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Am J Reprod Immunol. 2007 Mar;57(3):193-200.

Putative predictors of antibodies against follicle-stimulating hormone in female infertility: a study based on in vitro fertilization patients.

Haller K, Salumets A, Grigorova M, Talja I, Salur L, Béné MC, Laan M, Uibo R.

Department of Immunology, Institute of General and Molecular Pathology, Centre of Molecular and Clinical Medicine, University of Tartu, Biomedicum, Ravila Str. 19, Tartu 50411, Estonia.

PROBLEM: We have previously demonstrated the presence of naturally occurring antibodies against follicle-stimulating hormone (FSH) in patients with endometriosis and polycystic ovary syndrome (PCOS). Here, we investigated the parameters associated with anti-FSH antibodies in in vitro fertilization (IVF) patients. METHODS OF STUDY: The following parameters were studied in 135 patients: peripheral FSH levels, FSH beta-subunit gene (FSHB) haplotypes, history of previous IVF, and susceptibility to autoimmune reactions in general [seven common autoantibodies (against nuclear antigens on human and rodent substrates, smooth muscle, gastric parietal cells, beta2-glycoprotein I, cardiolipin, and thyroid peroxidase) and HLA-DQB1 alleles]. RESULTS: Although the anti-FSH levels were higher in patients when compared with controls, those higher levels were not associated with FSHB haplotypes. The anti-FSH IgM associated with (i) the levels of FSH in women with male and tubal factor infertility; (ii) the history of IVF in patients with PCOS, endometriosis, and unexplained infertility; and (iii) the production of common autoantibodies among all IVF patients. The anti-FSH IgA associated with HLA-DQB1*03. The anti-FSH IgG correlated with the values of anti-FSH IgA and IgM. CONCLUSION: Anti-FSH may be naturally occurring antibodies associated with peripheral FSH concentrations, but increased in infertile women with dysregulation of immune reactions and repeatedly performed IVF.

Fertil Steril. 2007 Sep;88(3):594-9. Epub 2007 Feb 12.

Decreased levels of peritoneal interleukin-1 receptor antagonist in patients with endometriosis and disease-related dysmenorrhea.

Zhang X, Wen J, Deng L, Lin J.

Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China.

OBJECTIVE: To determine the level of interleukin-1 receptor antagonist (IL-1ra) in peritoneal fluid (PF) and serum in patients with endometriosis. DESIGN: A prospective analytical study. SETTING: University-affiliated obstetrics and gynecology academic training hospital. PATIENT(S): One hundred eighteen patients underwent laparoscopy for benign gynecologic diseases. INTERVENTION(S): Peripheral blood and PF were obtained before and during surgical procedures, and the levels of IL-1ra were measured. MAIN OUTCOME MEASURE(S): The concentrations of IL-1ra in PF and serum were correlated with the presence of endometriosis, disease stage, and the phase of menstrual cycle. RESULT(S): Peritoneal fluid IL-1ra concentrations were significantly lower in patients with endometriosis than in patients without endometriosis. Peritoneal fluid IL-1ra concentrations decreased with the increased severity of endometriosis and also decreased in disease-related dysmenorrhea; serum IL-1ra levels showed no significant difference between the patients with and without endometriosis. The concentrations of IL-1ra in PF and serum were not correlated with the phase of menstrual cycle. CONCLUSION(S): Our results suggested that decreased levels of PF IL-1ra in patients with endometriosis and disease-related dysmenorrhea may play an important role in the pathogenesis of this disease.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):108-11. Epub 2007 Feb 9.

[Endometriosis: methodological aspects]

[Article in French]

Fauconnier A, Goffinet F, Canis M.

Med Hypotheses. 2007;69(2):282-6. Epub 2007 Feb 9.

Limbic associated pelvic pain: a hypothesis to explain the diagnostic relationships and features of patients with chronic pelvic pain.

Fenton BW.

Summa Health System, Department of Obstetrics and Gynecology, MED-2, 525 E Market St., Akron, OH 44303-2090, United States. fentonb@summa-health.org <fentonb@summa-health.org>

Limbic associated pelvic pain is a proposed pathophysiology designed to explain features commonly encountered in patients with chronic pelvic pain, including the presence of multiple pain diagnoses, the frequency of previous abuse, the minimal or discordant pathologic changes of the involved organs, the paradoxical effectiveness of many treatments, and the recurrent nature of the condition. These conditions include endometriosis, interstitial cystitis, irritable bowel syndrome, levator ani syndrome, pelvic floor tension myalgia, vulvar vestibulitis, and vulvodynia. The hypothesis is based on recent improvements in the understanding of pain processing pathways in the central nervous system, and in particular the role of limbic structures, especially the anterior cingulate cortex, hippocampus and amygdala, in chronic and affective pain perception. Limbic associated pelvic pain is hypothesized to occur in patients with chronic pelvic pain out of proportion to any demonstrable pathology (hyperalgesia), and with more than one demonstrable pain generator (allodynia), and who are susceptible to development of the syndrome. This most likely occurs as a result of childhood sexual abuse but may include other painful pelvic events or stressors, which lead to limbic dysfunction. This limbic dysfunction is manifest both as an increased sensitivity to pain afferents from pelvic organs, and as an abnormal efferent innervation of pelvic musculature, both visceral and somatic. The pelvic musculature undergoes tonic contraction as a result of limbic efferent stimulation, which produces the minimal changes found on pathological examination, and generates a further sensation of pain. The pain afferents from these pelvic organs then follow the medial pain pathway back to the sensitized, hypervigilant limbic system. Chronic stimulation of the limbic system by pelvic pain afferents again produces an efferent contraction of the pelvic muscles, thus perpetuating the cycle. This cycle is susceptible to disruption through blocking afferent signals from pelvic organs, either through anesthesia or muscle manipulation. Disruption of limbic perception with psychiatric medication similarly produces relief. Without a full disruption of both the central hypervigilance and pelvic organ dysfunction, pain recurs. To prevent recurrence, clinicians will need to include some form of therapy, either medical or cognitive, targeted at the underlying limbic hypervigilance. Further research into novel, limbic targeted therapies can hopefully be stimulated by explicitly stating the role of the limbic system in chronic pain. This hypothesis provides a framework for clinicians to rationally approach some of the most challenging patients in medicine, and can potentially improve outcomes by including management of limbic dysfunction in their treatment.

