... link between infertility and endometriosis? Almost 40% of women with infertility have endometriosis. Inflammation from endometriosis may damage the sperm or egg or interfere with their movement through the fallopian tubes and uterus. In severe ...
... and does not go away after treatment, a hysterectomy may be a “last resort” option. Endometriosis is ... removed at the same time you have the hysterectomy. There is a small chance that pain will ...
... Related information Infertility fact sheet Menstruation and the menstrual cycle fact sheet Pregnancy Endometriosis on the fallopian tubes, ... periods that last more than seven days Short menstrual cycles (27 days or fewer) A family member (mother, ...
... of peritoneal cells. In what's known as the "induction theory," experts propose that hormones or immune factors ... women who have had endometriosis. By Mayo Clinic Staff . Mayo Clinic Footer Legal Conditions and Terms Any ...
Endometriosis is a common finding in adolescents who have a history of chronic pelvic pain or dysmenorrhoea resistant to medical treatment, however the exact prevalence is unknown. Both early/superficial and advanced forms of endometriosis are found in adolescents, including ovarian endometriomas and deep endometriotic lesions. Whilst spontaneous resolution is possible, recent reports suggest that adolescent endometriosis can be a progressive condition, at least in a significant proportion of cases. It is also claimed that deep endometriosis has its roots in adolescence. Optimum treatment is far from clear and long term recurrence is still a significant problem. The most frequently reported treatment approach in the published literature is a combination of surgery and postoperative hormonal treatment with the combined oral contraceptives, progestins, levonorgestrel intrauterine system or gonadotrophin releasing hormone analogues. Use of gonadotrophin releasing hormone analogues and long term progestins should be carefully considered due to concerns over continuing bone formation in this age group. There is currently no consensus as to whether surgery should be avoided as much as possible to prevent multiple operations in the long term, or surgical treatment should be considered at an early stage before more severe lesions develop. Further research is required to determine which approach would offer a better long term outcome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Dovey, Serena; Sanfilippo, Joseph
The majority of women with endometriosis report symptoms starting in adolescence, yet endometriosis is often a delayed diagnosis in this patient population. Given that endometriosis is felt to be a progressive disease with increasing morbidities over time, such as structural defects and infertility, being more aggressive with pursuing the diagnosis is warranted. Once the diagnosis of endometriosis is made, various medical and surgical treatment modalities are available, and this article will review the most current treatment recommendations.
Kaabachi, Wajih; Kacem, Olfa; Belhaj, Rafik; Hamzaoui, Agnes; Hamzaoui, Kamel
Interleukin-37 (IL-37) has been identified as a novel anti-inflammatory cytokine. The present study aimed to evaluate the expression of IL-37 in serum and in peritoneal fluid to determine its clinical significance in endometriosis. Enzyme-linked immunosorbent assay (ELISA) was performed to examine serum IL-37 levels in patients with endometriosis and healthy controls. Peritoneal fluid IL-37 mRNA and NFκB expression were quantified by real-time reverse transcription polymerase chain reaction assays. The association of IL-37 levels with clinical factors and prognosis of endometriosis was analysed. We found that IL-37 levels in PF and in serum were significantly higher in patients with endometriosis compared to women without endometriosis (P=0.0005). IL-37 levels were highly expressed in PF [132.38±34.62pg/mL; P<0.0001] than in serum [74.10±13.49pg/mL] in endometriosis patients. IL-37 mRNA expression contrasted with NFκB mRNA expression in PF from patients with endometriosis. A significant inverse correlation was observed between IL-37 mRNA and NFκB mRNA expression. IL-37 expression correlates with endometriosis severity. The affected NFκB mRNA expression in endometriosis contributed the to exhibited increase of IL-37. The increased levels of IL-37 may dampen NFκB activation in endometriosis patients. Copyright © 2017. Published by Elsevier B.V.
Groisman, G M; Kerner, H
A multicystic mesothelioma of the omentum in a 36 year old woman consisted of a multicystic mass with foci of typical endometriosis and 'necrotic pseudoxanthomatous nodules'. The presence of endometriosis within multicystic mesothelioma has never been reported. Our findings support the hypothesis that endometriosis plays a rôle in the pathogenesis of multicystic mesothelioma and that this is a reactive rather than a neoplastic lesion.
Daraï, Emile; Cohen, Jonathan; Ballester, Marcos
The goal of this review was to assess the impact of colorectal endometriosis on spontaneous fertility and the potential benefit of Medically Assisted Reproduction (MAR) (in vitro fertilization and intrauterine insemination) and surgery on fertility outcomes. MEDLINE search for articles on fertility in women with DIE published between 1990 and December 2015 using the following terms: "deep endometriosis", "deep infiltrating endometriosis", "bowel endometriosis", "colorectal endometriosis", "fertility", "infertility", "IVF-ICSI", "Assisted Reproductive Techniques (ART)", and "MAR". Spontaneous pregnancy rate (PR) in patients undergoing resection of DIE but leaving in situ colorectal endometriosis was 26.5% (95% CI=14-39). PR after MAR was 27.4% (95% CI=19-35) and the overall PR was 37.9% (95% CI=29-37). After colorectal surgery, among the 855 patients with and without proved infertility, the spontaneous PR was 31.4% (95% CI=28-34) without difference between the groups. PR after MAR was 19.8% (95% CI=17-22). PR after MAR in patients with and without proved infertility was 21.4% (95% CI=18-25) and 15.5% (95% CI=11-20), respectively. The overall PR after colorectal surgery was 51.1% (95% CI=48-54). Our review supports a potential benefit of surgery on fertility outcomes for women with colorectal endometriosis. Further studies are required to determine whether surgical management should be first-intention or restricted to failure of MAR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Rogers, Peter A. W.; D’Hooghe, Thomas M.; Fazleabas, Asgerally; Gargett, Caroline E.; Giudice, Linda C.; Montgomery, Grant W.; Rombauts, Luk; Salamonsen, Lois A.; Zondervan, Krina T.
Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:19196878
... has been diagnosed with endometriosis. There are several theories about how the endometrial tissue actually gets outside the uterus in the first place. One theory suggests that the menstrual blood flow somehow "backs ...
Polak, Grzegorz; Bednarek, Wiesława; Wertel, Iwona; Kwaśniewski, Wojciech; Wasyluk, Tomasz; Raganowski, Piotr; Kotarski, Jan
The majority of adult women with endometriosis report that their symptoms started in adolescence. Early diagnosis and optimal treatment prevent disease progression and mitigate long-term morbidities, such as infertility and chronic pelvic pain.
... has been diagnosed with endometriosis. There are several theories about how the endometrial tissue actually gets outside the uterus in the first place. One theory suggests that the menstrual blood flow somehow "backs ...
Ottolina, Jessica; De Stefano, Francesca; Viganò, Paola; Ciriaco, Paola; Zannini, Piero; Candiani, Massimo
To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility status. Retrospective study (Canadian Task Force classification II-2). Departments of Thoracic Surgery and Obstetrics and Gynecology, San Raffaele Hospital, Milan, Italy. Sixteen females referred to the Department of Thoracic Surgery for treatment of spontaneous pneumothorax between January 2001 and January 2014 and referred to the outpatient clinic for gynecologic follow-up. Thoracoscopy for catamenial pneumothorax and laparoscopy for pelvic endometriosis. Characteristics of the patients, the presence of endometriosis, and their fertility status were statistically analyzed. Pelvic endometriosis was diagnosed in 9 patients (56.3%), but 6 patients did not undergo a laparoscopic procedure to confirm or exclude the disease. Seven of the affected patients (77.8%) had stage III-IV endometriosis. Two-thirds of the patients with pelvic endometriosis who attempted conception conceived spontaneously, as did all of the patients without histopathological confirmation of endometriosis. Thoracic endometriosis syndrome, characterized mainly by catamenial pneumothorax, is a relevant condition in patients affected by endometriosis. However, few previous studies have analyzed this condition from a gynecologic standpoint, in terms of characteristics of endometriosis and fertility status of affected women. Our findings support the presence of a strong association between catamenial pneumothorax and pelvic endometriosis, as well as a minimal effect of catamenial pneumothorax on fertility status, even in the presence of pelvic endometriosis. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.
Endometriosis affects a significant proportion of teenagers. Published studies suggest that laparoscopically confirmed endometriosis could be found in over 60% of adolescent girls undergoing laparoscopic investigation for pain, in 75% of girls with chronic pelvic pain resistant to treatment and in 70% of girls with dysmenorrhea and in approximately 50% of girls with chronic pelvic pain not necessarily resistant to treatment. Both early and advanced forms, including deep endometriosis have been reported to be present in teenagers. It has recently been claimed that deep endometriosis has its roots in teenage years. Risk factors include obstructive mullerian anomalies, family history, early menarche and early onset dysmenorrhea. Both surgical and medical treatment approaches are used for treatment in this age group, but care should be taken when treatment with GnRHa and progestins is being considered due to their potential impact on bone formation. Further studies are urgently needed to determine whether early diagnosis and treatment of teenage endometriosis lead to better long term outcomes or simply increase number of interventions without preventing progression of the disease.
Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G
Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease.
Dmitrieva, Natalia; Nagabukuro, Hiroshi; Resuehr, David; Zhang, Guohua; McAllister, Stacy L.; McGinty, Kristina A.; Mackie, Ken; Berkley, Karen J.
Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Here, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis’s abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments. PMID:20833475
Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G
Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease. PMID:21895474
Rodgers, Allison K; Falcone, Tommaso
Endometriosis is a common chronic disease that causes symptoms of pain and infertility. The pain syndrome can be quite incapacitating. The pain symptoms usually originate in the reproductive organs but can also involve the urinary or intestinal tracts if endometriosis implantation has occurred there. The presentation and physical appearance of endometriosis is extremely variable and can be characterized by a chronic intraperitoneal inflammatory process and adhesions. The only definitive diagnostic technique is laparoscopy. To review current literature on the treatment strategies for endometriosis. Review of Pubmed, Cochrane database and Medline for current review articles and studies regarding the current treatment strategies for endometriosis. Initial treatment is surgical or medical. Medical therapy is often used as a first-line therapy and can also be used in conjunction with those patients who undergo surgical therapy for pain. No medical therapy has proven effective for infertility. Medical therapy consists mostly of hormonal suppressive therapy in which the medication causes a downregulation of the hypothalamus-pituitary-ovarian pathway. Non-steroidal anti-inflammatory drugs and oral contraceptives are often used as an initial approach even without a definitive diagnosis. Progestins, such as oral norethindrone and depot medroxyprogesterone, are effective while using them but have a high recurrence rate. The norgestrol intrauterine device is also quite effective at relieving pain associated with endometriosis, especially pain arising during menses as well as from lesions in the rectovaginal tissue. Gonadotropin-releasing hormone agonists induce a pseudomenopausal state and have significant side effects, such as hot flashes and genital atrophy. 'Add-back' therapy with a progestin has been shown to relieve most of these drug related symptoms. Gonadotropin-releasing hormone agonists are also very effective at relieving symptoms of pain during treatment but are
Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.; Eason, R.L.; Boster, R.A.
It was found that female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was determined to be 7 years after the proton exposure. The doses and energies of the radiation received by the experimental animals were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event. It is concluded that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crew members. 15 references.
Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.; Eason, R.L.; Boster, R.A.
Female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was 7 years after exposure. The doses and energies of the radiation received were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event, leading to the conclusion that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crewmembers.
Cooney, Maureen A; Buck Louis, Germaine M; Hediger, Mary L; Vexler, Albert; Kostyniak, Paul J
Limited study of persistent organochlorine pesticides (OCPs) and endometriosis has been conducted. One hundred women aged 18-40 years who were undergoing laparoscopy provided 20 cm(3) of blood for toxicologic analysis and surgeons completed operative reports regarding the presence of endometriosis. Gas chromatography with electron capture was used to quantify (ng/g serum) six OCPs. Logistic regression was utilized to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for individual pesticides and groups based on chemical structure adjusting for current cigarette smoking and lipids. The highest tertile of aromatic fungicide was associated with a fivefold risk of endometriosis (aOR=5.3; 95% CI, 1.2-23.6) compared to the lowest tertile. Similar results were found for t-nonachlor and HCB. These are the first such findings in a laproscopic cohort that suggest an association between OCP exposure and endometriosis. More prospective studies are necessary to ensure temporal ordering and confirm these findings.
Berstein, Jane C.
Relation of an art therapist's personal story concerning her struggle to overcome endometriosis, and how her artwork has played a vital role in coping with the disease. Illustrated with a chronology of artwork produced during a bout with the illness. (JPS)
Berstein, Jane C.
Relation of an art therapist's personal story concerning her struggle to overcome endometriosis, and how her artwork has played a vital role in coping with the disease. Illustrated with a chronology of artwork produced during a bout with the illness. (JPS)
Burney, Richard O.; Giudice, Linda C.
Originally described over three hundred years ago, endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations. Endometriosis is an inflammatory, estrogen dependent condition associated with pelvic pain and infertility. This work reviews the disease process from theories regarding origin to the molecular basis for disease sequelae. A thorough understanding of the histopathogenesis and pathophysiology of endometriosis is essential toward the development of novel diagnostic and treatment approaches for this debilitating condition. PMID:22819144
Mihmanli, V; Ózkan, T; Genc, S; Cetinkaya, N; Uctas, H
Endometriosis is characterized by the presence of histologically normal endometrial glands and stroma outside the uterine cavity. Endometriosis predominantly locates on peritoneal surfaces, but it also affects the vagina, vulva, and perineum, usually secondary to surgical or obstetric trauma. Endometriosis in an episiotomy scar is a fairly rare phenomenon. The authors present a case of endometriosis in an episiotomy scar.
Rocha, Ana Luiza L.; Reis, Fernando M.; Taylor, Robert N.
A comprehensive review was performed to survey the role of angiogenesis in the pathogenesis of endometriosis. This is a multifactorial disease in which the development and maintenance of endometriotic implants depend on their invasive capacity and angiogenic potential. The peritoneal fluid of patients with endometriosis is a complex suspension carrying inflammatory cytokines, growth factors, steroid hormones, proangiogenic factors, macrophages, and endometrial and red blood cells. These cells and their signaling products concur to promote the spreading of new blood vessels at the endometriotic lesions and surroundings, which contributes to the endometriotic implant survival. Experimental studies of several antiangiogenic agents demonstrated the regression of endometriotic lesions by reducing their blood supply. Further studies are necessary before these novel agents can be introduced into clinical practice, in particular the establishment of the safety of anti-angiogenic medications in women who are seeking to become pregnant. PMID:23766765
Falcone, Tommaso; Lebovic, Dan I
Endometriosis is a relatively common chronic gynecologic disorder that usually presents with chronic pelvic pain or infertility. The societal effect of this disorder is enormous both in monetary costs and in quality of life. The diagnosis of the disease can only be definitively made with surgical intervention. Fertility may be enhanced with surgical intervention, but medical suppressive therapy has no role apart from in vitro fertilization. Assisted reproductive technology is associated with excellent outcomes. Management of endometriomas is particularly complex because surgical intervention may reduce ovarian reserve. Both medical and surgical treatment of endometriosis-associated chronic pelvic pain are effective in the short-term. Recurrence is common with both modalities. Recurrence after surgical intervention can be decreased with the use of postoperative suppressive medical therapy such as hormonal contraceptives. This article presents the different types of peritoneal disease found in endometriosis patients. The technique used to safely and completely remove the disease is discussed. The specific areas of involvement include the pelvic side wall, the cul-de-sac, and bladder peritoneum.
KOUKOURA, OURANIA; SIFAKIS, STAVROS; SPANDIDOS, DEMETRIOS A.
Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis. PMID:26934855
Boujenah, Jeremy; Salakos, Eleonora; Pinto, Mélodie; Shore, Joanna; Sifer, Christophe; Poncelet, Christophe; Bricou, Alexandre
The aim of our study was to compare the stage and severity of endometriosis in fertile and infertile women with congenital uterine malformations. We performed an observational study from September 2007 to December 2015 in a tertiary care university hospital and assisted reproductive technology center. A total of 52 patients with surgically proven uterine malformations were included. We compared 41 infertile patients with uterine malformations with 11 fertile patients with uterine malformation. The main outcome was the stage, score and type of endometriosis in regard to infertility and class of uterine malformation. The rate of endometriosis did not differ between the two groups (43.9 vs. 36.4%). The mean revised American Fertility Society score was higher in infertile patients with uterine malformations (19.02 vs. 6, p < 0.05). No significant difference was found in the rate of superficial peritoneal endometriosis (43.9 vs. 37.5%). Endometrioma and deep infiltrating endometriosis were associated with uterine malformations in infertile women, respectively 14.6 and 0%. No difference in the characteristics of endometriosis was found regarding the class of malformation. The association of uterine malformations and infertility may increase the severity of endometriosis and raise the issue of their diagnosis and management. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.
Stuparich, Mallory A; Donnellan, Nicole M; Sanfilippo, Joseph S
The recognition and management of endometriosis in the adolescent patient is challenging. A strong clinical suspicion for endometriosis should be maintained in the adolescent who suffers from acyclic pelvic pain as well as absenteeism from school and lack of participation in daily activities. Risk factors include the presence of an obstructive Mullerian anomaly, a family history of endometriosis, and conditions that prolong exposure to endogenous and exogenous estrogens. Empiric medical therapy with nonsteroidal anti-inflammatory drugs and combined oral contraceptive pills may be considered in most adolescents with endometriosis. Failure of empiric therapy may warrant diagnostic laparoscopy, which affords a concomitant opportunity for treatment via excision of endometriosis. Endometriotic implants in the adolescent tend to be more atypical, appearing red/flame-like, clear/polypoid, or vesicular. Endometriosis tends to recur more often in adolescents when compared with adults, and the role of postoperative medical therapy for the suppression of disease progression is not entirely clear. Current knowledge on the impact of adolescent endometriosis on future fertility is limited but overall reassuring.
Alves, João; Puga, Marco; Fernandes, Rodrigo; Pinton, Anne; Miranda, Ignacio; Kovoor, Elias; Wattiez, Arnaud
STUDY OBJECTIVE: To evaluate if laparoscopic treatment of ureteral endometriosis is feasible, safe, and effective and to determine if ureteral dilatation and/or the number of incisions increases complications.
Gon, Sonia; Barui, Gopi Nath; Majumdar, Bipasa; Baig, Sarfraz Jalia
The incidence of endometriosis of the appendix is reported to be just <1% of the total endometriosis cases. Laparoscopic visualization and diagnostic yield are of profound significance to women in whom gynecologic diseases such as endometriosis, pelvic inflammatory disease, ruptured ovarian follicles or tubal pregnancy may be the source of pain and mimic appendicitis. Therefore, lower abdominal pain in reproductive age group female must invite the attention of the surgeon or gynecologist to entertain the possibility of endometriosis since appendiceal endometriosis, while relatively uncommon in patients with endometriosis, is rare in the general population.
... endometriotic lesions, and fewer of the lesions showed advanced development ( PMID: 22464761 ). Researchers also looked at statins as a possible treatment for endometriosis. These drugs are known to control cholesterol levels, but they may also have anti- ...
... the American Society for Reproductive Medicine Endometriosis: Does It Cause Infertility? This fact sheet was developed in ... or intestines. This tissue can irritate structures that it touches, causing pain and adhesions (scar tissue) on ...
Endometriosis intestines due to its non-specific symptoms can pose diagnostic problems, a lack of or incorrect treatment worsens the quality of life, sometimes leading to serious complications. The differential diagnosis of abdominal pain, especially in patients of reproductive age should be taken disease into account. Often abdominal pain in young women are classified as a functional gastrointestinal disorder, and only carefully collected intelligence allows you to focus on the diagnosis of endometriosis, especially if the symptoms significantly impair quality of life. A woman 32 year old who was admitted to the department of gastroenterology because of increasing pain in the abdomen. Due to the deteriorating condition of the patient, the characteristics of mechanical obstruction on imaging studies was transferred to the surgical ward with suspected Crohn's disease. She was treated surgically. Histopathological examination found endometriosis. Endometriosis outside the sex system can lead to serious complications.
Morotti, Matteo; Vincent, Katy; Becker, Christian M
Pain is the central symptom in endometriosis and often persists despite treatment of the disease. Multiple mechanisms underlie endometriosis-associated pain including nociception, inflammation, and alterations in peripheral and central nervous system pain processing. As also occuring in other chronic conditions, pain in endometriosis is often associated with psychological distress and fatigue, both of which may amplify pain. It is hoped that in the future methods of phenotyping women on the basis of the underlying pain mechanisms will be developed, likely combining a critical evaluation of clinical symptoms and signs with laboratory and imaging tests. Optimal pain relief for an individual is more likely if her specific contributory pain mechanisms are identified and appropriately addressed. Such methods may also improve the selection of patients for clinical trials, potentially increasing the probability of identifying novel treatments for the many women with endometriosis for whom acceptable analgesia is not achieved. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
... factors appear to cause endometriosis. For years, the theory was that tissue fragments “shed” from the lining ... process experienced by many reproductive-age women. Newer theories speculate that some women may have an underlying ...
Hernández-Valencia, Marcelino; Zárate, Arturo
Endometriosis is the third cause of gynecological morbidity and the complications are associated to ectopically endometrial tissue implantation. The interest on this disease is the functional disability and its association with sterility. It has been established that endometrial growth is estrogen-dependent and that progesterone inhibits the cellular proliferation mediated by estrogens, therefore in endometriosis there is not an adequate response to hormonal signals that control the proliferative activity. It has been described that peritoneal fluid in women with endometriosis has high concentrations of cytokines, growth factors and activated macrophages, which have been shown to have adverse effects on fertility. Therefore, these are not the only causes of infertility since it has been described that women with endometriosis seem to have poor ovarian reserve and ovular quality. When there is infertility, the tendency is to treat the endometriosis due to the changes caused by ectopic tissue presented at the immunological level and in the structure of genital organs, which disturbs the conception process. It has been observed that endometriosis recurs after a surgical procedure. For this reason we should be consider all therapeutic possibilities.
BACKGROUND: Hormonally active environmental agents recently have been associated with the development of endometriosis. METHODS: We undertook a study to assess the relation between endometriosis, an estrogen dependent gynecologic disease, and 62 individual polychlorinated biphe...
BACKGROUND: Hormonally active environmental agents recently have been associated with the development of endometriosis. METHODS: We undertook a study to assess the relation between endometriosis, an estrogen dependent gynecologic disease, and 62 individual polychlorinated biphe...
Zhu, Xiaoshu; Hamilton, Kindreth D; McNicol, Ewan D
Endometriosis is a prevalent gynaecological condition, significantly affecting women's lives. Clinical presentations may vary from absence of symptoms to complaints of chronic pelvic pain, most notably dysmenorrhoea. The management of pain in endometriosis is currently inadequate. Acupuncture has been studied in gynaecological disorders but its effectiveness for pain in endometriosis is uncertain. To determine the effectiveness and safety of acupuncture for pain in endometriosis. We searched the Cochrane Menstrual Disorders and Subfertility Group (MSDG) Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, CNKI and TCMDS (from inception to 2010) and reference lists of retrieved articles. Randomised single or double-blind controlled trials enrolling women of reproductive age with a laparoscopically confirmed diagnosis of endometriosis and comparing acupuncture (body, scalp or auricular) to either placebo or sham, no treatment, conventional therapies or Chinese herbal medicine. Three authors independently assessed risk of bias and extracted data; we contacted study authors for additional information. Meta-analyses were not performed as only one study was included. The primary outcome measure was decrease in pain from endometriosis. Secondary outcome measures included improvement in quality of life scores, pregnancy rate, adverse effects and rate of endometriosis recurrence. Twenty-four studies were identified that involved acupuncture for endometriosis; however only one trial, enrolling 67 participants, met all the inclusion criteria. The single included trial defined pain scores and cure rates according to the Guideline for Clinical Research on New Chinese Medicine. Dysmenorrhoea scores were lower in the acupuncture group (mean difference -4.81 points, 95% confidence interval -6.25 to -3.37, P < 0.00001) using the 15-point Guideline for Clinical
Seval, Mehmet Murat; Cavkaytar, Sabri; Atak, Zeliha; Guresci, Servet
Endometriosis of the uterine cervix is a rare lesion that is generally asymptomatic in gynaecological practice. We present a case with postcoital bleeding due to a cervical mass mimicking cervical polyp or fibroma which was histologically proven as cervical endometriosis later. Cervical endometriosis should be considered in the differential diagnosis of cervical masses with postcoital bleeding. PMID:23376669
Seval, Mehmet Murat; Cavkaytar, Sabri; Atak, Zeliha; Guresci, Servet
Endometriosis of the uterine cervix is a rare lesion that is generally asymptomatic in gynaecological practice. We present a case with postcoital bleeding due to a cervical mass mimicking cervical polyp or fibroma which was histologically proven as cervical endometriosis later. Cervical endometriosis should be considered in the differential diagnosis of cervical masses with postcoital bleeding.
Belaisch, J; Allart, J-P
Endometriosis is a recurrent and painful disease which sometimes disturbs severely the quality of life of women who suffer from it. It is then logical to include a psychological back-up to its medical and surgical treatment. Nevertheless this support is not often offered to patients. One can hypothesize another and completely different way of seeing the problem: the mood swings and depression of endometriotic patients could possibly be, at least in some of them, the cause of the graft of endometrial cells and not the effect of pain and infertility. The mechanism of the development of endometriotic lesions could be related to a lowering of immune defences due to an alteration of the psycho-neuro-endocrino-immunologic network, resulting from difficult life experiences which mostly happen during adolescence. This concept may have beneficial effects for the patient whose case would be more understood in depth. But very few medical teams consider it worthwhile to include in their practices.
Rousset, Pascal; Gregory, Jules; Rousset-Jablonski, Christine; Hugon-Rodin, Justine; Regnard, Jean-François; Chapron, Charles; Coste, Joël; Golfier, François; Revel, Marie-Pierre
To evaluate magnetic resonance imaging (MRI) for diaphragmatic endometriosis diagnosis. Over a 2-year period, all diaphragmatic MRI performed in the context of diaphragmatic endometriosis were reviewed. Axial and coronal fat-suppressed T1- and T2-weighted sequences were analyzed by two independent readers for the presence of nodules, plaque lesions, micronodule clustering, or focal liver herniation. MR abnormalities were correlated to surgical findings in women surgically treated. Interobserver agreement was assessed by κ statistics. Twenty-three women with diaphragmatic endometriosis criteria comprised the population; 14 had surgical confirmation and nine had symptoms relief with hormonal treatment. MRI sensitivity was 83 % (19/23; 95 % confidence interval [CI]: 68, 98) for reader 1 and 78 % (18/23; 95 % CI: 61, 95) for reader 2. Kappa value was 0.86 (95 % CI: 0.47, 1.00). Readers 1 and 2 detected 35 and 36 lesions, respectively, all right-sided and agreed for 32 lesions on the type, location, and signal. Lesions were mostly nodules (23/32, 72 %), predominantly posterior (28/32, 87.5 %) and hyperintense on T1 (20/32, 63 %). MRI was negative for both readers in 2 surgically treated patients with small nodules or isolated diaphragmatic holes. MRI allows diaphragmatic endometriosis diagnosis with 78 to 83 % sensitivity and excellent interobserver agreement. • MRI allows the diagnosis of diaphragmatic endometriosis with up to 83 % sensitivity. • Diaphragmatic endometriosis lesions are better depicted on fat-suppressed T1-weighted sequences. • Diaphragmatic lesions, mostly hyperintense nodules, are right-sided and predominantly posterior. • MRI can help in timely diagnosis of diaphragmatic endometriosis.
Vlad, Anda M; Diaconu, Iulia; Gantt, Kira R
Endometriosis is a chronic, debilitating disease, associated with pelvic pain and infertility. Recent epidemiological studies suggest that women with endometriosis are at increased risk for ovarian cancer. Although the causative factors for both endometriosis and ovarian cancer remain largely unknown, several similarities between the proposed etiology of ovarian cancer and the observed pathophysiology of endometriosis have been reported. MUC1 glycoprotein is present in endometriotic lesions and overexpressed in epithelial ovarian tumors. We are currently studying immunity to MUC1 antigen in newly emerging preclinical models for endometriosis and ovarian cancer and exploring the potential for immune therapy/prevention with MUC1 in both diseases.
Brady, Paula C; Missmer, Stacey A; Laufer, Marc R
Endometriosis-the ectopic implantation of endometrial-like tissue-affects 10% of adolescent females and adults. Bladder involvement, causing dysuria and hematuria, occurs in a very small number of endometriosis patients. The patient presented at age 12 years with dysuria and pelvic pain. Laparoscopy revealed stage I endometriosis. Postoperatively, she reported persistent dysuria and passage of tissue in her urine. Cystoscopy showed diffuse erythema; urine cytology revealed glandular and spindle cells suggestive of endometriosis. She was transitioned from oral contraceptives to an intranasal gonadotropin-releasing hormone agonist, with symptom resolution. Intravesicular endometriosis coinciding with stage I disease supports a mechanism of endometriosis dissemination other than direct bladder infiltration. Patients with endometriosis who complain of urinary symptoms warrant assessment, because intravesicular bladder involvement cannot be excluded using pelviscopy. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
Tissue factor (TF), is a cellular receptor that binds the factor VII/VIIa to initiate the blood coagulation cascade. In addition to its role as the initiator of the hemostatic cascade, TF is known to be involved in angiogenesis via intracellular signaling that utilizes the protease activated receptor-2 (PAR-2). We now review the physiologic expression of TF in the endometrium and its altered expression in multiple cell types derived from eutopic and ectopic endometrium from women with endometriosis compared with normal endometrium. Our findings suggest that TF might be an ideal target for therapeutic intervention in endometriosis. We have employed a novel immunoconjugate molecule known as Icon and were able to eradicate endometrial lesions in a mouse model of endometriosis without affecting fertility. These findings have major implications for potential treatment in humans. PMID:24278684
... not even heard of: endometriosis. My endometriosis had advanced so much that it was wrapped around my abdomen. I have had four laparoscopic excision surgeries. My endometriosis isn’t gone, but it is ...
Halpern, Gabriela; Schor, Eduardo; Kopelman, Alexander
This literature review analyzed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with N-acetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis.
Dallaudière, B; Salut, C; Hummel, V; Pouquet, M; Piver, P; Rouanet, J-P; Maubon, A
Ectopic endometriosis is a common condition which is often underdiagnosed, where MRI can help make a diagnosis simply, non-invasively and without irradiation. However, imagery signs of it are enormously polymorphic with a wide range of possible locations. In this paper, we have tried to illustrate comprehensively all its MRI appearances depending on the different locations where it occurs.
Mazzeo, Carmelo; Gammeri, Emanuele; Foti, Agata; Rossitto, Maurizio; Cucinotta, Eugenio
L’endometriosi è una patologia non ancora del tutto conosciuta che colpisce il 6-10% della popolazione femminile generare e il 35-50% della popolazione femminile affetta da dolore pelvico e infertilità. La sede più frequente di malattia è rappresentata dall’ovaio e ciò sostiene l’ipotesi patogenetica della mestruazione retrograda. Viene descritto un caso di non comune localizzazione vulvare di endometriosi riscontrata in una paziente precedentemente operata per una cisti di Nuck. La donna aveva notato da qualche mese l’insorgenza di una tumefazione nella regione vulvare che le causava dolore e dispareunia che si accentuavano nel periodo mestruale. Il sospetto clinico di endometriosi non aveva avuto conferma negli esami strumentali preoperatori che non avevano evidenziato alterazioni patognomoniche, nè differenze dei reperti in fase pre mestruale e mestruale. Solo l’esame istologico della neoformazione asportata ha confermato la diagnosi. Inoltre gli Autori con la presente nota desiderano sottolineare come nella patogenesi dell’endometriosi vulvare debba essere tenuta in considerazione la presenza della pervietà del dotto peritoneovaginale o dotto di Nuck. Nel caso clinico descritto, infatti, la paziente era stata sottoposta due anni prima ad asportazione di una cisti di Nuck con obliterazione del dotto peritoneovaginale. Tuttavia già in quella fase clinica poteva essersi determinato un impianto endometriosico, che si era poi evidenziato con la formazione del nodulo in sede vulvare asportato chirurgicamente.
Schliep, K.C.; Mumford, S.L.; Peterson, C.M.; Chen, Z.; Johnstone, E.B.; Sharp, H.T.; Stanford, J.B.; Hammoud, A.O.; Sun, L.; Buck Louis, G.M.
STUDY QUESTION What are the pain characteristics among women, with no prior endometriosis diagnosis, undergoing laparoscopy or laparotomy regardless of clinical indication? SUMMARY ANSWER Women with surgically visualized endometriosis reported the highest chronic/cyclic pain and significantly greater dyspareunia, dysmenorrhea, and dyschezia compared with women with other gynecologic pathology (including uterine fibroids, pelvic adhesions, benign ovarian cysts, neoplasms and congenital Müllerian anomalies) or a normal pelvis. WHAT IS KNOWN ALREADY Prior research has shown that various treatments for pain associated with endometriosis can be effective, making identification of specific pain characteristics in relation to endometriosis necessary for informing disease diagnosis and management. STUDY DESIGN, SIZE, DURATION The study population for these analyses includes the ENDO Study (2007–2009) operative cohort: 473 women, ages 18–44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at one of 14 surgical centers located in Salt Lake City, UT or San Francisco, CA. Women with a history of surgically confirmed endometriosis were excluded. PARTICIPANTS/MATERIALS, SETTING AND METHODS Endometriosis was defined as surgically visualized disease; staging was based on revised American Society for Reproductive Medicine (rASRM) criteria. All women completed a computer-assisted personal interview at baseline specifying 17 types of pain (rating severity via 11-point visual analog scale) and identifying any of 35 perineal and 60 full-body front and 60 full-body back sites for which they experienced pain in the last 6 months. MAIN RESULTS AND THE ROLE OF CHANCE There was a high prevalence (≥30%) of chronic and cyclic pelvic pain reported by the entire study cohort regardless of post-operative diagnosis. However, women with a post-operative endometriosis diagnosis, compared with women diagnosed with other gynecologic disorders or a normal pelvis
Pluchino, Nicola; Freschi, Letizia; Wenger, Jean-Marie; Streuli, Isabelle
Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to hormonal imbalance, including estrogen synthesis, metabolism and responsiveness and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed. Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.
Upson, Kristen; Sathyanarayana, Sheela; De Roos, Anneclaire J.; Thompson, Mary Lou; Scholes, Delia; Dills, Russell; Holt, Victoria L.
Background Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. Objective To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. Methods We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. Results The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1–0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ΣDEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. Conclusions Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally
Endometriosis, a gynecologic pathology, is defined by the presence of a tissue similar to uterine endometrium, which is located in places other than physiologically appropriate. These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous, endogenous, or local hormonal stimuli. Endometriosis affects 8%–10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. In several instances, endometriosis persists as a minimal or mild disease, or it can resolve on its own. Other cases of endometriosis show severe symptomatology that ends when menopause occurs. Endometriosis can, however, reactivate in several postmenopausal women when iatrogenic or endogenous hormones are present. Endometriosis is occasionally accompanied by malignant ovarian tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is widely debated, and its variable morphology appears to represent a continuum of individual presentations and progressions. Endometriosis has no pathognomonic signs or symptoms; it is therefore difficult to diagnose. Because of its enigmatic etiopathogenesis, there is currently no satisfactory therapy for all patients with endometriosis. Treatments include medications, surgery, or combined therapies; currently, the only procedures that seem to cure endometriosis are hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the most controversial and enigmatic aspects of this disease. PMID:23956867
Signorile, Pietro G; Baldi, Alfonso
Endometriosis is a gynaecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Though there are several theories, research scientists remain unsure as to the definitive cause(s) of endometriosis. Considering the relevant health problems caused by endometriosis, all new information on the pathogenesis of this disease, may have important clinical implications. Goal of this article is to summarize the latest advances in the pathogenesis of endometriosis, with particular emphasis on the embryological theory, that has been recently re-proposed. The possible clinical implications of these findings will be discussed.
