P < 0.05) and returned to the baseline level at 12 months in both groups. In the leuprolide group, the intact osteocalcin concentration after 6 months was significantly higher than the baseline value, and after 12 months, it decreased to the baseline level. Our results indicate that the effect on BMD of 6 months’ treatment with GnRH analogues virtually resolves by 1 year after treatment, provided that drugs affecting bone metabolism are not given during this period.

J Exp Clin Assist Reprod. 2005 Aug 30;2(1):11

Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis.
Caballero V, Ruiz R, Sainz JA, Cruz M, Lopez-Nevot MA, Galan JJ, Real LM, de Castro F, Lopez-Villaverde V, Ruiz A.
BACKGROUND: Endometriosis is a complex disease affecting 10-15% of women at reproductive age. Very few genes are known to be altered in this pathology. RIP140 protein is an important cofactor of oestrogen receptor and many other nuclear receptors. Targeting disruption experiments of nrip1 gene in mice have demonstrated that nuclear receptor interacting protein 1 gene (nrip1), the gene encoding for rip140 protein, is essential for female fertility. Specifically, mice null for nrip1 gene are viable, but females are infertile because of complete failure of mature follicles to release oocytes at ovulation stage. The ovarian phenotype observed in mice devoid of rip140 closely resembles the luteinized unruptured follicle (LUF) syndrome that is observed in a high proportion of women affected of endometriosis or idiopathic infertility. Here we present a preliminary work that analyses the role of NRIP1 gene in humans. METHOD: We have sequenced the complete coding region of NRIP1 gene in 20 unrelated patients affected by endometriosis. We have performed genetic association studies by using the DNA variants identified during the sequencing process. RESULTS: We identified six DNA variants within the coding sequence of NRIP1 gene, and five of them generated amino acid changes in the protein. We observed that three of twenty sequenced patients have specific combinations of amino-acid variants within the RIP140 protein that are poorly represented in the control population (p=0.006). Moreover, we found that Arg448Gly, a common polymorphism located within NRIP1 gene, is associated with endometriosis in a case-control study (59 cases and 141 controls, pallele positivity test=0.027). CONCLUSIONS: Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis.

J Altern Complement Med. 2005 Aug;11(4):627-30.

The effect of chinese herbs on the cytokines of rats with endometriosis.
Qu F, Zhou J, Ma B.
Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.
Objective: The aim of this study was to study the regulatory function of Chinese medicine-YiWeiNing (YWN) on the cytokines of endometriosis (EM) model rats. Materials and Methods: After successfully creating EM models of rats, all were separated randomly into five groups: high dose of YWN (5.4 g/100 g), low dose of YWN (1.8 g/100 g), Danazol group (3.6 mg/100 g), a model group, and a false-operation group. They were then reviewed for the variation of the amount of TNF-alpha (tumor necrosis factor-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Results: The content of TNF-alpha, IL-6, and IL-8 in the peripheral blood of the model group was apparently higher than the false-operation group (p < 0.01), and YWN reduced the amount of TNF-alpha, IL-6, and IL-8 in the serums of the model group’s rats. This made these cytokines tend toward normal levels without an apparent variation, when compared with the false-operation group (p > 0.05). Conclusions: YWN can prevent the growth of ectopic endometrium by inhibiting the synthesis and secretion of TNF-alpha, IL-6, and IL-8.

J Reprod Med. 2005 Jul;50(7):513-23

Chronic inflammation of the vagina: treatment and relationship to autoimmunity.
Thomson JC.
National Women’s Hospital, Auckland, New Zealand. jthomson@world-net.co.nz

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