Fertil Steril. 2007 May;87(5):1231-4. Epub 2007 Feb 8.

Comment in:

Fertil Steril. 2007 Sep;88(3):764-5; author reply 765-6.

The levonorgestrel-releasing intrauterine system and endometriosis staging.

Gomes MK, Ferriani RA, Rosa e Silva JC, Japur de Sá Rosa e Silva AC, Vieira CS, Cândido dos Reis FJ.

Department of Gynecology and Obstetrics, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, Brazil.

This study aims to determine whether the levonorgestrel-releasing intrauterine system can influence American Society for Reproductive Medicine endometriosis staging scores, as assessed through second-look laparoscopies, and to compare the results with those obtained with a GnRH agonist. Both treatments reduced the extent of pelvic endometriotic lesions in patients with chronic pelvic pain.

Med Sci (Paris). 2007 Feb;23(2):198-204.

[The concept of endocrine disruption and human health]

[Article in French]

Cravedi JP, Zalko D, Savouret JF, Menuet A, Jégou B.

Inra, UMR 1089, Xénobiotiques, BP 3, 31931 Toulouse Cedex 9, France.

In Europe, endocrine disruptors (EDs) have been defined as substances foreign to the body that have deleterious effects on the individuals or their descendants, due to changes in endocrine function. In the United States, EDs have been described as exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of the natural ligands responsible for maintaining homeostasis and regulating body development. These two definitions are complementary, but both indicate that the effects induced by EDs probably involve mechanisms relating in some way to hormonal homeostasis and action. EDs are generally described as substances with anti-oestrogenic, oestrogenic, anti-androgenic or androgenic effects. More recently, other targets have been evidenced such as the thyroid and immune system. Many different EDs are present in the various compartments of the environment (air, water and land) and in foods (of plant and animal origin). They may originate from food packaging, combustion products, plant health treatments, detergents and the chemical industry in general. In addition to the potential effects of these compounds on adults, the sensitivity of embryos and fetuses to many of the xenobiotic compounds likely to cross the placenta has raised considerable concern and led to major research efforts. With the exception of the clearly established links between diethylstilbestrol, reproductive health abnormalities and cancers, very little is known for certain about the effects of EDs on human health. Given the lack of available data, current concerns about the possible involvement of EDs in the increase in the incidence of breast cancer, and possibly of endometriosis and early puberty in girls, remain hypothetical. Conversely, the deterioration in male reproductive health is at the heart of preoccupations and progress in analyses of the relationship between EDs and human health. This literature review aims to describe the current state of knowledge about endocrine disruption, focusing in particular on the problem of food contaminants.

Int J Gynecol Cancer. 2007 Jan-Feb;17(1):290-3.

Metastatic low-grade endometrial stromal sarcoma of clitoris: report of a case.

Androulaki A, Papathomas TG, Alexandrou P, Lazaris AC.

Department of Pathology, Laiko General Hospital of Athens, Athens, Greece.

Low-grade endometrial stromal sarcoma (ESS) is an uncommon neoplasm, which has a highly recurrent nature. A review of the literature revealed that only one case of low-grade ESS, arising within the vulva from a focus of endometriosis, has been previously published. We describe an additional case of low-grade ESS arising within the vulva and to the best of our knowledge the first report of low-grade ESS metastasized to clitoris. A 46-year-old woman was admitted to our hospital due to a heavy uterine bleeding. A physical examination revealed a lesion in clitoris, which exhibited a densely cellular mesenchymal neoplasm on microscopy. On the basis of the pathologic features alone, a differential diagnosis of a low-grade ESS and cellular leiomyoma was considered. Seven months later, the patient presented again with excessive uterine bleeding and a total hysterectomy was performed. A tumor of white-tan, whorled appearance was found. Its features were suggestive of low-grade ESS. Taking into account the possible extrauterine location of an ESS and reviewing the first case, a diagnosis of rare low-grade ESS metastasized to clitoris was made.

Int J Gynecol Cancer. 2007 Jan-Feb;17(1):242-7.

Endometriosis is characterized by an impaired localization of laminin-5 and alpha3beta1 integrin receptor.

Giannelli G, Sgarra C, Di Naro E, Lavopa C, Angelotti U, Tartagni M, Simone O, Trerotoli P, Antonaci S, Loverro G.

Departments of Internal Medicine, Immunology, and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Piazza Giulio Cesare 11, 70124 Bari, Italy.

Endometriosis is an estrogen-correlated benign disease characterized by a marked ability of endometrial-like cells to invade and proliferate outside uterine cavity, resembling for some invasive aspect the cancer growth. The molecular mechanisms regulating endometrial cell invasiveness are mostly unknown, although interactions between extracellular matrix (ECM) proteins and their transmembrane receptors, integrins, are likely to play a central role. In particular, laminin (Ln)-5 could be closely involved, as it is in cancer. We have investigated the expression of Ln-1, Ln-5, and collagen IV (Coll IV) ECM proteins and their receptors, alpha3beta1 and alpha6beta4 integrins, in atrophic, proliferative, and secretive endometrium and in endometriosis. The results show that Ln-5, but not Ln-I and Coll IV, is altered in secretive endometrium as well as in endometriosis tissues. No alterations are observed in atrophic or proliferative endometrium. Consistently, the polarization of both integrin subunits alpha3 and beta1, but not alpha6 and beta4, is altered in secretive endometrium and endometriosis tissues, but not in atrophic and proliferative endometrium. These results seem to suggest that Ln-5 and alpha3beta1 could be involved in the invasive mechanism of endometriosis. The altered expression of Ln-5, by upregulating matrix metalloproteases activity, suggest an invading process similar to that of many cancer processes.