Young, Kate; Fisher, Jane; Kirkman, Maggie
Endometriosis is a complex, chronic condition with known psychological and social implications for women. Little is known about clinicians' perceptions of the psychosocial aspects of endometriosis and associated care. To describe clinicians' perceptions of women's experiences of living with endometriosis and of the provision of psychosocial care for endometriosis. A qualitative approach was taken using semi-structured interviews with eight gynaecologists and four general practitioners who provide care to women with endometriosis in Victoria, conducted by telephone and in person from June to December 2014. Clinicians' perceptions of women's experiences of endometriosis were consistent with those reported by women, particularly when discussing potential infertility. However, less comprehensive descriptions of the effects of endometriosis on women's work and social life and intimate relationships were observed. Some clinicians asserted that endometriosis is caused by poor mental health. General practitioners positioned themselves as best placed to provide psychosocial care to women with endometriosis; gynaecologists suggested various potential providers but rarely themselves. Most clinicians assessed themselves as not being adequately trained to understand and provide care for the psychosocial aspects of endometriosis; half of the gynaecologists did not believe it was necessary for them to do so. The findings of this research demonstrate clinicians' need for further support in the provision of psychosocial care for women with endometriosis, potentially through expanded clinical guidelines and professional development opportunities. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.
Mu, Fan; Rich-Edwards, Janet; Rimm, Eric B; Spiegelman, Donna; Forman, John P; Missmer, Stacey A
An altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years. Multivariable Cox proportional hazards models were applied. In 1989, there were 4244 women with laparoscopically confirmed endometriosis and 91 554 women without. After adjusting for demographic, anthropometric, family history, reproductive, dietary, and lifestyle risk factors prospectively, comparing women with laparoscopically confirmed endometriosis to women without, the relative risks were 1.25 (95% confidence interval, 1.21-1.30) for development of hypercholesterolemia and 1.14 (95% confidence interval, 1.09-1.18) for hypertension. Conversely, the relative risks of developing laparoscopically confirmed endometriosis were 1.22 (95% confidence interval, 1.15-1.31) comparing women with hypercholesterolemia to women without and 1.29 (95% confidence interval, 1.18-1.41) comparing women with hypertension to women without. The strength of associations of laparoscopically confirmed endometriosis with hypercholesterolemia or hypertension was strongest among women aged ≤40 and weakened as age increased (P values for interaction <0.001). We observed that ≈45% of the associations between endometriosis and hypercholesterolemia and hypertension could be accounted for by treatment factors after endometriosis diagnosis, including greater frequency of hysterectomy/oophorectomy and earlier age for this surgery. In this large cohort study, laparoscopically confirmed
Bulletti, Carlo; Montini, Anna; Setti, Paolo Levi; Palagiano, Antonio; Ubaldi, Filippo; Borini, Andrea
To evaluate the role of parturition in the recurrence of endometriosis. Retrospectively analyzed, prospectively obtained data. Unit of Physiopathology of Reproduction, Health Care Unit of Rimini, and University of Bologna Cervesi General Hospital, Cattolica, Italy. Three hundred forty-five patients with stage II-IV endometriosis, dysmenorrhea, and infertility were treated for endometriosis and divided into four groups according to parity and mode of parturition. The patients were laparoscopically treated for endometriosis upon the occurrence and recurrence of the disease. Ultrasound measurements of the uterine internal ostium (IOS) were performed at each study interval. Degree of dysmenorrhea, occurrence and recurrence of endometriosis, and uterine IOS measurements were established and related to parity and mode of parturition. After parturition, dysmenorrhea recurrence was significantly higher in nulliparous women than in women with vaginal parturition. The endometriosis recurrence rate was higher in women who did not have vaginal parturition. The IOS significantly enlarged after vaginal delivery but not after cesarean delivery. There were significant negative correlations between IOS and the recurrence of endometriosis and dysmenorrhea. Odds ratios indicated that as the IOS enlarged, the risk of recurrence decreased. Vaginal parturition plays a protective role in the recurrence of endometriosis. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Yuk, Jin-Sung; Park, Eun-Ju; Seo, Yong-Soo; Kim, Hee Jin; Kwon, Seon-Young; Park, Won I.
Abstract The aim of this cross-sectional study was to compare the prevalence of thyroid diseases between women with and without endometriosis. We established the endometriosis group according to diagnosis codes, surgery codes, and gonadotropin-releasing hormone agonist codes using the Korean Health Insurance Review and Assessment Service—National Inpatients Sample (HIRA-NIS) from 2009 to 2011. Four controls were randomly matched to each endometriosis case. Thyroid disease cases were selected using the thyroid disease diagnosis code (E0X). Among the 1,843,451 women sampled, 5615 had endometriosis; 22,460 controls were matched to the endometriosis cases. After adjustment for age and sampling year, Graves disease was associated with endometriosis (odds ratio [OR]: 2.52; 95% CI: 1.30–4.88; P < 0.01), while hypothyroidism was not (OR: 1.17; 95% CI: 0.90–1.52; P = 0.25). Autoimmune hypothyroidism was also not associated with endometriosis (OR: 1.61; 95% CI: 0.88–2.94; P = 0.12). This study revealed an association between Graves disease and endometriosis. PMID:26962803
Birnbaum, Linda S; Cummings, Audrey M
A potential connection exists between exposure to organochlorine chemicals and the increasing prevalence of endometriosis. Evidence shows that dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of endometrial tissue implanted into rodents in a surgically induced model of endometriosis. The mechanism of the connection between organochlorine chemicals and endometriosis is not clear. Effects on growth factors, cytokines, and hormones (components of the immune and endocrine systems) are potential means of mediating the possible promotion of endometriosis by dioxins. Studies on epidemiology and on structure-activity relationships of organochlorine chemicals and endometriosis have been additional approaches to this problem. In this regard, toxic equivalence (TEQ) appears to be an important determinant of the effects of organochlorine chemicals on endometriosis. In this article, we review the literature related to endometriosis and dioxins and attempt to integrate the various sources of information that bolster the hypothesis connecting dioxins and endometriosis. PMID:11781160
Hoffman, Caroline S.; Small, Chanley M.; Blanck, Heidi Michels; Tolbert, Paige; Rubin, Carol; Marcus, Michele
Purpose We examined the association between endometriosis and exposure to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) among women inadvertently exposed to PBBs in 1973. Methods Serum PBB and PCB were measured in the late 1970s. Women self-reported endometriosis at interview in 1997. We constructed Cox models to estimate the relative incidence of endometriosis in relation to PBB and PCB levels. Results Seventy-nine of 943 women (9%) reported endometriosis. Compared to women with low PBB exposure (≤ 1 parts per billion [ppb]), women with moderate PBB (1–4 ppb) (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.39–1.31) and high PBB (≥ 4 ppb) (HR = 0.90; 95% CI, 0.51–1.59) exposure did not have increased incidence of endometriosis. Increased incidence of endometriosis was suggested among women exposed to moderate PCB (5–8 ppb) (HR = 1.67; 95% CI, 0.91–3.10) and high PCB (≥ 8 ppb) (HR = 1.68; 95% CI, 0.95–2.98) levels compared to low PCB exposure (≤ 5 ppb). Conclusions Our study does not support an association between PBB exposure and endometriosis. Findings for serum PCB level are consistent with an emerging body of literature suggesting an association between PCB exposure and endometriosis. PMID:17448678
Ahn, Soo Hyun; Monsanto, Stephany P; Miller, Caragh; Singh, Sukhbir S; Thomas, Richard; Tayade, Chandrakant
Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis.
Grzechocinska, Barbara; Wielgos, Miroslaw
Although there is confirmed an association between endometriosis and infertility, precise standards of managements have not yet been established. Ablation of endometriotic lesions plus adhesiolysis in minimal to mild endometriosis is more effective than diagnostic laparoscopy alone in improving fertility. Suppression of ovarian function and hormonal treatment alone are not effective in improving fertility. In women with stage I/II endometriosis associated infertility, expectant management or IUI after laparoscopy can be considered for younger patients. Women 35 years of age or older should be treated with IUI or IVF-ET. IVF pregnancy rate are lower in women with endometriosis than in those with tubal infertility. For women with stage III/IV endometriosis who fail to conceive following conservative surgery IVF-ET is should be offered.
Ahn, Soo Hyun; Singh, Vinay; Tayade, Chandrakant
Endometriosis is a debilitating gynecologic disease affecting millions of women across the world, with symptoms including dysmenorrhea, chronic pelvic pain, and infertility. Theorized to stem from the phenomenon of retrograde menstruation, the diagnosis of endometriosis is typically delayed by 8-10 years owing to misinterpretation of symptoms as common menstrual cramps in adolescent girls and young women. With increased incidence of endometriosis in young girls correlated with earlier menarche, the development of diagnostic biomarkers is imperative for diagnosing and treating women afflicted with endometriosis as early as we can. In the past few years, multiple reviews highlighted the list of potential diagnostic candidates in peritoneal fluid, blood, urine, and endometrial biopsies from endometriosis patients in different stages of disease and menstrual cycle. In this review, we explore the opportunities and challenges facing the field of diagnostic biomarkers for endometriosis. We highlight the importance of eutopic endometrium as a source of potential diagnostic biomarkers by looking at the expression levels of noncoding RNA in tissue as well as in blood. Finally, we discuss some of the challenges that hinder our efforts in validating candidate diagnostic biomarkers for endometriosis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Ropacka-Lesiak, Mariola; Świder-Musielak, Joanna; Wójcicka, Małgorzata; Łyczywek, Anna; Skrzypek, Maciej; Waliszewski, Wojciech
The article presents a case of deep intestinal endometriosis in a 27-year-old woman who complained of dysmenorrhea and infertility. The diagnostic process included ultrasonography as well as colonoscopy, barium enema and CT imaging. Because of the presence of two distant changes which involved nearly the full thickness of the rectal wall and the major part of its circumference, the decision to perform an anterior rectal resection with a simultaneous retroperitoneal colorectostomy was made. The Knight technique was implemented. The surgery involved the anterior rectal resection, the transverse rectal stump closure by use of a stapling device (TA50), and the creation of colorectal circular anastomosis with the CEEA 31 stapler.
Barlas, Dündar; Bozkurt, Süleyman; Kaya, Mehmet Altan; Celik, Faik
Endometriosis is defined as the presence of ectopic functional endometrial tissue outside the uterine cavity. The most common locations are within the pelvis. Unusual sites ofendometriosis outside the pelvis have been reported, including the bladder, intestine, appendix, surgical scars, hernia sac, lung, kidney, and extremities. The diagnosis of scar endometriosis is usually not difficult and is based on history and physical examination. We report here two cases who developed endometriosis on the abdominal wall in the rectus abdominis muscle and were treated with local excisions.
Arumugam, K; Welluppilai, S
The social class distribution in 147 patients confirmed to have endometriosis at laparoscopy was done to see if the disease was associated with affluence. Two hundred and eighty-one patients confirmed not to have endometriosis was used as controls. The patients were derived from a background population for which the social class characteristics was known. Endometriosis was significantly (p < 0.001) associated with social class 1 and 2. However there was no association between social class distribution and the severity of the disease developed.
Becker, Christian M.; Laufer, Marc R.; Stratton, Pamela; Hummelshoj, Lone; Missmer, Stacey A.; Zondervan, Krina T.; Adamson, G. David; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.
Objective To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Setting Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. Patient(s) None. Intervention(s) A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. Main Outcome Measure(s) The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. Result(s) SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. Conclusion(s) This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition. PMID:25150390
Langan, K L; Farrell, M E; Keyser, E A; Salyer, B A; Burney, R O
Endometriosis is a debilitating gynecologic disorder causing pelvic pain and infertility and characterized by the implantation of endometrial tissue to extrauterine locations. Though aspects of the condition remain enigmatic, the molecular pathophysiology of endometriosis appears to be clarifying. Estrogen dependence of the disease is a sentinel endocrine feature and reduction of estrogen bioavailability is the therapeutic principle upon which traditional treatment and prevention approaches have been based. Endometriosis is a chronic inflammatory condition associated with lesional neoangiogenesis and attenuated progesterone action at the level of the endometrium. The elucidation of the molecular pathways mediating these observations has revealed new targets for directed medical and surgical treatment. This paper will review current approaches to the management of endometriosis in the context of the molecular pathophysiology.
Chatzikokkinou, Paraskevi; Thorfinn, Johan; Angelidis, Ioannis K; Papa, Giovanni; Trevisan, Giusto
Cutaneous endometriosis of the umbilicus is an unusual condition with unclear pathogenetic mechanisms that might be mistaken for a malignant condition. A 46-year-old woman presented with a cutaneous black mass in the umbilicus. The lesion was removed surgically and histological analyses revealed that it consisted of endometrial tissue. There was no recurrence at 18-month follow-up. Endometriosis of the umbilicus is a rare condition and the pathogenesis is not completely elucidated. According to one theory, intraperitoneal endometrial tissue is translocated during endoscopic surgery or other surgical procedures that involve the umbilicus. However, in this case there was no history of abdominal wall surgery. We conclude that endometriosis is important to consider in cases of unclear skin lesions of the umbilicus, even in cases with no previous abdominal surgery. Moreover, umbilical endometriosis of the skin can have different appearances that resemble malignant tumors, and radical surgery with histology is therefore indicated.
... in the intestine or lower abdomen Painful bowel movements or painful urination during menstrual periods Heavy menstrual periods Premenstrual spotting or bleeding between periods In addition, women who are diagnosed with endometriosis may have painful ...
... Information Clinical Trials Resources and Publications How do health care providers diagnose endometriosis? Skip sharing on social media ... under a microscope, to confirm the diagnosis. 1 Health care providers may also use imaging methods to produce ...
Budinetz, T; Sanfilippo, J S
Endometriosis continues to plague women of reproductive age. It is a chronic disease leading to a decreased quality of life, infertility, and increased societal costs. The gold standard for diagnosis remains visualization and or biopsy of lesions at the time of intraoperative diagnosis, i.e. laparoscopy or laparotomy. The severity of pain does not correlate with the stage of endometriosis, which complicates the treatment process. Hormonal therapies have long been used as a treatment for endometriosis. Therapy is targeted at symptom relief as a cure is lacking. While some regimes use hormonal therapy exclusively, others combine such with surgical excision of lesions. Although hormonal modalities are successful in alleviating or suppressing symptoms, they fail to treat the infertility associated with endometriosis. Therefore, those, desiring to achieve pregnancy should be excluded from hormonal treatment in the short term. Future studies are needed to understand the pathophysiology and allow design of specific, targeted treatment.
Ussia, Anastasia; Betsas, George; Corona, Roberta; De Cicco, Carlo; Koninckx, Philippe R
Massive hemorrhagic ascites (4470 mL, range 1-10 L) in women with endometriosis is a rare condition occurring predominantly in black women. Of the 43 case reports published, 42 are compatible with the hypothesis that the hemorrhagic ascites is predominantly a consequence of excessive ovarian transudation similar to a Meigs syndrome. Indeed, bilateral ovariectomy cures the condition without recurrences, whereas after unilateral ovariectomy or cystectomy recurrence rate is more than 50%; during ovarian suppression by luteinizing hormone-releasing hormone agonist ascites disappears, but reappears after treatment. Superficial pelvic endometriosis also contributes to the ascites because after superficial endometriosis destruction the recurrence rate is only 4 in 14. Based on these data, it is suggested, to scrutinize the ovaries for tumors given the analogy with Meigs syndrome. In women desiring fertility, conservative treatment with destruction of endometriosis only can be attempted given the cure rate of some 20%. It is unknown what the effect of ovulation induction would be.
Dunselman, G A J; Vermeulen, N; Becker, C; Calhaz-Jorge, C; D'Hooghe, T; De Bie, B; Heikinheimo, O; Horne, A W; Kiesel, L; Nap, A; Prentice, A; Saridogan, E; Soriano, D; Nelen, W
What is the optimal management of women with endometriosis based on the best available evidence in the literature? Using the structured methodology of the Manual for ESHRE Guideline Development, 83 recommendations were formulated that answered the 22 key questions on optimal management of women with endometriosis. The European Society of Human Reproduction and Embryology (ESHRE) guideline for the diagnosis and treatment of endometriosis (2005) has been a reference point for best clinical care in endometriosis for years, but this guideline was in need of updating. This guideline was produced by a group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to January 2012 and consensus within the guideline group on all recommendations. To ensure input from women with endometriosis, a patient representative was part of the guideline development group. In addition, patient and additional clinical input was collected during the scoping and review phase of the guideline. NA. The guideline provides 83 recommendations on diagnosis of endometriosis and on the treatment of endometriosis-associated pain and infertility, on the management of women in whom the disease is found incidentally (without pain or infertility), on prevention of recurrence of disease and/or painful symptoms, on treatment of menopausal symptoms in patients with a history of endometriosis and on the possible association of endometriosis and malignancy. We identified several areas in care of women with endometriosis for which robust evidence is lacking. These areas were addressed by formulating good practice points (GPP), based on the expert opinion of the guideline group members. Since 32 out of the 83 recommendations for the management of women with endometriosis could not be based on high level evidence and therefore were GPP, the guideline group formulated
Xie, Jing; Kvaskoff, Marina; Li, Yunhui; Zhang, Mingfeng; Qureshi, Abrar A.; Missmer, Stacey A.; Han, Jiali
STUDY QUESTION Is there a relationship between severe teenage acne and endometriosis? SUMMARY ANSWER Endometriosis is positively associated with severe teenage acne. WHAT IS KNOWN ALREADY No studies have specifically explored a possible association between severe acne in adolescence and risk of endometriosis. STUDY DESIGN, SIZE, DURATION This prospective cohort study used data collected from 88 623 female nurses from September 1989 to June 2009 as part of the Nurses' Health Study II (NHS II) cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS Regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for endometriosis among women with and without severe teenage acne. Multivariate models were adjusted for established risk factors of endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE A total of 4 382 laparoscopically confirmed endometriosis cases were documented during 1 132 272 woman-years of follow-up. Compared with women without a history of severe teenage acne, women who had severe teenage acne had a 20% increased risk of endometriosis (HR = 1.20, 95% CI: 1.08–1.32). The association was not affected by adjusting for use of tetracycline or isotretinoin. LIMITATIONS AND REASONS FOR CAUTION The HR is likely to be underestimated since we only included endometriosis cases confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is primarily Caucasian, which may limit generalization to more ethnically diverse populations. WIDER IMPLICATIONS OF THE STUDY The results of this study suggest that severe teenage acne is associated with an increased risk of endometriosis. As a visible and non-invasive clinical indicator, severe teenage acne may be useful for early detection of endometriosis. We bring this counter-intuitive association to the attention of clinicians for the benefit of the patient and an early diagnosis of endometriosis. STUDY FUNDING/COMPETING INTEREST This study was funded by research grant CA176726 from the
Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.
BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between
Xie, Jing; Kvaskoff, Marina; Li, Yunhui; Zhang, Mingfeng; Qureshi, Abrar A; Missmer, Stacey A; Han, Jiali
Is there a relationship between severe teenage acne and endometriosis? Endometriosis is positively associated with severe teenage acne. No studies have specifically explored a possible association between severe acne in adolescence and risk of endometriosis. This prospective cohort study used data collected from 88 623 female nurses from September 1989 to June 2009 as part of the Nurses' Health Study II (NHS II) cohort. Regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for endometriosis among women with and without severe teenage acne. Multivariate models were adjusted for established risk factors of endometriosis. A total of 4 382 laparoscopically confirmed endometriosis cases were documented during 1 132 272 woman-years of follow-up. Compared with women without a history of severe teenage acne, women who had severe teenage acne had a 20% increased risk of endometriosis (HR = 1.20, 95% CI: 1.08-1.32). The association was not affected by adjusting for use of tetracycline or isotretinoin. The HR is likely to be underestimated since we only included endometriosis cases confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is primarily Caucasian, which may limit generalization to more ethnically diverse populations. The results of this study suggest that severe teenage acne is associated with an increased risk of endometriosis. As a visible and non-invasive clinical indicator, severe teenage acne may be useful for early detection of endometriosis. We bring this counter-intuitive association to the attention of clinicians for the benefit of the patient and an early diagnosis of endometriosis. This study was funded by research grant CA176726 from the National Institute of Health. M.K. is supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078). The funding agencies had no role in the design of the study, in the analysis and
D’Hooghe, Thomas M.; Fazleabas, Asgerally; Giudice, Linda C.; Montgomery, Grant W.; Petraglia, Felice; Taylor, Robert N.
Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:23427182
Upson, Kristen; Sathyanarayana, Sheela; Scholes, Delia; Holt, Victoria L.
Objective To study early-life factors in relation to endometriosis risk in adulthood. Design Population-based case-control study. Setting Women’s Risk of Endometriosis (WREN) study was conducted among female enrollees ages 18-49 years of a large, integrated healthcare system in western Washington State. Patients Cases (n=310) were women diagnosed for the first time with endometriosis between years 1996-2001 and controls (n=727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population. Interventions None. Main outcome measures Adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother’s age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant’s mother or other family member. Results We observed that women who were regularly fed soy formula as infants had over twice the risk of endometriosis compared to unexposed women (aOR 2.4, 95% CI: 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI: 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI: 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null. Conclusion Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood. PMID:26211883
Fanton, J.W.; Golden, J.G. )
Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.
Parente Barbosa, C; Bentes De Souza, A M; Bianco, B; Christofolini, D M
Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.
Hirota, Yasushi; Tranguch, Susanne; Daikoku, Takiko; Hasegawa, Akiko; Osuga, Yutaka; Taketani, Yuji; Dey, Sudhansu K
Endometriosis is a common gynecological disease that affects approximately 10% of women of childbearing age. It is characterized by endometrial growth outside the uterus and often results in inflamed lesions, pain, and reduced fertility. Although heightened estrogenic activity and/or reduced progesterone responsiveness are considered to be involved in the etiology of endometriosis, neither the extent of their participation nor the underlying mechanisms are clearly understood. Heterogeneous uterine cell types differentially respond to estrogen and progesterone (P(4)). P(4), primarily acting via its nuclear receptor (PR), activates gene transcription and impacts many reproductive processes. Deletion of Fkbp52, an immunophilin cochaperone for PR, results in uterine-specific P(4) resistance in mice, creating an opportunity to study the unique aspects of P(4) signaling in endometriosis. Here we explored the roles of FKBP52 in this disease using Fkbp52(-/-) mice. We found that the loss of FKBP52 encourages the growth of endometriotic lesions with increased inflammation, cell proliferation, and angiogenesis. We also found remarkable down-regulation of FKBP52 in cases of human endometriosis. Our results provide the first evidence corroborated by genetic studies in mice for a potential role of an immunophilin cochaperone in the etiology of human endometriosis. This investigation is highly relevant for clinical application, particularly because P(4) resistance is favorably indicated in endometriosis and other gynecological diseases.
Hirota, Yasushi; Tranguch, Susanne; Daikoku, Takiko; Hasegawa, Akiko; Osuga, Yutaka; Taketani, Yuji; Dey, Sudhansu K.
Endometriosis is a common gynecological disease that affects approximately 10% of women of childbearing age. It is characterized by endometrial growth outside the uterus and often results in inflamed lesions, pain, and reduced fertility. Although heightened estrogenic activity and/or reduced progesterone responsiveness are considered to be involved in the etiology of endometriosis, neither the extent of their participation nor the underlying mechanisms are clearly understood. Heterogeneous uterine cell types differentially respond to estrogen and progesterone (P4). P4, primarily acting via its nuclear receptor (PR), activates gene transcription and impacts many reproductive processes. Deletion of Fkbp52, an immunophilin cochaperone for PR, results in uterine-specific P4 resistance in mice, creating an opportunity to study the unique aspects of P4 signaling in endometriosis. Here we explored the roles of FKBP52 in this disease using Fkbp52−/− mice. We found that the loss of FKBP52 encourages the growth of endometriotic lesions with increased inflammation, cell proliferation, and angiogenesis. We also found remarkable down-regulation of FKBP52 in cases of human endometriosis. Our results provide the first evidence corroborated by genetic studies in mice for a potential role of an immunophilin cochaperone in the etiology of human endometriosis. This investigation is highly relevant for clinical application, particularly because P4 resistance is favorably indicated in endometriosis and other gynecological diseases. PMID:18988805
Fadhlaoui, Anis; Gillon, Tessa; Lebbi, Issam; Bouquet de Jolinière, Jean; Feki, Anis
The aim of this mini review is to determine the relationship between endometriosis and urinary tract symptoms and to investigate the consequences of surgical treatment of mild to severe endometriosis, especially deep lesions, on the vesico-sphincteral function (lower urinary tract function). We performed a literature review by searching the MEDLINE database for articles published between 2000 and 2014, limiting the searches to the words: urinary tract, vesico-sphincteral, dysfunction, endometriosis, symptoms, and surgery. The incidence of vesico-sphincteral symptoms in endometriosis varies from 3.4 up to 15.4%. The frequency of such symptoms seems to be under estimated because of a lack of specific questionnaire including urinary symptoms. Urodynamic evaluation could help to detect unsuspected abnormalities. It seems that endometriosis surgery (particularly deep infiltrating lesions) is a purveyor of de novo urinary dysfunction, with an incidence varying from 6.8 up to 17.5%. Nerve sparing processes such as neuro-navigators or neuro-stimulators seem to be promising techniques to avoid postoperative urinary tract dysfunction. A precise anamnesis and the use of specific validated questionnaires (IPSS and BFLUTS) improve the screening of vesico-sphincteral symptoms in case of endometriosis. No recommendation can be found in the literature about the place of urodynamic evaluation. Most publications lack of proof and therefore do not allow making recommendations about optimal treatment of endometriotic lesions to avoid urinary tract disorders.
Dun, Erica C; Wong, Serena; Lakhi, Nisha A; Nehzat, Ceana H
To report the medical and surgical management of a rare case of recurrent moss-like endometriosis and associated hemorrhagic ascites. Video description of the case, demonstration of the surgical technique, discussion of the histology, and review of endometriosis-associated ascites. Tertiary referral center. A 26-year-old nulliparous woman of Nigerian heritage with recurrent hemorrhagic ascites due to endometriosis. Three years previously she underwent an exploratory laparotomy for similar symptoms, and 7 L of hemorrhagic ascites were evacuated from her abdomen. Friable lesions covering the peritoneum of the uterus, bladder, and pouch of Douglas were biopsied and consistent with endometriosis. After her initial surgery, the patient was hormonally suppressed with goserelin for 3 months and oral medroxyprogesterone for 1 year. She then stopped the medications to attempt pregnancy but was unsuccessful. She used clomiphene for 3 months, and the ascites reaccumulated. The patient was started on depot leuprolide and oral norethindrone, but the ascites persisted. The patient underwent small-diameter laparoscopy using a multipuncture technique, evacuation of 7.8 L of hemorrhagic ascites, enterolysis, appendectomy, chromopertubation, and treatment of the endometriosis. Diffuse olive-green "mossy" endometriosis lesions blanketed the pelvic and abdominal peritoneum. The endometriosis was surgically resected with a combination of peritoneal stripping, excision with carbon dioxide laser, and ablation with neutral argon plasma. Examination of the ascites showed scattered hemosiderin-laden macrophages in a background of red blood cells. Histology of the olive-green mossy lesions revealed dense sheets of hemosiderin-laden macrophages and rare foci of endometriosis. Surgical reports in deidentified patients are exempted from Institutional Review Board approval. The patient gave consent to use photography and images for the video article. No postoperative hormone suppression was
Ventskivs'ka, I B
The article contains results of case follow-up of 84 female patients with genital endometriosis. In the above patients, different combination of enzyme therapy and surgical treatment were instituted depending on the site of endometriosis and gravity of the pathological process. On the basis of the secured findings criteria are recommended for the policy of treating patients with genital endometriosis.
Dave, Atman A; Margolin, Daniel J
Umbilical endometriosis is a fairly rare clinical entity with unclear pathogenesis. We report the case of a 27-year-old woman who presented with a painful umbilical mass and discharge. Imaging performed was inconclusive, and surgical excision of the site with margins revealed endometriosis on microscopic examination. The incidence of umbilical endometriosis, its pathogenesis, clinical manifestations, workup, and management are discussed. PMID:28097077
D'Hooghe, T M; Bambra, C S; Raeymaekers, B M; Koninckx, P R
To determine the incidence of spontaneous endometriosis over a 32-month period in baboons with initially normal pelves. In this observational longitudinal study, which was performed at the Institute of Primate Research, Nairobi (Kenya), 24 baboons with laparoscopically confirmed normal pelves underwent 67 serial laparoscopies (mean 2.8 +/- 1.9, median 3, range 1-6) after 1-3 months (n = 8), 4-6 months (n = 11), 7-9 months (n = 9), 10-12 months (n = 17), 13-15 months (n = 6), 16-18 months (n = 4), 19-21 months (n = 3), 22-24 months (n = 4), 25-27 months (n = 1), and 30-32 months (n = 4). During each laparoscopy, the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map, and the endometriosis score and stage were tabulated according to the revised classification of the American Fertility Society. Taking into account the variable length of follow-up, we used life-table analysis to calculate the cumulative incidence of endometriosis. The cumulative incidence of minimal endometriosis (proven by histology) was 64% up to 32 months of follow-up. The eight baboons that developed proven endometriosis were followed over longer periods of time and had undergone more laparoscopies than the animals that did not develop the condition. There is a high incidence of minimal endometriosis in baboons, which increases with the time of follow-up and the number of repeat laparoscopies.
Vitonis, Allison F.; Vincent, Katy; Rahmioglu, Nilufer; Fassbender, Amelie; Buck Louis, Germaine M.; Hummelshoj, Lone; Giudice, Linda C.; Stratton, Pamela; Adamson, G. David; Becker, Christian M.; Zondervan, Krina T.; Missmer, Stacey A.
Objective To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. Patients None. Intervention(s) Development of a self-administered endometriosis patient questionnaire (EPQ), based on  systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases);  literature evidence; and  several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. Result(s) The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. Conclusion(s) The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and–after a first review after 1 year–triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect. PMID:25256930
Nezhat, Camran; Li, Anjie; Abed, Sozdar; Balassiano, Erika; Soliemannjad, Rose; Nezhat, Ceana H.; Nezhat, Farr
Background and Objectives: The relationship between leiomyoma and endometriosis is poorly understood. Both contribute to considerable pain and may cause subfertility or infertility in women. We conducted this retrospective study to assess the rate of coexistence of endometriosis in women with symptomatic leiomyoma. The primary outcome measured was the coexistence of histology-proven endometriosis in women with symptomatic leiomyoma. Methods: This is a retrospective review of a data-based collection of medical records of 244 patients treated at a tertiary medical center, who were evaluated for symptomatic leiomyoma from March 2011 through December 2015. Of those, 208 patients underwent laparoscopic or laparoscopic-assisted myomectomy or hysterectomy. All patients provided consent for possible concomitant diagnosis and treatment of endometriosis. The remaining 36 patients underwent medical therapy and were excluded from the study. All patients who had myomectomy or supracervical hysterectomy underwent minilaparotomy for extracorporeal morcellation and specimen removal beginning in April 2012. Results: Of the 208 patients with the presenting chief concern of symptomatic leiomyoma and who underwent surgical therapy, 181 had concomitant diagnoses of leiomyoma and endometriosis, whereas 27 had leiomyoma. Of the 27 patients, 9 also had adenomyosis. Patients with only fibroid tumors were, on average, 4.0 years older than those with endometriosis and fibroids (mean age, 44 vs 40 ± SD). Patients with both pathologies were also more likely to present with pelvic pain and nulliparity than those with fibroid tumors alone. Conclusions: In our patient population, 87.1% of patients with a chief concern of symptomatic fibroids also had a diagnosis of histology-proven endometriosis, which affirms the need for concomitant diagnosis and intraoperative treatment of both conditions. Overlooking the coexistence of endometriosis in women with symptomatic leiomyoma may lead to suboptimal
Endometriosis is a growth of endometrial tissue outside the uterine cavity which is responsive to hormonal stimulation. Extrapelvic endometriosis is less common of which skin is the most common site. The patient presents with mass, pain and cyclic symptoms. Subcutaneous endometriosis is very rare and has been reported only thrice in the literature. We report a case where the patient with lower abdominal pain and dyspareunia. Dyspareunia due to subcutaneous endometriosis has not been reported before when there is no evidence of intrapelvic endometriosis on laparoscopy.
Méndez Fernández, R; Barrera Ortega, J
Endometriosis is common in women of reproductive age; it can cause pelvic pain and infertility. It is important to diagnose endometriosis and to thoroughly evaluate its extension, especially when surgical treatment is being considered. Magnetic resonance imaging (MRI) with careful examination technique and interpretation enables more accurate and complete diagnosis and staging than ultrasonography, especially in cases of deep pelvic endometriosis. Furthermore, MRI can identify implants in sites that can be difficult to access in endoscopic or laparoscopic explorations. In this article, we describe the appropriate MRI protocol for the study of pelvic endometriosis and the MRI signs of pelvic organ involvement. It is necessary to know the subtle findings and to look for them so we can ensure that they are not overlooked. We describe clinical grading systems for endometriosis and review the diagnostic efficacy of MRI in comparison with other imaging techniques and surgery. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
Allerstorfer, Christina; Enzelsberger, Simon H.; Shebl, Omar Josef; Mayer, Richard Bernhard
Background. It has been suggested that, during pregnancy, endometriosis can cause a variety of disease-related complications. Objectives. The purpose of the study was to find out if women with histologically confirmed endometriosis do have a higher risk of adverse pregnancy outcome and if they suffer from a higher rate of complications during labor. Study Design. 51 women who underwent surgery because of deeply infiltrating endometriosis in the General Hospital Linz and the Women's General Hospital Linz and who gave birth in the Women's General Hospital Linz after the surgery were included in our survey. Results. 31 women (60.8%) had a spontaneous delivery and in 20 women (39.2%) a caesarean section was performed. There were no cases of third- and fourth-degree perineal lacerations. Collectively there were 4 cases (7.8%) of preterm delivery and one case (2.0%) of premature rupture of membranes. In two women (6.5%) a retained placenta was diagnosed. Conclusions. Our study is the first description on delivery modes after surgery for deeply infiltrating endometriosis. We did not find an elevated risk for perineal or vaginal laceration in women with a history of surgery for deeply infiltrating endometriosis, even when a resection of the rectum or of the posterior vaginal wall had been performed. PMID:27517050
Monsivais, Diana; Bray, Jeffrey D; Su, Emily; Pavone, Mary Ellen; Dyson, Matthew T; Navarro, Antonia; Kakinuma, Toshiyuki; Bulun, Serdar E
To define altered gene expression networks in endometriosis. Experiments using endometriotic tissues and primary cells. Division of Reproductive Biology Research, Northwestern University. Premenopausal women. Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients). Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis. Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis. The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions. Published by Elsevier Inc.
Monsivais, Diana; Bray, Jeffrey D.; Su, Emily; Pavone, Mary Ellen; Dyson, Matthew T.; Navarro, Antonia; Kakinuma, Toshiyuki; Bulun, Serdar E.
Objective To define altered gene expression networks in endometriosis. Design Experiments using endometriotic tissues and primary cells. Setting Division of Reproductive Biology Research, Northwestern University Patients Premenopausal women. Interventions Matched samples of eutopic endometrium and ovarian endometriosis (n=8 patients) were analyzed by microarray and verified in a separate set of tissues (n=6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n=12 patients). Main Outcomes Measures Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis. Results Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produce cortisol, the biologically active glucocorticoid, were strikingly higher, whereas mRNA levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor (GR) mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor (TNF) robustly induced mRNA and protein levels of HSD11B1 and GR, but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that TNF stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis. Conclusion The pro-inflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions. PMID:22521153
Ahn, Soo Hyun; Monsanto, Stephany P.; Miller, Caragh; Singh, Sukhbir S.; Thomas, Richard; Tayade, Chandrakant
Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis. PMID:26247027
Kavoussi, Shahryar K
Superovulation (SO)/Intrauterine insemination (IUI) has been used as a treatment approach for endometriosis-associated infertility. The existing medical literature regarding SO in endometriosis patients is composed of heterogeneous studies that differ in terms of study design, SO protocols, the addition of IUI, and comparison groups. There is a need for more well-designed studies to further investigate the efficacy of SO in women with endometriosis-associated infertility. Although in vitro fertilization (IVF) is most effective and is significantly superior to other treatments in endometriosis patients, most of the existing studies suggest some benefit of SO/IUI in infertility patients with early-stage disease. Therefore, SO/IUI is a reasonable early fertility treatment option for women with endometriosis who desire a short trial of potentially more cost-effective treatment options prior to pursuing an IVF cycle and those for whom IVF is not a feasible or desirable option. It appears that gonadotropins are most effective for SO in this patient population even though more head-to-head comparisons are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Medina, Melissa G.; Lebovic, Dan I.