Int J Gynecol Cancer. 2007 Jan-Feb;17(1):37-43.

Risk of developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan.

Kobayashi H, Sumimoto K, Moniwa N, Imai M, Takakura K, Kuromaki T, Morioka E, Arisawa K, Terao T.

Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. hirokoba@naramed-u.ac.jp

Although some studies have indicated that endometriosis may increase the risk of developing ovarian cancer, there are no data from epidemiologic studies in Japan. We prospectively analyzed all cases of ovarian endometrioma enrolled in the prefecture-wide Shizuoka Cohort Study on Endometriosis and Ovarian Cancer Programme, which was initiated in 1985. To evaluate the risk of ovarian cancer by time periods subsequent to ovarian endometrioma diagnosis, a cohort of 6,398 women with a clinically documented ovarian endometrioma in Shizuoka between 1985 and 1995 was identified from the Shizuoka Cancer Registry (SCR), with follow-up through 2002. Ovarian cancer incidence among cohort members was ascertained by linkage to the SCR using a unique person-identification number. Standardized incidence ratios (SIR) and their 95% confidence intervals (CI) were computed by a use of prefecture-wide rates of ovarian cancer, adjusted for age and calendar year. During follow-up of up to 17 years of the ovarian endometrioma cohort, 46 incident ovarian cancers were identified, yielding that the ovarian cancer risk was elevated significantly among patients with ovarian endometrioma (SIR = 8.95, 95% CI = 4.12-15.3). The SIR did not increase with increasing follow-up duration. The risk increased with increasing age at ovarian endometrioma diagnosis, with a SIR equal to 13.2 (95% CI = 6.90-20.9) in women above 50 years of age. Our findings for the first time support the hypothesis that ovarian endometrioma increases the subsequent risk of developing ovarian cancer in Shizuoka, Japan.

Aktuelle Urol. 2007 Jan;38(1):55-8.

[Endometriosis involving the ureter. The Erlangen experience exemplified by two case reports]

[Article in German]

Zugor V, Schott GE.

Urologische Universitätsklinik mit Poliklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen. vahudin.zugor@uro.imed.uni-erlangen.de

INTRODUCTION: Endometriosis is a benign proliferation of discarded or ectopic endometrial mucus membranes which retain the histological features and biological reactions of uterine mucus membranes. This tissue is not capable of independent proliferation but is subject to the influence of estrogen progesterone. In this report we describe the clinical course of two patients with histologically proven endometriosis with participation of the uteral region and uronephrosis. CASE REPORT 1: Left-sided uronephrosis was diagnosed in a 36-year-old female during a sonographic examination for hypertension. Our gynaecologists obtained histological proof of endometriosis by laparoscopy. Two days after the laparoscopic detection of foci of endometriosis in the intestine, Douglas’ pouch, ovaries as well as in the region of the left terminal ureter, a left percutaneous renal fistula was created under sonographic and radiological control. After resection of the afflicted section of the ureter, implantation of a new left ureter was performed by means of a psoas-hitch plasty. CASE REPORT 2: A 30-year-old female presented with a months-long history of dyspareunia, pain on palpation of the Douglas’ pouch, occasional pain on bowel movements and back pain. In addition she had been trying for years to become pregnant. On sonography renal congestion grade III was detected. After admission and appropriate preparation, one week later an open laparotomy with lysis of intestinal as well as uterine adhesions, salpingectomy and, by the urologist, partial left uteral resection with new implantation by the psoas-hitch technique. CONCLUSIONS: Endometriosis of the urinary tract is a rare occurrence affecting 1 – 2 % of all endometriosis patients with the urinary bladder being the most commonly affected site. Endometriosis with involvement of the ureter is often diagnosed very late because of the rareness of this situation and its asymptomatic course. An individual therapy plan depending first of all on the patient’s age, desire for children, and the extent of the endometriosis foci should always be attempted.

Int J Gynaecol Obstet. 2007 Mar;96(3):206-7. Epub 2007 Feb 7.

Serum CA-125 in the diagnosis of endometriosis.

Rosa E Silva AC, Rosa E Silva JC, Ferriani RA.

Department of Gynecology and Obstetrics, Division of Human Reproduction and Gynecological Endoscopy, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, São Paulo, Brazil.

Minerva Chir. 2007 Feb;62(1):69-72.

[Late complication after colon self-expandable metal stent placement: a case report]

[Article in Italian]

Pericoli Ridolfini M, Sofo L, Di Giorgio A, Gourgiotis S, Di Miceli D, Alfieri S, Doglietto GB.

Unità di Chirurgia Digestiva, Dipartimento di Scienze Chirurgiche, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, 9 Piano, ala B, Largo A. Gemelli 8, 00168 Rome, Italy. marcoprmed@libero.it

Treatment of acute colorectal malignant obstruction, by using self-expandable metallic stents is useful for both palliative and decompressive therapy before the final surgical treatment. In this case, the patient may be benefit from a period of medical optimization prior to undergoing planned surgical resection by a colorectal surgeon. This is a minimally invasive procedure, relatively safe, which obviates the need for colostomy for evacuation relieving physical and psychological burden and contributing the improvement of quality of life. Furthermore, this method also has the advantage of being cost-effective. The previous experience in the benign biliary stenosis allowed the extension of using the metallic stents also for the treatment of benign colorectal diseases (diverticular occlusion, anastomotic strictures, colonic endometriosis). Complications of colon self-expandable metallic stents placement may occur during the procedure and soon after placement (early complications) or, rarely, late after insertion (late complications). These include bleeding, re-obstruction, pain, tenesmus, stent migration, and perforation. The authors report a case of an 81 year-old woman with inoperable rectal carcinoma with liver metastasis who underwent palliative treatment of self-expanding metallic stent endoscopic placement. One month later, the patient presented with acute abdomen at Accidents and Emergencies Department. The diagnosis was a late rectosigmoid junction perforation by stent placement.

Drugs. 2007;67(2):215-35.

Treatment approaches for painful bladder syndrome/interstitial cystitis.

Theoharides TC.