The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently, investigators have revealed specific nerve fibers present in endometriotic tissue, with existing parallels between density and pain severity. The aim of this review is to compile a comprehensive review of existing literature on endometriosis-related nerve fiber detection, and the effects of medical therapy on these neural fibers. We performed a systematic literature-based review using Medline and PubMed of nerve fibers detected in eutopic endometrium, endometriotic lesions, and the peritoneum. Various arrangements of significant medical terms and phrases consisting of endometriosis, pelvic pain, nerve fiber detection/density in endometriosis, and diagnoses methodology, including treatment and detection were applied in the search. Subsequent references used were cross-matched with existing sources to compile all additional similar reports. Similar nerve fibers were detected within lesions, endometrium, and myometrium, though at varying degrees of density. Hormonal therapy is widely used to treat endometriosis and was shown to be related to a reduction in fiber density. A direct result of specific nerve fiber detection within eutopic endometrial layers points to the use of a minimally invasive endometrial biopsy technique in reducing delay in diagnosis and subsequent possible preservation of fertility. PMID:19657753
Vercellini, Paolo; Frontino, Giada; Pietropaolo, Giuliana; Gattei, Umberto; Daguati, Raffaella; Crosignani, Pier Giorgio
"Deep endometriosis" includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. The available evidence suggests the same pathogenesis for deep infiltrating vesical and rectovaginal endometriosis (i.e., intraperitoneal seeding of regurgitated endometrial cells, which collect and implant in the most dependent portions of the peritoneal cavity and the anterior and posterior cul-de-sac, and trigger an inflammatory process leading to adhesion of contiguous organs with creation of false peritoneal bottoms). According to anatomic, surgical, and pathologic findings, deep endometriotic lesions seem to originate intraperitoneally rather than extraperitoneally. Also the lateral asymmetry in the occurrence of ureteral endometriosis is compatible with the menstrual reflux theory and with the anatomic differences of the left and right hemipelvis. Peritoneal, ovarian, and deep endometriosis may be diverse manifestations of a disease with a single origin (i.e., regurgitated endometrium). Based on different pathogenetic hypotheses, several schemes have been proposed to classify deep endometriosis, but further data are needed to demonstrate their validity and reliability. Drugs induce temporary quiescence of active deep lesions and may be useful in selected circumstances. Progestins should be considered as first-line medical treatment for temporary pain relief. However, in most cases of severely infiltrating disease, surgery is the final solution. Great importance must be given to complete and balanced counseling, as awareness of the real possibilities of different treatments will enhance the patient's collaboration.
Muñoz-Hernando, Leticia; Muñoz-Gonzalez, Jose L; Marqueta-Marques, Laura; Alvarez-Conejo, Carmen; Tejerizo-García, Álvaro; Lopez-Gonzalez, Gregorio; Villegas-Muñoz, Emilia; Martin-Jimenez, Angel; Jiménez-López, Jesús S
Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included “endometriosis” matched with “medical treatment”, “new treatment”, “GnRH antagonists”, “Aromatase inhibitors”, “selective progesterone receptor modulators”, “anti-TNF α”, and “anti-angiogenic factors”. Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs. PMID:26089705
Esmaeilzadeh, Seddigheh; Mirabi, Parvaneh; Basirat, Zahra; Zeinalzadeh, Mahtab; Khafri, Soraya
Background: The association of endometriosis with hyperprolactinemia is controversial. Objective: The present study aimed to determine the frequency of endometriosis and association of prolactin with endometriosis in infertile women. Materials and Methods: 256 infertile women who underwent diagnostic laparoscopy for the evaluation of infertility, referred to Fatemezahra Infertility and Reproductive Health Research Center were included in a cross-sectional study. The presence of endometriosis was evaluated. To investigate the association of endometriosis with hyperprolactinemia, the patients whose infertility was not caused by endometriosis were included as control group. Serum prolactin (PRL) level was measured in both groups. The comparison of basal serum PRL levels between the two groups was performed, using independent t-test. One way ANOVA was used to determine PRL association with endometriosis stages. Results: The frequency of endometriosis was found to be 29%. PRL levels were significantly higher in endometriosis group compared to control group (23.02±1.25 vs. 17.22±1.22 respectively, p=0.004). Statistically significant associations were found between staging of endometriosis and prolactin levels (p=0.01). Conclusion: Hyperprolactinemia may be associated with endometriosis and its progression. PMID:26000006
... the disease and leave your organs in place. Hysterectomy is surgery to remove your uterus, fallopian tubes, ... the uterus, fallopian tubes, and both ovaries (a hysterectomy) gives you the best chance for a cure. ...
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Minocha, A; Davis, M S; Wright, R A
A 35-year-old female presented with recurrent right lower quadrant pain, nausea, and vomiting. She was afebrile with diffuse abdominal tenderness. Plain x-ray of abdomen revealed small bowel obstruction. A barium x-ray of the small bowel showed stricture of the terminal ileum. A CT scan of the abdomen showed a 6-cm mass in right lower quadrant. She was empirically managed as having Crohn's disease. She underwent laparotomy after failure of medical management with high-dose steroids. There was ulceration and narrowing of terminal ileum. Frozen sections revealed endometriosis. Ileocecectomy was performed. Histopathology of resected specimen confirmed the diagnosis of endometriosis, and there was no evidence of chronic inflammatory bowel disease or neoplasia. Ileal endometriosis should be considered in the differential diagnosis of Crohn's disease in menstruating females presenting with perimenstrual symptoms.
Leone Roberti Maggiore, Umberto; Scala, Carolina; Remorgida, Valentino; Venturini, Pier Luigi; Del Deo, Fabio; Torella, Marco; Colacurci, Nicola; Salvatore, Stefano; Ferrari, Stefano; Papaleo, Enrico; Candiani, Massimo; Ferrero, Simone
Over the past 30 years, gonadotropin-releasing hormone agonists (GnRH-a) have been used to induce a hypoestrogenic status in women with endometriosis with the aim to cause an improvement in pain symptoms similar to that observed after menopause. Triptorelin is one of the most commonly used GnRH-a. This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of triptorelin and gives the readers a complete overview of the studies on the clinical efficacy, tolerability and safety of this agent in patients with endometriosis. The studies reviewed in the current manuscript demonstrate the efficacy of triptorelin in improving pain symptoms caused by endometriosis. Further, this effect is confirmed by the reduction in the volume of the endometriotic nodules during treatment. Future research should evaluate whether the pre-operative administration of triptorelin prior to surgical excision of endometriomas may be useful in preserving the ovarian reserve.
Dargenio, R; Corbucci, M G; Lamanna, M A; Garcea, N
Clinical and experimental evidence showed an increased concentration of prostaglandins in peritoneal fluid in cases of endometriosis. The aim of this study was to verify whether an antiprostaglandin drug can restore fertility in cases of endometriosis. For this reason endometriosis was induced in 4 groups of 10 rats. Group A was treated with indomethacin both in the pre-ovulatory and in the post-ovulatory phase. Group B was treated in the pre-ovulatory phase. Group C was treated in the post-ovulatory phase. Group D was not treated. Ten other rats (group E) underwent a sham operation and were used as a control. Twelve days after mating, gestational sacs and corpora lutea were counted and the nidation index was calculated. Only indomethacin administered during the pre-ovulatory phase completely restored fertility in these rats.
Tosti, Claudia; Pinzauti, Serena; Santulli, Pietro; Chapron, Charles; Petraglia, Felice
Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest
Kistner, R W
Infertility has a 30-40% incidence in women with endometriosis. However, conservative surgical procedures can result in pregnancy for 40-90% of these patients. The pregnancy rate is influenced by 5 factors: 1) extent of the disease, 2) age, 3) history of previous surgery for endometriosis, 4) duration of infertility before surgery, and 5) length of postsurgical follow-up. The factor responsible for infertility among women with endometriosis is believed to be an inadequacy of the tubo-ovarian motility secondary to fibrosis and scarring, which results in imperfect ovum acceptance by the fimbriae. Therapy encompasses 4 approaches: 1) prophylaxis, 2) observation and analgesia, 3) suppression of ovulation, and 4) surgical treatment. Pregnancy is suggested as the optimal prophylactic treatment for endometriosis since the symptoms and signs regress during gestation and for varying periods thereafter. This regression is probably due to a combination of anovulation and amenorrhea caused by adenohypophyseal suppression. It may also be due to a transformation of functioning endometriotic tissue into decidua by increasing levels of chorionic estrogen and progesterone. If pregnancy is not desired, anovulation can be secured by the administration of sex hormones. Pseudopregnancy for 6 months, induced by norgestrel plus ethinyl estradiol or norethynodrel plus mestranol, can lead to pregnancy in 50% of patients whose only abnormality is surface ovarian endometriosis within 1 year of cessation of therapy. Short periods of pseudopregnancy are also advocated after conservative surgery if all areas of endometriosis cannot be excised. 40-50% of these patients can expect to become pregnant within 24 months. The incidence of postoperative tubo-ovarian adhesions may be diminished by use of dexamethasone and promethazine.
Marino, Jennifer L.; Holt, Victoria L.; Chen, Chu; Davis, Scott
Objectives Endometriosis is the presence of functioning endometrial glands and stroma outside the uterine cavity, most often in the pelvic peritoneal cavity. Women with endometriosis commonly have dysmenorrhea, dyspareunia, pain, menorrhagia and/or metrorrhagia; disease complications can include adhesions, chronic pain, and infertility. This exploratory case-control study investigated the relationship between lifetime occupational history and surgically confirmed endometriosis in a population-based sample. Methods Interviews were conducted with cases, all reproductive-aged female enrollees of a large health-maintenance organization first diagnosed with surgically confirmed endometriosis between April 1, 1996 and March 31, 2001 and randomly selected controls from the reproductive-aged female enrollee list from the same time period. Each reported job was coded using US Census Occupations and Industries codes, and jobs were classed into categories. Having ever worked an occupation in a given job class was compared to never having done so using unconditional logistic regression. Results Having ever worked as a flight attendant, service station attendant, or health worker, particularly as a nurse or health aide, was associated with increased risk of endometriosis (flight attendant: OR 9.80, 95% CI 1.08 - 89.02; service station attendant: OR 5.77, 95% CI 1.03 -32.43; health worker: OR 1.49, 95% CI 1.03 - 2.15). Income and education did not make a difference in the odds ratio estimates for the occupations examined. Conclusions This exploratory study suggests that having ever worked as a flight attendant, service station attendant, or health worker, particularly as a nurse, may be associated with an increased risk of endometriosis. PMID:19377833
Tran, C.; Even, M.; Carbonnel, M.; Preaux, F.; Isnard, F.; Rault, A.; Rouanne, M.; Ayoubi, J. M.
We report the case of a patient who developed a vesicoovarian fistula on an endometriosis abscessed cyst. The patient presented with an advanced endometriosis stage IV complicated with a right ovarian abscessed cyst of 10 cm. A first coelioscopy with cystectomy was realized. After surgery, a voiding cystography highlighted a fistula between the ovarian abscess and the bladder. A second surgery by median laparotomy was realized with the resection of the right ovarian abscess and the resection of vesical fistula. PMID:25152819
Abrão, Mauricio Simões; Borrelli, Giuliano Moysés; Clarizia, Roberto; Kho, Rosanne Marie; Ceccaroni, Marcello
Endometriosis has clearly three distinct clinical presentations and deep endometriosis, especially compromising the rectosigmoid is probably the most concerning one for both patients and surgeons. Currently, with the available tools, it is mandatory to have a precise diagnostic of this type of disease prior to indication of treatment. Strategies to manage this form of endometriosis will take into account several involved aspects, such as age of the patient, reproductive desire or infertility, clinical symptoms, as well as the extension and localization of the disease. Treatment could vary from more conservative to more radical depending on those aspects. As we pointed out in this article, the key to manage colorectal endometriosis is to start with a good diagnosis. Knowing exactly what is the extension and localization of the disease and knowing the patient's wishes as well as the clinical complaints, surgeons are able to define the best option for each patient. Critical points should always be discussed; for example, patients chosen to have clinical treatment should be aware of important issues regarding the follow-up, while patients undergoing surgery must be advised about all surgical possibilities and related complications.
Hagiwara, Y; Hatori, M; Moriya, T; Terada, Y; Yaegashi, N; Ehara, S; Kokubun, S
We report a case of endometriosis in the right inguinal region, attached to the right round ligament in a 28-year-old woman. At the age of 20, laparoscopic left ovarian cystectomy and pelvic adhesiolysis for endometriosis was carried out. She noticed a right tender groin mass 7 months previously, and the tumour size fluctuated with the menstrual cycle. A poorly circumscribed elastic hard mass, measuring 3 cm in diameter, was palpated in her right inguinal region. Magnetic resonance imaging showed a 2.5 cm x 2.5 cm mass in the right inguinal canal and a 5.4 cm x 6.8 cm mass was seen in the left ovary. The mass enlarged during menstruation. The groin mass was removed, in addition to carrying out laparoscopic ovarian cystectomy. At operation, the groin mass was found to be in continuity with the round ligament of extraperitoneal portion. Histological diagnosis of endometriosis was made in both ovarian and inguinal tumours. After surgery, the pain disappeared completely. Worth mentioning is that MRI clearly showed the change of tumour size depending on the menstrual cycle, which aided in arriving at the correct diagnosis of endometriosis in an unusual location.
A potential connection exists between the increasing prevalence of endometriosis and exposure to organochlorine chemicals. There is evidence that dioxin (2,3,7,8-TCDD) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of end...
Singh, Sukhbir S; Suen, Michael W H
Endometriosis-associated pelvic pain and subfertility may be managed medically in many cases; however, the surgical management of this insidious disease remains a necessary part of the treatment algorithm. Laparoscopy for diagnosis alone is rarely indicated with the advancements in preoperative imaging. When surgery is performed, the ideal goal would be a therapeutic and effective surgical intervention based on the preoperative evaluation. Surgery for women with pain due to endometriosis may be indicated in patients who cannot or do not wish to take medical therapies; acute surgical or pain events; deep endometriosis; during concomitant management of other gynecologic disorders; and patients seeking fertility with pain. The role of surgery for endometriosis-related subfertility may be considered in those with hydrosalpinges undergoing IVF; management of ovarian endometriomas in specific circumstances; and when a patient requests surgery as an alternative to assisted reproductive technology (ART). Surgery for ovarian endometriomas requires special attention due to the risk of potential harm on future fertility. Finally, a combined approach of surgery followed by postoperative medical therapy offers the best long-term outcomes for recurrence of disease and symptoms. A patient-centered approach and a goal-oriented approach are essential when determining the options for care in this population. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
A potential connection exists between the increasing prevalence of endometriosis and exposure to organochlorine chemicals. There is evidence that dioxin (2,3,7,8-TCDD) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of end...
Pollack, Anna Z.; Buck Louis, Germaine M.; Chen, Zhen; Peterson, C. Matthew; Sundaram, Rajeshwari; Croughan, Mary S.; Sun, Liping; Hediger, Mary L.; Stanford, Joseph B.; Varner, Michael W.; Palmer, Christopher D.; Steuerwald, Amy J.; Parsons, Patrick J.
There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18–44 years were recruited into an operative cohort, along with 131 similarly-aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research. PMID:23892002
Polak, Grzegorz; Barczyński, Bartłomiej; Kwaśniewski, Wojciech; Bednarek, Wiesława; Wertel, Iwona; Derewianka-Polak, Magdalena; Kotarski, Jan
The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF) and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis and 119 women with serous (n = 78) or dermoid (n = 41) ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease.
Gupta, Asish; Bhatnagar, Atul; Seth, B N; Dang, Arbinder; Gupta, Vineeta
Endometriosis is the ectopic presence of endometrial tissue outside the uterus. Though on its own endometriosis is not a rare lesion, the involvement of the urinary tract is rare but with the bladder being the most commonly affected organ. Endometriosis is usually seen in females between the ages of 30-40 years and may occur due to fluctuating levels of oestrogen and progesterone. Clinically the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been suggested that ultrasonography should be done either before or during menstruation as the lesion becomes more evident and a biopsy taken during this period is a strong aid in reaching a final diagnosis. We report here an unusual case of bladder endometriosis where the patient came with severe pelvic pain and an endoluminal mass seen on the ultrasonographic report. Based on these findings a differential of transitional cell carcinoma was given which was ruled out based on the cystoscopic findings.
Triolo, Onofrio; Laganà, Antonio Simone; Sturlese, Emanuele
Chronic pelvic pain (CPP) could be considered nowadays a deep health problem that challenges physicians all over the world. This because its aetiology is still unclear, the course of the disease could vary a lot among different patients and through time in the same patient, and the response to treatments is not every time successful. Among women who underwent laparoscopy for CPP, endometriosis is found in about 1/3 of the cases, while only 25% of women with histological confirmed endometriosis are asymptomatic. A wide range of variables may exert their influence on the resulting pain syndrome in endometriosis; for example, score according to American society for reproductive medicine (rASRM), size of the sub-peritoneal and pelvic wall implants, Douglas obliteration, previous surgery. It is widely accepted nowadays that central nervous system (CNS) and peripheral nervous system (PNS) seems to influence each other and this interconnection play a key role in pain modulation. Moreover, the phenomena induced by endometriosis in the pelvis, including the breakdown of peritoneal homeostasis and the induction of the production of proinflammatory and proangiogenic cytokines, are responsible of altered innervations and modulation of pain pathways in these patients. There are many proposed medical and surgical approach to treat this painful syndrome, although there is necessity of more efforts to create new non-invasive strategies that set a more accurate diagnosis of the causes of endometriotic-related CPP, and therefore facilitate its eradication. PMID:23671540
Jang, Hye-In; Kim, Sung-Eun; Lee, Yoo-Young; Choi, Chel-Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo
Extra pelvic endometriosis is considered to be rare. This paper reports a case of catamenial hemoptysis accompanied by subcutaneous endometriosis in 26-year-old woman. A computed tomography scan of the chest revealed a focal ground-glass opacity lesion in the posterior segment of the right upper lobe. Histopathology confirmed the diagnosis of endometriosis of right lung and concurrent subcutaneous endometriosis. She was treated with surgical resection of the endometriosis lesions on two different sites and perioperative gonadotropin-releasing hormone agonist therapy. The 6-month follow-up after combination treatment showed no recurrence. Though long-term follow-up result is needed, aggressive treatment using combination treatment (surgery and perioperative medication) should be considered for symptomatic extra pelvic endometriosis. PMID:28344969
Polat, Mehtap; Yaralı, İrem; Boynukalın, Kübra; Yaralı, Hakan
Endometriosis is an enigmatic disease affecting 10-15% of reproductive aged women and is encountered in 25-35% of women suffering from infertility. IVF is an effective tool to overcome endometriosis-associated infertility when expectant management or surgery fails. Direct IVF should be envisioned if the female age is greater than 38 year and infertility is long lasting. Likewise, semen characteristics or tubal status that is incompatible with natural conception mandates going straight to IVF. IVF, not only bypasses the distortion of pelvic anatomy associated with advanced stage endometriosis, but also removes gametes from a hostile peritoneal environment. In this article, we address the impact, if any, of endometriosis and endometriomason IVF outcome, whether surgical treatment of early-stage disease, endometriomas or deep infiltrating endometriosis would enhance pregnancy rates in IVF, which protocol to employ for controlled ovarian hyperstimulation for IVF and finally the impact, if any, of controlled ovarian hyperstimulation for IVF on progression of endometriosis.
Houtmeyers, P; Ceelen, W; Gillardin, J M; Dhondt, M; Pattyn, P
Although gastrointestinal endometriosis is an uncommon and often unexpected finding, the best treatment requires removal of all endometriotic lesions. The purpose of our study was to report our experience with the diagnosis and treatment of bowel endometriosis. From January 1997 to January 2004, 13 patients (mean 35.7y ; range 21-55y) were operated for bowel endometriosis. We noted: age, history of endometriosis, previous pregnancies, preoperative investigations and symptoms, operative procedure and intraoperative findings. Follow-up varied between one month postoperative examination and seven years. Presenting symptoms of the cases were: acute appendicitis (3), dysmenorrhoea (7), constipation (6), pelvic pain (2), rectal bleeding (3) and dyspareunia (2). Operative management was performed in accordance with the anatomical distribution. Seven patients had a history of previous operations and multifocal involvement was present in 61.5% of cases. At a median follow-up of 12.2 months, 83.3% had complete relief of their initial complaints, with only one reoperation needed. The pregnancy rate after surgery was 66.6%. Preoperative tests were: ultrasound for ovarian endometriomas, coloscopy, barium enema, vaginal palpation for detecting rectovaginal involvement, MRI and CT scan. These tests predicted the extension of endometriotic process correctly in 50% of the cases. Endometriosis of the sigmoid and rectum is rare but can give rise to severe gastrointestinal and pelvic symptoms. Preoperative investigations are not infallible in predicting the extent of the disease, sometimes placing the surgeon before a dilemma, because it involves mostly young women in the reproductive phase of life. The colorectal surgeon, therefore, should seek the advice of an experienced gynaecologist and vice versa. Removal of all endometriotic lesions is mandatory for obtaining an optimal relief of symptoms.
Akpınar, Süha; Çelebioğlu, Emre
Endometriosis is a benign gynecological disease that is characterized by the presence of functional endometrial tissue outside the uterus. Although the ovaries and uterine ligaments are the most common locations, urinary tract involvement especially the bladder endometriosis is a rare entity in women of reproductive age with clinical symptoms of cyclical urgency, hematuria and suprapubic pain. We herein present magnetic resonance imaging (MRI) findings of spontaneous bladder endometriosis case with cyclical hematuria symptoms. PMID:26029655
Casper, Robert F
This issue of Fertility and Sterility contains four articles by the World Endometriosis Research Foundation whose present objective is global standardization of the collection of phenotypic data and biological samples, designated as the Endometriosis Phenome and Biobanking Harmonisation Project. The aim is to facilitate large-scale international, multicenter trials that are robust, and will result in biomarker and treatment targets to advance research in endometriosis.
Kobayashi, Shigeru; Sasaki, Morio; Goto, Tatsuya; Asakage, Naoki; Sekine, Masayuki; Suzuki, Takahisa; Tsukada, Kenji; Yamasaki, Shigetaka; Ukawa, Shiro
A case of endometrioid adenocarcinoma supposedly arising from endometriosis of the rectum is reported. Malignant transformation is uncommon but a well-known complication of endometriosis. In the present case, it was proved by histopathological findings and immunophenotype such as cytokeratin7+/cytokeratin20-/estrogen receptor+. The cause of rectal endometriosis in this case might have been related with previously received hormone replacement therapy for ovarian endometriosis. Following surgical removal of the lesion, this patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, although this kind of therapy is still controversial as to its effectiveness.
Shadbolt, Naomi A; Parker, Melissa A; Orthia, Lindy A
Endometriosis is estimated to affect approximately 10% of women. Although early detection may enhance health outcomes and fertility, there is a recognised diagnostic delay of 6.7 years. There are limited data on ways to discuss endometriosis with young women. The aims of the present study were to determine what young women know about endometriosis, what young women want to know about endometriosis and how this is best communicated to promote early detection. Women aged 16-25 years were invited to complete an online survey that was advertised via Facebook, email, Twitter and flyers at high schools and a university. In all, 131 women responded to the survey. Fifty-two percent of participants had heard of endometriosis, 89% thought teenagers should be educated about endometriosis and 78% thought that young men should also be educated about the condition. Favoured sources for obtaining information were schools (40%), the Internet (22%) and magazines (13%). Participants were most comfortable talking to a doctor (75%), parent (59%) or friend (51%). Participants primarily wanted to know about the disease, its symptoms, risk factors and treatment. Many participants' descriptions of endometriosis were vague or inaccurate. The results of the present study indicate that young women are keen to learn about endometriosis, particularly its symptoms. Preferential sources of information appear to be schools or the Internet, and young women appear more comfortable talking to doctors. SO WHAT? To promote early detection of endometriosis, health promotion activities should direct their information towards sources that young women prefer.
Akçay, A; Altun, B; Usalan, C; Ulusoy, S; Erdem, Y; Yasavul, U; Turgan, C; Caglar, S
Endometriosis is a common disease but ureteral involvement is relatively rare. Ureteric endometriosis is mostly unilateral. Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. We present the cyclical acute renal failure associated with menstruation in a patient who developed severe bilateral ureteral obstruction due to endometriosis. Physicians should be aware of this uncommon but serious manifestation of endometriosis, especially if the clinical presentation is cyclical acute renal dysfunction in a premenopausal woman.
Miranda, L; Settembre, A; Capasso, P; Piccolboni, D; De Rosa, N; Corcione, F
Two cases of endometriosis infiltrating the round ligament and associated with an inguinal hernia are presented. The initial diagnosis was irreducible hernia, since this rare association often causes unusual preoperative symptoms and diagnostic problems. Diagnosis is frequently made by histologic examination. Surgery is the treatment of choice both for hernia and for endometriosis, and is locally curative. However, in a fertile woman with a painful mass in the inguinal region the possibility of endometriosis should be considered, and if suspected at inguinal exploration a laparoscopy should be made to rule out the presence of intraperitoneal endometriosis.
Matalliotakis, I; Cakmak, H; Matalliotakis, M; Kappou, D; Arici, A
Women with endometriosis frequently suffer from autoimmune inflammatory diseases, allergies and asthma. This study was conducted to examine whether the prevalence of allergies is higher in patients with endometriosis than in the control group, and to show potential correlation with endometriosis stages. We evaluated the medical files of 501 women with laparoscopically-diagnosed endometriosis and 188 women without endometriosis enrolled in Yale University Hospital. Main outcome measures used were allergy on medications, complaints of sinus or perennial allergic rhinitis, asthma, family history of allergic disease, and correlation with stages of endometriosis. Our results indicated that the overall risk of women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9-6.3) (p < 0.001). Significant excesses were identified for medications, sinus allergic rhinitis, and asthma; also, women with endometriosis were significantly more likely to report a positive family history of allergies. Overall, our study indicated a link between endometriosis and increased risk of allergic autoimmune disorders that should further be explored.
Streuli, I; Gaitzsch, H; Wenger, J-M; Petignat, P
Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause. Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be used in cases of pain recurrence after surgery. Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions. The evidence is currently insufficient to support a conclusion about the optimal hormone replacement therapy for women with endometriosis. The question of malignant transformation of endometriosis in response to hormone replacement therapy in women with a history of endometriosis remains unanswered and needs a long-term follow-up study to evaluate the risk of an adverse outcome. Further studies should be performed to determine the optimal management of menopausal women with endometriosis.
Guo, Sun-Wei; Zhang, Qi; Liu, Xishi
Exposure to chronic stress before and well after the induction of endometriosis is reported to increase lesion sizes in rats, but it is unclear whether stress, exposed shortly after the induction of endometriosis, would also promote the development of endometriosis, nor is it clear what the underlying possible molecular mechanism is. This study was undertaken to test the hypothesis that chronic stress can promote the development of endometriosis. A prospective randomized mouse experiment was conducted that subjected mice with induced endometriosis to predator stress. In addition, a cross-sectional immunohistochemistry study was performed in ectopic and eutopic endometrial tissue samples from age- and roughly menstrual phase-matched women with ovarian endometriomas. It was found that the chronic psychogenic stress induced epigenetic changes in the hippocampus in mouse independent of endometriosis. It was also found that chronic psychogenic stress induced epigenetic changes in the hippocampus of mice with endometriosis, and seemingly activated the adrenergic signalling in ectopic endometrium, resulting in increased angiogenesis and accelerated growth of endometriotic lesions. Thus, chronic psychogenic stress promotes endometriosis development, raising the possibility that the use of anti-depressants in cases of prolonged and intense stress might forestall the negative impact of stress on the development of endometriosis. Copyright Â© 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Saha, Rama; Marions, Lena; Tornvall, Per
To examine the validity of self-reported endometriosis and to improve the reliability of questionnaires by including endometriosis-related questions. Analysis of survey questionnaire data. Cross-sectional study. Cohort of 26, 898 female twins aged 20-60 years at interview, who participated in either of two surveys (1998-2002 or 2005-2006). None. Endometriosis diagnosis in the Swedish National Inpatient Registry (IPR). The self-reported endometriosis diagnoses and endometriosis-related questions from a nationwide population-based twin registry were linked with the IPR. Fairly good agreement was found between the self-reported and IPR data on endometriosis. The receiver operating characteristics (ROC) curves showed fairly good predictive ability of self-reported endometriosis to have a confirmed endometriosis diagnosis in the IPR with an area under the curve (AUC) 0.79 (95% confidence interval [CI], 0.77-0.81). Further, the predictive ability increased to AUC 0.89 (95% CI, 0.88-0.90) when there was additional information about infertility and age. Our results indicate that self-reported data on endometriosis are moderately accurate and may be useful in studies when register data are not available. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Ashrafi, Mahnaz; Sadatmahalleh, Shahideh Jahanian; Akhoond, Mohammad Reza; Talebi, Mehrak
Background Endometriosis affects women’s physical and mental wellbeing. Symptoms include dyspareunia, dysmenorrhea, pelvic pain, and infertility. The purpose of this study is to assess the correlation between some relevant factors and symptoms and risk of an endometriosis diagnosis in infertile women. Materials and Methods A retrospective study of 1282 surgical patients in an infertility Institute, Iran between 2011 and 2013 were evaluated by laparoscopy. Of these, there were 341 infertile women with endometriosis (cases) and 332 infertile women with a normal pelvis (comparison group). Chi-square and t tests were used to compare these two groups. Logistic regression was done to build a prediction model for an endometriosis diagnosis. Results Gravidity [odds ratio (OR): 0.8, confidence interval (CI): 0.6-0.9, P=0.01], parity (OR: 0.7, CI: 0.6-0.9, P=0.01), family history of endometriosis (OR: 4.9, CI: 2.1-11.3, P<0.001), history of galactorrhea (OR: 2.3, CI: 1.5-3.5, P=0.01), history of pelvic surgery (OR: 1.9, CI: 1.3-2.7, P<0.001), and shorter menstrual cycle length (OR: 0.9, CI: 0.9-0.9, P=0.04) were associated with endometriosis. Duration of natural menstruation and age of menarche were not correlated with subsequent risk of endometriosis (P>0.05). Fatigue, diarrhea, constipation, dysmenorrhea, dyspareunia, pelvic pain and premenstrual spotting were more significant among late-stage endometriosis patients than in those with early-stage endometriosis and more prevalent among patients with endometriosis than that of the comparison group. In the logistic regression model, gravidity, family history of endometriosis, history of galactorrhea, history of pelvic surgery, dysmenorrhoea, pelvic pain, dysparaunia, premenstrual spotting, fatigue, and diarrhea were significantly associated with endometriosis. However, the number of pregnancies was negatively related to endometriosis. Conclusion Endometriosis is a considerable public health issue because it affects many
Backonja, Uba; Buck Louis, Germaine M.; Lauver, Diane R.
Background Endometriosis has been associated with a lean body habitus. However, we do not understand whether endometriosis is also associated with other characteristics of adiposity, including adipose tissue distribution and amount of visceral adipose tissue (VAT; adipose tissue lining inner organs). Having these understandings may provide insights on how endometriosis develops—some of the physiologic actions of adipose tissue differ depending on tissue amount and location, and are related to proposed mechanisms of endometriosis development. Objectives To review the literature regarding overall adiposity, adipose tissue distribution and/or VAT, and endometriosis. Methods We reviewed and synthesized studies indexed in PubMed and/or Web of Science. We included studies that had one or more measures of overall adiposity, adipose tissue distribution, and/or VAT, and women with and without endometriosis for comparison. We summarized the findings and commented on the methods used and potential sources of bias. Results Out of 366 identified publications, 19 (5.2%) were eligible. Two additional publications were identified from reference lists. Current research included measures of overall adiposity (e.g., body figure drawings) or adipose tissue distribution (e.g., waist-to-hip ratio), but not VAT. The weight of evidence indicated that endometriosis was associated with low overall adiposity and with a preponderance of adipose tissue distributed below the waist (peripheral). Discussion Endometriosis may be associated with being lean or having peripherally distributed adipose tissue. Well-designed studies with various sampling frameworks and precise measures of adiposity and endometriosis are needed to confirm associations between adiposity measures and endometriosis, and delineate potential etiologic mechanisms underlying endometriosis. PMID:26938364
Kvaskoff, Marina; Mu, Fan; Terry, Kathryn L.; Harris, Holly R.; Poole, Elizabeth M.; Farland, Leslie; Missmer, Stacey A.
BACKGROUND Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If
Isci, H; Gonenc, G; Yigiter, A B; Guducu, N; Dünder, I
Uterine scar endometriosis is an extremely rare entitiy. As the surgical procedures of the uterus increases through time, scar endometriosis may be diagnosed more often in the future. A case of uterine scar endometriosis is presented with complaints of menstruation lasting one day with associated pelvic pain. When a cystic mass in the site of previous surgery is diagnosed, scar endometriosis must be considered.
Pandey, Deeksha; Coondoo, Ambika; Shetty, Jyothi; Mathew, Stanley
A 39-year-old woman with a left-sided inguinal swelling was referred to us with a diagnosis of inguinal hernia. On asking leading questions, the patient gave a typical history of cyclical pain and increased swelling during menstruation. Fine-needle aspiration biopsy revealed endometrial glands. Preoperatively, the extent of the endometriotic lesion was delineated using MRI. The lesion was approached through the patient's caesarean scar for cosmetic reasons and excised in toto. Final diagnosis was round ligament endometriosis. The patient was asymptomatic at 3, 6 and 12 months’ follow-up. This case re-emphasises the fact that endometriosis is an enigmatic disease and can be found anywhere in the body. Thus, a woman of reproductive age presenting with any cyclical symptom should be asked about its relation to her menstrual cycle. PMID:25827916
Redwine, D B; Sharpe, D R
Intestinal and urinary tract involvement by endometriosis may be symptomatic, particularly when invasive disease is present. Even in expert hands, complete excision of all invasive disease cannot be accomplished laparoscopically in every case. The practitioner must balance enthusiasm for the advantages of a laparoscopic approach with limitations of time and skill. Laparoscopy should be abandoned in a particular case if a better job can be performed by laparotomy. Hysterectomy with castration may not relieve symptoms due to invasive disease.
Jiménez, Jesus S; Barbero, Patricia; Tejerizo, Alvaro; Guillén, Carmen; Strate, Carol
To report a case of uncommon endometriosis located in the Nuck's duct and its laparoscopic resolution. Case report. Gynecologic department at 12 de Octubre University Hospital, Madrid. A 35-year-old woman, gravida 1 para 1, presented with an inguinal right mass. She had a right nephrectomy because of acute pyelonephritis. Computed tomography showed a cystic lesion that was suggestive of a Nuck's duct cyst. Fine-needle aspiration cytology was performed, and endometriosis was determined. Cyst removal and closure of the internal inguinal ring's defect by the laparoscopic approach. Disease free. The intervention was successfully performed by laparoscopic approach. The postoperative evolution was good, and the patient was discharged 2 days after surgery. Inguinal or Nuck's duct are both uncommon locations for endometriosis; therefore, it is difficult to suspect in patients without a surgical history. Once identified, the treatment involves removal of the endometrioma and repair of the internal inguinal ring. A laparoscopic approach should be considered when possible. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Wilczyński, Miłosz; Wiecka-Płusa, Monika; Antosiak, Beata; Maciołek-Blewniewska, Grazyna; Majchrzak-Baczmańska, Dominika; Malinowski, Andrzej
The aim of the study was a retrospective analysis of the medical records of patients who underwent surgery due to deep infiltrating rectovaginal endometriosis (mainly with the use of the 'shaving' technique). We analysed 160 cases of patients who underwent surgery due to the deep infiltrating rectovaginal endometriosis in our ward between 2003-2014. Depending on lesion localization, disease severity and clinical characteristics, three possible ways of operation were proposed: laparoscopic, vaginal or a combined vagino-laparoscopic approach. A total of 120 patients underwent laparoscopic removal of the endometrial lesions, whereas 17 were operated vaginally and 23 with the use of the combined approach. Nodule resection was successfully performed in all cases. The combined vagino-laparoscopic operations were characterized by the longest operating time. The rate of perioperative complications was low in the group of patients who underwent laparoscopic or combined operations. The necessity of bowel wall suturing occurred in 15 cases. This procedure was performed in order to strengthen the bowel wall (in cases when no perforation occurred) or due to bowel resection during surgery. Unexpected bowel perforation occurred in only 5 cases. Conclusions: Vaginal, laparoscopic and the combined vagino-laparoscopic surgeries can be safely performed in cases of deep rectovaginal endometriosis.
May, K.E.; Conduit-Hulbert, S.A.; Villar, J.; Kirtley, S.; Kennedy, S.H.; Becker, C.M.
BACKGROUND Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage. METHODS We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine. RESULTS We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful. CONCLUSIONS Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test. PMID:20462942
Badipatla, Kanthi Rekha; Vupputuri, Anisha; Niazi, Masooma; Blaise, Marie-Nirva; Nayudu, Suresh Kumar
Endometriosis is a common gynecological condition wherein there is an ectopic implantation of the uterine endometrial tissue. While several diagnostic modalities are described for the condition, laparoscopy remains the gold standard. There is still an undiscovered area to diagnose colonic endometriosis at an earlier stage. We present a case report of a reproductive age woman with cyclical rectal bleeding diagnosed with colonic endometriosis with colonoscopy and biopsy using saline injection lift and sampling technique. We in our report try to impress the fact that this differential should always be considered in the appropriate clinical setting, especially in women of childbearing age and in such cases, deeper tissue sampling techniques should be sought for, given better diagnostic yield. This may be clinically important given that it may aid in earlier diagnosis and thereby early initiation of appropriate therapy before the disease takes a complicated route. It may also be helpful in avoiding unnecessary surgery, along with the morbidity, complications and costs associated with same. PMID:28270880
Okeson, Danelle M; Higbie, Christine T; Mylniczenko, Natalie D; Haynes, April; Bennett, Suzanne; Klocke, Emily; Carpenter, James W
Endometriosis has been reported in humans, great apes, and Old World monkeys. Although cases are noted anecdotally in Mandrillus spp., and a previously reported case was noted on postmortem examination, to the authors' knowledge, no previous reports of case management have been published in the peer-reviewed literature. This paper describes the medical and surgical management of endometriosis in two mandrills (Mandrillus sphinx).
Nezhat, Camran; Littman, Eva D; Lathi, Ruth B; Berker, Bulent; Westphal, Lynn M; Giudice, Linda C; Milki, Amin A
Many will agree that the use of laparoscopy to diagnose and potientially treat endometriosis in patients who suffer from infertility has been superseded by IVF and sometimes oocyte donation, especially in older patients. The findings of our study add another dimension to management of endometriosis in the setting of infertility and emphasize the importance of keeping laparoscopy in the infertility management equation.
Endometriosis is a clinical entity characterized by the presence of normal endometrial mucosa abnormally implanted in locations other than the uterine cavity. Endometriosis can be either endopelvic or extrapelvicdepending on the location of endometrial tissue implantation. Despite the rarity of extrapelvic endometriosis, several cases of endometriosis of the gastrointestinal tract, the urinarytract, the upper and lower respiratory system, the diaphragm, the pleura and the pericardium, as well as abdominal scars loci have been reported in the literature. There are several theories about the pathogenesis and the pathophysiology of endometriosis. Depending on the place of endometrial tissue implantation, endometriosis can be expressed with a wide variety of symptoms. The diagnosis of this entity is neither easy nor routine. Many diagnostic methods clinical and laboratory have been used, but none of them is the golden standard. The multipotent localization of endometriosis in combination with the wide range of its clinical expression should raise the clinical suspicion in every woman with periodic symptoms of extrapelvic organs. Finally, the therapeutic approach of this clinical entity is also correlated with the bulk of endometriosis and the locum that it is found. It varies from simple observation, to surgical treatment and treatment with medication as well as a combination of those. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1968087883113362. PMID:24294950
DeClerck, Brittney K; Post, Miriam D; Wisell, Joshua A
Endometriosis is a disease process characterized by ectopic endometrial tissue. Involvement most commonly occurs in the lower pelvis, outside the uterine cavity, but can occur elsewhere, including the skin. Cutaneous endometriosis is a rare manifestation of this disease, with decidualization occurring in a very small minority of cases, almost always seen in pregnant females. Cutaneous involvement of endometriosis may present a diagnostic problem for the pathologist, particularly in the event of decidualization. Decidualization may mimic a malignancy and as a result may result in unnecessary diagnostic studies for the patient. We present a case of a nonpregnant patient with decidualized cutaneous endometriosis, discuss the histopathologic and immunohistochemical features of this entity, and review the pertinent literature on this subject. To our knowledge, this is the second reported case of cutaneous decidualized endometriosis in a nonpregnant female.
Miller, Jessica E.; Ahn, Soo Hyun; Monsanto, Stephany P.; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant
Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure. PMID:27740937
Miller, Jessica E; Ahn, Soo Hyun; Monsanto, Stephany P; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant
Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.
Governini, Laura; Carrarelli, Patrizia; Rocha, Ana Luiza Lunardi; Leo, Vincenzo De; Luddi, Alice; Arcuri, Felice; Piomboni, Paola; Chapron, Charles; Bilezikjian, Louise M; Petraglia, Felice
The present study investigated expression and protein localization of FOXL2 messenger RNA (mRNA) in endometrium of healthy women and in patients with endometriosis during endometrial cycle. In endometriotic lesions, FOXL2 mRNA and protein were evaluated and a possible correlation with activin A mRNA expression changes was also studied. Endometrium was collected from healthy women (n = 52) and from women with endometriosis (n = 31) by hysteroscopy; endometriotic tissues were collected by laparoscopy (n = 38). FOXL2 gene expression analysis in endometrium of healthy women showed a significant expression and no significant changes in mRNA levels between proliferative and secretory phases; a similar pattern was observed in endometrium of patients with endometriosis. Immunohistochemical evaluation showed that FOXL2 protein localized in stromal and glandular cells and colocalized with SUMO-1. FOXL2 mRNA expression was 3-fold higher in endometriosis than in healthy endometrium (P < .01) and a positive correlation between FOXL2 and activin A mRNA was found (P < .05) in endometriosis. In conclusion, FOXL2 mRNA expression and its protein localization do not change during endometrial cycle in eutopic endometrium from healthy individuals or patients with endometriosis; the hyperexpression of FOXL2 in endometriotic lesions suggests an involvement of this transcriptional regulator, probably associated with activin A expression and related to the pathogenesis of endometriosis. © The Author(s) 2014.
Franco-Murillo, Yanira; Miranda-Rodríguez, José Antonio; Rendón-Huerta, Erika; Montaño, Luis F.; Cornejo, Gerardo Velázquez; Gómez, Lucila Poblano; Valdez-Morales, Francisco Javier; Gonzalez-Sanchez, Ignacio
Objective: Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium. Design: Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle. Results: Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis. Conclusion: Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways. PMID:25194152
Roberts, Lisa M.; Reich, Harry
Objective: To present a case of recurrent catamenial pneumothorax and diaphragmatic endometriosis that was managed thoracoscopically. A review of the literature is also presented. Methods: A-28-year-old woman presented with bloody stools, chronic constipation, and chest pain. A review of systems was positive for monthly chest pain associated with her menses. A preoperative chest x-ray revealed a right pneumothorax. Colonoscopy revealed biopsy proven endometriosis of the sigmoid colon. A pelvic computed tomography scan revealed bilateral complex, cystic and solid adenexal lesions. Results: A right thoracoscopy was performed. A lesion on the right hemidiaphragm was excised and confirmed to be endometriosis. A wedge section of lung tissue containing a bleb was resected and also contained endometriosis. Three months later, the patient underwent laparoscopic excision of her pelvic endometriosis, including a low anterior rectal resection. Five months later, she presented again with right-sided chest pain. A thoracoscopic right total pleurectomy was performed for recurrent pneumothorax. Conclusion: Pulmonary endometriosis may present as chest pain, shortness of breath, or hemoptysis associated with menstrual cycles. This case emphasizes the importance of a careful review of systems in patients with known endometriosis. Management now includes an endoscopic alternative and all of its known benefits. PMID:14626406
Greene, Alexis D.; Lang, Stephanie A.; Kendziorski, Jessica A.; Sroga-Rios, Julie M.; Herzog, Thomas J.; Burns, Katherine A.
Endometriosis currently affects ∼5.5 million reproductive-aged women in the U.S. with symptoms such as painful periods (dysmenorrhea), chronic pelvic pain, pain with intercourse (dyspareunia), and infertility. It is defined as the presence of endometrial tissue outside the uterine cavity and is found predominately attached to sites within the peritoneal cavity. Diagnosis for endometriosis is solely made through surgery as no consistent biomarkers for disease diagnosis exist. There is no cure for endometriosis and treatments only target symptoms and not the underlying mechanism(s) of disease. The nature of individual predisposing factors or inherent defects in the endometrium, immune system, and/or peritoneal cavity of women with endometriosis remains unclear. The literature over the last 5 years (2010-2015) has advanced our critical knowledge related to hormones, hormone receptors, immune dysregulation, hormonal treatments, and the transformation of endometriosis to ovarian cancer. In this review, we cover the aforementioned topics with the goal of providing the reader an overview and related references for further study to highlight the progress made in endometriosis research, while concluding with critical areas of endometriosis research that are urgently needed. PMID:27165051
Vegheş, Simina; Lupaşcu, Ivona; David, Cristina; Vişan, Valeria; Vasiliu, Veronica
Our purpose was to define the best way of treating tubal infertility caused by endometriosis. We have studied 24 patients with tubal infertility caused by endometriosis; the etiology has been laparoscopically established in the 2nd Clinic of Obstetrics and Gynecology Iaşi. The endometriosis score (r-AFS) was used to establish the therapy. We performed laparoscopic treatment when endometriosis was visible. Postoperative medical therapy (Diphereline, 3 months) was indicated; patients with ,,unpigmented endometriosis" received the same medical therapy. The rate of pregnancies in patients that had benefit of combined therapy: surgical and medical (n=9) was superior (44.4%) to that obtained in patients that were only surgical treated (n=15): 26.6% (Spearman correlation--0.6595, p < 0.0012). Endometriosis is an important etiological factor in female infertility. The pathway is mechanic as well as chemical and it justifies the combined therapy. There are better results, as fertility prognosis in patients with endometriosis that receive both, surgical and medical therapy.
Mekaru, Keiko; Yagi, Chiaki; Asato, Kozue; Masamoto, Hitoshi; Sakumoto, Kaoru; Aoki, Yoichi
There have been very few reports on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with stage I/II endometriosis. The objective of this study was to investigate IVF-ET outcomes in women with early-stage endometriosis. We enrolled 35 women less than 40 years with unexplained infertility who underwent IVF-ET into the study. We compared 18 women with stage I/II endometriosis according to the revised American Society for Reproductive Medicine classification for endometriosis, who underwent 39 IVF-ET cycles (En (+) group) with 17 women without endometriosis who underwent 41 IVF-ET cycles (En (-) group). Higher requirements of total gonadotropin, a lower percentage of high-quality embryos of all fertilized eggs (9.0% vs. 16.3%), a relatively lower pregnancy rate (33.3% vs. 41.5%), and a lower live birth rate (25.6% vs. 34.1%) were observed in the En (+) group. Although no significant effect on IVF-ET outcome was observed, ovarian response may be decreased in women with stage I/II endometriosis. Considering the decreased number of high-quality embryos in the En (+) group, stage I/II endometriosis may have detrimental effects on embryo quality.
Rogers, Peter A W; D'Hooghe, Thomas M; Fazleabas, Asgerally; Gargett, Caroline E; Giudice, Linda C; Montgomery, Grant W; Rombauts, Luk; Salamonsen, Lois A; Zondervan, Krina T
Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.
Bedaiwy, Mohamed A; Alfaraj, Sukinah; Yong, Paul; Casper, Robert
Endometriosis affects 1 in 10 women of reproductive-age. The current treatments are surgical and hormonal but have limitations, including the risk of recurrence, side effects, contraceptive action for women who desire pregnancy, and cost. New treatments include gonadotropin-releasing hormone analogues, selective progesterone (or estrogen) receptor modulators, aromatase inhibitors, immunomodulators, and antiangiogenic agents. Further research is needed into central sensitization, local neurogenesis, and the genetics of endometriosis to identify additional treatment targets. A wider range of medical options allows for the possibility of precision health and a more personalized treatment approach for women with endometriosis.
Bhat, Rani A; Teo, Melissa; Bhat, Akhil Krishnanand
Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis.
Bhat, Rani A.; Teo, Melissa; Bhat, Akhil Krishnanand
Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis. PMID:24936277
Petresin, J.; Wolf, J.; Emir, S.; Müller, A.; Boosz, A. S.
The incidence of endometriosis is increasing. Particularly during pregnancy and labour, clinicians should be alert to possible endometriosis-associated complications or complications of previous endometriosis treatment, despite a low relative risk. In addition to an increased rate of early miscarriage, complications such as spontaneous bowel perforation, rupture of ovarian cysts, uterine rupture and intraabdominal bleeding from decidualised endometriosis lesions or previous surgery are described in the literature. Unfavourable neonatal outcomes have also been discussed. We report on an irreducible ovarian torsion in the 16th week of pregnancy following extensive endometriosis surgery, and an intraabdominal haemorrhage due to endometriosis of the bowel in the 29th week of pregnancy. PMID:27570252
Mathur, S; Peress, M R; Williamson, H O; Youmans, C D; Maney, S A; Garvin, A J; Rust, P F; Fudenberg, H H
Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:6759000
Antonelli, Alessandro; Finotto, Elena; Zambolin, Tiziano; Fisogni, Simona; Simeone, Claudio
Intrinsic ureteral endometriosis is a very rare condition. A 41 y. o. woman with right hydroureteronephrosis and other aspecific symptoms came to our attention. The CT scan showed an ureteral obstacle causing the hydroureteronephrosis. She underwent ureterorenoscopy with biopsies of the lesion that did not result to be diriment. Suspecting a ureteral neoplasm, the patient then underwent ureteral resection and ureterocystoneostomy, and the extemporary histological examination resulted as endometriosis. The abdominal exploration showed a parametrial and a peritoneal growth - both compatible with the extemporary histological examination - that were also excised. The post-operative course was uneventful. The definitive hystological examination confirmed the perioperatory diagnosis. Intrinsic ureteral endometriosis is confirmed as a rare pathology with an indefinite clinical presentation; its typical presentation, namely cyclic hematuria, seems to be an anecdotal feature. Therefore the diagnostics of intrinsic ureteral endometriosis is still difficult even despite such a striking presentation.
Cela, Vito; Obino, Maria E; Sergiampietri, Claudia; Simi, Giovanna; Papini, Francesca; Pinelli, Sara; Freschi, Letizia; Artini, Paolo G
The advent of robot-assisted laparoscopy (RAL) represents an important innovation and has opened new perspectives for treatment of endometriosis, in particular in deep infiltrating endometriosis (DIE). RAL could offer several technical advantages in treating this complex disease, such as 3D vision, tremor filtration and better surgical ergonomy, would be able to improve surgical performances without increasing in surgical time, blood loss, intra- and postoperative complications and it reduces the rates of conversion to laparotomy. Additionally thanks to its reduced learning curve compared to conventional laparoscopy, facilitates the training of less experienced surgeons. For these reason DIE might be one of the best indications for robot assisted laparoscopy in gynecologic surgery. However, very few retrospective studies, small cases series and only a randomized clinical trial were reported. Further randomized control trial comparing CL to RAL for different stage of endometriosis and the different type of procedure performed would be mandatory in order to define potential benefits of RAL for endometriosis surgery.
Zhao, Luyang; Gu, Chenglei; Huang, Ke; Han, Weidong; Fu, Meng; Meng, Yuanguang
Endometriosis is a common gynecological disease with high prevalence, while its etiology and pathophysiology have remained to be fully elucidated. Previous evidence suggested that this disorder may be in part or completely of somatic origin. However, traditional endometrial samples may not be ideal for investigation, as target cells, including epithelial and stromal cells, in endometriotic lesions are too sparse to be analyzed. Recently, capture microdissection techniques have been used to overcome these limitations and eliminate tissue heterogeneity in endometriosis research. Therefore, the present review summarized the alterations in epithelial and stromal cells in endometriosis tissues isolated through capture microdissection, outlined recent progress and provided directions for future investigation of the pathogenesis of endometriosis. PMID:27882213
Fassbender, Amelie; Burney, Richard O.; O, Dorien F.; D'Hooghe, Thomas; Giudice, Linda
Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium. PMID:26240814
Lee, Alice W; Templeman, Claire; Stram, Douglas A; Beesley, Jonathan; Tyrer, Jonathan; Berchuck, Andrew; Pharoah, Paul P; Chenevix-Trench, Georgia; Pearce, Celeste Leigh
To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Pooled genetic analysis. University hospital. Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. None. Endometriosis-associated genetic variation and ovarian cancer. There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions. Copyright © 2016. Published by Elsevier Inc.
Bulun, Serdar E.; Monsavais, Diana; Pavone, Mary Ellen; Dyson, Matthew; Xue, Qing; Attar, Erkut; Tokunaga, Hideki; Su, Emily J.
Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future. PMID:22271293
Tariverdian, Nadja; Theoharides, Theoharis C.; Siedentopf, Friederike; Gutiérrez, Gabriela; Jeschke, Udo; Rabinovich, Gabriel A.; Blois, Sandra M.
Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis. PMID:17621704
Bulun, Serdar E; Cheng, You-Hong; Yin, Ping; Imir, Gonca; Utsunomiya, Hiroki; Attar, Erkut; Innes, Joy; Julie Kim, J
Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in the US. The biologically active estrogen estradiol (E2) is the best-defined mitogen for the growth and inflammation processes in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins. Moreover, progesterone-induced molecular changes in the eutopic (intrauterine) endometrial tissue of women with endometriosis are either blunted or undetectable. These in vivo observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptors (PRs) and the lack of the PR isoform named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on stromal cells to induce secretion of paracrine factor(s). These unknown factor(s) act on neighboring epithelial cells to induce the expression of the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes the biologically active estrogen E2 to estrone (E1). In endometriotic tissue, progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this local mitogen. The cellular and molecular mechanisms underlying progesterone resistance and failure to metabolize E2 in endometriosis are reviewed.
Bruner-Tran, Kaylon L.; Yeaman, Grant R.; Crispens, Marta A.; Igarashi, Toshio M.; Osteen, Kevin G.
Laboratory and population-based studies suggest that exposure to environmental toxicants may be one of several triggers for the development of endometriosis. We discuss evidence that modulation of the endometrial endocrine-immune interface could mechanistically link toxicant exposure to the development of this disease. Capsule Summary: Environmental toxicant exposure induces an inflammatory-like endometrial response that may promote the development of endometriosis. PMID:18394613
Pontikaki, A; Sifakis, S; Spandidos, D A
Endometriosis is a chronic gynecological disease with a wide spectrum of clinical manifestations that affects approximately 10% of women of reproductive age. Recent reviews have demonstrated the connection between endometriosis and breast cancer, which represents the most frequently diagnosed female cancer and the most common cause of cancer-related mortality among women worldwide. The aim of this study was to conduct a survey of available published epidemiological studies indicating the association between endometriosis and breast cancer, and simultaneously to categorize the results based on the strength of the association, with the intention of the critical evaluation of the existing data. We performed a rigorous search of the PubMed/Medline database, using the key words 'endometriosis' and 'breast cancer' for all studies published in the English language until September 2015. We found 4 retrospective cohort studies, 4 case-control studies and 3 case-cohort studies that demonstrated a notable risk for developing breast cancer among women with endometriosis. By contrast, we also found 5 case-control studies, 1 prospective cohort study, 1 case-cohort study and 1 cross-sectional study that demonstrated a negative association between endometriosis and breast cancer. In conclusion, as regards the clarification of a 'robust' or 'weak' association between endometriosis and breast cancer, no definite conclusions could be drawn, due to the limited number of studies and the limitations of each of these studies. New well-designed, prospective cohort or randomized control trials with long-term follow-up are warranted in order to provide evidence-based clinical recommendations for proper counseling, screening and treatment strategies for patients with endometriosis, and hence to improve public health.
Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini
Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu, rich in inflammatory markers and pain-inducing prostaglandins PGE2/PGF2α and lipid peroxides, and the endometriotic tissue is innervated with nociceptors. Our clinical study showed the abundance of oxidatively-modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively-modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (i) the detection of lipoprotein derived oxidation-sensitive pain molecules, (ii) the ability of such molecules to induce nociception, and (iii) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins similar to that seen in the PF. The oxidatively-modified lipoproteins induced hypothermia (intra-cerebroventricular) in CD-1 mice and nociception in the Hargreaves paw-withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin-E and N-acetylcysteine and the NSAID, indomethacin suppressed the pain inducing ability of oxidatively-modified lipoproteins. Treatment of human endometrial cells with oxidatively-modified lipoproteins or PF from women with endometriosis showed up-regulation of similar genes belonging to the opioid and inflammatory pathways. Our finding that oxidatively-modified lipoproteins can induce nociception has a broader impact not only in the treatment of endometriosis-associated pain but also in other diseases associated with chronic pain. PMID:25599233
Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini
Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu and is rich in inflammatory markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2α, and lipid peroxides; and the endometriotic tissue is innervated with nociceptors. Our clinical study showed that the abundance of oxidatively modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules, (2) the ability of such molecules to induce nociception, and (3) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF. Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular) in CD-1 mice and nociception in the Hargreaves paw withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin E and N-acetylcysteine, and the nonsteroidal anti-inflammatory drug indomethacin suppressed the pain-inducing ability of oxidatively modified lipoproteins. Treatment of human endometrial cells with oxidatively modified lipoproteins or PF from women with endometriosis showed upregulation of similar genes belonging to opioid and inflammatory pathways. Our finding that oxidatively modified lipoproteins can induce nociception has a broader impact not only on the treatment of endometriosis-associated pain but also on other diseases associated with chronic pain.
Alkatout, I; Egberts, J-H; Mettler, L; Doniec, M; Wedel, T; Jünemann, K-P; Becker, T; Jonat, W; Schollmeyer, T
Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50 % of teenagers and up to 32 % of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60 % and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep
Wang, Bin; Zhang, Rongrong; Jin, Fan; Lou, Hangying; Mao, Yuchan; Zhu, Wenting; Zhou, Wei; Zhang, Ping; Zhang, Jun
Endometriosis is one of the main causes for female infertility. Previous studies suggested that perfluoroalkyl substances (PFASs), a group of ubiquitous environmental chemicals with properties of endocrine disruption and reproductive toxicity, were risk factors for endometriosis but there lacks direct evidence on the possible role of PFASs in endometriosis-related infertility. To fill this gap, we examined the association between PFASs and endometriosis-related infertility among Chinese reproductive-age women in a case-control study, which comprised 157 surgically confirmed endometriosis cases and 178 controls seeking infertility treatment because of male reproductive dysfunction in 2014 and 2015. Blood specimens were collected at the enrollment and analyzed for ten PFASs. Logistic regression was utilized to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for individual PFAS compound. Plasma concentrations of perfluorobutane sulfonic acid (PFBS) were associated with an increased risk of endometriosis-related infertility (second vs. lowest tertile: OR=3.74, 95% CI: 2.04, 6.84; highest vs. lowest tertile: OR=3.04, 95% CI: 1.65, 5.57). This association remained consistent when we restricted to subjects with no previous pregnancy (second vs. lowest tertile: OR=2.91, 95% CI: 1.28, 6.61; highest vs. lowest tertile: OR=3.41, 95% CI: 1.52, 7.65) or to subjects without other gynecologic pathology (second vs. lowest tertile: OR=4.65, 95% CI: 2.21, 9.82; highest vs. lowest tertile: OR=3.36, 95% CI: 1.58, 7.15). Plasma concentrations of perfluoroheptanoic acid (PFHpA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were inversely associated with endometriosis-related infertility, but the associations were attenuated in the sensitivity analyses. Our preliminary evidence suggests that exposure to PFBS may increase the risk of female infertility due to endometriosis. Future prospective studies are necessary to confirm these
Borghese, B; Vaiman, D; de Ziegler, D; Chapron, C
Endometriosis is a very frequent and debilitating disease responsible for a considerable socio-economic toll. In spite of that, its pathogenesis remains enigmatic. Endometriosis is hold for a multifactorial pathology resulting from the mixed effects of environmental and genetic factors. To date, few susceptibility factors have been reported, with the exception of some polymorphisms in estrogen and progesterone receptors. Large-scale expressional studies have clearly demonstrated that endometriosis is a hormone-dependant disease, characterized by three main features: (i) inflammation, (ii) excessive production of estrogens, and (iii) progesterone resistance. Endometriosis is also considered as a benign metastatic disease, closely linked to cancer. However, the risk of malignant transformation appears to be very limited, likely by a systematic repression of the genes involved in cell cycle and a specific regulation of the HOX genes. Lastly, endometriosis might result from abnormalities of the eutopic endometrium, which show the same molecular alterations than the ectopic endometrium, to a lesser extent however. These alterations, possibly occurring during the embryonic life through epigenetic and genetic predisposition, could lead to an earlier and non-invasive diagnosis for endometriosis.
Dell'oro, M; Collinet, P; Robin, G; Rubod, C
Deep endometriosis is a frequent disease that affects reproductive age women. This disease is characterized by the presence of functional endometrium-like tissue outside the uterus. The common sites of extragenital endometriosis are the bowel and the urinary tract. This disease is also associated with infertility. Furthermore, this disease can cause physical and psychological damage. Therefore, it is really important to develop a multidisciplinary approach in the aim to offer the appropriate treatment. The multidisciplinary team approach for endometriosis is developing to improve the understanding of endometriosis and a multidisciplinary committee for endometriosis was developed in our center. During this meeting, gynecologic, digestive surgeons, urologist, radiologist, procreative medical assistance physicians analyse the case. The role of surgery, before, after or as an alternative to in vitro fertilization (IVF) must be defined. The role of the medical treatment before or after the surgery, before the IVF shall be discussed in order to propose the optimal treatment. In fact, radical surgery is no more recommended and minimally invasive conservative surgery is encouraged in order to preserve the fertility. The multidisciplinary approach permits an appropriate optimal and personalised management of this multifocal disease. The multidisciplinary team approach helps in the development of evidence-based guidelines for the diagnosis and management of endometriosis.
Benali, Silvia; Giannuzzi, Diana; Mantovani, Roberto; Castagnaro, Massimo; Falomo, Maria Elena
Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2~4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis. PMID:22705739
Stilley, Julie A W; Birt, Julie A; Sharpe-Timms, Kathy L
Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%-15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman's reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis.
Vidakovic, Snezana; Milic, Natasa; Jeremic, Katarina; Markovic, Milos; Milosevic-Djeric, Ana; Lazovic-Radonjic, Gordana
Summary Background The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. Methods This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann – Whitney test. Results There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). Conclusions Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis. PMID:28356866
Glavind, Maria Tølbøll; Forman, Axel; Arendt, Linn Håkonsen; Nielsen, Karsten; Henriksen, Tine Brink
To study the association between endometriosis and risk of pre-eclampsia, cesarean section, postpartum hemorrhage, preterm birth, and small for gestational age (SGA), in a large Danish birth cohort, while taking fertility treatment into account. Population-based study. Not applicable. A total population of 82,793 singleton pregnancies from the Aarhus Birth Cohort (1989 through 2013); 1,213 women had a diagnosis of endometriosis, affecting 1,719 pregnancies. None. Pre-eclampsia, cesarean section, postpartum hemorrhage, preterm birth, and SGA. Endometriosis was associated with an increased risk of preterm birth (adjusted odds ratio [AOR] 1.67, 95% confidence interval [CI] 1.37-2.05), with the risk being highest for very preterm birth (AOR 1.91, 95% CI 1.16-3.15). Compared with unaffected women, women with endometriosis also had an increased risk of pre-eclampsia (AOR 1.37, 95% CI 1.06-1.77) and cesarean section (AOR 1.83, 95% CI 1.60-2.09). Assisted reproductive technology did not explain these findings. No association was found between endometriosis and postpartum hemorrhage or SGA. Women with endometriosis were at increased risk of pre-eclampsia, preterm birth, and cesarean section, irrespective of use of assisted reproductive technology. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Somigliana, Edgardo; Busnelli, Andrea; Benaglia, Laura; Viganò, Paola; Leonardi, Marta; Paffoni, Alessio; Vercellini, Paolo
The clinical management of women with deep peritoneal endometriosis remains controversial. The debate focuses mainly on the precise role of hormonal medical treatment and surgery and on the most suitable surgical technique to be used. In particular, considering the risks of second-line surgery, prevention of recurrences after first-line surgery is a priority in this context. Post-surgical medical therapy has been advocated to improve the effectiveness of surgery and prevent recurrences. However, adjuvant therapy, i.e. a short course of 3-6 months of hormonal therapy after surgery, has been proven to be of limited or no benefit for endometriosis in general and for deep peritoneal endometriosis in particular. On the other hand, two cohort studies suggest a beneficial effect of prolonged hormonal therapy after surgery for deep endometriosis. Even if this evidence is too weak to confidently advocate systematic administration of prolonged medical therapy after surgery, we argue in favour of this approach because of the strong association of deep endometriosis with other disease forms. In fact, women operated on for deep endometriosis may also face recurrences of endometriomas, superficial peritoneal lesions and pelvic pain in general. The demonstrated high effectiveness of prolonged postoperative therapy for the prevention of endometriomas' formation and dysmenorrhea recurrence should thus receive utmost consideration in the decision-making process. Copyright © 2017 Elsevier B.V. All rights reserved.
Egekvist, Anne G; Marinovskij, Edvard; Forman, Axel; Kesmodel, Ulrik S; Riiskjaer, Mads; Seyer-Hansen, Mikkel
The aim of the study was to assess the risk of surgery after initial conservative treatment of rectosigmoid endometriosis in relation to demographic data. The study was conducted on the tertiary endometriosis referral unit, Aarhus University Hospital. Medical records, from patients seen from January 2009 onwards with a diagnosis of rectosigmoid endometriosis and more than 6 months' follow up were audited. Demographic data, results of magnetic resonance imaging and time to secondary surgery for rectosigmoid endometriosis were registered. Data on 238 patients diagnosed with rectosigmoid endometriosis were included. In all, 78 (32.8%) patients had primary surgery, 27 (11.3%) had secondary surgery and 133 (55.9%) continued conservative treatment throughout the observation period. Patients who underwent primary or secondary surgery were younger than patients continuing conservative treatment. In a tertiary referral center where about half of patients with rectosigmoid endometriosis were scheduled for conservative treatment, more than 80% of these avoided surgery. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.
Liu, Kai; Zhang, Wei; Liu, Songyang; Dong, Bingfei; Liu, Yahui
Hepatic endometriosis is one of the rarest disorders characterized by the presence of ectopic endometrium in the liver. To our knowledge, only 21 cases of hepatic endometrioma have been described in the medical literature. We report a case of a 36-year-old primiparous female with hepatic endometriosis forming a large cystic mass. The patient presented once with severe right quadrant pain as her only symptom and no history of endometriosis. Complete blood count and biochemical tests were normal. Abdominal ultrasonography and computed tomography scans suggested the presence of a 6.5 × 6.0 cm cystic mass in segment III of the liver. The mass was completely removed by local liver resection. The intraoperative frozen sections suggested a diagnosis of hepatic endometriosis. The diagnosis was confirmed through histological immunostaining without intrinsic abnormality. A preoperative diagnosis of hepatic endometriosis is made on the basis of considering the possibility in advance. Hepatic endometriosis should be considered in the differential diagnosis of a cystic liver mass despite conducting exhaustive investigations in the absence of characteristic clinical and radiological features. Histological examination is essential, and surgery remains the treatment of choice.
Avcioğlu, Sümeyra Nergiz; Altinkaya, Sündüz Özlem; Küçük, Mert; Demircan-Sezer, Selda; Yüksel, Hasan
Objective. The aim of this study was to investigate whether platelet indices-mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) would be useful as noninvasive biomarkers for determining the severity of endometriosis. Methods. A retrospective review of the medical charts of 164 patients diagnosed with endometriosis and who were operated on between 2001 and 2013 was performed. The stage of endometriosis was determined according to revised American Society for Reproductive Medicine criteria. Results. In patients with advanced endometriosis (Stages 3-4), PLT, PCT levels were found to be significantly higher and MPV, PDW values to be significantly lower when compared to initial endometriosis (Stages 1-2). In addition, there was a significant positive correlation between PLT (r: 0.800, P: 0.001) and PCT (r: 0.727, P: 0.002) and the inflammatory marker white blood cell count (WBC). Conclusion. Our finding may not sufficient for employing platelet indices solely in this differential diagnosis, but our finding could provide a suggestion for clinical physicians so that attention is paid to the value of platelet indices and that these may be taken into account when making decisions about the initial or advanced stages of endometriosis. PMID:25006484
Friend, David R
Endometriosis and uterine fibroids (also known as uterine leiomyomas) are serious medical conditions affecting large numbers of women worldwide. Many women are asymptomatic but those with symptoms require medical intervention to relieve chronic pain and dysmenorrhea and to address infertility. Drug delivery has played a role in reducing some of the symptoms associated with endometriosis and uterine fibroids. Use of drug delivery systems for both conditions can roughly be divided into two categories: (1) existing systems designed for other indications such as contraception for symptomatic relief and (2) development of novel systems aimed at addressing some of the underlying biochemical changes associated with endometriosis and uterine fibroids such as oxidative stress, angiogenesis, and matrix degradation. The latter drug delivery approaches rely heavily on nanotechnology. Existing systems that deliver estrogens and/or progestins include vaginal rings, transdermal patches, and intrauterine systems. Long-acting implantable contraceptives such as Implanon® and injectables such as Depo-Provera® have found use in treating endometriosis. Similarly, long-acting GnRH products (e.g., Lupron Depot®) are used to treat endometriosis. Other drugs formulated in long-acting formulations include intravaginal rings capable of delivering selective progesterone receptor modulators, androgens such as danazol, and aromatase inhibitors (e.g., anastrozole). Nanoparticles composed of silica, poly(lactic-co-glycolic acid), cerium oxide, dendrimers, and chitosan/polyethyleneamine have all been investigated to improve treatment of endometriosis and to a lesser extent, uterine fibroids.
Mishra, Vineet V.; Nanda, Sakshi; Gandhi, Khushali; Aggarwal, Rohina; Choudhary, Sumesh; Gondhali, Raveendra
BACKGROUND: Female sexual dysfunction (FSD) in Indian women is often overlooked due to cultural beliefs and considered as social taboos. Sexuality is an important and integral part of life. There are many causes of sexual dysfunction, but the prevalence of FSD in endometriotic patients is still underdiagnosed. MATERIALS AND METHODS: Study design - Cross-sectional observational study conducted at tertiary care center, from June 2015 to March 2016. Sample size - Fifty-one patients in reproductive age group (18–47 years) who were diagnosed with endometriosis on diagnostic laparoscopy were included. Methods - FSD was assessed with a detailed 19-item female sexual function index questionnaire. All six domains of sexual dysfunction, i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain were studied. Exclusion - Patients with other gynecological, medical or surgical history were excluded. RESULTS: Out of 51 patients with endometriosis, 47.06% of patients had sexual dysfunction. With the increase in staging of endometriosis, sexual dysfunction prevalence is also rising. FSD was 100% in patients with severe endometriosis as compared to 33.33% in minimal endometriosis. CONCLUSION: Every individual deserves good sexual life. The sexual dysfunction associated with endometriosis should also be taken into consideration while managing these patients. PMID:28216913
Wei, Jian-Jun; William, Josette; Bulun, Serdar
Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592
Polak, Grzegorz; Wertel, Iwona; Kwaśniewski, Wojciech; Derewianka-Polak, Magdalena; Kotarski, Jan
Despite many years of extensive investigations and increasing number of studies, the pathogenesis of endometriosis remains unclear Accumulated data suggests that disrupted iron metabolism may induce oxidative stress in the peritoneal cavity of endometriosis patients.
Rogers, Peter A W; D'Hooghe, Thomas M; Fazleabas, Asgerally; Giudice, Linda C; Montgomery, Grant W; Petraglia, Felice; Taylor, Robert N
Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.(1) A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.
Kervancioglu, Selim Andic, Cagatay; Bayram, Nazan; Telli, Cumali; Sarica, Akif; Sirikci, Akif
Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.
Bawazeer, Naif A; Al-Jifree, Hatim M; Gari, Abdulrahim M
The malignant transformation of persistent endometriotic implants into endometrioid adenocarcinoma is rare, especially after remote hysterectomy and salpingo-oophorectomy (TAH-BSO), and there are few cases reported in the English language literature. Patients receiving estrogen replacement therapy are common among the reported cases. We present a case that demonstrates the possibility of malignant transformation in a 53-year-old female, known case of endometriosis, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with no evidence of malignancy in the final pathology report. After 9 years, she presented with lower abdominal mass, and histopathological studies confirmed the diagnosis of well-differentiated endometrioid adenocarcinoma. The possibility of malignant transformation and possible risk factors are discussed with a brief literature review.