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, Massachusetts, USA. theoharis.theoharides@tufts.edu

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a disease of unknown aetiology, characterised by severe pressure and pain in the bladder area or lower pelvis that is frequently or typically relieved by voiding, along with urgency or frequency of urination in the absence of urinary tract infections. PBS/IC occurs primarily in women, is increasingly recognised in young adults, and may affect as many as 0.1-1% of adult women. PBS/IC is often comorbid with allergies, endometriosis, fibromyalgia, irritable bowel syndrome and panic syndrome, all of which are worsened by stress. As a result, patients may visit as many as five physicians, including family practitioners, internists, gynaecologists, urologists and pain specialists, leading to confusion and frustration. There is no curative treatment; intravesical dimethyl sulfoxide, as well as oral amitriptyline, pentosan polysulfate and hydroxyzine have variable results, with success more likely when these drugs are given together. Pilot clinical trials suggest that the flavonoid quercetin may be helpful. Lack of early diagnosis and treatment can affect outcomes and leads to the development of hyperalgesia/allodynia.

Fertil Steril. 2007 Aug;88(2):497.e15-7. Epub 2007 Feb 2.

Struma ovarii coincident with Hashimoto’s thyroiditis: an unusual cause of hyperthyroidism.

Morrissey K, Winkel C, Hild S, Premkumar A, Stratton P.

Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1109, USA.

OBJECTIVE: To report the identification of struma ovarii in a patient with a history of struma ovarii and new hyperthyroidism. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A woman with hyperthyroidism who has struma ovarii coincident with Hashimoto’s thyroiditis. INTERVENTION(S): Laparoscopic salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Measurement of thyroid hormone parameters before and after surgery. RESULT(S): After removal of the second struma ovarii, hyperthyroidism resolved. CONCLUSION(S): In a patient with two different causes of abnormal thyroid function, it is important to seek an encompassing clinical scenario.

Fertil Steril. 2007 Feb;87(2):417.e17-9.

Isolated infiltrative endometriosis of the sciatic nerve: a report of three patients.

Possover M, Chiantera V.

Department of Obstetrics and Gynecology, St. Elisabeth Hospital, Cologne, Germany. MarcPossover@aol.com <MarcPossover@aol.com>

OBJECTIVE: To report that isolated endometriosis of the sciatic nerve without further manifestation of endometriosis does exist. DESIGN: We describe our technique of laparoscopic neurolysis of the sciatic nerve and the sacral plexus. SETTING: Department of Gynecology and Obstetrics, St. Elisabeth Hospital, affiliated with the University of Cologne, Cologne, Germany. PATIENT(S): Three female patients with isolated endometriotic infiltration of the endopelvic portion of the sciatic nerve. INTERVENTION(S): Elective laparoscopic neurolysis of the sciatic nerve with removal of endometriosis. MAIN OUTCOME MEASURE(S): Disparition of pain in the patients and histologic information of the endometriosis. RESULT(S): Isolated endometriosis of the sciatic nerve and/or the sacral plexus does exist without any further endometriosis genitalis externa manifestations. CONCLUSION(S): In young patients with sciatica of an unknown genesis, an endometriosis of the sciatic nerve must be evoked, and a laparoscopic exploration of the sciatic nerve must be discussed.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):173-8. Epub 2007 Feb 2.

[Extragenital endometriosis]

[Article in French]

Nisolle M, Pasleau F, Foidart JM.

Service de Gynécologie – Obstétrique, Université de Liège, CHU, Hôpital de la Citadelle, 1, boulevard du 12(e) de Ligne, 4000 Liège, Belgique. michelle.nisolle@chrcitadelle.be

Parietal, appendiceal, pleuropulmonary and diaphragmatic endometriosis represent 5% of endometriosis cases. Diagnosis and management of these extra-genital localisations are described according to the literature. Parietal endometriosis usually requires large resection of the tumor. Appendiceal endometriosis is frequently observed in cases of digestive endometriosis. Induration or rigidity of the appendix due to the presence of deep infiltrating endometriosis justifies appendicectomy. Thoracic and diaphragmatic endometriosis is characterized by the presence of typical symptoms during the perimenstrual periode. Medical treatment obtaining therapeutic amenorrhea is firstly administered and surgery is indicated in cases of symptoms recurrence.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):141-50. Epub 2007 Feb 2.

[Guidelines for the management of painful endometriosis]

[Article in French]

Roman H.

Clinique Gynécologique et Obstétricale, CHU Charles-Nicolle, 1, rue de Germont, 76031 Rouen cedex, France. horace.roman@gmail.com

OBJECTIVES: To establish guidelines for the medical and surgical management of painful endometriosis. MATERIAL AND METHODS: An exhaustive review on Medline and Cochrane Database between 1980 and 2006 was performed. RESULTS: GnRH agonists, progestins, continuous monophasic oral contraceptives and danazol have a suppressive effect on dysmenorrhoea, nonmenstrual pain and dyspareunia (grade A). Surgical treatment is effective in painful endometriosis (grade B). Complete surgical excision of deep endometriotic lesions with conservation of uterus and ovaries has a limited term efficacy on pain relief (grade C). A multidisciplinary approach is recommended (grade C). The use of the psychotherapy improves the management of chronic pain (grade A). There is a lack of information concerning the therapeutic strategy able to prevent recurrences. Whether endometriosis recurrences occur, medical treatment should be the first line approach (expert opinion). A hysterectomy with salpingo-oophorectomy and complete excision of the lesions is efficient in women with pain recurrence who no longer desire pregnancy (grade C). CONCLUSION: Medical and surgical treatments have a limited term efficacy on painful endometriosis (grade A). The benefit/risk relationship, depending on secondary effect therapy, should be assessed on a case to case basis.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):119-28. Epub 2007 Feb 2.

[Management of endometriosis: clinical and biological assessment]

[Article in French]

Panel P, Renouvel F.