Bawazeer, Naif A.; Al-Jifree, Hatim M.; Gari, Abdulrahim M.
The malignant transformation of persistent endometriotic implants into endometrioid adenocarcinoma is rare, especially after remote hysterectomy and salpingo-oophorectomy (TAH-BSO), and there are few cases reported in the English language literature. Patients receiving estrogen replacement therapy are common among the reported cases. We present a case that demonstrates the possibility of malignant transformation in a 53-year-old female, known case of endometriosis, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with no evidence of malignancy in the final pathology report. After 9 years, she presented with lower abdominal mass, and histopathological studies confirmed the diagnosis of well-differentiated endometrioid adenocarcinoma. The possibility of malignant transformation and possible risk factors are discussed with a brief literature review. PMID:25399218
Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N.; Nyholt, Dale R.; Morris, Andrew P.; Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G.; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T.; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G.; Bruinsma, Fiona; Kjaer, Susanne K.; Hildebrandt, Michelle A.T.; Liang, Dong; Lu, Karen H.; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A.; Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Brooks-Wilson, Angela; Olson, Sara H.; McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.; Cook, Linda S.; Le, Nhu D.; Gilks, C. Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P.; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R.; Narod, Steven A.; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J.; Wu, Anna H.; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M.; Fridley, Brooke L.; Winham, Stacey J.; Bandera, Elisa V.; Poole, Elizabeth M.; Morgan, Terry K.; Risch, Harvey A.; Goode, Ellen L.; Schildkraut, Joellen M.; Webb, Penelope M.; Pearce, Celeste L.; Berchuck, Andrew; Pharoah, Paul D.P.; Montgomery, Grant W.; Zondervan, Krina T.; Chenevix-Trench, Georgia; MacGregor, Stuart
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18–0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07–0.89 and 0.40, 95% CI = 0.05–0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11–0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. PMID:26231222
Vlek, Stijn L; Lier, M C I; Ankersmit, M; Ket, Johannes C F; Dekker, J J M L; Mijatovic, V; Tuynman, J B
Endometriosis is a common disease associated with pelvic pain and subfertility. Laparoscopic surgical treatment has proven effective in endometriosis, but is hampered by a high rate of recurrence. The aim of this systematic review was to evaluate the intraoperative identification of endometriosis by enhanced laparoscopic imaging techniques, focusing on sensitivity and specificity. A systematic review was conducted according to PRISMA guidelines in PubMed, Embase, Cochrane Library, and Web of Science. Published prospective studies reporting on enhanced laparoscopic imaging techniques during endometriosis surgery were included. General study characteristics and reported outcomes, including sensitivity and specificity, were extracted. Nine studies were eligible for inclusion. Three techniques were described: 5-ALA fluorescence (5-ALA), autofluorescence (AFI), and narrow-band imaging (NBI). The reported sensitivity of 5-ALA and AFI for identifying endometriosis ranged from 91% to 100%, compared with 48% to 69% for conventional white light laparoscopy (WL). A randomized controlled trial comparing NBI + WL with WL alone reported better sensitivity of NBI (100% vs 79%; p < .001). All 9 studies reported an enhanced detection rate of endometriotic lesions with enhanced imaging techniques. Enhanced imaging techniques are a promising additive for laparoscopic detection and treatment of endometriosis. The 5-ALA, AFI, and NBI intraoperative imaging techniques had a better detection rate for peritoneal endometriosis compared with conventional WL laparoscopy. None of the studies reported clinical data regarding outcomes. Future studies should address long-term results, such as quality of life, recurrence, and need for reoperation. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.
Furuya, Masataka; Masuda, Hirotaka; Hara, Kanako; Uchida, Hiroshi; Sato, Kenji; Sato, Suguru; Asada, Hironori; Maruyama, Tetsuo; Yoshimura, Yasunori; Katabuchi, Hidetaka; Tanaka, Mamoru; Saya, Hideyuki
Although endometriosis is a benign disease, it shares some features with cancers, such as invasiveness and the potential to metastasize. This study sought to investigate the epithelial-mesenchymal transition status in human endometriotic lesions. Thirteen endometriosis patients and 10 control women without endometriosis undergoing surgery for benign indications were recruited. We examined the expression of E-cadherin, vimentin, and epithelial-mesenchymal transition-induced transcriptional factors, such as Snail and ZEB1, by immunohistochemistry. We evaluated the expression of each marker in epithelial cells of both endometriotic lesions (ovarian endometrioma, deep infiltrating endometriosis, adenomyosis) and normal endometria. The correlation between ZEB1 expression and serum level of CA125 was also investigated. Immunohistochemical analysis revealed that although E-cadherin, vimentin, and Snail were expressed in epithelia of normal endometria and endometriotic lesions, ZEB1 expression was only expressed in epithelia of endometriotic lesions. Additionally, ZEB1 was most frequently observed in epithelial cells of invasive endometriosis. The endometriosis patients with high serum CA125 level were more likely to have ZEB1-positive lesions. This is the first observation of ZEB1 expression in epithelial cells of benign disease. The preferential expression of ZEB1 in epithelial cells of endometriotic lesions suggests that these cells may have, at least in part, a higher level of mesenchymal features possibly via ZEB1-driven epithelial-mesenchymal transition than normal endometria and that ZEB1 can be a potential indicator of invasiveness or severity of endometriosis. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.
Berlac, Janne Foss; Hartwell, Dorthe; Skovlund, Charlotte Wessel; Langhoff-Roos, Jens; Lidegaard, Øjvind
The objective of this study was to assess obstetrical complications and neonatal outcomes in women with endometriosis as compared with women without endometriosis. National cohort including all delivering women and their newborns in Denmark 1997-2014. Data were extracted from the Danish Health Register and the Medical Birth Register. Logistic regression analysis provided odds ratios (OR) with 95% confidence intervals (CI). Sub-analyses were made for primiparous women with a singleton pregnancy and for women with endometriosis who underwent gynecological surgery before pregnancy. In 19 331 deliveries, women with endometriosis had a higher risk of severe preeclampsia (OR 1.7, 95% CI 1.5-2.0), hemorrhage in pregnancy (OR 2.3, 95% CI 2.0-2.5), placental abruption (OR 2.0, 95% CI 1.7-2.3), placenta previa (OR 3.9, 95% CI 3.5-4.3), premature rupture of membranes (OR 1.7, 95% CI 1.5-1.8), and retained placenta (OR 3.1, 95% CI 1.4-6.6). The neonates had increased risks of preterm birth before 28 weeks (OR 3.1, 95% CI 2.7-3.6), being small for gestational age (OR 1.5, 95% CI 1.4-1.6), being diagnosed with congenital malformations (OR 1.3, 95% CI 1.3-1.4), and neonatal death (OR 1.8, 95% CI 1.4-2.1). Results were similar in primiparous women with a singleton pregnancy. Gynecological surgery for endometriosis before pregnancy carried a further increased risk. Women with endometriosis had a significantly higher risk of several complications, such as preeclampsia and placental complications in pregnancy and at delivery. The newborns had increased risk of being delivered preterm, having congenital malformations, and having a higher neonatal death rate. Pregnant women with endometriosis require increased antenatal surveillance. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.
Dinsdale, Natalie L; Crespi, Bernard J
Hippocrates attributed women's high emotionality - hysteria - to a 'wandering womb'. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin's associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.
Cassini, Diletta; Cerullo, Guido; Miccini, Michelangelo; Manoochehri, Farshad; Ercoli, Alfredo; Baldazzi, Gianandrea
Deep pelvic endometriosis is a complex disorder that affects 6% to 12% of all women in childbearing age. The incidence of bowel endometriosis ranges between 5.3% and 12%, with rectum and sigma being the most frequently involved tracts, accounting for about 80% of cases. It has been reported that segmental colorectal resection is the best surgical option in terms of recurrence rate and improvement of symptoms. The aim of this study is to analyze indications, feasibility, limits, and short-term results of robotic (Da Vinci Surgical System)-assisted laparoscopic rectal sigmoidectomy for the treatment of deep pelvic endometriosis. Between January 2006 and December 2010, 19 women with bowel endometriosis underwent colorectal resection through the robotic-assisted laparoscopic approach. Intraoperative and postoperative data were collected. All procedures were performed in a single center and short-term complications were evaluated. Nineteen robotic-assisted laparoscopic colorectal resections for infiltrating endometriosis were achieved. Additional procedures were performed in 7 patients (37%). No laparotomic conversion was performed. No intraoperative complications were observed. The mean operative time was 370 minutes (range = 250-720 minutes), and the estimated blood loss was 250 mL (range = 50-350 mL). The overall complication rate was 10% (2 rectovaginal fistulae). Deep pelvic endometriosis is a benign condition but may have substantial impact on quality of life due to severe pelvic symptoms. We believe that robotic-assisted laparoscopic colorectal resection is a feasible and relatively safe procedure in the context of close collaboration between gynecologists and surgeons for treatment of deep pelvic endometriosis with intestinal involvement, with low rates of complications and significant improvement of intestinal symptoms.
Sayegh, Lamia; Fuleihan, Ghada El-Hajj; Nassar, Anwar H
The aim of this paper is to review the evidence from studies that evaluated the relationship between vitamin D and endometriosis. Comprehensive review. Systematic literature search in Medline for relevant publications from 1946 until June 2013. Endometriosis risk may be influenced by dietary vitamin D intake and plasma hydroxyvitamin D concentration. Vitamin D receptor and vitamin D metabolizing enzymes, 24-hydroxylase and 1-α hydroxylase, are found in the normal cycling endometrium and also in the eutopic and ectopic endometrium of women with endometriosis. The endometrium is a target of 1, 25 dihydroxyvitamin D actions through regulation of specific genes and via immunomodulation. The endometrium in endometriosis expresses dysregulation of some vitamin D enzymes and receptors. If vitamin D and its metabolites are implicated in endometriosis-associated infertility, it is likely through interference with HOXA10 gene expression. The Gc2 phenotype of vitamin D binding protein is prevalent in women with endometriosis and may be implicated in its pathogenesis. In a mouse model, Elocalcitol, a VDR-agonist was shown to reduce the development of endometriotic lesions and recurrence. A biological plausibility for a role of vitamin D, as an immunomodulator and anti-inflammatory agent, in the pathogenesis and treatment of endometriosis is suggested in this article, but is difficult to illustrate due to sparse evidence from human studies limited primarily to case-control studies. A significant knowledge gap precludes the establishment of a clear cause-effect relationship. The intriguing leads presented herein need to be investigated further with placebo-controlled supplementation trials. © 2013.
Buck Louis, Germaine M; Backonja, Uba; Schliep, Karen C; Sun, Liping; Peterson, C Matthew; Chen, Zhen
Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs <1.0 denote a longer TTP or diminished fecundity. Approximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ≈29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently <1.0, irrespective of endometriosis staging, CIs included 1. Women with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment.
Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N; Nyholt, Dale R; Morris, Andrew P; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Gilks, C Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Risch, Harvey A; Goode, Ellen L; Schildkraut, Joellen M; Webb, Penelope M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Montgomery, Grant W; Zondervan, Krina T; Chenevix-Trench, Georgia; MacGregor, Stuart
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
Trabert, Britton; De Roos, Anneclaire J.; Schwartz, Stephen M.; Peters, Ulrike; Scholes, Delia; Barr, Dana B.; Holt, Victoria L.
Background Endometriosis, a gynecologic disorder affecting 8–10% of reproductive-age women in the United States, is defined as the presence of endometrial tissue outside the uterus and is linked to pelvic pain and infertility. Environmental contaminants, including polychlorinated biphenyls (PCBs), are hypothesized to contribute to endometriosis risk through effects on steroid hormones. Objective We evaluated serum concentrations of certain noncoplanar PCBs, which have no or only weak dioxin-like properties, as risk factors for endometriosis. Methods In a case–control study of Group Health enrollees in western Washington State, 20 PCB congeners were measured in serum from surgically confirmed endometriosis cases that were newly diagnosed between 1996 and 2001 (n = 251) and from female controls matched for age and reference year (n = 538). Results Summed and estrogenic PCB concentrations were not associated with endometriosis risk [summed: odds ratio (OR) = 1.3; 95% confidence interval (CI), 0.8–2.2; estrogenic: OR = 1.1; 95% CI, 0.8–1.4]. Although several congener-specific ORs were statistically above or below the null (PCB 170: third quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9; PCB 196: third quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7; PCB 201: second vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; third quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), there were no overall consistent patterns of endometriosis risk. Conclusions Taken in context with other North American studies, our findings suggest that noncoplanar PCB concentrations consistent within the range of exposure currently observed in western Washington State do not contribute meaningfully to endometriosis risk. PMID:20423815
Brown, Julie; Farquhar, Cindy
This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis. The objective of this overview was to summarise the evidence from Cochrane systematic reviews on treatment options for women with pain or subfertility associated with endometriosis. Published Cochrane systematic reviews reporting pain or fertility outcomes in women with clinically diagnosed endometriosis were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation (protocols and titles) for future inclusion. The reviews, protocols and titles were identified by searching the Cochrane Database of Systematic Reviews and Archie (the Cochrane information management system) in March 2014.Pain-related outcomes of the overview were pain relief, clinical improvement or resolution and pain recurrence. Fertility-related outcomes were live birth, clinical pregnancy, ongoing pregnancy, miscarriage and adverse events.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed using the AMSTAR tool. The quality of the evidence for each outcome was assessed using GRADE methods. Review findings were summarised in the text and the data for each outcome were reported in 'Additional tables'. Seventeen systematic reviews published in The Cochrane Library were included. All the reviews were high quality. The quality of the evidence for specific comparisons ranged from very low to moderate. Limitations in the evidence included risk of bias in the primary studies, inconsistency between the studies, and imprecision in effect estimates. Pain relief (14 reviews) Gonadotrophin-releasing hormone (GnRH) analogues One systematic review reported low quality evidence of an overall benefit for GnRH analogues compared with placebo or no treatment. Ovulation suppression Five systematic reviews reported on medical treatment using ovulation suppression. There
Kodati, V L; Govindan, S; Movva, S; Ponnala, S; Hasan, Q
Endometriosis is the presence of endometrial cells and stroma at ectopic sites outside the uterine cavity. The natural history of endometriosis is uncertain, its etiology unknown, the clinical presentation inconsistent, diagnosis difficult and the treatment poorly standardized. It causes significant morbidity due to pelvic pain and infertility among 15-25% of women during their reproductive age. The benign disease causes peritoneal inflammation, fibrosis, adhesions and ovarian cysts but displays features of malignancy, like neo-vascularization, local invasion and distant metastasis. Mechanical, hormonal, immunological, environmental and genetic factors have been implicated in its etiology but provide inconclusive explanations. Present study was carried out on ectopic and eutopic endometriotic tissue specimens collected during laproscopy/laprotomy from cases of endometriosis. mRNA was isolated from the tissues and converted to cDNA by RT and subsequently subjected to differential display Polymerase Chain Reaction using seven sets of arbitrary primers. A unique band was identified only in the ectopic endometriotic tissue, which was sequenced. BLAST search results revealed sequence homology to shigella bacterial DNA leading us to hypothesize that infection may be playing a role in the etiology of endometriosis. This is the first report implicating the role of bacterial infection in the etiology of endometriosis. Shigella is known to invade the mucosa of the colon through the feco-oral route causing Shigellosis. The pathogenesis of shigellosis involves inflammation, ulceration, haemorrhage, tissue destruction and fibrosis of the colonic mucosa resulting in abdominal pain and diarrhoea/dysentery, this is similar to the pathogenesis of endometriosis which also involves inflammation, haemorrhage, tissue destruction and fibrotic adhesions of the pelvic peritoneum resulting in abdominal pain and infertility. The non-motile shigella bacteria invade the deeper mucosal layers
Furuya, Kenta; Otsuka, Hajime; Koezuka, Satoshi; Makino, Takashi; Hata, Yoshinobu; Wakayama, Megumi; Shibuya, Kazutoshi; Iyoda, Akira
Pulmonary endometriosis is a gynecological disorder in which endometrial tissue grows outside of the uterine cavity. Usually, the ectopic implants are located in the pelvis and manifest as dysmenorrhea, chronic pelvic pain, or infertility. Pulmonary endometriosis sometimes occurs in the pleurae and can result in catamenial pneumothorax; however, true pulmonary endometriosis, tissue growing in the lung itself, is rare. We report a 22-year-old patient with pulmonary endometriosis and catamenial hemoptysis. Pulmonary endometriosis was proved histologically and treated successfully by wedge resection using video-assisted thoracoscopic surgery.
Kimball, Kristopher J.; Gerten, Kimberly A.; Conner, Michael G.; Richter, Holly E.
Background Umbilical endometriosis is rare and can be a challenging diagnosis in the absence of classic signs and symptoms. Case A case of severe primary spontaneous umbilical endometriosis with foci of plasma cell endometritis and diffuse stromal lymphvascular presence is reported. Conclusion Despite a lengthy differential, endometriosis must be considered in the evaluation of an umbilical mass. The presence of plasma cell endometritis and stromal lymphvascular elements in the absence of pelvic endometriosis lend evidence to the theory of lymphvascular transport as an etiology of extra-pelvic endometriosis. PMID:18251362
Ishida, Chiharu; Mori, Masahiko; Nakamura, Kae; Tanaka, Hiromasa; Mizuno, Masaaki; Hori, Masaru; Iwase, Akira; Kikkawa, Fumitaka; Toyokuni, Shinya
Endometriosis is observed in ∼10% of reproductive age women. Ovarian endometriosis not only causes dysmenorrhea but also causes infertility and a high risk of adenocarcinoma. Due to its scattered nature, complete surgical resection is difficult. Endometriosis consists of glandular and stromal cells. Previously, we showed that endometrial stromal cells (ESCs) play a role in the protection against pathologic events caused by monthly repeated hemorrhage. Here, we undertook a preclinical study of non-thermal plasma (NTP) as a surgical treatment of endometriosis. Epithelial cells were most sensitive to NTP-activated medium in vitro, whereas ectopic ESCs were most resistant. We then transplanted excised uteruses into BALB/c mice from donors of the same strain with estradiol supplementation. Four weeks after the transplantation, we exposed NTP to each endometriotic lesion after laparotomy. Immunohistochemical analysis revealed that immediately after NTP exposure, epithelial cells exhibited significantly higher levels of nuclear immunostaining for 8-hydroxy-2'-deoxyguanosine than did stromal cells. Four weeks after NTP exposure, the total surface area consisting of endometriotic cysts was significantly smaller with less epithelial proliferative activity than the helium-exposed control, whereas the number of endometriotic lesions had not changed. Therefore, NTP exposure may be useful to prevent the progression and recurrence of endometriosis.
Letsiou, Sophia; Peterse, Dirkje P; Fassbender, Amelie; Hendriks, Margriet M; van den Broek, Niels J; Berger, Rudolf; O, Dorien F; Vanhie, Arne; Vodolazkaia, Alexandra; Van Langendonckt, Anne; Donnez, Jacques; Harms, Amy C; Vreeken, Rob J; Groothuis, Patrick G; Dolmans, Marie-Madeleine; Brenkman, Arjan B; D'Hooghe, Thomas M
To identify metabolites that are associated with and predict the presence of endometriosis. Metabolomics study using state-of-the-art mass spectrometry approaches. University hospital and universities. Twenty-five women with laparoscopically confirmed endometriosis (cases) and 19 women with laparoscopically documented absence of endometriosis (controls). None of the women included in this study had received oral contraception or GnRH agonists for a minimum of 1 month before blood collection. Plasma collection. Metabolite profiles were generated and interrogated using multiple mass spectrometry methods, that is, high performance liquid chromatography coupled with negative mode electrospray ionization tandem mass spectrometry, UPLC-MS/MS, and ultra performance liquid chromatography-electroSpray ionization-quadrupole time-of-flight (UPLC-ESI-Q-TOF). Metabolite groups investigated included phospholipids, glycerophospholipids, ether-phospholipids, cholesterol-esters, triacylglycerol, sphingolipids, free fatty acids, steroids, eicosanoids, and acylcarnitines. A panel of acylcarnitines predicted the presence of endometriosis with 88.9% specificity and 81.5% sensitivity in human plasma, with a positive predictive value of 75%. However, due to data limitations the outcome of the receiver operating characteristic curve analysis was not significant. A diagnostic model based on acylcarnitines has the potential to predict the presence and stage of endometriosis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Binda, Maria Mercedes; Donnez, Jacques; Dolmans, Marie-Madeleine
Endometriosis is a chronic estrogen-dependent inflammatory disease of unclear etiology that affects 15-20% of women of reproductive age. Efforts are now focusing on understanding new mechanisms involved in its physiopathology, like novel target pathways and different molecules. There is evidence that mast cells (MCs) play a role in this disease. This article summarizes recent achievements in preclinical studies and clinical activities investigating the role of MCs in endometriosis. Targeting MCs might offer new alternatives to treat this disease. Areas covered: A systematic literature search was performed (PubMed, Cochrane Library and ClinicalTrials.gov) using the keywords 'endometriosis and mast cells'. All relevant articles (34) found in PubMed were examined and their reference lists reviewed in order to pinpoint further studies for potential inclusion. Expert opinion: Since endometriosis is a multifactorial disease, and considering that numbers of MCs and activated MCs were clearly increased in endometriotic lesions in both animals and humans, use of MC stabilizers and inhibitors may prove to be effective to treat endometriosis and its associated pain. However, more data from preclinical studies and clinical trials will help to better define the status of MCs in the treatment of this pathology.
Reis, Fernando M.; Petraglia, Felice; Taylor, Robert N.
BACKGROUND The recruitment of immune cells by chemokines and the regulation of endometrial cell apoptosis are critical aspects of endometriosis biology. Here, we review the local (paracrine) and systemic hormone (endocrine) modulation of these two specific, but highly related phenomena. METHODS We searched Pubmed for items published in English between September 1991 and September 2011 and selected the studies evaluating the effects of hormones on chemokines or apoptosis in normal human endometrium and endometriosis. RESULTS Estradiol has proinflammatory and antiapoptotic effects in endometrial cells, and these effects appear to be exacerbated in women with endometriosis. In these women, physiological estradiol concentrations are able to induce an enhanced inflammatory response mediated by local chemokine production and to reinforce mechanisms of cell survival mediated by extracellular signal-regulated kinases and Bcl-2. The main effect of progestogens is to inhibit interleukin-8 and other chemokines in stromal cells from both eutopic and ectopic endometrium. Progesterone is also effective in inducing apoptosis in endometrial and endometriotic cells through the inhibition of Bcl-2 and nuclear factor-κB. CONCLUSIONS Estrogens and progestogens modulate chemotaxis and apoptosis in human endometrium and endometriotic cells and tissues. These endocrine and paracrine pathways are perturbed in women with endometriosis, contributing to inflammatory responses, abnormal tissue remodeling, therapeutic refractoriness and disease persistence. Ultimately, they promote adhesion formation and the clinical symptoms of pelvic pain and infertility. A more detailed understanding of the molecular mechanisms involved will offer new opportunities for novel pharmacological strategies to diagnose and treat endometriosis. PMID:23539633
Santos, Tânia Mara Vieira; Pereira, Ana Maria Gomes; Lopes, Reginaldo Guedes Coelho; Depes, Daniela De Batista
To assess lag time between onset of symptoms and diagnosis of endometriosis in patients followed up at the Outpatients Clinic of Endometriosis and Chronic Pelvic Pain, at the Hospital do Servidor Público Estadual de São Paulo "Francisco Morato de Oliveira", from January 2003 to November 2009. In a retrospective analytical study, a total of 310 women with endometriosis confirmed by surgery and pathological examination were evaluated in the period from January 6, 2003 to November 29, 2009. Data were gathered through revision of the follow-up visit forms at the specialized outpatients clinic and medical records. The software Epi-Info 3.3.2 was used for statistical analysis. The mean lag time between onset of symptoms and confirming diagnosis of endometriosis was 46.16 months (3.84 years), ranging from 6 to 324 months. Patients aged under 20 years had a mean time until diagnosis of 2.8 years (33.6 months, range of 6 to 144 months). In patients aged 20-29 years, it was 3.51 years (42.18 months, range 6-192 months). In those aged 30-40 years, the mean time was 4.14 years (49.69 months, range 6-324 months). And in women age over 40 years, it was 3.15 years (37.86 months, range 6-216 months). The lag time between onset of symptoms and diagnosis of endometriosis was shorter, as compared to other national and international evaluations.
Luppi, Stefania; Ricci, Giuseppe
The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. In the last decades, an impressive amount of pharmacological agents have been tested for the treatment of endometriosis-associated pelvic pain. However, only a few of these have been introduced into clinical practice. Following the results of the controlled studies available, to date, the first-line treatment for endometriosis associated pain is still represented by oral contraceptives used continuously. Progestins represent an acceptable alternative. In women with rectovaginal lesions or colorectal endometriosis, norethisterone acetate at low dosage should be preferred. GnRH analogues may be used as second-line treatment, but significant side effects should be taken into account. Nonsteroidal anti-inflammatory drugs are widely used, but there is inconclusive evidence for their efficacy in relieving endometriosis-associated pelvic pain. Other agents such as GnRH antagonist, aromatase inhibitors, immunomodulators, selective progesterone receptor modulators, and histone deacetylase inhibitors seem to be very promising, but there is not enough evidence to support their introduction into routine clinical practice. Some other agents, such as peroxisome proliferator activated receptors-γ ligands, antiangiogenic agents, and melatonin have been proven to be efficacious in animal studies, but they have not yet been tested in clinical studies. PMID:25165691
Juneja, Sunil Kumar; Tandon, Pooja; Chopra, Isha
Scar endometriosis is an infrequent type of extrapelvic endometriosis. The most common extrapelvic form of endometriosis is cutaneous endometriosis, involving scar tissues occurring after obstetric or gynecologic procedures such as episiotomy, hysterotomy, cesarean section, and even laparoscopic surgery. The clinical presentation of scar endometriosis, i.e., tender swellings, mimics other dermatological and/or surgical conditions and delays the diagnosis. Scar endometriosis very rarely can get complicated with uterocutaneous fistula with a reported incidence of very few cases in world literature. We report a case of a 36-year-old woman presenting with scar endometriosis with complicated uterocutaneous fistula 11 years after her last lower segment cesarean section, managed successfully with laparotomy-fistulectomy and sleeve resection of the bladder with repair followed by successful subsequent spontaneous conception and pregnancy terminated by lower segment cesarean section. PMID:27857904
Menakaya, U; Reid, S; Lu, C; Gerges, B; Infante, F; Condous, G
To develop and assess the performance of a preoperative ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis. This was a multicenter prospective and retrospective cohort study on consecutive women with suspected endometriosis who underwent laparoscopy between June 2009 and July 2013. Each woman underwent a systematic transvaginal ultrasound evaluation to assess the pelvis for different phenotypes of endometriosis, and the diagnostic performance of ultrasound for these different phenotypes was evaluated relative to the gold standard, laparoscopy. A three-stage preoperative UBESS was developed to assess the severity of pelvic endometriosis, based on the histological phenotypes of endometriosis, the anatomical locations of deep infiltrating endometriosis and their sonographic markers of local invasiveness. The three stages of UBESS (I-III) were then correlated with the three levels of complexity of laparoscopic surgery for endometriosis described by the Royal College of Obstetricians and Gynaecologists (Levels 1-3). The end-points were the diagnostic performance of UBESS to predict the level of complexity of laparoscopic surgery for endometriosis, i.e. UBESS stage I to predict Level-1 laparoscopic surgery, UBESS stage II to predict Level-2 laparoscopic surgery and UBESS stage III to predict Level-3 laparoscopic surgery. The analysis included 192 women, with a mean ± SD age at diagnosis of endometriosis of 23.7 ± 9.3 years and a mean duration of symptoms prior to presentation of 42 months. Predominant reported locations of pelvic pain were left iliac fossa (32%), right iliac fossa (29.5%) and lower abdomen (61%) and predominant symptoms included dyspareunia (57.5%), dysmenorrhea (58.5%) and dyschezia (41.5%). The accuracy, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of UBESS I for predicting a requirement for Level-1
Bruner-Tran, Kaylon L; Eisenberg, Esther; Yeaman, Grant R; Anderson, Ted A; McBean, Judith; Osteen, Kevin G
The cyclic expression of matrix metalloproteinases (MMPs) by human endometrium has been suggested to play a role in the invasive process necessary to establish endometriosis. The ability of progesterone exposure to inhibit endometrial MMP-3 and MMP-7 expression requires the local action of TGF beta and may also be linked to the local production of retinoic acid by stromal cells. A continuous expression of several MMPs in endometriotic lesions has been reported, indicating a failure of progesterone or locally produced factors to suppress these enzymes. To address cell-specific MMP regulation associated with endometriosis, we examined expression of MMP-3 and MMP-7 mRNA in eutopic endometrium and endometriotic lesions acquired during the secretory phase of the menstrual cycle. We examined the in vitro regulation of MMP-3 and MMP-7 protein in similar tissues. We also examined the in vitro regulation of MMP secretion by progesterone, retinoic acid, and TGF beta in endometriosis tissues relative to the establishment of experimental disease. Our studies indicate that either eutopic or ectopic tissue from women with endometriosis exhibit patterns of altered MMP regulation in vivo. A lack of responsiveness to progesterone was demonstrated in vitro, associated with a failure to suppress MMP expression and an enhanced ability of the tissue to establish experimental endometriosis. However, in vitro treatments with retinoic acid and TGF beta restored the ability of progesterone to suppress MMPs in vitro and prevented the establishment of experimental disease.
Liu, Haiyuan; Lang, Jing He
Summary Endometriosis (EM) is one of the most common diseases which severely affect the health and reproductive function of women of childbearing age. There are fundamental abnormal changes within the eutopic endometrium of women with endometriosis compared to normal endometrium of women without endometriosis. Eutopic endometrium shows enhanced ability of proliferation, implantation and angiogenesis, and greater probability of escaping the unfavorable conditions of the ectopic environment. Therefore, the character of eutopic endometrium determines the fate of the backward-flowing endometrial tissue – to live or to die. The abnormal endometrial tissue in EM patients flows backward to the pelvic cavity, completing a 3-step procedure of pathogenesis (attachment-aggression-angiogenesis), and ultimately develops into EM. Abnormal eutopic endometrium may also play important roles in endometriosis-associated infertility. This recognition regarding the pathogenesis of endometriosis ultimately will help to discover new methods for diagnosis and treatment. Endometrial markers for micro-invasive diagnosis and direct treatment of eutopic endometrium as the origin of the disease should be further investigated. PMID:21455119
Basta, Antoni; Brucka, Aleksandra; Górski, Jarosław; Kotarski, Jan; Kulig, Bartosz; Oszukowski, Przemysław; Poreba, Ryszard; Radowicki, Stanisław; Radwan, Jerzy; Sikora, Jerzy; Skret, Andrzej; Skrzypczak, Jana; Szyłło, Krzysztof
Endometriosis is defined by endometrial glands and stroma outside of the endometrial cavity Three types of endometriosis have been described: peritoneal endometriosis, ovarian endometriosis and deep infiltrating endometriosis. Endometriosis afflicts 6-15% of women population. It occurs mainly in the group of women in reproductive age, but also in the group of minors and approximately 3% of women after menopause. Within the group of women suffering from infertility the frequency of endometriosis increased to 35-50% of cases. Endometriosis is associated with pain symptoms which can bear the character of pain occurring periodically and altering into constant pain, dysmenorrhea, dyspareunia, dysuria and dyschezia. The correlation between the stage of endometriosis and intensity of pain symptoms not always has to be proportionate. Laparoscopy can be perceived as a standard procedure in endometriosis diagnostics as it allows simultaneous treatment. Profound interview as well as visual diagnostics (USG, MRI) should precede laparoscopy Treatment of endometriosis can be divided into pharmacological and surgical treatment, which can be invasive or non-invasive. The type of treatment depends on patient's age and her procreation plans, occurring ailments and endometriosis type. Important role is played by adjuvant treatment such as appropriate diet and lifestyle. Treatment of advanced endometriosis should be conducted in reference centres that are appointed with adequate equipment and have the possibility of interdisciplinary treatment. Presented standards can digest and outline the order of proceedings both in diagnostics and endometriosis treatment. The research group believes that the above compilation will facilitate undertaking appropriate decision in diagnosis and treatment of the disease, which will subsequently contribute to therapeutic success.
Matta, Jaime L.; Flores, Idhaliz; Morales, Luisa M.; Monteiro, Janice; Alvarez-Garriga, Carolina; Bayona, Manuel
Introduction Breast cancer (BC) and endometriosis are important reproductive health diseases for women. Although endometriosis is not a malignant condition, some of its characteristics mimic that of a malignancy. Endometriosis is associated with increased risk of certain cancers; however, whether it alters BC risk is unclear. This study evaluates the association of endometriosis and BC and explores whether DNA repair capacity (DRC) plays a role in such a relationship. Materials and Methods A case-control study of 991 women (385 with BC and 606 controls, all recruited over 5 years) was undertaken in Puerto Rico. Eighty participants with self-reported surgically diagnosed endometriosis were identified, 20 of whom also had a diagnosis of BC. Data from a structured questionnaire and DRC measurements were assessed to determine the association between BC, DRC, and endometriosis. Results Participants with BC cases were 50% less likely to have history of endometriosis (OR = 0.5 95%CI: 0.3, 0.9, p = 0.038) than women without BC controls. Findings that did not reach statistical significance included the following: women with history of endometriosis had a slightly higher DRC level than those without it; BC cases and history of endometriosis were less likely to have had endometriosis diagnosis before age 38 as compared to controls with endometriosis. Discussion Here we report an inverse association between endometriosis and BC, the former possibly conferring a protective effect on the latter. Although the mechanisms involved are unknown they may include protection provided by higher DRC and or hormonal treatments for endometriosis. A larger sample of endometriosis cases is necessary to confirm these results and answer the question of whether a higher DRC capacity may contribute to this potential protection, and to identify other factors at play. PMID:25473592
Canlorbe, Geoffroy; Laas, Enora; Cortez, Annie; Daraï, Emile
Vulvar endometriosis can occur after surgery or trauma and cause dyspareunia. A 30-year-old woman presented with orificial dyspareunia lasting for 5 months. Her history was marked by a vaginal birth without perineal injury and the removal of a cyst from the left Bartholin’s gland. On examination, we observed a selectively painful, superficial and retractile lesion, 5 mm in diameter at the junction of the hymen at some distance from the bartholinitis scar. Endometriosis was suspected due to the exacerbation of pain during menses. The surgery consisted of excision of the hymenal area of the painful lesion. Pathological examination confirmed the presence of endometrial tissue. The painful symptoms resolved and no additional treatment was administered. Any vulvar lesion, regardless of its appearance and location, can be related to endometriosis. Surgical resection is recommended to relieve the symptoms and provide histological proof. PMID:24671316
Fazleabas, Asgerally T
The development of a baboon model of induced endometriosis, which recapitulates the retrograde menstruation hypothesis, has greatly facilitated our understanding of the early events associated with the disease process. Sequential analysis of the eutopic endometrium following the establishment of disease suggests that the development of progesterone resistance is a gradual process and becomes evident after 6 months of disease induction. This resistance is manifested by a decreased responsiveness of the progesterone receptor and its chaperone immunophilins as well as epigenetic modifications of progesterone-regulated genes. In comparative studies, the time-dependent changes observed in the baboon eutopic endometrium are similar to those that have been reported to be altered in women with endometriosis. The baboon model therefore provides insight into the potential mechanisms by which genes in the eutopic endometrium are dysregulated and how this alteration results in infertility that is associated with endometriosis.