Service de Gynécologie – Obstétrique, Centre Hospitalier de Versailles, Hôpital André-Mignot, 177, rue de Versailles, 78157 Le Chesnay, France. ppanel@ch-versailles.fr

No symptom is pathognomonic for endometriosis. Main symptoms are pain (chronic pelvic pain, dysmenorrhea, deep dyspareunia, pain on defecation, cyclic pain) and infertility (grade C). There is no relation between rAFS endometriosis classification and symptoms intensity and frequency (grade B). Endometriosic lesions location and symptoms type are related to each other as well as symptoms intensity and lesions deepness or adhesion numbers (grade B). Clinical evidence is the same for infertile endometriosic women (grade C). Screening for depression is required among patients suffering from chronic endometriosic pelvic pain (grade C). Clinical examination includes: 1) retrocervix area inspection as well as upper part of posterior vaginal wall in search for typical bluish lesions (grade B); 2) vaginal examination in search for: a) uterosacral ligaments nodules (grade B); b) pain in uterosacral ligaments extension (grade B); 3) re-examination during menstruation increases its performance (grade B). No biological check-up in endometriosis diagnosis is necessary (grade A). CA 125 increase is related to: endometriomas and deep lesions volume (grade B), surgically treated infertile women prognosis (grade B). Presurgical endometriosis diagnosis is bettered by using diagnosis pattern in selected population (grade B). Rating scales are recommended in diagnosis and therapeutic follow up (grade B). Quality of life scales are useful to evaluate therapeutic efficiency (grade B).

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):113-8. Epub 2007 Jan 31.

[Endometriosis anatomoclinical entities]

[Article in French]

Fritel X.

Service de Gynécologie et Obstétrique, CHD Félix-Guyon, 97417 Saint-Denis cedex, île de la Réunion, France. x-fritel@chd-fguyon.fr

The aim of this literature review is to precise definition, anatomoclinical entities and natural history of endometriosis to allow clinical guideline establishment. DEFINITION: Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterus. This histologic definition does not implicate symptoms. Macroscopic lesions supposed to be endometriosis are not always confirmed by histology. Histology is recommended to confirm endometriosis. Negative histology does not exclude endometriosis. ANATOMOCLINICAL ENTITIES: Three endometriosis entities are described: peritoneal endometriosis, ovarian endometrial cyst, and deeply infiltrating endometriosis. There is no evidence to establish a different pathogenesis of theses entities. ENDOMETRIOSIS NATURAL HISTORY: It is not well known. It may progress or regress with or without treatment. There is no evidence of treatment in case of asymptomatic endometriosis. There is an association between endometriosis and ovarian cancer. The risk of endometriosis malignant transformation is still a subject of controversy. There is no evidence for a specific oncologic follow-up of woman having endometriosis.

BMJ. 2007 Feb 3;334(7587):249-53.

Comment in:

BMJ. 2007 Feb 17;334(7589):328.

Endometriosis.

Farquhar C.

Department of Obstetrics and Gynaecology, National Women’s Hospital, University of Auckland, Auckland, New Zealand. c.farquhar@auckland.ac.nz

Hum Pathol. 2007 Aug;38(8):1160-3. Epub 2007 Feb 1.

Comment in:

Hum Pathol. 2009 Apr;40(4):603-4.

Recommendations for the reporting of fallopian tube neoplasms.

Longacre TA, Oliva E, Soslow RA; Association of Directors of Anatomic and Surgical Pathology.

Department of Pathology, Stanford University, Stanford, CA 94305, USA. longacre@stanford.edu

Primary malignancies of the fallopian tube are extremely uncommon, in part due to (admittedly arbitrary) definitional criteria. By convention, epithelial tumors that involve the ovary or peritoneal surfaces are considered to have arisen either in the ovary or endometrium or, in absence of significant ovarian or endometrial involvement, in the peritoneum, irrespective of whether or not the fallopian tube mucosa is also involved. Evidence from the World Health Organization and more recently, from case-control studies of BRCA mutation carriers suggests the fallopian tube may have a more direct role in the development of at least some of these carcinomas. An alternative hypothesis for the origin of ovarian and peritoneal carcinoma has even been proposed, based on the concept of transport and implantation of malignant cells from the tube to the ovary and peritoneum. Malignancies in the fallopian tube can therefore be classified as (1) arising primarily in the fallopian tube, either from preexisting endometriosis (or more rarely, a mature teratoma) or directly from tubal mucosa with metastasis to adjacent tissues; (2) arising in the ovary, endometrium, or peritoneum with metastasis to the tubal serosa or mucosa; or (3) arising primarily in the fallopian tube as well as in the ovary, endometrium, or peritoneum (simultaneous primary tumors). Since there are currently no evidence based criteria for distinguishing primary tubal carcinoma from primary ovarian or primary endometrial carcinoma in patients with high stage disease, the Association of Directors of Anatomic and Surgical Pathology recommended strategies for assignment of site of origin are based on current standard practices.

Dig Dis Sci. 2007 Mar;52(3):767-9.

Endometrioma of the large bowel.

Kanthimathinathan V, Elakkary E, Bleibel W, Kuwajerwala N, Conjeevaram S, Tootla F.

Department of Surgery, North Oakland Medical Centers, 461 West Huron, Pontiac, Michigan 48341, USA. drvenkat2000@gmail.com

Mol Biol Cell. 2007 Apr;18(4):1272-81. Epub 2007 Jan 31.

Junction protein shrew-1 influences cell invasion and interacts with invasion-promoting protein CD147.

Schreiner A, Ruonala M, Jakob V, Suthaus J, Boles E, Wouters F, Starzinski-Powitz A.

Institute of Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, D-60323 Frankfurt am Main, Germany.

Shrew-1 was previously isolated from an endometriotic cell line in our search for invasion-associated genes. It proved to be a membrane protein that targets to the basolateral membrane of polarized epithelial cells, interacting with E-cadherin-catenin complexes of adherens junctions. Paradoxically, the existence of adherens junctions is incompatible with invasion. To investigate whether shrew-1 can indeed influence cellular invasion, we overexpressed it in HT1080 fibrosarcoma cells. This resulted in enhanced invasiveness, accompanied by an increased matrix metalloprotease (MMP)-9 level in the supernatant, raising the question about the role of shrew-1 in this process. Logic suggested we looked for an interaction with CD147, a known promoter of invasiveness and MMP activity. Indeed, genetics-based, biochemical, and microscopy experiments revealed shrew-1- and CD147-containing complexes in invasive endometriotic cells and an interaction in epithelial cells, which was stronger in MCF7 tumor cells, but weaker in Madin-Darby canine kidney cells. In contrast to the effect mediated by overexpression, small interfering RNA-mediated down-regulation of either shrew-1 or CD147 in HeLa cells decreased invasiveness without affecting the proliferation behavior of HeLa cells, but the knockdown cells displayed decreased motility. Altogether, our results imply that shrew-1 has a function in the regulation of cellular invasion, which may involve its interaction with CD147.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):179-85. Epub 2007 Jan 30.

[Adenomyosis]

[Article in French]

Fernandez H, Donnadieu AC.

Service de Gynécologie – Obstétrique et d’Histologie – Embryologie – Cytogénétique à Orientation Biologique et Génétique de la Reproduction, Hôpital Antoine-Béclère, APHP, 92141 Clamart cedex, France. herve.fernandez@abc.ap-hop-paris.fr

Diagnostic adenomyosis is done by pathologist (grade A). Adenomyosis is usually asymptomatic (grade C). Symptomatic adenomyosis gives pains and/or bleedings (grade C). Hysterosalpingography is not included in diagnostic strategy (grade B). Sonography has a good sensitivity and can be exclusively used for therapeutic strategy (grade B). MRI is pertinent but only useful in case of associated lesions (grade B). Hysterectomy is the gold standard for symptomatic patients without desire of pregnancy (grade B). Medical treatments are: IUD with levonorgestrel, Gn-RH analog, antigonadotrope progestin (grade C). Uterine artery embolisation is not recommended (professional agreement). Endometrial resection/destruction are indicated in case of menorraghia (grade C).

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):135-40. Epub 2007 Jan 30.

[Endometriosis: good practice rules for diagnostic laparoscopy]

[Article in French]

Poncelet C, Ducarme G.

Services de Gynécologie – Obstétrique et de Médecine de la Reproduction, CHU Jean-Verdier, APHP, avenue du 14-Juillet, 93143 Bondy cedex, France. christophe.poncelet@jvr.aphp.fr

The interest for diagnostic laparoscopy for the diagnosis of endometriosis is not longer discussed. Indications could be pelvic pain, infertility, menorragia, and/or organic ovarian tumour. Several lesions, typical and non typical, have been described and should be recognized. Histological confirmation seems suitable even though the correlation with visual inspection is not perfect. New laparoscopic techniques seem interesting to increase diagnostic relevance. Visual inspection should be associated with palpation. For deep infiltrating endometriotic lesions diagnostic laparoscopy has shown its limits. Precisions concerning peri-operative methods and operative reports are described. The place of the different classifications has been discussed.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):112. Epub 2007 Jan 30.

[Endometriosis: the patients’ point of view]

[Article in French]

Ludzay D.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):129-34. Epub 2007 Jan 30.

[Endometriosis imaging]

[Article in French]

Maubon A, Bazot M.

Service de Radiologie et Imagerie Médicale, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges cedex, France. antoine.maubon@unilim.fr

Pelvic endometriosis primarily affects the ovaries, pelvic peritoneum, utero-sacral ligaments, Douglas pouch, vagina, rectum and bladder. Clinical assessment is difficult, and imaging proves necessary to determine location and extent of the disease. We review pelvic endometriosis with regards to imaging modalities: technical considerations, imaging patterns, diagnostic performance and respective place of ultrasound and MRI.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):106-7. Epub 2007 Jan 30.

[Endometriosis is a simple disease!]

[Article in French]

Canis M.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):162-72. Epub 2007 Jan 30.

[Surgical management of endometriosis]

[Article in French]

Golfier F, Sabra M.

Service de Chirurgie Gynécologique et Cancérologie, Centre Hospitalier Lyon sud, 69495 Pierre-Bénite, France. francois.golfier@chu-lyon.fr

Both laparoscopic techniques (excision and ablation) for the treatment of superficial peritoneal endometriosis are equally effective (EL2). For the treatment of ovarian endometriomas larger than 3 cm, laparoscopic cystectomy is superior to drainage and coagulation (EL1). Excision of deep rectovaginal endometriosis with or without rectal invasion significantly reduces endometriosis-associated pain (EL4). Laparoscopic partial bladder cystectomy is easier for dome endometriosis than vesical base lesions (EL4). Hysterectomy with ovarian conservation is associated with a high risk of pain recurrence (EL4). Despite bilateral oophorectomy, pain recurrence can occur with hormonal treatment (EL2). Rates of major (ureteral, vesical, intestinal or vascular) complications of endometriosis surgery range from 0.1 to 15% of patients. Higher rates are more common with deep endometriosis surgery (EL2). Patients should be aware of these specific major complications. It is advisable to explain that pain improves, either partially or completely, in about 80% of patients.

J Gynecol Obstet Biol Reprod (Paris). 2007 Apr;36(2):151-61. Epub 2007 Jan 30.

[Endometriosis related infertility]

[Article in French]

Pouly JL, Canis M, Velemir L, Brugnon F, Rabischong B, Botchorichvili R, Jardon K, Peikrishvili R, Mage G, Janny L.