Djokovic, Dusan; Calhaz-Jorge, Carlos
Emerging evidence indicates that somatic stem cells (SSCs) of different types prominently contribute to endometrium-associated disorders such as endometriosis. We reviewed the pertinent studies available on PubMed, published in English language until December 2014 and focused on the involvement of SSCs in the pathogenesis of this common gynecological disease. A concise summary of the data obtained from in vitro experiments, animal models, and human tissue analyses provides insights into the SSC dysregulation in endometriotic lesions. In addition, a set of research results is presented supporting that SSC-targeting, in combination with hormonal therapy, may result in improved control of the disease, while a more in-depth characterization of endometriosis SSCs may contribute to the development of early-disease diagnostic tests with increased sensitivity and specificity. Key message: Seemingly essential for the establishment and progression of endometriotic lesions, dysregulated SSCs, and associated molecular alterations hold a promise as potential endometriosis markers and therapeutic targets. PMID:25593975
Taylor, Robert N.; Kane, Maureen A.; Sidell, Neil
Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/ or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease. PMID:26132929
Akinola, R A; Akinola, O I; Alakija, A; Wright, K O
A 26 year old Nigerian nulliparous woman who presented in the medical emergency unit of a teaching hospital was referred after two weeks of management to the gynecology casualty with a diagnosis of malignant left ovarian cyst, because of the ascites, massive haemorrhagic pleural effusion, a left ovarian mass and an elevated C-125 marker. However, exploratory laparotomy, cytologic and histological examination of the pleural fluid and biopsied specimens revealed endometriosis. We present a case of intra and extra-pelvic endometriosis which simulated a malignant ovarian lesion and was histologically confirmed by cytology of the haemorrhagic pleural effusion and biopsy of the ovarian mass and peritoneal deposits obtained at laparotomy. This is to draw the attention of clinicians to endometriosis as a cause of pleural effusion, ascites and groin swelling which can simulate ovarian cancer.
Walczak, Piotr; Kruszewski, Janusz Wiesław; Sobczak, Ewa; Szefel, Jarosław
Intussusception of the caecum occurs about twenty times less frequently in adults as compared to children and in 90% of these cases is caused by intestinal tumors. Intussusception of the ileum usually causes intestinal obstruction which requires urgent surgical intervention. So far only a few cases of intussusception due to the presence of endometrial tumor have been described. The clinical course, imaging and laboratory tests are not specific for endometriosis. The macroscopic appearance of the tumor during laparotomy is also not diagnostic. In case of endometriosis, the diagnosis can only be made on the basis of the histopathological examination of the excised tumor In this report, we present the diagnostic process and treatment of a patient with intussusception of the ileum to the ascending and transverse colon due to cecal tumor During the operation, the surgeon suspected a cancerous tumor and performed a right hemicolectomy The final diagnosis of endometriosis was made on the basis of the histopathological analysis.
Canlorbe, Geoffroy; Laas, Enora; Cortez, Annie; Daraï, Emile
Vulvar endometriosis can occur after surgery or trauma and cause dyspareunia. A 30-year-old woman presented with orificial dyspareunia lasting for 5 months. Her history was marked by a vaginal birth without perineal injury and the removal of a cyst from the left Bartholin's gland. On examination, we observed a selectively painful, superficial and retractile lesion, 5 mm in diameter at the junction of the hymen at some distance from the bartholinitis scar. Endometriosis was suspected due to the exacerbation of pain during menses. The surgery consisted of excision of the hymenal area of the painful lesion. Pathological examination confirmed the presence of endometrial tissue. The painful symptoms resolved and no additional treatment was administered. Any vulvar lesion, regardless of its appearance and location, can be related to endometriosis. Surgical resection is recommended to relieve the symptoms and provide histological proof.
Rodriguez–Urrego, Paula A; Dulcey–Hormiga, Isabel C; Barrera–Herrera, Luis E; Suarez–Zamora, David A; Palau–Lazaro, Mauricio A; Buritica–Cifuentes, Catalina
Endometriosis involving the uterine cervix is a rare condition that can lead to diagnostic errors in the interpretation of Pap smear. We report the case of a 41-year-old patient in whom the initial Pap smear revealed three-dimensional clusters of glandular cells with elongated nuclei, occasional mitosis, and atypia, which was interpreted as atypical glandular cells, not otherwise specified (NOS). The patient was taken to colposcopy and endocervical biopsy. Colposcopy was normal and the biopsy presented glands with elongated nuclei and surrounded by endometrial stroma admixed with normal endocervical glands. Immunohistochemical studies were reactive for CD10 in the stromal cells and vimentin in endometrioid glands. The findings were consistent with cervical endometriosis. Endometriosis in the cervix is an uncommon pathology that mimics malignancy and may be interpreted as atypical or glandular neoplasia in the cytology. PMID:28182083
Lukovich, Péter; Csibi, Noémi; Rigó, János; Bokor, Attila
A number of the patients suffer from endometriosis increased in the past decades and the cases have became more serious. The most critical complication of bowel endometriosis is the large bowel obstruction. Up to recently, 16 similar case reports of large bowel endomteriosis causing obstruction, with detailed medical history have been published in the literature in English language. Since 2007 535 female have been treated in the 1st Gynaecological Department with endometriosis, out of them three patients from emergency surgery in the history because of large bowel obstruction. Symptoms suggesting endometriosis or previous intervention due to endometriosis were detected in 59% (13/21) of the cases. Preoperative ultrasound, computertomography, magnetic resonance imaging did not give correct diagnosis. Colonoscopy was carried out before the primary operation in 61% (13/21) and after the surgery in 24% (5/21) of the cases, but none of them confirmed endometriosis. Although all the patients developed obstruction, only in 5% (1/19) of the patients was the mucosa infiltrated by the endometriosis. In a young female patient, intestinal obstruction can be caused by bowel endometriosis. Identification of colonoscopic signs (rigidity, impression, kinking) of endometriosis may help to avoid unnecessary extension of intestinal resection. Gynaecologists should take part in the operations. Orv. Hetil., 2016, 157(49), 1960-1966.
Barkan, Güliz A; Naylor, Bernard; Gattuso, Paolo; Küllü, Sevgi; Galan, Kristine; Wojcik, Eva M
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This study evaluates the cytomorphologic features of endometriosis in various cytologic specimen types [fine-needle aspiration (FNA), effusion cytology (EF), touch imprint (ToP), and cervical smear (PAP)], and assesses the key elements helpful in recognizing this lesion. A total of 18 cases (8 FNA, 4 EF, 5 ToP, and 1 PAP) of cytologically diagnosed and histologically/clinically confirmed endometriosis diagnosed between 1988 and 2006 comprises the material for this study. The morphologic features evaluated of the three components included: cellularity, presence of sheets of glandular cells, three-dimensional (3D) glandular clusters, tubular structures, single cells, syncytial groups of stromal cells, stromal cells entrapped within basement membrane (BM)-like material, cytologic atypia, presence of mitotic figures, and hemosiderin-laden histiocytes. Endometrial glands, stroma, and hemosiderin-laden histiocytes were all identified in 14/18 (77.8%) cases. FNA specimens were more cellular than that of both EF and ToP specimens. Tubular structures, 3D glandular clusters, stromal cells entrapped in BM and syncytial stromal groups were more common in FNAs, and ToPs compared with the EFs. The ratio of the endometrial glandular and stromal cells was similar in all specimen types. Atypia and mitotic figures were rarely encountered. Diagnosis of endometriosis could be made independently on either smears/ThinPrep(™) slides or on cell blocks in all cases where these preparations were available. On follow up, none of the patients developed malignancy. Endometriosis can be reliably and safely diagnosed in various cytologic materials. Cytologic atypia is uncommon. Components of endometriosis could show minor morphologic alterations in different specimen types.
Barkan, Güliz A; Naylor, Bernard; Gattuso, Paolo; Küllü, Sevgi; Galan, Kristine; Wojcik, Eva M
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This study evaluates the cytomorphologic features of endometriosis in various cytologic specimen types [fine-needle aspiration (FNA), effusion cytology (EF), touch imprint (ToP), and cervical smear (PAP)], and assesses the key elements helpful in recognizing this lesion. A total of 18 cases (8 FNA, 4 EF, 5 ToP, and 1 PAP) of cytologically diagnosed and histologically/clinically confirmed endometriosis diagnosed between 1988 and 2006 comprises the material for this study. The morphologic features evaluated of the three components included: cellularity, presence of sheets of glandular cells, three-dimensional (3D) glandular clusters, tubular structures, single cells, syncytial groups of stromal cells, stromal cells entrapped within basement membrane (BM)-like material, cytologic atypia, presence of mitotic figures, and hemosiderin-laden histiocytes. Endometrial glands, stroma, and hemosiderin-laden histiocytes were all identified in 14/18 (77.8%) cases. FNA specimens were more cellular than that of both EF and ToP specimens. Tubular structures, 3D glandular clusters, stromal cells entrapped in BM and syncytial stromal groups were more common in FNAs, and ToPs compared with the EFs. The ratio of the endometrial glandular and stromal cells was similar in all specimen types. Atypia and mitotic figures were rarely encountered. Diagnosis of endometriosis could be made independently on either smears/ThinPrep(™) slides or on cell blocks in all cases where these preparations were available. On follow up, none of the patients developed malignancy. Endometriosis can be reliably and safely diagnosed in various cytologic materials. Cytologic atypia is uncommon. Components of endometriosis could show minor morphologic alterations in different specimen types. Diagn. Cytopathol. 2013. © 2013 Wiley Periodicals, Inc.
Hwang, Sun Mi; Lee, Chung Won; Lee, Byung Seok; Park, Joo Hyun
To analyze the diagnostic profiles and treatment outcomes of patients with thoracic endometriosis at a university hospital. A retrospective review of medical records was performed for patients diagnosed with thoracic endometriosis at Gangnam Severance Hospital, Yonsei University College of Medicine, between January 2007 and January 2014. Fifteen patients (median age, 35 years; range, 23-48 years) were evaluated. Patients presented with catamenial hemoptysis (n=8), or catamenial pneumothorax (n=7). Patients with catamenial pneumothorax were significantly older than those presenting with hemoptysis (P=0.0002). Only 3 patients (20%) had coexisting pelvic endometriosis. All patients underwent chest computed tomography; lesions were shown to predominantly affect the right lung (right lung, n=13, 86.7%; left lung, n=2, 13.3%), and were mainly distributed on the right upper lobe (n=9, 60%). Ten patients underwent video-assisted thoracoscopic surgery, and 1 patient underwent a thoracotomy. Intraoperatively, endometriosis-specific findings were observed in 8/11 patients (72.7%); a further 5/11 patients (45.4%) had histologically detectable endometriosis. Over the follow-up period (mean, 18.4 months; range, 2-65 months) 5/15 patients (33%) had clinical signs of recurrence. Recurrence was not detected in any of the 5 catamenial pneumothorax patients that received adjuvant hormonal therapy after surgery. The diagnosis and management of thoracic endometriosis requires a multidisciplinary approach, based upon skillful differential diagnosis, and involving careful gynecologic evaluation and assessment of the cyclicity of pulmonary symptoms. Imaging findings are non-specific, though there may be laterality towards the right lung. Since symptom recurrence is more common in those with presenting with pneumothorax, post-operative adjuvant medical therapy is recommended.
Patel, Bansari G; Rudnicki, Martin; Yu, Jie; Shu, Yimin; Taylor, Robert N
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment. © 2017 Nordic Federation of
Lima, Raquel; Abdalla-Ribeiro, Helizabet; Nicola, Ana Luisa; Eras, Aline; Lobao, Anna; Ribeiro, Paulo Ayroza
To evaluate the association between ultrasound measurements of endometriosis nodules on the uterosacral ligament (USL) and the risk of ureteral involvement, as well as to assess whether associations with other ultrasound variables increase the sensitivity and specificity of the diagnosis of ureteral endometriosis. Cross-sectional, observational study. University hospital. Four hundred sixty-three women with deep infiltrating endometriosis (DIE). Patients diagnosed with DIE underwent transvaginal ultrasound endometriosis mapping before laparoscopic surgery for full excision of endometriotic lesions. Preoperative ultrasound evaluation, intra- and postoperative assessment, and anatomopathologic confirmation. Of the 463 patients who participated in the study, 111 (23.97%) presented with endometriosis nodules with USL involvement on ultrasound examination conducted by a single radiologist. Receiver operating characteristic curve analysis showed that the size of the USL nodule had a statistically significant association with ipsilateral ureteral involvement. After multivariate logistic regression, the variables reduction in ovarian mobility, ureteral changes on the right side, size of the USL nodule, and presence of endometrioma on the left side were significantly associated with a ureteral endometriosis nodule. However, the combined result for the variables cited was worse than the diagnostic analysis using only the size of the USL nodule. Uterosacral ligament nodules with ultrasound measurements of 1.75 cm and 1.95 cm on the right and left sides, respectively, significantly increase the risk of ureteral involvement. Even with the association of other ultrasound variables, there was no improvement in sensitivity. Therefore, USL nodule size is a key measure for therapeutic planning and consent of the patient. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Dos Bispo, Ana Paula Santos; Ploger, Christine; Loureiro, Alessandra Fernandes; Sato, Hélio; Kolpeman, Alexander; Girão, Manoel João Batista Castello; Schor, Eduardo
To assess function and prevalence of spasms and trigger points of the pelvic floor muscles in women with deep endometriosis. One hundred and four (104) patients were assessed. Group 1 (G1) was composed of 52 subjects diagnosed with deep endometriosis proven by magnetic resonance imaging (MRI); Group 2 (G2) was composed of 52 women with no signs of endometriosis. Subjects from both G1 and G2 were seen at the Division of Pelvic Pain and Endometriosis and at Center for Prevention of Sexually Transmitted Diseases, both at Federal University of São Paulo (UNIFESP), respectively. A full physical therapy evaluation was carried out, including medical history, presence of dyspareunia and physical examination, which included detailed evaluation of pelvic floor muscles and occurrence of muscle spasm, trigger point and muscle function. The average age of the subjects in the study group was 36.4 and 30.9 years in the control group (p = 0.002). A greater prevalence of deep dyspareunia was found in the subjects in the endometriosis group when compared to the control group (p = 0.010). Women in G1 had higher prevalence of muscle spasms. In this group, 53.9 % had spasms-compared to only 17.3 % of women in G2 (p < 0.001). On the other hand, no significant difference between the groups (p = 0.153) was found while searching for the presence of trigger points. Women with deep endometriosis have increased prevalence of pelvic floor muscle spasms when compared to the control group.
Tanaka, Yukiko; Mori, Taisuke; Ito, Fumitake; Koshiba, Akemi; Takaoka, Osamu; Kataoka, Hisashi; Maeda, Eiko; Okimura, Hiroyuki; Mori, Takahide; Kitawaki, Jo
Endometriosis is a chronic inflammatory disease associated with altered immune response to endometrial cells facilitating the implantation and proliferation of ectopic endometrial tissues. Although regulatory T (Treg) cells play a key role in T cell-mediated immune response and development of immune disorders, their significance in endometriosis remains to be elucidated. Recently, CD4+CD45RA- forkhead box protein 3 (Foxp3)hi T cells, activated Treg cells, have been identified as a functionally true suppressive population of Treg cells. To investigate the role of Treg cells in endometriosis. Three Treg cell fractions (resting Treg cells, activated Treg cells, and non-Treg cells) were examined using flow cytometry in the endometrioma, endometrium, peritoneal fluid, and peripheral blood obtained from women with (n = 27) and without (n = 28) endometriosis. A mouse model of endometriosis was made in Foxp3tm3Ayr/J (Foxp3DTR) C57BL/6 Treg cell-depleted mice (n = 28). In women with endometrioma, the proportion of activated Treg cells in the endometrioma and the endometrium, but not in the peritoneal fluid or peripheral blood, was significantly decreased compared with that in women without endometriosis. In Foxp3DTR/diphtheria toxin mice, the number and weight of endometriotic lesions, inflammatory cytokine levels and angiogenetic factors were significantly increased compared with those in control mice. Treg cell deficiency exaggerates local inflammation and angiogenesis and simultaneously facilitates the attachment and growth of endometrial implants. The findings provide an insight into dysregulated immune response for the pathogenesis and development.
Soliman, Ahmed M; Du, Ella Xiaoyan; Yang, Hongbo; Wu, Eric Q; Haley, Jane C
Hysterectomy and laparoscopy are the two most common surgical options used to treat women with endometriosis, yet the disease may still recur. This study aimed to determine the long-term retreatment rates among endometriosis patients in the United States who received either hysterectomy or laparoscopy. Patients aged 18-49 years with endometriosis who underwent hysterectomy or laparoscopy were identified in the Truven Health MarketScan claims database (2004-2013). The retreatment rate up to 8 years after the initial surgery was estimated using Kaplan-Meier survival analysis. The relative risk of retreatment among patients with hysterectomy versus laparoscopy was assessed using a Cox proportional hazard model. A total of 24,915 patients with endometriosis who underwent hysterectomy and 37,308 patients with endometriosis who underwent laparoscopy were identified. The estimated retreatment rates were 3.3%, 4.7%, and 5.4% in the 2nd, 5th, and 8th year following hysterectomy, respectively, while the rates following laparoscopy were 15.8%, 27.5%, and 35.2%, respectively. The hazard ratio of retreatment was 0.157 (95% confidence interval [CI]: 0.146-0.169) comparing hysterectomy to laparoscopy. In the sensitivity analysis, which expanded the definition of retreatment by including medical treatments, the retreatment rate increased by a factor of 11-14 for the hysterectomy cohort and by a factor of 2-4 for the laparoscopy cohort, and the hazard ratio of retreatment rate for hysterectomy versus laparoscopy was 0.490 (95% CI: 0.477-0.502). Our study results indicated that the disease retreatment rate after laparoscopy is high among patients with endometriosis; even hysterectomy does not guarantee freedom from retreatment.
Gómez Arzapalo, E; Gorozpe Calvillo, J I
Endometriosis is an ailment which has no exact etiology due to its uncertain genesis, its inception can develop unnoticed, its silent evolution makes it difficult to identify it until a cardinal symptom appears and its semeiology provides us facts to integrate a diagnosis, it is an entity that does not have relation while and/or with the reproductive stage, neither with the parity, but we are aware it occurs in its different stages, varying from 9% to 33% in the reproductive cycle, it can be recurring after being medically or surgically treated, appearing endometriomas in it or in the infundibulum stump in the latter case. It is characterized by a collagenosis, endometrio abnormal implant out of the uterus cavity, thereby generating and inflammatory process in the zone of implant, increasing the cytokines production (polypeptide secreted by the lymphocytes and macrophages playing an important role in the immunological response), involving a dysfunction in the hypothalamus-pituitary-ovarian, altering the endocrinos physiology; regarding the genetic aspect, alterations in the chromosomes 4.9 in the Endometriosis frames have been found. The human semen preparation with half Ham F 10 enriched with ascorbic acid is described. In cases of permeable tubes or FIVTE.
Merviel, P; Lourdel, E; Sanguin, S; Gagneur, O; Cabry, R; Nasreddine, A
The SPRM (selective progesterone receptor modulators) are agonists and/or antagonists of progesterone receptor. They are responsible for anovulation, amenorrhea and a lower prostaglandin levels, which leads to an improvement in pain and regression of lesions in endometriosis. On the endometrium, a particular aspect, the progesterone receptor modulator-associated endometrial changes (PAEC), raises additional studies to verify its harmlessness. However, due to the lack of hypoestrogenism and metabolic effects with these drugs, it is very likely that the SPRM will in the near future an important place in the treatment of endometriosis.
Gingold, Julian A.; Falcone, Tommaso
Surgical management of endometriosis has been shown to improve dysmenorrhea at all disease stages and is recommended in severe disease for treatment of infertility. Deeply infiltrating endometriosis (DIE) produces thick inflammatory tissue that precludes visualization of anatomical landmarks and distorts normal anatomy. Excision of DIE poses several technical and surgical challenges that mandate a clear understanding of the anatomy of the pelvic sidewall. This review details relevant surgical anatomy and addresses the principles of safe retroperitoneal entry, ureterolysis and excision of endometriotic lesions. Proper use of these techniques should facilitate safe and successful surgery for management of DIE. PMID:27642583
Background The anti-mullerian hormone (AMH) is a member of the transforming growth factor β (TGF-β) superfamily, which is responsible of the regression of the mullerian duct. AMH is expressed in the normal endometrium, where, acting in a paracrine fashion, negatively regulates cellular viability. Our objective was to evaluate the in vitro effects of the treatment with AMH of endometriosic cells. Methods AMH expression in human endometriosis glands was evaluated by immunohistochemistry. RT-PCR has been used to quantify the expression levels of AMH and AMH RII isoforms, as well as of cytochrome P450 in both endometriosis epithelial and stromal cells Effects of AMH and AMH-cleaved treatment in endometriosis cells were evaluated by flow-cytometry analysis. Finally, it has been evaluated the effect of plasmin-digested AMH on cytochrome P450 activity. Results AMH and AMH RII isoforms, as well as cytochrome P450, were expressed in both endometriosis epithelial and stromal cells. Treatment of endometriosis stromal and epithelial cell growth with AMH was able to induce a decrease in the percentage of cells in S phase and increase percentage of cells in G1 and G2 phase; coherently, decreased cell viability and increased percentage of cells death fraction was observed. The plasmin-digested AMH was able to suppress most of the cytochrome P450 activity, causing an increase of pre-G1 phase and of apoptosis induction treating with plasmin-digested AMH in both cell lines, most marked in the epithelial cells. Conclusions The data produced suggest a possible use of AMH as therapeutic agents in endometriosis. PMID:24886254
Regiani, Thais; Cordeiro, Fernanda Bertuccez; da Costa, Lívia do Vale Teixeira; Salgueiro, Jéssica; Cardozo, Karina; Carvalho, Valdemir Melechco; Perkel, Kayla Jane; Zylbersztejn, Daniel Suslik; Cedenho, Agnaldo Pereira; Lo Turco, Edson Guimarães
Endometriosis is a chronic gynecological condition that affects 10-32% of women of reproductive age and may lead to infertility. The study of protein profiles in follicular fluid may assist in elucidating possible biomarkers related to this disease. For this, follicular fluid samples were obtained from women with tubal factor or minimal male factor infertility who had pregnancy outcomes after in vitro fertilization (IVF) treatment (control group, n = 10), women with endometriosis (endometriosis group, n = 10), along with the endometrioma from these same patients were included (endometrioma group, n = 10). For proteomic analysis, samples were pooled according to their respective groups and normalized to protein content. Proteins were analyzed by in tandem mass spectrometry (MS(E)) Spectra processing and the ProteinLynx Global Server v.2.5. was used for database searching. Data was submitted to the biological network analysis using Cytoscape 2.8.2 with ClueGO plugin. As a result, 535 proteins were identified among all groups. The control group differentially or uniquely expressed 33 (6%) proteins and equal expression of 98 (18%) proteins was observed in the control and endometriosis groups of which 41 (7%) proteins were further identified and/or quantified. Six (1%) proteins were observed in both the endometriosis and endometrioma groups, but 212 (39%) proteins were exclusively identified and/or quantified in the endometrioma group. There were 9 (1%) proteins observed in both the control and endometrioma groups and there were 139 (25%) proteins common among all three groups. Distinct differences among the protein profiles in the follicular fluid of patients included in this study were found, identifying proteins related to the disease progression and IVF success. Thus, some pathways related to endometriosis are associated with the presence of specific proteins, as well as the absence of others. This study provides a first step to the development of more sensitive
Khan, Zaraq; Zanfagnin, Valentina; El-Nashar, Sherif A; Famuyide, Abimbola O; Daftary, Gaurang S; Hopkins, Matthew R
To evaluate the risk factors, presentation, and outcomes in cases of abdominal wall endometriosis. A case-control study (Canadian Task Force classification II-2). An academic medical center. A total of 102 (34 cases and 68 controls) were included. Surgical resection of abdominal wall endometriosis. Cases underwent surgical excision for abdominal wall endometriosis at Mayo Clinic from January 1, 2000, through December 31, 2013. For each case, 2 controls were randomly selected from a list of women who had surgery in the same year with minimal (American Society for Reproductive Medicine stage I-II) endometriosis. A chart review was completed for variables of interest. Regression models were used to identify independent risk factors associated with abdominal wall endometriosis. In 14 years, 2539 women had surgery for endometriosis at Mayo Clinic. Of these, only 34 (1.34%) had abdominal wall endometriosis. The mean age was 35.2 ± 5.9 years, and the median parity was 2 (range, 0-5). Clinical examination diagnosed abdominal wall endometriosis in 41% of cases, with the cesarean delivery scar being the most common site (59%). There was a strong correlation between the size of the lesion on clinical examination compared with the size of the pathology specimen (r(2) = 0.74, p < .001). When compared with controls, cases had significantly higher parity and body mass index, more cyclic localized abdominal pain, less dysmenorrhea, longer duration from the start of symptoms to surgery, and more gynecologic surgeries for symptoms without cure. In the final multivariable model, cyclic localized abdominal pain, absence of dysmenorrhea, and previous laparotomy were independently associated with abdominal wall endometriosis with adjusted odds ratios of 10.6 (95% CI 1.85-104.4, p < .001), 12.4 (95% CI 1.64-147.1, p < .001), and 70.1 (95% CI 14.8-597.7, p < .001), respectively, with an area under the curve for the receiver operating characteristic of 0.94 (95% CI, 0
Sakr, Sharif; Naqvi, Hanyia; Komm, Barry; Taylor, Hugh S
Endometriosis is a disease defined by the ectopic growth of uterine endometrium. Stem cells contribute to the generation of endometriosis as well as to repair and regeneration of normal endometrium. Here we demonstrate that the selective estrogen receptor modulator bazedoxifene (BZA), administered with conjugated estrogens (CEs), leads to regression of endometriosis lesions as well as reduction in stem cell recruitment to the lesions. Female mice underwent transplantation of male bone marrow. Endometrium was transplanted in the peritoneal cavity of half to create experimental endometriosis. Mice with or without experimental endometriosis were randomized to BZA/CE or vehicle treatment. Endometriosis lesions, bone marrow-derived mesenchymal stem cell engraftment of the lesions, and eutopic endometrium as well as ovarian stimulation were assessed. BZA treatment significantly reduced lesion size, gland number, and expression of proliferation marker proliferating cell nuclear antigen. Ovarian weight was not affected. Stem cells were recruited to the endometriosis lesions, and this recruitment was dramatically reduced by BZA/CE treatment. Stem cell engraftment was reduced in the uterus of animals with endometriosis; however the number of stem cells engrafting the uterus was completely restored by treatment with BZA/CE. Competition between endometriosis and the eutopic endometrium for a limited supply of stem cells and depletion of normal stem cells flux to the uterus is a novel mechanism by which endometriosis interferes with endometrial function and fertility. BZA/CE not only treats lesions of endometriosis, it also dramatically reduces stem cell recruitment to the lesions and restores stem cell engraftment of the uterine endometrium.
Manganaro, L; Fierro, F; Tomei, A; Irimia, D; Lodise, P; Sergi, M E; Vinci, V; Sollazzo, P; Porpora, M G; Delfini, R; Vittori, G; Marini, M
Endometriosis represents an important clinical problem in women of reproductive age with high impact on quality of life, work productivity and health care management. The aim of this study is to define the role of 3T magnetom system MRI in the evaluation of endometriosis. Forty-six women, with transvaginal (TV) ultrasound examination positive for endometriosis, with pelvic pain, or infertile underwent an MR 3.0T examination with the following protocol: T2 weighted FRFSE HR sequences, T2 weighted FRFSE HR CUBE 3D sequences, T1 w FSE sequences, LAVA-flex sequences. Pelvic anatomy, macroscopic endometriosis implants, deep endometriosis implants, fallopian tube involvement, adhesions presence, fluid effusion in Douglas pouch, uterus and kidney pathologies or anomalies associated and sacral nervous routes were considered by two radiologists in consensus. Laparoscopy was considered the gold standard. MRI imaging diagnosed deep endometriosis in 22/46 patients, endometriomas not associated to deep implants in 9/46 patients, 15/46 patients resulted negative for endometriosis, 11 of 22 patients with deep endometriosis reported ovarian endometriosis cyst. We obtained high percentages of sensibility (96.97%), specificity (100.00%), VPP (100.00%), VPN (92.86%). Pelvic MRI performed with 3T system guarantees high spatial and contrast resolution, providing accurate information about endometriosis implants, with a good pre-surgery mapping of the lesions involving both bowels and bladder surface and recto-uterine ligaments. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Zhou, Jiayi; Lu, Yingying; Wang, Zehua; Liu, Haiou; Xu, Congjian
Background Despite enormous efforts to dissect the role of endometriosis in ovarian cancer development, the difference in prognosis between ovarian cancer patients with or without endometriosis remains elusive. The purpose of this study is to assess the association between endometriosis and the prognosis in patients with ovarian cancer. Results Ovarian cancer arising in endometriosis tended to be presented as clear cell histology, early stage, less intraperitoneal metastasis and ascites, and lower CA125 level compared with those without endometriosis. Multivariate Cox regression analysis identified endometriosis as an independent prognostic factor for progression free survival (P = 0.002) and overall survival (P = 0.009) in all patients and especially for early stage. A nomogram integrating endometriosis, FIGO stage and CA125 was established to predict progression free survival and overall survival. Materials and methods This study retrospectively enrolled 196 ovarian cancers arising or not in endometriosis judged by adjunctive use of CD10 immunohistochemistry in conjunction with H&E staining specimens. Clinicopathologic variables, progression-free survival (PFS) and overall survival (OS) were recorded. Kaplan-Meier analysis was performed to compare survival curves. Cox regression models were used to analyze the effect of endometriosis on PFS and OS. A prognostic nomogram was constructed based on the independent prognostic factors identified by multivariate analysis. Conclusions Endometriosis is an independent predictor of prognosis in ovarian cancer patients. PMID:27992377
Liu, Xing-Ya; Wang, Hong-Jing; Xu, Pan; Chen, Jing; Pan, Hai-Ying; Liu, Ya
To investigate the expressions of Livin and phosphate and tension homology deleted on chromsome ten (PTEN) protein in the cancerous tissues of ovary endometriosis. Immunohistochemistry EliVision was used to examine the expressions of Livin and PETN protein in 19 samples of ovary endometriosis cancerous tissues, 30 samples of ovary endometriosis tissues and 30 samples of ovarian benign tumor tissues. The positive expression rate of Livin in ovary endometriosis cancerous tissues (68%) was obviously higher than that in ovary endometriosis tissues (36%) and benign tumor tissues (13%)( P<0.05). The positive expression rate of PTEN in ovary endometriosis cancerous tissues (16%) was obviously lower than that in ovary endometriosis tissues (65%) and benign tumor tissues (80%)( P<0.01). There was no correlations between positive expressions of Livin and age, clinical stage, grading, histological type and lymphatic metastasis of ovary endometriosis cancer ( P>0.05), the same result was also found for PTEN. Livin and PTEN expression presented an obviously negative correlation in ovary endometriosis cancer ( r=-0.559, P=0.001). Up-regulation of Livin expression and down-regulation of PTEN may be involved in the occurrence and development of ovary endometriosis cancerization.
Yu, Chao-Qin; Shi, Shu-Fang; Liu, Yu-Huan; Wang, Rui-Xia; Song, Yan-Hua; Yu, Jin
To explore the method of primary culture for endometriotic cells and to find out the differences in morphological manifestations among endometriotic cells and eutopic endometrial cells sampled from patients with endometriosis and endometriosis-free women. Endometriotic and eutopic endometrial cells were cultured by modified method of primary culture. The endometriotic cell types were observed and differentiated under optical and electron microscopes. The success rates for culture of eutopic endometrial cells from endometriosis-free women and patients with endometriosis were 91.67% and 93.75% respectively. The success rate for culture of endometriotic cells was 75.00%. The size of endometriotic glandular cells was similar to those of eutopic endometrial glandular cells from endometriosis-free women and patients with endometriosis. The chromatin was manifold and the nucleus was augmented in the endometriotic glandular cells. The endometriotic stromal cells were smaller than the eutopic endometrial stromal cells from endometriosis-free women and patients with endometriosis. Many tiny villi and protuberances on plasma membrane could be seen in the endometriotic stromal cells. The success rate for culture of endometriotic cells can be elevated through improving the method of primary culture. The ultrastructures of endometriotic glandular and stromal cells are obviously different from those of eutopic endometrial glandular and stromal cells from endometriosis-free women and patients with endometriosis.
De Sanctis, Paola; Elmakky, Amira; Farina, Antonio; Caramelli, Elisabetta; Seracchioli, Renato; Mabrouk, Mohamed; Mignemi, Giuseppe; Venturoli, Stefano; Villa, Gioia; Guerrini, Manuela; Manuzzi, Linda; Montanari, Giulia; Valvassori, Luisa; Zucchini, Cinzia
Endometriosis is an invasive disease. Its diagnosis depends on laparoscopy, which is traumatic and associated with potential complications. The aim of this study was to develop a rapid, reliable, and less invasive diagnostic test for endometriosis. We hypothesized that genes related to cell invasion would be transcriptionally upregulated in endometriosis, and tested whether blood levels of their transcripts might be used as biomarkers of endometriosis. We used quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) to quantify the mRNA levels of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-3 (MMP-3), and MMP-9 in peripheral blood from 20 patients with mild/intermediate endometriosis, 20 patients with severe endometriosis and 20 endometriosis-free subjects. Our results indicate that circulating mRNA for MMP-3 is significantly higher in patients with endometriosis than in control patients, regardless of the degree of severity. Conversely, the level of circulating mRNA for VEGFA and MMP-9 did not distinguish patients from controls. MMP-3 mRNA is a promising peripheral blood marker that discriminates between patients with endometriosis and healthy subjects. Our results support the possibility of finding genes suitable for diagnostic qRT-PCR for endometriosis in peripheral blood and should be explored further. Copyright © 2010 S. Karger AG, Basel.
Costa, I R; Silva, R C P C; Frare, A B; Silva, C T X; Bordin, B M; Souza, S R; Ribeiro Júnior, C L; Moura, K K V O
We investigated a possible link between endometriosis and polymorphism of the progesterone receptor gene (PROGINS). The endometriosis group consisted of 54 patients with a diagnosis of endometriosis by laparoscopy, and the control group comprised 44 women without endometriosis. Genotypes for PROGINS polymorphisms (A1/A1, A1/A2 and A2/A2) were determined by polymerase chain reaction and analyzed on a 2% agarose gel stained with ethidium bromide. The frequency of polymorphic genotypes (A1/A2 and A2/A2) was significantly higher in patients with endometriosis (33%) than in the control group (16%). We conclude that there is a significant correlation between PROGINS polymorphism and endometriosis.
Cirstoiu, M; Bodean, O; Secara, D; Munteanu, O; Cirstoiu, C
Endometriosis is a common, benign, chronic, estrogen-dependent disorder. The endometrial tissue implants itself outside the uterus and can be usually found in the pelvis or, in rare cases, it can be found nearly anywhere in the body. There are no pathognomonic symptoms of this disease, therefore, in some cases the tumors are incidentally discovered during surgery. Deep infiltrative endometriosis (DIE) is a rare form of this condition, which mostly affects the uterosacral ligaments, the rectovaginal space, and the upper third of the posterior vaginal wall, the bowel, and the urinary tract. We present the case of a 29-year-old pregnant female who was diagnosed with infiltrative endometriosis during the cesarean section at 38 weeks of gestation. The tumors involving the vesicouterine peritoneum had a tendency of infiltrating the urinary bladder, but the patient had been completely asymptomatic prior to this incidental discovery. As cited by literature, the discovery and management of urinary endometriosis, as well as that of other localizations of DIE, is not based on high-level evidence data, but rather on case-series reported by surgical teams working in different centers worldwide. PMID:23599823
Strehl, Johanna D; Hackl, Janina; Wachter, David L; Klingsiek, Peter; Burghaus, Stefanie; Renner, Stefan P; Fasching, Peter A; Hartmann, Arndt; Beckmann, Matthias W
Context: In the last two decades, a color based concept of disease activity in peritoneal endometriosis has been in use in the clinical context, with red lesions being considered active and black or white lesions being interpreted as less active or dormant. Objective: Our aim was to analyze 4 main color categories of peritoneal endometriosis (black, white, red and brown) in one single patient group using histomorphological and immunohistochemical methods. Design: 65 endometriosis lesions (30 black, 17 white, 11 brown, 7 red) were resected from 47 premenopausal, nulliparous women which had not received exogenous hormones for at least six months prior to the operation. Specimen workup, histomorphological analysis and immunohistochemical analysis were performed in a standardized manner. Results: The color categories showed a broad overlap in proliferative activity and hormone receptor expression. Differences were found in lesion morphology. Adjacent stromal reaction in particular showed a marked increase from red through brown and black to white lesions. Differences were also seen in gland pattern and gland content. Conclusions: Lesion colors in peritoneal endometriosis seem to be determined by gland content and a varying adjacent stromal reaction and more likely reflect an aging process than different levels of disease activity. PMID:24427335
Bulun, Serdar E; Monsivais, Diana; Kakinuma, Toshiyuki; Furukawa, Yuichi; Bernardi, Lia; Pavone, Mary Ellen; Dyson, Matthew
Endometriosis has been initially described as the presence of ectopic endometrial tissue on pelvic organs or in extrapelvic sites; and this has been used as its key pathologic feature ever since. Endometriosis responds to fluctuations in estrogen and progesterone by growth and inflammation, leading to pain aggravated by menses. It was proposed that pelvic endometriosis primarily originate from retrograde menstruation of a critical number of eutopic endometrial cells with stem characteristics. This postulate is supported by the molecular defects found in ectopic endometriotic tissue. Genome-wide differences in CpG methylation between eutopic endometrial and endometriotic stromal cells are present. Defective CpG methylation affecting several genes that encode key transcription factors such as GATA6, steroidogenic factor-1, and estrogen receptor-β in endometriosis gives rise to overproduction of local estrogen and prostaglandins and suppression of progesterone receptor. Progesterone receptor deficiency leads to progesterone resistance, resulting in decreased retinol uptake and retinoic acid production and altered retinoic acid action. These molecular defects collectively give rise to poor cellular differentiation, enhanced survival, and increased inflammation, which are the biological hallmarks of endometriotic tissue.
Roos-Eysbouts, Yalck; De Bie-Rocks, Bianca; Van Dijk, Jolanda; Nap, Annemiek W
BACKGROUND/AIM STUDY QUESTION: Endometriosis is associated with a significant reduction in the quality of life and higher depression and anxiety rates. The Dutch Endometriosis Society (ES) was founded to increase the recognition and knowledge in patients and health care professionals, stimulate research and improve care. This study was conducted to explore the characteristics of the members and evaluate their needs and expectations. A descriptive questionnaire-based survey was conducted among all members of the ES. The response rate was 51% (n = 571). ES members appear to be highly educated women with a wide variety of endometriosis-related symptoms resulting in considerable restrictions in daily life. Information transmission was considered the main aim of ES (97%), whereas 56% expected social support, and 38% expected advocacy. The majority (71%) reported an improvement in their quality of life after contact with the ES. The results of this study underline patients' primary quest for information about endometriosis. Patient support groups such as ES can fulfil a useful role in disseminating knowledge from medical professionals to those suffering a chronic illness, resulting in a greater understanding and ultimately increasing their quality of life. © 2015 S. Karger AG, Basel.
Holdsworth-Carson, Sarah J; Fung, Jenny N; Luong, Hien T T; Sapkota, Yadav; Bowdler, Lisa M; Wallace, Leanne; Teh, Wan Tinn; Powell, Joseph E; Girling, Jane E; Healey, Martin; Montgomery, Grant W; Rogers, Peter A W
Do endometriosis risk-associated single nucleotide polymorphisms (SNPs) found at the 12q22 locus have effects on vezatin ( ITALIC! VEZT) expression? The original genome-wide association study (GWAS) SNP (rs10859871), and other newly identified association signals, demonstrate strong evidence for ITALIC! cis-expression quantitative trait loci (eQTL) effects on ITALIC! VEZT expression. GWAS have identified several disease-risk loci (SNPs) associated with endometriosis. The SNP rs10859871 is located within the ITALIC! VEZT gene. ITALIC! VEZT expression is altered in the endometrium of endometriosis patients and is an excellent candidate for having a causal role in endometriosis. Most of the SNPs identified from GWAS are not located within the coding region of the genome. However, they are likely to have an effect on the regulation of gene expression. Genetic variants that affect levels of gene expression are called expression quantitative trait loci (eQTL). Samples for genotyping and ITALIC! VEZT variant screening were drawn from women recruited for genetic studies in Australia/New Zealand and women undergoing surgery in a tertiary care centre. Coding variants for ITALIC! VEZT were screened in blood from 100 unrelated individuals (endometriosis-dense families) from the QIMR Berghofer Medical Research Institute dataset. SNPs at the 12q22 locus were imputed and reanalysed for their association with endometriosis. Reanalysis of endometriosis risk-association was performed on a final combined Australian dataset of 2594 cases and 4496 controls. Gene expression was performed on 136 endometrial samples. eQTL analysis in whole blood was performed on 862 individuals from the Brisbane Systems Genetics Study. Endometrial tissue-specific eQTL analysis was performed on 122 samples (eutopic endometrium) collected following laparoscopic surgery. VEZT protein expression studies employed ITALIC! n = 56 (western blotting) and ITALIC! n = 42 (immunohistochemistry) endometrial samples
Environmental PCB and Pesticide Exposure and Risk of Endometriosis
Germaine M. Buck1, John M. Weiner2, Hebe Greizerstein3, Brian Whitcomb1, Enrique Schisterman1, Paul Kostyniak3, Danelle Lobdell4, Kent Crickard5, and Ralph Sperrazza5
1Epidemiology Branch, Division o...
Savaris, R. F.; Ali, S.; Brophy, S.; Tomazic-Allen, S.; Chwalisz, K.
Endometriosis affects up to 10% of women of reproductive age and 176 million women worldwide. The prevalence in women with infertility is between 30% and 50% but may be higher in women with pelvic pain, interstitial cystitis, or irritable bowel syndrome. Cytokeratin 19 has been suggested as a potential biomarker in urine for the diagnosis of this condition. The objective of this study was to prospectively determine the accuracy and the performance of a urinary cytokeratin 19 (uCYFRA 21-1) test for diagnosing endometriosis. Ninety-eight consecutive women who underwent laparoscopy had a urinary sample obtained before surgery and were included in the study. Endometriosis was diagnosed by laparoscopy and pathology in 64.3% (63 of 98 women). The estimates and 95% confidence intervals for sensitivity, specificity, positive and negative predictive values, and likelihood ratios were 11.1% (4.5%-21.5%), 94.3% (80.8%-99.3%), 77.7% (39.9-97.1), 37% (27-47.9), 1.94 (0.43-8.86), and 0.94 (0.84-1.06), respectively. Despite the high specificity, the uCYFRA 21-1 test has limited value for clinical practice to discriminate between women with and without endometriosis. PMID:25296695
Cervantes Villarreal, E; García Zamarripa, H R; Herrera Prado, E; Barrón Vallejo, J
The therapeutical effectiveness of gestrinone in endometriosis treatment, as well as its long term side effects, were evaluated. Prospective, clinical trial. At "Dr. Alejandro Castanedo Kimball" Hospital (PEMEX). Salamanca, Guanajuato. México. Thirty women with laparoscopically confirmed endometriosis, were studied. Subjects received 2.5 mg. of gestrinone two times per week for 6 months. Laparoscopy was performed before treatment, and clinical response was determined by second laparoscopy after 6 months. The pregnancy rate, frequency of side effects and recurrence of symptoms were determined. Median total endometriosis scores and symptoms decreased significantly after treatment. Four pregnancies were observed after treatment. The principal side effects were: ponderal increase, changes in the voice and hirsutism. However, the side effects disappeared after one year of clinical survey. The results indicate that gestrinone is effective in the treatment of pelvic endometriosis. In despite of a clear benefic effect on stage of the disease and symptoms; the use of gestrinone should weigh the risk-benefit (cost versus metabolic side effects) of treatment.
Coutinho, Antônio; Bittencourt, Leonardo Kayat; Pires, Cíntia E; Junqueira, Flávia; Lima, Cláudio Márcio Amaral de Oliveira; Coutinho, Elisa; Domingues, Marisa A; Domingues, Romeu C; Marchiori, Edson
Deep pelvic endometriosis is an important gynecologic disorder that is responsible for severe pelvic pain and is defined as subperitoneal invasion that exceeds 5 mm in depth. Deep pelvic endometriosis can affect the retrocervical region, uterosacral ligaments, rectum, rectovaginal septum, vagina, urinary tract, and other extraperitoneal pelvic sites. It is commonly associated with dysmenorrhea, dyspareunia, pelvic pain, urinary tract symptoms, and infertility. Because surgery remains the best therapeutic option for affected patients, the accurate preoperative assessment of the extension of endometriotic disease is extremely important. Pelvic magnetic resonance (MR) imaging is a noninvasive method with high spatial resolution that allows multiplanar evaluation of deep pelvic endometriosis and good tissue characterization, but without the use of ionizing radiation or iodinated contrast agents. MR imaging yields important findings that help grade the disease and identify subperitoneal lesion extension and other associated disease entities, thereby facilitating accurate diagnosis and adequate treatment. Radiologists should be familiar with the MR imaging findings of deep infiltrating endometriosis in various anatomic locations so that they can provide information that allows adequate presurgical counseling.
Mellado, Bruna H; Falcone, Ananda C M; Poli-Neto, Omero B; Rosa E Silva, Julio C; Nogueira, Antonio A; Candido-Dos-Reis, Francisco J
To evaluate the perceptions of women with endometriosis and chronic pelvic pain regarding their social ties. A qualitative study was undertaken of women with chronic pelvic pain and endometriosis. Focus groups discussions among four to six participants were performed until saturation at the Clinics Hospital of Ribeirão Preto Medical School, Ribeirão Preto, southwest Brazil, between February 2013 and January 2014. Transcripts were analyzed according to the grounded theory approach and the emerging categories were coded using the WebQDA platform. Six focus group discussions took place, with a total of 29 patients. Social isolation was the main emerging theme. Social isolation was associated with a lack of understanding about endometriosis symptoms and with resignation in face of recurrent pain episodes. Avoiding partner intimacy and isolation from family and friends were components of social isolation. Women with endometriosis develop progressive social isolation after the onset of chronic pelvic pain. This finding is important for the multidisciplinary management of the disease. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Mettler, L.; Jürgensen, A.; Volkov, N. I.; Kulakov, V.; Parwaresch, M. R.
The aim of present study was to investigate the occurence of different lymphocyte subsets in the endometrium of endometriosis patients and in healthy women on every day of the menstrual cycle with special emphasis to the proliferative activity of endometrial cells with Ki-S3 antibody. We also conducted immunohistochemical studies of T-lymphocytes, B-lympho-cytes, macrophages, natural-killer-cells and also of antigens class II of the histocompatibility complex (HLA-DR) during the different phases of the menstrual cycle in endometriosis and non-endometriosis patients. Endometrial lymphocyte subsets show equal quantity and distribution in endometriosis patients and in the control group. After a peak in the early preoliferative phase the absolute number of T-lymphocytes decreases while a predominance of T-suppressor/cytotoxic T-lymphocytes (CD8) compared to T-helper/inducer lymphocytes (CD4) occurs towards the end of the menstrual cycle. It can be concluded that endometrium as the potential parent epithelia of endometriotic lesions seems not to be altered in its lymphatic cell content compared to healthy women. Furthermore endometrium is clearly characterised as part of the mucosa associated lymphatic tissue (MALT). T-lymphocytes show specific quantitative changes due to different phases of the menstrual cycle. PMID:18493428
Moawad, Nash S; Caplin, Andrea
Rectovaginal endometriosis is the most severe form of endometriosis. Clinically, it presents with a number of symptoms including chronic pelvic pain, dysmenorrhea, deep dyspareunia, dyschezia, and rectal bleeding. The gold standard for diagnosis is laparoscopy with histological confirmation; however, there are a number of options for presurgical diagnosis, including clinical examination, transvaginal/transrectal ultrasound, magnetic resonance imagining, colonoscopy, and computed tomography colonography. Treatment can be medical or surgical. Medical therapies include birth control pills, oral progestins, gonadotropin-releasing hormone agonists, danazol, and injectable progestins. Analgesics are often used as well. Surgery improves up to 70% of symptoms. Surgery is either ablative or excisional, and is conducted via transvaginal, laparoscopic, laparotomy, or combined approaches. Common surgical techniques involve shaving of the superficial rectal lesion, laparoscopic anterior discoid resection, and low anterior bowel resection and reanastomosis. Outcomes are generally favorable, but postoperative complications may include intra-abdominal bleeding, anastomotic leaks, rectovaginal fistulas, strictures, chronic constipation, and the need for reoperation. Recurrence of rectal endometriosis is a possibility as well. Other outcomes are improved pain-related symptoms and fertility. Long-term outcomes vary according to the management strategy used. This review will provide the most recent approaches and techniques for the diagnosis and treatment of rectovaginal endometriosis. PMID:24232977
Hastings, Julie M; Fazleabas, Asgerally T
Endometriosis is one of the most common causes of chronic pelvic pain and infertility in women in the reproductive age group. Although the existence of this disease has been known for over 100 years our current knowledge of its pathogenesis and the pathophysiology of its related infertility remains unclear. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed a model of this disease in the non-human primate, the baboon (Papio anubis). Intraperitoneal inoculation of autologous menstrual endometrium results in the development of endometriotic lesions with gross morphological characteristics similar to those seen in the human. Multiple factors have been implicated in endometriosis-associated infertility. We have described aberrant levels of factors involved in multiple pathways important in the establishment of pregnancy, in the endometrium of baboons induced with endometriosis. Specifically, we have observed dysregulation of proteins involved in invasion, angiogenesis, methylation, cell growth, immunomodulation, and steroid hormone action. These data suggest that, in an induced model of endometriosis in the baboon, an increased angiogenic capacity, decreased apoptotic potential, progesterone resistance, estrogen hyper-responsiveness, and an inability to respond appropriately to embryonic signals contribute to the reduced fecundity associated with this disease. PMID:17118171
Environmental PCB and Pesticide Exposure and Risk of Endometriosis
Germaine M. Buck1, John M. Weiner2, Hebe Greizerstein3, Brian Whitcomb1, Enrique Schisterman1, Paul Kostyniak3, Danelle Lobdell4, Kent Crickard5, and Ralph Sperrazza5
1Epidemiology Branch, Division o...
Han, Sang Jun; O'Malley, Bert W.
BACKGROUND Endometriosis is defined as the colonization and growth of endometrial tissue at anatomic sites outside the uterine cavity. Up to 15% of reproductive-aged women in the USA suffer from painful symptoms of endometriosis, such as infertility, pelvic pain, menstrual cycle abnormalities and increased risk of certain cancers. However, many of the current clinical treatments for endometriosis are not sufficiently effective and yield unacceptable side effects. There is clearly an urgent need to identify new molecular mechanisms that critically underpin the initiation and progression of endometriosis in order to develop more specific and effective therapeutics which lack the side effects of current therapies. The aim of this review is to discuss how nuclear receptors (NRs) and their coregulators promote the progression of endometriosis. Understanding the pathogenic molecular mechanisms for the genesis and maintenance of endometriosis as modulated by NRs and coregulators can reveal new therapeutic targets for alternative endometriosis treatments. METHODS This review was prepared using published gene expression microarray data sets obtained from patients with endometriosis and published literature on NRs and their coregulators that deal with endometriosis progression. Using the above observations, our current understanding of how NRs and NR coregulators are involved in the progression of endometriosis is summarized. RESULTS Aberrant levels of NRs and NR coregulators in ectopic endometriosis lesions are associated with the progression of endometriosis. As an example, endometriotic cell-specific alterations in gene expression are correlated with a differential methylation status of the genome compared with the normal endometrium. These differential epigenetic regulations can generate favorable cell-specific NR and coregulator milieus for endometriosis progression. Genetic alterations, such as single nucleotide polymorphisms and insertion/deletion polymorphisms of NR
Nothnick, Warren B.; Al-Hendy, Ayman; Lue, John R.
Endometriosis represents a major medical concern in women of reproductive age. One of the major hurdles in successful treatment of endometriosis that remains is the limitation in the process of timely disease diagnosis. A simple blood test for endometriosis-specific biomarkers would offer a timelier, accurate diagnosis for the disease allowing earlier treatment intervention. While there have been considerable efforts to identify such biomarkers, no clear choice for such non-invasive diagnostic tools have been identified. MicroRNAs are small non-coding RNAs which have been intensively evaluated as biomarkers for several diseases and may hold promise for endometriosis diagnosis. In this review, we highlight the need for non-invasive testing for endometriosis, discuss the potential use of miRNAs as diagnostic tools for this disease, and consider potential limitations in the use of these small RNA molecules as diagnostic markers for endometriosis. PMID:25757811
Ness, Roberta B; Modugno, Francesmary
Chronic inflammation has been implicated in a variety of cancers. In this review, we consider associations between endometriosis and cancers both local (ovarian) and distant (breast). We review the epidemiological data linking endometriosis to ovarian and breast cancers. We then consider evidence for a role for sex steroid hormones and for inflammation in the aetiology of each of these cancers. Finally, we consider that endometriosis may promote alterations in sex steroid hormones and inflammatory mediators. A possible explanation for the association between endometriosis and these reproductive cancers may then be local and systemic enhancement of aberrant inflammatory and hormonal mediators. If this hypothesis is true, endometriosis may need to be considered as a risk factor for ovarian and breast cancers, triggering increasingly intensive surveillance. Moreover, treatments for endometriosis may require consideration of the impact on long-term cancer risk.
Greaves, Erin; Horne, Andrew W.; Jerina, Helen; Mikolajczak, Marta; Hilferty, Lisa; Mitchell, Rory; Fleetwood-Walker, Sue M.; Saunders, Philippa T. K.
Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis. PMID:28281561
Greaves, Erin; Horne, Andrew W; Jerina, Helen; Mikolajczak, Marta; Hilferty, Lisa; Mitchell, Rory; Fleetwood-Walker, Sue M; Saunders, Philippa T K
Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.
Zheng, Qiaomei; Lu, Jingjing; Li, Rui; Hu, Chen; Liu, Peishu
To identify the level of periostin in serum and peritoneal washing fluids (PWF) from women with and without endometriosis, as well as to explore the potential of periostin as a biomarker of endometriosis. Samples were obtained from 184 women with and without endometriosis. Concentrations of periostin in PWF and blood were measured by enzyme-linked immunosorbent assay. Levels of periostin both in serum and PWF were notably elevated in women with endometriosis in both the proliferative and secretory phase. Combined with dysmenorrhea and infertility, two potential covariates, the serum periostin had a sensitivity of 75.00%, specificity of 65.00%, and area under the curve (AUC) of 0.774, whereas the PWF periostin had a sensitivity of 94.23%, specificity of 90.00%, and AUC of 0.967 for the diagnosis of endometriosis. Serum and PWF periostin concentrations may be new potential biomarkers for endometriosis, especially when combined with dysmenorrhea and infertility.
Karadag, Mert Ali; Aydin, Turgut; Karadag, Ozge Idem; Aksoy, Huseyin; Demir, Aslan; Cecen, Kursat; Tekdogan, Umit Yener; Huseyinoglu, Urfettin; Altunrende, Fatih
Endometriosis can be defined as the presence of endometrial glandular and stromal tissue outside the uterus. Affected sites of endometriosis can even be the urinary tract. Here, we present the case of a 30-year-old woman with right ureteral endometriosis. This case was important due to the unusual localization and no signs of the disease except for hydroureteronephrosis. A 30-year-old Caucasian woman with para 2 was admitted to our department for right side flank pain, dysuria and suprapubic pain. She had no complaints of vaginal discharge, bleeding or painful menstruation. Her menstrual cycles were normal and lasting for three to four days. She did not have a history of any surgical interventions. A physical examination revealed a right side costovertebral angle and suprapubic tenderness. Laboratory test results including a complete blood count, serum biochemical analysis, urine analysis and urine culture were normal. Urinary ultrasonography showed right side hydroureteronephrosis with renal cortical thinning. We suspected a right ureteral stone obstructing the ureter and a computed tomography scan was performed. The computed tomography scan revealed similar right side hydroureteronephrosis with obstruction of the ureter. No signs of stone were observed on the scan. Retrograde pyelography and diagnostic ureterorenoscopy were performed and they showed a focal stricture with a length of approximately 3 cm at the distal ureteral part and secondary hydroureteronephrosis. Open partial ureterectomy and ureteroneocystostomy with Boari flap were performed. The pathologic specimen of her ureter demonstrated intrinsic endometriosis of the right ureter with endometrial glandular cells and stromal tissue. Clinicians should suspect ureteral endometriosis in premenopausal women with unilateral or bilateral distal ureteral obstruction of uncertain cause. The main goals of the treatment should be preservation of renal function, relief of obstruction and prevention of recurrence.
Elia, Stefano; De Felice, Laura; Varvaras, Dimitrios; Sorrenti, Giuseppe; Mauriello, Alessandro; Petrella, Giuseppe
Introduction Catamenial pneumothorax (CP) is a spontaneous recurrent pneumothorax occurring in women in reproductive age. The etiology of CP has been associated with thoracic endometriosis and is its most common presentation. Presentation of case A case of right catamenial pneumothorax in a 38 year old woman is presented in which three episodes of CP occurred within 72 h of menses in a 6 month period. The patient underwent videothoracoscopy that revealed a solitary localization of diaphragmatic endometriosis. After surgical pleurodesis and based on final pathology of resected lesion, hormonal treatment was started. The outcome was uneventful and the patients is symptom-free at 6 months. Discussion Catamenial pneumothorax (CP) is a rare clinical entity characterized by lung collapse during menstruation, believed to be secondary to pleural endometriosis. Nearly all catamenial pneumothorax occur on the right side as pleural lesions are almost exclusively right-sided. Diagnostic imaging is based on high resolution computed tomography (HRCT) and, preferably, magnetic resonance imaging (MRI) since it is able to detect the blood products in the endometrial deposits. However the lack of macroscopic findings at surgery makes this condition still under-diagnosed. Based on the solitary diaphragmatic localization of endometriosis in our case we preferred to limit surgery to videothoracoscopic pleurodesis and start hormonal treatment with successful outcome. Conclusion Catamenial pneumothorax is the most common presentation of thoracic endometriosis syndrome and should always be suspected in women in childbearing age. Treatment option are still debated but best results are achieved by videothoracoscopic pleurodesis combined with hormonal therapy. PMID:25981153
Kizilay, Gulnur; Uz, Yesim Hulya; Seren, Gulay; Ulucam, Enis; Yilmaz, Ali; Cukur, Ziya; Kayisli, Umit Ali
Endometriosis is one of the most common chronic gynecological diseases. The aim of the study was to examine the effects of curcumin and/or deferoxamine on cell proliferation in a rat model of endometriosis. Thirty female 12-week-old albino Wistar rats, weighing 200-250 g, were used in this study. All the rats underwent ovariectomy and 0.1-mg β-estradiol 17-valerate pellets were placed intraperitoneally. An experimental model of endometriosis was created in all the animals. To create the experimental model, an approximately 1-cm long section of the uterus was taken, primarily from the right horn of the uterus. Autologous fragments were then placed between the peritoneum and muscle. The animals were divided into 3 groups: Group A, treated only with the vehicle used for curcumin and deferoxamine; group B, treated with curcumin (100 mg/kg body weight); and group C, treated with deferoxamine + curcumin (100 mg/kg body weight). After biopsy samples were obtained, the sections were stained with hematoxylin and eosin. Immunostaining for cytokeratin-7 and proliferating cell nuclear antigen (PCNA) was performed. Blood iron levels were measured using a Perkin Elmer AAnalyst 800 Atomic Absorption Spectrophotometer. The endometrial implant size increased in Group A, but treatment with curcumin (p = 0.01) and deferoxamine + curcumin (p = 0.007) reduced the implant size. In ectopic endometrial epithelial cells, there were significant decreases in PCNA immunoreactivity between groups A and B (p = 0.044) and between groups A and C (p = 0.033). Treatment with curcumin alone and/or in combination with deferoxamine contributed to a reduction in implant size and cell proliferation in a rat endometriosis model. Iron-chelating agents may act in the same manner when used in women with endometriosis; however, further studies from different perspectives are still needed.
Koppan, A; Hamori, J; Vranics, I; Garai, J; Kriszbacher, I; Bodis, J; Rebek-Nagy, G; Koppan, M
To assess potential individual factors influencing quality of life and pain scores of patients suffering from histologically confirmed endometriosis. Study using a questionnaire among patients of reproductive age undergoing laparoscopy with a presumed diagnosis of endometriosis. Details of fertility, previous treatments and quality of life, sexual activity, as well as linear pain scores for several symptoms, were recorded. Details of intraoperative findings were also collected and only those data were used where endometriosis was intraoperatively and histologically proven. A questionnaire before surgery gathered information from women on the following groups of variables: age, marital status, education, reproductive and medical history including previous pregnancies and parity, knowledge of accompanying pelvic disorders, regular sport activity, as well as general quality of life estimates including self-image. Pelvic pain was scored using a visual analogue scale. Data were statistically evaluated. Eighty-one patients complaining about persistent pelvic pain were later intraoperatively and histologically proven to have endometriosis. Thirty-one of them (38.2%) reported regular sport as part of their daily life schedule while 50 of them (61.8%) performed no physical activity at all. Fourteen patients among regular exercisers and 33 patients among those without physical activity reported the effectiveness of painkillers for pelvic pain, corresponding to 45.1% and 66% of these subgroups, respectively (difference statistically significant, p<0.05). Based on our results, we can conclude, that taking painkillers might be less effective among endometriosis patients performing regular daily sport activities, and, thus it might impose them to an unnecessary burden of possible side-effects.
Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej
To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.
Samartzis, Eleftherios P.; Noske, Aurelia; Dedes, Konstantin J.; Fink, Daniel; Imesch, Patrick
Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review. PMID:24036443
Harada, Takashi; Taniguchi, Fuminori; Onishi, Kazunari; Kurozawa, Youichi; Hayashi, Kunihiko; Harada, Tasuku
Background Endometriosis, which occurs in approximately 10% of women of reproductive age, is defined as the presence of endometrial tissue outside the uterus. Women with endometriosis are more likely to have difficulty conceiving and tend to receive infertility treatment, including assisted reproductive technology (ART) therapy. There has not yet been a prospective cohort study examining the effects of endometriosis on pregnancy outcome in pregnant Japanese women. Methodology This was a prospective cohort study of the incidence of obstetrical complications in women with endometriosis using data of the Japan Environment & Children’s Study (JECS). Included in this study were 9,186 pregnant women in the JECS with or without a history of endometriosis who gave birth or stillbirth or whose pregnancy was terminated with abortion between February and December 2011. Main Outcome Measures The effects of endometriosis on pregnancy outcome. Results Of the 9,186 pregnant women in the JECS, 4,119 (44.8%) had obstetrical complications; 330 participants reported a diagnosis of endometriosis before pregnancy, and these women were at higher risk for complications of pregnancy than those without a history of endometriosis (odds ratio (OR) = 1.50; 95% confidence interval (CI) 1.20 to 1.87). Logistic regression analyses showed that the adjusted OR for obstetrical complications of pregnant women who conceived naturally and had a history of endometriosis was 1.45 (CI 1.11 to 1.90). Among pregnant women with endometriosis, the ORs of preterm premature rupture of the membranes (PROM) and placenta previa were significantly higher compared with women never diagnosed with endometriosis who conceived naturally or conceived after infertility treatment, except for ART therapy (OR 2.14, CI 1.03–4.45 and OR 3.37, CI 1.32–8.65). Conclusions This study showed that endometriosis significantly increased the incidence of preterm PROM and placenta previa after adjusting for confounding of the
Young, Vicky J.; Brown, Jeremy K.; Saunders, Philippa T. K.; Duncan, W. Colin; Horne, Andrew W.
Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05) and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05). The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05) in expression of genes associated with tumorigenesis (MAPK8, CDC6), epithelial-mesenchymal transition (NOTCH1), angiogenesis (ID1, ID3) and neurogenesis (CREB1) in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation. PMID:25207642
Yasui, Toshiyuki; Hayashi, Kunihiko; Nagai, Kazue; Mizunuma, Hideki; Kubota, Toshiro; Lee, Jung-Su; Suzuki, Shosuke
Background The prevalence and risk factors for endometriosis may differ according to diagnosis methodologies, such as study populations and diagnostic accuracy. We examined risk profiles in imaging-diagnosed endometriosis with and without surgical confirmation in a large population of Japanese women, as well as the differences in risk profiles of endometriosis based on history of infertility. Methods Questionnaires that included items on sites of endometriosis determined by imaging techniques and surgical procedure were mailed to 1025 women who self-reported endometriosis in a baseline survey of the Japan Nurses’ Health Study (n = 15 019). Results Two hundred and ten women had surgically confirmed endometriosis (Group A), 120 had imaging-diagnosed endometriosis without a surgical procedure (Group B), and 264 had adenomyosis (Group C). A short menstrual cycle at 18–22 years of age and cigarette smoking at 30 years of age were associated with significantly increased risk of endometriosis (Group A plus Group B), while older age was associated with risk of adenomyosis (Group C). In women with a history of infertility, a short menstrual cycle was associated with a significantly increased risk of endometriosis in both Group A and Group B, but risk profiles of endometriosis were different between Group A and Group B in women without a history of infertility. Conclusions Women with surgically confirmed endometriosis and those with imaging-diagnosed endometriosis without surgery have basically common risk profiles, but these risk profiles are different from those with adenomyosis. The presence of a history of infertility should be taken into consideration for evaluation of risk profiles. PMID:25716280
Qian, R Y; Wu, X; Sheng, J; Zheng, P; Zhou, Q; Duan, A H; Zhang, J P; Zhang, Y L; Lu, D
Objective: To explore the application of endometriosis fertility index (EFI) in guidance after laparoscopic surgery of endometriosis patients combined with infertility and to explore methods to improve pregnancy rate in different EFI groups. Methods: A prospective research was done in endometriosis patients combined with infertility in Beijing Obstetrics and Gynecology Hospital from January 2010 to June 2011, after laparoscopic surgery, these 146 patients were divided into 3 groups by EFI score. Using different pregnancy guidance, these patients had 5 years follow-up. Results: (1) The 5 years overall pregnancy rate was 89.0% (130/146). The pregnancy rate was 95.7% (45/47) in EFI≥9 group, 92.8% (77/83) in EFI 5-8 group and 8/16 in EFI≤4 group, three groups were all reach satisfactory pregnancy rate; the rate of the first two groups had no statistically significance (P=0.498), but had significant difference with the last group (P<0.01). (2) In EFI≥5 patients, pregnancy rate was the highest in 6 months after operation; in EFI≥9 group, the pregnancy rate was 66.7% (30/45), and EFI 5-8 group was 50.6% (39/77). (3) EFI≥9 group had the highest natural pregnancy rate [83.6% (46/55)], natural pregnancy rate was significant statistical different in different EFI groups (P=0.001). Conclusions: EFI score is a useful evaluation in predicting and guiding pregnancy in endometriosis patients combined with infertility after laparoscopic surgery. EFI score guidance, strict post-operation management and positive pregnancy scheme could significantly improve the pregnancy rate of endometriosis patients with infertility.
Kawano, Yukie; Nasu, Kaei; Hijiya, Naoki; Tsukamoto, Yoshiyuki; Amada, Kohei; Abe, Wakana; Kai, Kentaro; Moriyama, Masatsugu; Narahara, Hisashi
Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. The objective of the study was to determine the epigenetically silenced genes by histone deacetylation in endometriosis. Histone deacetylase-1 target mRNAs that were up-regulated by valproic acid (VPA) treatment in endometriotic cyst stromal cells (ECSCs) were identified by a global mRNA microarray technique. We identified 5 candidate genes and chose CCAAT/enhancer-binding protein α (C/EBPα) for further functional experiments. C/EBPα mRNA and protein expression is attenuated in ECSCs, and the expression was up-regulated by VPA stimulation. Immunohistochemical stainings also confirmed the decreased staining for C/EBPα protein in endometriotic tissues. VPA treatment resulted in an accumulation of acetylated histones H3 and H4 in the promoter region of the C/EBPα gene in ECSCs. The compulsory expression of C/EBPα in ECSCs directed the inhibition of cell proliferation and the induction of apoptosis. C/EBPα knockdown by small interfering RNA directed the stimulation of cell proliferation and the resistance to apoptosis in normal eutopic endometrial stromal cells. The expressions of peroxisome proliferator-activated receptor-γ (PPARγ), period homolog 2 (PER2), p53, apoptosis-inducing factor, mitochondrion-associated 1 (AIFM1), Bax, caspase-8, caspase-10, p16(INK4a), p21(Waf1/Cip1), cyclin-dependent kinase (cdk) 2, and cdk4 were down-regulated by C/EBPα knockdown. Our findings suggest that an epigenetically suppressed tumor suppressor gene is involved in the pathogenesis of endometriosis by creating the proliferative, antiapoptotic, and other disease-specific characteristics of endometriosis. The results also suggest that histone deacetylase inhibitors are promising agents for the treatment of endometriosis.
Brogniez, A.; Mordon, Serge R.; Devoisselle, Jean-Marie; Querleu, Denis; Brunetaud, Jean Marc
The main problem of endometriosis is the detection of microscopic and atypical lesions. The successful destruction of these endometriotic sites depends on their detection. This study aimed to develop a spectrofluorometric method to increase the sensitivity of detection of endometriosis. A surgical-induced endometriosis was performed in ten rabbits. Five weeks later, the fluorescence of these endometriotic lesions was studied after injection of tamoxifen and local application of eosin. This fluorescence was compared with that of healthy broad ligament and that obtained without tamoxifen and without eosin. A spectral analysis showed a specific fluorescence of eosin-tamoxifen association, more intense than autofluorescence and selectively observed within endometriosis.