Département de Gynécologie – Obstétrique et de Reproduction Humaine, Polyclinique Hôtel-Dieu, CHU de Clermont-Ferrand, BP 69, 63003 Clermont-Ferrand, France. jlpouly@chu-clermontferrand.fr

From the literature, the crucial knowledge were drawn among endometriosis related infertility. Endometriosis is an important factor of infertility in minimal or light stages and a major one in mild or moderate stages. Thus, a laparoscopy must be performed to confirm endometriosis when suggestive clinical or biological signs exist. In absence of them, laparoscopy can be delayed after intra-uterine inseminations (IUI). The first line treatment is laparoscopic surgery. Its efficacy is proven. It is useless to prescribe a post-operative medical treatment (GnRH analogues). Surgery leads to 25 to 40% of deliveries. It is dependant on age, infertility duration, tubo-ovarian adhesion and tubes involvement. But, surgery can be avoided and the patient is directly referred to In Vitro Fertilization (IVF) when the lesions extension is so important that surgery exposes to complications or when there is a permanent other indication for IVF (severe male infertility). When infertility persists 6 to 12 months after surgery and without patent recurrence, ovulation stimulations and IUI are performed as the second line treatment. After IUI failure, or in case of recurrence, IVF must be applied. A second surgery is not recommended. The IVF results are not impaired by the presence of endometriosis and even of endometriomas. Thus, it is useless to operate again endometriosis before IVF. In opposition, in severe stages or in cases of recurrence, a pre-IVF medical treatment (GnRH analogues) improves the results. IVF do not increased the risk of endometriosis acute growth. In case of infertility and pain, infertility is considered as the first target. But medical treatment can be prescribed between the IVF attempts.

Med Clin (Barc). 2007 Jan 13;128(1):1-6.

[Overexpression and prognostic value of p53 and HER2/neu proteins in benign ovarian tissue and in ovarian cancer]

[Article in Spanish]

Coronado Martín PJ, Fasero Laiz M, García Santos J, Ramírez Mena M, Vidart Aragón JA.

Departamento de Obstetricia y Ginecología, Hospital Clínico San Carlos, Martín Lagos s/n, 28040 Madrid, Spain. pcoronadom@sego.es

BACKGROUND AND OBJECTIVE: To investigate the prognostic value of p53 and HER2/neu overexpression in epithelial ovarian cancer (EOC). PATIENTS AND METHOD: p53 and HER2/neu immunostaining were performed in 198 tissue samples, 124 EOC, 44 benign ovarian tumors and 30 normal ovaries. Nuclear p53 and membranous HER2/neu immunostaining were evaluated. RESULTS: Neither p53 nor HER2/neu overexpression was seen in the benign ovarian tumors. HER2/neu immunostaining was observed in one normal ovary. P53 overexpression was found in 25% EOC and was related with advanced stage, endometrioid, clear cell and undifferentiated types, grade G3, and sub-optimal surgery. HER2/neu immunostaining was observed in 24.2% and it was associated with advanced stage, clear cell and undifferentiated types, and suboptimal surgery. Both, p53 and HER2/neu overexpression decreased overall and progression-free survival, but in the multivariant analysis, only HER2/neu overexpression was an independent prognostic factor of overall survival (RR = 2.8; 95% confidence interval [CI], 1.2-5.6) and recurrence (RR = 2.8; 95% CI, 1.1-7.1). Simultaneous p53 and HER2/neu overexpression made the prognosis worse (p < 0.01). CONCLUSIONS: HER2/neu overexpression (but not p53 overexpression) is a major prognostic factor in EOC.

Int J Colorectal Dis. 2007 Dec;22(12):1551-3. Epub 2007 Jan 30.

High-grade endometrial stromal sarcoma arising from colon endometriosis.

Chen CW, Ou JJ, Wu CC, Hsiao CW, Cheng MF, Jao SW.

Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1925-30. Epub 2007 Jan 29.

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/gamma c(null) immunodeficient mice.

Masuda H, Maruyama T, Hiratsu E, Yamane J, Iwanami A, Nagashima T, Ono M, Miyoshi H, Okano HJ, Ito M, Tamaoki N, Nomura T, Okano H, Matsuzaki Y, Yoshimura Y.

Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial cells transplanted beneath the kidney capsule of NOD/SCID/gamma(c)(null) immunodeficient mice. In addition to the endometrium-like structure, hormone-dependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by in vivo bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule.

Fertil Steril. 2007 Apr;87(4):982-4. Epub 2007 Jan 29.

Cognate chemokine receptor 1 messenger ribonucleic acid expression in peripheral blood as a diagnostic test for endometriosis.

Agic A, Xu H, Rehbein M, Wolfler MM, Ebert AD, Hornung D.

We investigated the expression of the cognate chemokine receptor 1 (CCR1) messenger ribonucleic acid, a G-protein-coupled cognate chemokine receptor with high affinity for RANTES (Regulated upon Activation, Normal T cells Expressed and Secreted), in peripheral blood leukocytes of women with and without endometriosis, and its potential use as a diagnostic test for endometriosis. Because patients with an earlier diagnosis of this disease have a better treatment outcome and a reduced recurrence rate, CCR1 mRNA measurement in the peripheral blood of patients with suspected endometriosis might give us a new perspective in diagnosing and treating this disease earlier and better.

J Adolesc Health. 2007 Feb;40(2):151-7. Epub 2006 Nov 29.

Extended cycling of combined hormonal contraceptives in adolescents: physician views and prescribing practices.

Gerschultz KL, Sucato GS, Hennon TR, Murray PJ, Gold MA.

University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

PURPOSE: We sought to determine the practices of physicians who prescribe for adolescents extended cycles of combined hormonal contraception, in which hormones are taken for longer than 21 days and menstruation is delayed. METHODS: Five hundred physicians from the membership rosters of the Society for Adolescent Medicine and the North American Society for Pediatric and Adolescent Gynecology were asked to complete an online 39-question survey. RESULTS: The 222 respondents (44% of those contacted) were mostly pediatricians (55%) and gynecologists (34%). Ninety percent reported having ever prescribed extended cycles of hormonal contraception to adolescents, and 33% said extended cycles make up more than 10% of their total combined hormonal contraceptive prescriptions. Respondents most commonly prescribed extended cycles to accommodate patients’ requests to induce amenorrhea for specific events (82%) or for fewer menses per year (72%), and to treat menorrhagia (68%), dysmenorrhea (65%), and endometriosis (62%). The most commonly prescribed extended regimen was 84 continuous hormone days followed by 7 hormone-free days (46%), most often with an oral contraceptive containing 30 mug of ethinyl estradiol. Gynecologists were more likely than other physicians to prescribe extended cycles frequently, to prescribe hormone-free intervals shorter than 7 days, and to prescribe continuous regimens that eliminate the hormone-free interval completely. CONCLUSIONS: Physicians prescribe extended cycles of combined hormonal contraceptives to adolescents to accommodate patient requests and to treat common gynecologic conditions. Currently, a variety of extended cycling regimens are prescribed, suggesting that further study is needed to determine the optimal regimen for this subset of patients and their individual needs

Fertil Steril. 2007 May;87(5):1173-9. Epub 2007 Jan 25.

Effect of endometrioma cyst fluid exposure on peritoneal adhesion formation in a rabbit model.

Smith LP, Williams CD, Doyle JO, Closshey WB, Brix WK, Pastore LM.

Department of Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, Virginia.

OBJECTIVE: To determine whether copious lavage and suction of human endometrioma fluid placed in the peritoneal cavity of rabbits reduces adhesion formation compared to no lavage. DESIGN: Prospective, randomized, blinded study. SETTING: Academic research environment. ANIMAL(S): Twenty-four female New Zealand white rabbits. INTERVENTION(S): Rabbits randomized into three groups: [1] laparoscopy with instillation of human endometrioma material, no lavage; [2] laparoscopy with instillation of human endometrioma material, followed by clearance of all visible endometrioma fluid by saline lavage and suction; [3] laparoscopy alone. MAIN OUTCOME MEASURE(S): Six weeks after laparoscopy, adhesions scored by laparotomy using standard visual assessment scoring system and histologic microscopic evaluation. Data evaluated using Kruskal-Wallis and median nonparametric tests. RESULT(S): For groups 1, 2, and 3, respectively, mean total clinical adhesion scores were 0.67 (95% confidence interval [CI] -0.87, 2.2), 3.67 (95% CI 1.27, 6.07), and 0 (95% CI 0, 0). Group 2 had statistically significantly higher mean adhesion scores compared to group 1. Histologic adhesion scores followed the trend of clinical adhesion scores. CONCLUSION(S): In this rabbit model, human endometrioma fluid exposure in the peritoneal cavity is not associated with adhesion formation. Instillation of endometrioma fluid followed by copious saline lavage is strongly associated with adhesion formation.

Am J Pathol. 2007 Feb;170(2):590-8.

Aberrant expression of leptin in human endometriotic stromal cells is induced by elevated levels of hypoxia inducible factor-1alpha.

Wu MH, Chen KF, Lin SC, Lgu CW, Tsai SJ.

Department of Obstetrics & Gynecology, Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China.

Elevated expression of leptin in endometriotic tissue results in an increase in stromal cell proliferation and may contribute to the development of endometriosis. However, the underlying mechanism responsible for aberrant expression of leptin is not known. We hypothesize that aberrant expression of leptin in endometriotic stroma may be regulated by increased levels of hypoxia-inducible factor-1alpha (HIF-1alpha), the master transcription factor that controls gene expression in response to hypoxia. Herein we show that the mRNA and protein levels of HIF-1alpha were greater in ectopic endometriotic tissue compared with its eutopic counterpart. Exposure of eutopic endometrial stromal cells under hypoxic conditions or treated with desferrioxamine (DFO, chemical hypoxia) resulted in a time-dependent increase in leptin gene expression. A promoter activity assay demonstrated that HIF-1alpha induced leptin promoter activity after DFO treatment. Chromatin immunoprecipitation assay further demonstrated that binding of HIF-1alpha to leptin promoter was evident after DFO treatment. Finally, depletion of HIF-1alpha by short interference RNA abolished leptin expression in ectopic endometriotic stromal cells. Taken together, our data demonstrate that aberrant expression of leptin in ectopic endometriotic stromal cells is induced, at least in part, by an elevated level of HIF-1alpha in these cells, providing new insights into the etiology of endometriosis.

Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000069.

Update of:

Cochrane Database Syst Rev. 2000;(2):CD000069.

Danazol for unexplained subfertility.

Hughes E, Brown J, Tiffin G, Vandekerckhove P.

McMaster University, Department of Obstetrics and Gynaecology, 1200 Main St West, Room HSC-4F7, Hamilton, Ontario, CanadaL8N 3Z5. hughese@mcmaster.ca

BACKGROUND: The synthetic androgen Danazol, was developed in the 1970’s as a treatment for endometriosis. Its use was soon advocated in women with unexplained subfertility. Two randomised trials were subsequently conducted to assess the effectiveness of danazol in this population. OBJECTIVES: The objective of this review was to assess the effect of danazol on live birth rate in women with unexplained subfertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Sub-fertility Group’s specialised register of trials (searched November , 2006) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 4, 2006), MEDLINE (1966-November 2006), EMBASE (1980 – November 2006) and reference lists of articles. SELECTION CRITERIA: Randomised trials of danazol compared with placebo or no treatment in women with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers EH and GT. MAIN RESULTS: Two trials involving seventy-one women were included. There was no statistically significant difference in the live birth/ ongoing pregnancy rate between danazol and placebo at the end of treatment (OR 1.16, 95% CI 0.0 to 8.29; P=0.36) or at the end of follow-up (OR 2.41; 95% CI 0.59, 9.82; P=0.22). There was no significant difference in clinical pregnancies following treatment (OR 0.14, 95% CI 0.01, 2.26; P=0.17), however there were significantly more clinical pregnancies during the follow-up period in the danazol group compared with the placebo group (OR 3.15, 95%CI 0.98, 10.10; P<0.05). Multiple side effects were reported. AUTHORS’ CONCLUSIONS: Available data demonstrate no evidence of the benefit of danazol for unexplained subfertility. Although there is insufficient evidence to be certain of this, the need for contraception during treatment and the adverse effects and costs of danazol, make its use for this problem unwarranted. The increased pregnancy rate in the long term follow-up data may be attributable to additional therapies and did not influence the live birth/ongoing pregnancy data.

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