Background Endometriosis is a common but bothersome gynecological disease, and Chinese herbal medicine (CHM) is used for treating endometriosis. The aim of this study is to explore CHM network and core treatments for endometriosis by analyzing nationwide CHM prescription database. Methods From 1998 to 2013, the CHM prescriptions made primarily for endometriosis among women diagnosed with endometriosis (ICD-9-CM code: 671) by gynecologists during their reproductive age were collected. CHM network analysis was then carried out by using association rule mining and social network analysis. Results A total of 12,986 CHM prescriptions made for endometriosis were analyzed. There were 556 kinds of CHM ever used, and, in average, each prescription was composed of 6.2 CHMs. Gui-Zhi-Fu-Ling-Wan (GZFLW) was used most frequently, followed by Cyperus rotundus (28.1% and 18.8% of all prescriptions, resp.). Additionally, the combination of Cyperus rotundus with GZFLW (8.0%) was the most frequently used combination of two CHMs. CHM network showed that GZFLW was the core CHM for endometriosis and graphically demonstrated the extensive coverage of TCM syndromes and pathogenesis of endometriosis. Conclusions CHM network provides graphical demonstration and summary of commonly used CHMs for endometriosis, and further studies are warranted based on these findings. PMID:28740539
Perelló, Maria; Martínez-Zamora, Maria A; Torres, Ximena; Munrós, Jordina; Llecha, Silvia; De Lazzari, Elisa; Balasch, Juan; Carmona, Francisco
The purpose of the study was to develop an easily applicable predictive model to predict deep infiltrating endometriosis in patients with ovarian endometrioma. We performed a retrospective analysis of 178 consecutive women with ovarian endometrioma who underwent surgery, with histological confirmation and complete removal of endometriosis in the Hospital Clinic of Barcelona. Several markers were prospectively obtained and compared between the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma and women with only ovarian endometrioma. Multiple logistic regression analysis was performed to create a model to predict the presence of deep infiltrating endometriosis and internal validation was later performed. Of the 178 patients studied, 80 (45%) were classified in the ovarian endometrioma group and 98 (55%) in the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma. The independent variables to predict deep infiltrating endometriosis were: at least one previous pregnancy, a past history of surgery for endometriosis and the mean endometriosis-associated pelvic pain score. The area under the ROC curve was 0.91 (95% confidence interval: 0.86-0.94), with an optimal cut-off of the predicted probability of 0.54. The sensitivity of the model was 80% and the specificity 84%. This model predicts the development of deep infiltrating endometriosis in patients with ovarian endometriomas allowing prioritization of women for referral to specialized centers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Scheerer, Claudia; Bauer, Petia; Chiantera, Vito; Sehouli, Jalid; Kaufmann, Andreas; Mechsner, Sylvia
To identify and characterize endometriosis-associated immune cell infiltrates (EMaICI). Furthermore, to define occurrence and size of EMaICI in various types of endometriosis. Immune cells were characterized in samples of 60 premenopausal women with histological proven endometriosis. Therefore, immunohistochemical staining with monoclonal antibodies for CD3, CD4, CD8, CD45RO, CD25, CD56, CD68, and CD20 on sections of paraffin-embedded endometriotic tissue was performed. EMaICI were observed in all the types of endometriosis, and characterized as T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), antigen-experienced T lymphocytes"memory cells" (CD45RO+), macrophages (CD68+), and B lymphocytes (CD20+). The maximum frequency of EMaICI and their distribution per endometriotic lesion (EML) was observed in peritoneal endometriosis (pEM) and in ovarian endometriosis (Ov. EM). In myometrium from adenomyosis (M/AM), EMaICI occurrence was lower and smaller in size in comparison with EMaICI seen in other forms of endometriosis. EMaICI were negative for regulatory T cells (CD25+ high, FoxP3+) and natural killer cells (NK cells, CD56+). Numerous and brisk EMaICI comprising several types of immune cells in all endometriosis forms suggest acute immunological reactions within the microenvironment of endometriosis lesions.
de Freitas, Cláudia V. Marques; Câmara, Sara Filipa Camacho; Vieira, José Joaquim Nunes
Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. It affects 3 to 10 percent of women of reproductive age. Umbilical endometriosis is rare, with an estimated incidence of 0.5–1.0% among all cases of endometriosis, and is usually secondary to prior laparoscopic surgery involving the umbilicus. In this report, we described a case of umbilical endometriosis treated with surgical resection and highlight the great importance of medical history compared to complementary diagnostic tests that can be sometimes inconclusive. PMID:27747115
Kistner, R W
This paper outlines methods of therapy utilizing newer combinations of estrogens and progestins. The specific agent and length of treatment depends on the extent of disease, severity of symptoms, presence of infertility and response to pseudopregnancy. Structural formulas for 19 synthetic preparations are shown. Of 36 patients with proven endometriosis in which pseudopregnancy was induced by the use of these newer agents, satisfactory objective in 82%. Pregnancy occurred later in 6 of 10 patients who had previously been infertile and wished to become pregnant. The optimum maintenance dose is 4-6 mg of chlormadinone acetate or ethnodiol diacetate with .2 mg of mestranol and 5-10 mg of megestrol acetate with .2 mg of ethniyl estradiol. Dosage is increased only when break through bleeding occurs. Gain in weight occurred in almost 1/2 of the patients. The decidual reaction was just as great as that produced formerly by large doses of Enovid. In a more recent study 60 patients were treated with Norlestrin, 20 with Lyndiol and 20 with Ovral. Satisfactory objective and subjective remissions were obtained in 89%. Pregnancy has occurred subsequently in 17 to 43 patients who desired pregnancy. All infants have been normal. The optimum maintenance doses seem to be 10-15 mg if Norlestrin, 2.5-5 mg Lyndiol or .5-1 mg of Ovral. The most common side effect was weight gain in 35%. These agents may be used prior to conservative surgery in order to soften areas of fibrotic endometriosis or to pinpoint areas otherwise overlooked. The length of preoperative treatment depends on the extent of disease, 6 weeks being usual. The indication for prolonged pseudopregnancy is recurrent endometriosis following surgery, also proven vaginal endometriosis. Subsequent to conservative surgery, 12 to 24 weeks of therapy are given in order to inhibit ovulation and prevent reactivation of any remaining areas of endometriosis. Tables show commercial combinations and dosage regimens. Nausea, break
Centini, Gabriele; Zannoni, Letizia; Lazzeri, Lucia; Buiarelli, Paolo; Limatola, Gianluca; Petraglia, Felice; Seracchioli, Renato; Zupi, Errico
Endometriosis is a chronic benign disease affecting women of fertile age, associated with pelvic pain and subfertility, often with negative impacts on quality of life. Meetings involving 5 gynecologists skilled in endometriosis management and 2 informatics technology consultants competent in data management and website administration were enlisted to create an endometriosis databank known as ENEAS (Enhanced Endometriosis Archiving Software). This processing system allows users to store, retrieve, compare, and correlate all data collected in conjunction with different Italian endometriosis centers, with the collective objective of obtaining homogeneous data for a large population sample. ENEAS is a web-oriented application that can be based on any open-source database that can be installed locally on a server, allowing collection of data on approximately 700 items, providing standardized and homogeneous data for comparison and analysis. ENEAS is capable of generating a sheet incorporating all data on the management of endometriosis that is both accurate and suitable for each individual patient. ENEAS is an effective and universal web application that encourages providers in the field of endometriosis to use a common language and share data to standardize medical and surgical treatment, with the main benefits being improved patient satisfaction and quality of life.
Maignien, Chloé; Santulli, Pietro; Gayet, Vanessa; Lafay-Pillet, Marie-Christine; Korb, Diane; Bourdon, Mathilde; Marcellin, Louis; de Ziegler, Dominique; Chapron, Charles
Assisted reproductive technology is one of the therapeutic options offered for managing endometriosis-associated infertility. Yet, published data on assisted reproductive technology outcome in women affected by endometriosis are conflicting and the determinant factors for pregnancy chances unclear. We sought to evaluate assisted reproductive technology outcomes in a series of 359 endometriosis patients, to identify prognostic factors and determine if there is an impact of the endometriosis phenotype. This was a retrospective observational cohort study, including 359 consecutive endometriosis patients undergoing in vitro fertilization or intracytoplasmic sperm injection, from June 2005 through February 2013 at a university hospital. Endometriotic lesions were classified into 3 phenotypes-superficial peritoneal endometriosis, endometrioma, or deep infiltrating endometriosis-based on imaging criteria (transvaginal ultrasound, magnetic resonance imaging); histological proof confirmed the diagnosis in women with a history of surgery for endometriosis. Main outcome measures were clinical pregnancy rates and live birth rates per cycle and per embryo transfer. Prognostic factors of assisted reproductive technology outcome were identified by comparing women who became pregnant and those who did not, using univariate and adjusted multiple logistic regression models. In all, 359 endometriosis patients underwent 720 assisted reproductive technology cycles. In all, 158 (44%) patients became pregnant, and 114 (31.8%) had a live birth. The clinical pregnancy rate and the live birth rate per embryo transfer were 36.4% and 22.8%, respectively. The endometriosis phenotype (superficial endometriosis, endometrioma, or deep infiltrating endometriosis) had no impact on assisted reproductive technology outcomes. After multivariate analysis, history of surgery for endometriosis (odds ratio, 0.14; 95% confidence ratio, 0.06-0.38) or past surgery for endometrioma (odds ratio, 0.39; 95
Matalliotakis, Michail; Goulielmos, George N; Matalliotaki, Charoula; Trivli, Alexandra; Matalliotakis, Ioannis; Arici, Aydin
The aim of this retrospective study was to evaluate endometriosis in adolescent and young girls and further to review the menstrual, reproductive characteristics, and risk factors. We reviewed the medical records of adolescent and young girls with endometriosis from 2 different countries. Data were collected and analyzed from charts of 900 patients with endometriosis. Fifty-five female adolescents aged between 13 and 21 years (mean age 18.3 years) participated in our series. This study was conducted in the Obstetric and Gynecology Department of Venizeleio General Hospital of Crete and involved all patients diagnosed with endometriosis between 1996 and 2016. Statistical methods included χ(2) and Mann-Whitney U test. Of 900 patients with endometriosis we found 55 female adolescents (6.1%). The mean age was 18.3 ± 2.3 years, significantly younger compared with the advanced endometriosis patients (32.7 ± 7.2; P < .001). Regarding the menstrual reproductive and others characteristics, we observed several differences in adolescent young girls compared with the advanced age endometriosis group. The factors associated with an increased risk for young women include age at menarche, dysmenorrhea, history of asthma, and a positive family history of endometriosis. Additionally, we report on 16 of 55 (32%) adolescent women with endometriosis and congenital malformations (P < .01) and 5 patients who were diagnosed with dry eye syndrome. There is an association between endometriosis in adolescent and young women and risk factors including early menarche, early onset of dysmenorrhea, history of asthma, previous surgical procedures, obstructive genital anomalies, and family history of endometriosis. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
Johnson, Candice Y; Grajewski, Barbara; Lawson, Christina C; Whelan, Elizabeth A; Bertke, Stephen J; Tseng, Chih-Yu
This study aimed to (i) compare odds of endometriosis in a cohort of flight attendants against a comparison group of teachers and (ii) investigate occupational risk factors for endometriosis among flight attendants. We included 1945 flight attendants and 236 teachers aged 18-45 years. Laparoscopically confirmed endometriosis was self-reported via telephone interview, and flight records were retrieved from airlines to obtain work schedules and assess exposures for flight attendants. We used proportional odds regression to estimate adjusted odds ratios (OR adj) and 95% confidence intervals (95% CI) for associations between exposures and endometriosis, adjusting for potential confounders. Flight attendants and teachers were equally likely to report endometriosis (OR adj1.0, 95% CI 0.5-2.2). Among flight attendants, there were no clear trends between estimated cosmic radiation, circadian disruption, or ergonomic exposures and endometriosis. Greater number of flight segments (non-stop flights between two cities) per year was associated with endometriosis (OR adj2.2, 1.1-4.2 for highest versus lowest quartile, P trend= 0.02) but block hours (taxi plus flight time) per year was not (OR adj1.2, 95% CI 0.6-2.2 for highest versus lowest quartile, P trend=0.38). Flight attendants were no more likely than teachers to report endometriosis. Odds of endometriosis increased with number of flight segments flown per year. This suggests that some aspect of work scheduling is associated with increased risk of endometriosis, or endometriosis symptoms might affect how flight attendants schedule their flights.
Johnson, Candice Y; Grajewski, Barbara; Lawson, Christina C; Whelan, Elizabeth A; Bertke, Stephen J; Tseng, Chih-Yu
Objectives This study aimed to (i) compare odds of endometriosis in a cohort of flight attendants against a comparison group of teachers and (ii) investigate occupational risk factors for endometriosis among flight attendants. Methods We included 1945 flight attendants and 236 teachers aged 18–45 years. Laparoscopically confirmed endometriosis was self-reported via telephone interview, and flight records were retrieved from airlines to obtain work schedules and assess exposures for flight attendants. We used proportional odds regression to estimate adjusted odds ratios (ORadj) and 95% confidence intervals (95% CI) for associations between exposures and endometriosis, adjusting for potential confounders. Results Flight attendants and teachers were equally likely to report endometriosis (ORadj 1.0, 95% CI 0.5–2.2). Among flight attendants, there were no clear trends between estimated cosmic radiation, circadian disruption, or ergonomic exposures and endometriosis. Greater number of flight segments (non-stop flights between two cities) per year was associated with endometriosis (ORadj 2.2, 1.1–4.2 for highest versus lowest quartile, P trend= 0.02) but block hours (taxi plus flight time) per year was not (ORadj 1.2, 95% CI 0.6–2.2 for highest versus lowest quartile, P trend=0.38). Conclusion Flight attendants were no more likely than teachers to report endometriosis. Odds of endometriosis increased with number of flight segments flown per year. This suggests that some aspect of work scheduling is associated with increased risk of endometriosis, or endometriosis symptoms might affect how flight attendants schedule their flights. PMID:26645630
Thomsen, Line H; Schnack, Tine H; Buchardi, Kristina; Hummelshoj, Lone; Missmer, Stacey A; Forman, Axel; Blaakaer, Jan
The objective of this review was to evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis. A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale. Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of epithelial ovarian cancer among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre- or postmenopausal), nulliparity, hyperestrogenism (endogenous or exogenous), premenopausal status at endometriosis diagnosis, solid compartments as well as larger size of endometrioma (≥9 cm in diameter at endometriosis diagnosis) were all associated with an increased risk of ovarian cancer. A subgroup of women with endometriosis characterized by endometriosis observed through surgery or imaging after the age of 45 years, nulliparity, postmenopausal status at endometriosis diagnosis, larger size of endometrioma (>9 cm) at endometriosis diagnosis, hyperestrogenism (endogenous or exogenous) and/or cysts with solid compartments may have an elevated risk of epithelial ovarian cancer. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.
Cicinelli, Ettore; Trojano, Giuseppe; Mastromauro, Marcella; Vimercati, Antonella; Marinaccio, Marco; Mitola, Paola Carmela; Resta, Leonardo; de Ziegler, Dominique
To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry. Case-control study. University hospital. Women with and without endometriosis who have undergone hysterectomy. Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis. CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells. The prevalence of CE was statistically significantly higher in the women with endometriosis as compared with the women who did not have endometriosis (33 of 78, 42.3% vs. 12 of 78, 15.4% according to hysteroscopy; and 30 of 78, 38.5% vs. 11 of 78, 14.1% according to histology). The women were divided into two groups, 115 patients without CE and 41 patients with CE. With univariate analysis, parity was associated with a lower risk for CE, and endometriosis was associated with a statistically significantly elevated risk of CE. Using multivariate analysis, parity continued to be associated with a lower incidence of CE, whereas endometriosis was associated with a 2.7 fold higher risk. The diagnosis of CE is more frequent in women with endometriosis. Although no etiologic relationships between CE and endometriosis can be established, this study suggests that CE should be considered and if necessary ruled out in women with endometriosis, particularly if they have abnormal uterine bleeding. Identification and appropriate treatment of CE may avoid unnecessary surgery. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J
Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724
This paper analyses the gynaecological literature on endometriosis, particularly endometriosis classification, to evaluate the epistemological concepts it uses. A qualitative content analysis was conducted on a sample of gynaecological literature published between 1985 and 2000, a period that witnessed the explosion of both evidence-based and patient-centred models of medicine, with their dwelling emphases on science and experience. It was found that the discourse of science is used strategically in this literature as a formal epistemology to lend weight to authors' claims and to guide medical thinking and research. However, gynaecologists also use the notion of experience to assert their own credibility and to question the credibility of other experts. In fact, accounts of their own experience and the experiential accounts of their patients are foundational to gynaecologists' claims-making activities, including their engagement with scientific research.
Luisi, Stefano; Pizzo, Alessandra; Pinzauti, Serena; Zupi, Errico; Centini, Gabriele; Lazzeri, Lucia; Di Carlo, Costantino; Petraglia, Felice
Endometriosis is a model of a benign gynecologic disease associated with two major symptoms: pain and infertility. When becomes chronic, severe psychological and neuroendocrine changes may occur. The high levels of perceived stress caused by symptoms cause a neuroendocrine disequilibrium thus contributing to the progression of the disease. Elevated stress levels alter hormonal secretions, mood and behavior, sexual disorders and appetite custom. Inflammatory comorbidities may be associated with elevated stress in endometriotic patients (inflammatory bowel disease, fibromyalgia, chronic fatigue) and even autoimmune diseases (thyroid disease, systemic lupus erythematosus, multiple sclerosis). Neurogenic mechanisms are described in endometriotic lesions and they affect peripheral and central nervous system of these patients increasing pain sensitivity and stress reactivity. In conclusion, endometriosis is a disease which affects reproductive and neuroendocrine functions with a great impact on women's health and quality of life.
Wang, D Z; Wang, Z Q; Zhang, Z F
According to the method of differentiation of symptom complexes of traditional Chinese medicine (TCM), endometriosis is a disease of blood stasis and mass in the lower portion of abdomen. 76 cases were treated by TCM prescription named endometriotic pill No 1 with rhubarb as the main ingredient. The chief functions of the rhubarb were removing blood stasis, disintegrating mass and purgation. The total effective rate was 80.26%. Among them, the effective rate of dysmenorrhea was 88.89%, that of pelvic pain was 66.72%, that of intercourse pain 72.12%, and diminishing in size of mass or nodule 22.15%; 3 cases of 22 infertility got pregnant (13.63%). The results revealed that the endometriotic pill No 1 yielded distinct improvement in the treatment of endometriosis, including clinical symptoms and signs, laboratory assay of blood rheology, serum Ig, subgroup of T lymphocyte (OKT system) and PG.
Taylor, Robert N.; Yu, Jie; Torres, Paulo B.; Schickedanz, Aimee C.; Park, John K.; Mueller, Michael D.; Sidell, Neil
Like tumor metastases, endometriotic implants require neovascularization to proliferate and invade into ectopic sites within the host. Endometrial tissue, with its robust stem cell populations and remarkable regenerative capabilities, is a rich source of proangiogenic factors. Among the most potent and extensively studied of these proteins, vascular endothelial growth factor has emerged as a critical vasculogenic regulator in endometriosis. Accordingly, angiogenesis of the nascent endometriotic lesion has become an attractive target for novel medical therapeutics and strategies to inhibit vascular endothelial growth factor action. Vascular endothelial growth factor gene regulation in endometrial and endometriosis cells by nuclear receptors, other transcription factors, and also by infiltrating immune cells is emphasized. New data showing that oxidative and endoplasmic reticulum stress increase vascular endothelial growth factor expression are provided. Finally, we review the clinical implications of angiogenesis in this condition and propose potential antiangiogenic therapies that may become useful in the control or eradication of endometriotic lesions. PMID:19001553
Almassinokiani, Fariba; Almasi, Alireza; Akbari, Peyman; Saberifard, Mahboubeh
Background: To determine the role of Letrozole, an aromatase inhibitor, in the treatment of endometriotic pain. Methods: In this prospective, randomized, controlled clinical trial in minimally invasive surgery research center, 51 women with pelvic endometriosis and endometriotic pain (dyspareunia, dysmenorrhea, pelvic pain) score of 5 or more (for at least one of these endometriotic pain), after laparoscopic diagnosis and conservative laparoscopic surgery were treated with either Letrozole plus OCP (n=25) or only OCP (n=26) for 4 months continuously. Results: Using VAS test, the score of dyspareunia, dysmenorrhea and pelvic pain 4 months after the laparoscopic surgery declined significantly in both groups but the difference between results of the two groups was not significant. Conclusion: Both treatment modalities showed comparable effectiveness in the treatment of pains related to endometriosis and in comparison with OCP, Letrozole did not affect the outcome. PMID:25664308
Vercellini, Paolo; Meana, Marta; Hummelshoj, Lone; Somigliana, Edgardo; Viganò, Paola; Fedele, Luigi
Women with endometriosis have a substantial increase in risk of deep dyspareunia with respect to the general female population of corresponding age. This symptom has personal and intimate implications, including unfavorable emotional impact in partners. Deep dyspareunia caused by endometriosis can be viewed as an originally visceral type of pain secondary to chronic inflammation (nociception) but with several superimposed components, including hyperalgesia, abnormal cortical perception, and psychological factors. Therefore, a simplistic biometric approach does not allow a comprehensive and elaborated assessment of the global impact of the symptom on women's sexual function, psychological well-being, body-image, self-esteem, and relational adjustment. We suggest 10 specific issues to be addressed in future research on a clinically as well as scientifically neglected aspect of female health. Time has come to address this physically and psychologically distressing affliction without embarrassment and with a decidedly multidisciplinary perspective.
Tosti, Claudia; Biscione, Antonella; Morgante, Giuseppe; Bifulco, Giuseppe; Luisi, Stefano; Petraglia, Felice
Endometriotic lesions are associated with hormonal imbalance, including increased estrogen synthesis, metabolism and progesterone resistance. These hormonal changes cause increased proliferation, inflammation, pain and infertility. Hormonal imbalances are targets for treatment. Therapeutic strategies and innovations of hormonal drugs for endometriosis are increasing. Acting on estrogen receptors are hormonal drugs decreasing systemic and local estrogen synthesis (GnRH analogs, GnRH antagonists, Aromatase inhibitors) or estrogen activity (selective estrogen receptor modulators). The progesterone resistance is counteracted by progestins (Medroxyprogesterone acetate, Dienogest, Danazol, Levonorgestrel) or by Selective progesterone receptor modulators, a class of drugs under development. The future trend will be to define new drugs to use for prolonged period of time and with poor side effects considering endometriosis a chronic disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ferrero, Hortensia; Buigues, Anna; Martínez, Jessica; Simón, Carlos; Pellicer, Antonio; Gómez, Raúl
To date, several groups have generated homologous models of endometriosis through the implantation of endometrial tissue fluorescently labeled by green fluorescent protein (GFP) or tissue from luciferase-expressing transgenic mice into recipient animals, enabling noninvasive monitoring of lesion signal. These models present an advantage over endpoint models, but some limitations persist; use of transgenic mice is laborious and expensive, and GFP presents poor tissue penetration due to the relatively short emission wavelength. For this reason, a homologous mouse model of endometriosis that allows in vivo monitoring of generated lesions over time and mimics human lesions in recipient mice would be most desirable. In this regard, using C57BL/6 and B6N-Tyrc-Brd/BrdCrCrl mice, we optimized a decidualization protocol to obtain large volumes of decidual endometrium and mimic human lesions. Subsequently, to obtain a more robust and reliable noninvasive monitoring of lesions, we used the fluorescent reporter mCherry, which presents deeper tissue penetration and higher photostability, showing that endometrial tissue was properly labeled with 1 × 108 PFU/mL mCherry adenoviral vectors. mCherry-labeled endometriotic tissue was implanted in recipient mice, generating lesions that displayed characteristics typical of human endometriotic lesions, such as epithelial cells forming glands, local inflammation, collagen deposits, and new vessel formation. In vivo monitoring demonstrated that subcutaneous implantation on ventral abdomen of recipient mice provided the most intense and reliable signal for noninvasive lesion monitoring over a period of at least 20 days. This homologous model improves upon previously reported models of endometriosis and provides opportunities to study mechanism underlying endometriotic lesion growth and progression. We created a cost-effective but accurate homologous mouse model of endometriosis that allows the study of growth and progression of
As gynaecologists frequently function as “general practitioners” for women, gynaecologists are frequently confronted with questions which initially appear to have only a tenuous connection to their field. Chronic pain syndromes represent a particular challenge, especially as pain syndromes are often associated with severe psychosocial stress for the affected woman. This article discusses some of the psychometric aspects of chronic pain in endometriosis and fibromyalgia together with practical therapeutic approaches. PMID:26640283
Bullon, Pedro; Navarro, Jose Manuel
Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved. Revise new inflammatory pathogenic mechanisms involved in endometriosis, namely inflammasome. Literature review for the updating of data to give new clues for different options of treatments. Inflammasome has been described as a multiprotein complex and is considered a key regulator of the innate and adaptive host response that surveys the cytosol and other compartments into the cell. It is involved in the immediate detection and responds to the presence of danger- and pathogen-associated molecular patterns named DAMPs and PAMPs respectively, and has been described in several cells, mainly on immune cells of the myeloid lineage and epithelial cells in tissues with mucosal surfaces. Four inflammasome are formed in a stimulus-dependent manner of distinct composition. They are the Noll Like Receptors (NLR) proteins Nlrp1b, Nlrp3, Nlrc4, and Nlrp6, as well as the absent in melanoma 2 (AIM2). They activate the production of IL-1β and IL-18 that induce a host response such as pyroptosis, a proinflammatory cell death and the secretion of leaderless cytokines and growth factors. Inflammasome is linked to atherosclerosis, periodic fever syndromes, vitiligo, Crohn's disease, gout, asbestosis, silicosis, Alzheimer's disease and periodontitis. Endometriosis has been related with IL-1β and Another NLR, Nlrp7, was correlated with myometrial invasion in human endometrial cancer tissue. These new clues regarding the pathogenic mechanisms involving the inflammasome may be crucial in the future development for endometriosis therapy. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Ohlsson Teague, E. Maria C.; Van der Hoek, Kylie H.; Van der Hoek, Mark B.; Perry, Naomi; Wagaarachchi, Prabhath; Robertson, Sarah A.; Print, Cristin G.; Hull, Louise M.
Endometriosis is a prevalent gynecological disease characterized by growth of endometriotic tissue outside the uterine cavity. MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development. We assessed miRNA expression by microarray analysis in paired ectopic and eutopic endometrial tissues and identified 14 up-regulated (miR-145, miR-143, miR-99a, miR-99b, miR-126, miR-100, miR-125b, miR-150, miR-125a, miR-223, miR-194, miR-365, miR-29c and miR-1) and eight down-regulated (miR-200a, miR-141, miR-200b, miR-142-3p, miR-424, miR-34c, miR-20a and miR-196b) miRNAs. The differential expression of six miRNAs was confirmed by quantitative RT-PCR. An in silico analysis identified 3851 mRNA transcripts as putative targets of the 22 miRNAs. Of these predicted targets, 673 were also differentially expressed in ectopic vs. eutopic endometrial tissue, as determined by microarray. Functional analysis suggested that the 673 miRNA targets constitute molecular pathways previously associated with endometriosis, including c-Jun, CREB-binding protein, protein kinase B (Akt), and cyclin D1 (CCND1) signaling. These pathways appeared to be regulated both transcriptionally as well as by miRNAs at posttranscriptional level. These data are a rich and novel resource for endometriosis and miRNA research and suggest that the 22 miRNAs and their cognate mRNA target sequences constitute pathways that promote endometriosis. Accordingly, miRNAs are potential therapeutic targets for treating this disease. PMID:19074548
Rivlin, M.E.; Krueger, R.P.; Wiser, W.L.
A case is reported in which a woman was diagnosed with ureteral obstruction secondary to endometriosis after cystourethrogram, retrograde pyelogram and a renal scan. After unsuccessful treatment with danazol, a retroperitoneal ureteroneocystotomy was performed. The ureter was found to be obstructed by dense fibrous tissue that contained endometrial glands. It was concluded that danazol is unlikely to relieve endometriotic ureteric obstruction once dense fibrosis has occurred. 8 references, 2 figures.
Ranaweera, R K M D C D; Gamage, S M K; Ubayawansa, D H B; Kumara, M M J
Intussusception is invagination of a proximal segment of bowel into the distal segment in telescopic manner. Although intussusception is common among children, intussusception secondary to terminal ileal endometriosis in an adult is a very rare encounter. We present such a case of intussusception in a Sri Lankan female. A 43 year old Sri Lankan female presented to the surgical casualty unit with features of a subacute intestinal obstruction. Her past surgical and medical histories were unremarkable. On examination she was haemodynamically stable with distended abdomen and there was generalized tenderness. There was no guarding or rigidity. No masses were palpable. Bowel sounds were increased. Her urine was negative for Human Chorionic Gonadotrophin hormone. Full blood count revealed an increased white blood cell count with predominant number of neutrophils. Plain abdominal X-ray film showed dilated small bowel loops with empty rectum and distal colon. Patient underwent emergency exploratory laparotomy. An annular growth at terminal ileum was noted. Proximal bowel loops were distended. There was no free fluid in the abdomen. Ileo caecal tuberculosis was suspected and right hemicolectomy was performed. Uterus and bilateral ovaries appeared normal. Post surgical recovery was uneventful. The pathologist has noted endometriosis of terminal ileum contributing to the stricture formation and intussusception at the site. Following recovery patient was referred to a Gynaecologist for management of endometriosis. Though terminal ileal endometriosis is a very rare cause of intussusception it is important to consider the possibility of it, especially when a female patient of reproductive age presents with symptoms and signs of intestinal obstruction.
Szubert, Maria; Ziętara, Magdalena; Suzin, Jacek
Endometriosis with its estimated incidence rate of ∼7-10% of women of reproductive age is a disease with the wide spectrum of symptoms depending on form and localization of endometrial foci. One clinical form of endometriosis is deep infiltrating endometriosis (DIE), most difficult to manage and generating a lot of direct and indirect treatment costs. We search the literature from PubMed database to establish the role of conservative treatment of DIE. Randomised controlled trials are lacking but in experts opinion hormonal treatment should be the first-line treatment in DIE. After evaluation of pain or other symptoms, second-line therapy with GnRH analogs or danazol should be offered or minimally invasive surgery. Consensus is not made whether surgery is the best therapeutic treatment for affected patients. Strong depending on surgeon's experience conservative surgery should be offered if the total excision of DIE foci is possible, which is essential for a successful outcome. If available treatment options do not release pain associated with DIE, experimental treatment in clinical trials should be discussed with patients.
Ni, H J; Zhang, Z; Dai, Y D; Zhang, S Y
Objective: To establish a model of endometriosis in immunodeficient nude mice and compare the outcome of the model construction between two different techniques. Methods: Eighteen nude mice were divided into 2 groups, with 9 mice in each group. All nude mice received a subcutaneous transplantation of endometrial fragments, followed by sutured the wounded skin (sutured group) or not (no-sutured group). Then the success rate of the model construction, inflammation of the wounds and the animal survival rate in the two groups were analyzed. Result: In no-sutured group, the survival rate of animal and the success rate of the model construction were 9/9 and 8/9 respectively, with 8/9 survival rate and 7/9 success rate in sutured group. No significant difference was found between the two groups. And no obvious inflammation was presented in the wounds for both groups. Conclusion: It is an effective method to establish animal model of endometriosis by subcutaneous transplantation in nude mice. After transplantation, it does not affect the outcome of the survival rate of the animal and the success rate of the model construction whether we suture the wounded skin. Considering the shorter operation time, we found it's a simpler and time saving method to establish endometriosis by subcutaneously transplanting endometrial fragments in nude mice with no skin-sutured. And this model is worth of promotion.
Endometriosis is a common and painful condition affecting women of reproductive age. While the underlying pathophysiology is still largely unknown, much advancement has been made in understanding the progression of the disease. In recent years, a great deal of research has focused on non-invasive diagnostic tools, such as biomarkers, as well as identification of potential therapeutic targets. In this article, we will review the etiology and cellular mechanisms associated with endometriosis as well as the current diagnostic tools and therapies. We will then discuss the more recent genomic and proteomic studies and how these data may guide development of novel diagnostics and therapeutics. The current diagnostic tools are invasive and current therapies primarily treat the symptoms of endometriosis. Optimally, the advancement of “-omic” data will facilitate the development of non-invasive diagnostic biomarkers as well as therapeutics that target the pathophysiology of the disease and halt, or even reverse, progression. However, the amount of data generated by these types of studies is vast and bioinformatics analysis, such as we present here, will be critical to identification of appropriate targets for further study. PMID:24927773
Sato, Hélio; Nogueira-de-Souza, Naiara C; D'Amora, Paulo; Silva, Ismael D C G; Girão, Manoel J B C; Schor, Eduardo
To evaluate the association of intron 1 and exon 1 polymorphisms in the estrogen receptor alpha gene (ER-alpha) with endometriosis in women. Association study. Endometriosis Unit, Federal University of São Paulo. The control group consisted of volunteers older than 45 years who had no evidence of endometriosis antecedents. Two groups with the disease were evaluated: the first group had stage I or II endometriosis and the second group stage III or IV. Polymerase chain reaction (PCR) followed by digestion with HaeIII and MspI endonucleases (RFLP) were applied to detect intron 1 and exon 1 polymorphisms, respectively, in a total of 125 controls and 105 affected women. Frequency and distribution of HaeIII and MspI polymorphisms in ER-alpha. No significant differences in the frequency of polymorphisms either in intron 1 or exon 1 of ER-alpha were found when endometriosis patients were compared with control subjects. Furthermore, the frequency of ER-alpha polymorphisms within the two different groups of patients with disease was statistically similar. The odds ratio between presence of intron 1 single-nucleotide polymorphisms (SNP) and endometriosis was 0.904, and the odds ratio between exon 1 SNP and endometriosis was 0.976. The evaluated polymorphisms were not associated with endometriosis.
Christensen, B; Schindler, A E
Limitation of morphological diagnostic and possible misinterpretations are shown in a patient with anamnestic ovarian endometriosis. In cases of "chocolate cysts" it is necessary to differentiate between ovarian endometriosis and functional cysts. Hints for the existence of a functional cyst are an atypical past history or perioperative findings. Biochemical analysis of the cyst fluid may lead to a correct diagnosis.
Endometriosis consists of the growth of endometrial tissue outside the uterus. A rat model of endometriosis is available to evaluate the potential for environmental chemicals to promote the disease but may he relatively insensitive for the evaluation of the hazard of certain comp...
Jun, Sunny Hee; Lathi, Ruth B
We describe five patients who developed significant pelvic pain, requiring narcotics, during a controlled ovarian hyperstimulation cycle and who were surgically diagnosed with significant endometriosis. Severe pain, especially if it requires narcotics, is unusual for patients undergoing controlled ovarian hyperstimulation and may be an indicator of endometriosis.
Tu, Frank; Bajzak, Krisztina; Lamvu, Georgine; Guzovsky, Olga; Agnelli, Rob; Peavey, Mary; Winer, Wendy; Albee, Robert; Sinervo, Ken
Objective: To serve as a pilot feasibility study for a randomized study of excision versus ablation in the treatment of endometriosis by (1) estimating the magnitude of change in symptoms after excision only at multiple referral centers and (2) determining the proportion of women willing to participate in a randomized trial. Methods: We performed a multicenter prospective study of women undergoing excision for endometriosis (Canadian Task Force class II-3) at Duke University Center for Endometriosis Research & Treatment (currently the Saint Louis University Center for Endometriosis), Center for Endometriosis Care, Northshore University Health System, Memorial University (Canada), and Florida Hospital. The study comprised 100 female patients, aged 18 to 55 years, with endometriosis-suspected pelvic pain. The intervention was laparoscopic excision only of the abnormal peritoneum suspicious for endometriosis. The main outcome measures were quality of life, pelvic pain, dysmenorrhea, dyspareunia, and bowel and bladder symptoms. Results: The mean follow-up period was 8.5 months. Excision of endometriosis showed a significant reduction in all pain scores except bowel symptoms, as well as significant improvement in quality of life. Of the patients, 84% were willing to participate in a randomized study. Conclusions: Quality of life is a needed primary outcome for any randomized study comparing excision versus ablation. A multicenter comparative trial is feasible, although quality assurance would have to be addressed. Patients were willing to be randomized even at surgical referral centers. PMID:23743377
de Lima, Camila Bruna; Cordeiro, Fernanda Bertuccez; Camargo, Mariana; Zylbersztejn, Daniel Suslik; Cedenho, Agnaldo Pereira; Bertolla, Ricardo Pimenta; Lo Turco, Edson Guimarães
This observational study aimed to establishing a relationship between lipid peroxidation and endometriosis in women undergoing controlled ovarian hyperstimulation. A total of 79 women were divided into two groups: (i) controls (tubal or male factor); and (ii) endometriosis (stages III/IV). The endometriosis diagnosis was confirmed by videolaparoscopy and the controlled ovarian stimulation protocol was similar to all patients. Follicular fluid (FF) lipid peroxidation levels were determined through the quantification of malondialdehyde. Statistical analysis was performed using parametric and non-parametric tests, logistic regression was performed to estimate the chance of achieving a pregnancy in each group and a moving average was calculated for the endometriosis group. Peroxidation levels in the endometriosis group were significantly higher when compared to controls. The moving average showed a decrease of MDA levels in the endometriosis group with increasing female age. Moreover, women with endometriosis who were under 33 years of age were 4.3 times more likely to achieve a pregnancy than women above that age. In conclusion, endometriosis is associated with increased FF oxidative stress (OS) in patients undergoing in vitro fertilization (IVF). Also, increasing age is associated with a decrease in severity of the oxidative status, but a decreased chance of pregnancy.
Barcellos, Marcio Bezerra; Lasmar, Bernardo; Lasmar, Ricardo
During the evaluation of patients with endometriosis, recognizing the location and characteristics of lesions is fundamental to define the type and evaluate the response of treatment, as well as for the preoperative surgical planning. However, the non-invasive diagnostic tests have specific limitations making the diagnostic laparoscopy been recommended as a tool necessary for the diagnosis of endometriosis lesions despite the high cost and the risks involved in this procedure. To evaluate the feasibility of mapping endometriosis lesions using clinical signs and image evaluation, comparing the pre- and postoperative findings of patients submitted to surgical treatment. A retrospective and prospective study included all patients who underwent surgical treatment for deep endometriosis between March 2011 and November 2014, at two centers of endometriosis in Rio de Janeiro. The positive finds registered during the clinical and image evaluation were compared with the surgical and histopathological results using a new instrument: the Lasmar's MAP of endometriosis 46 patients were included, age ranging from 23 to 47 years. For each site of endometriosis lesions, sensitivity, specificity, positive and negative predictive value, the positive and negative likelihood ratios and accuracy were calculated. The results show a high sensitivity, specificity and accuracy of the preoperative clinical evaluation to identify the main sites of endometriosis lesions without the use of diagnostic laparoscopy.
Al-Rubae'i, Salwa H N; Naji, Tamara Sami; Turki, Kisma M
Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of endometriosis in Iraqi women patients in the last years. Cytochrome P450c17a1 (CYP17), a gene that codes for a key enzyme (cytochrome P450c17a1) in a rate-limiting step of estrogen biosynthesis has attracted considerable attention as an important gene for endometriosis. To evaluate the relationship between common genetic variations in CYP17 and endometriosis risk and determine the main effects of those variations on the gene expression. A women-based case control study of Iraqi women aged range (23-46), the associations between selected single-nucleotide polymorphisms (SNPs) in the CYP17 gene and endometriosis diagnosis in fifty women and thirty disease-free controls were evaluated. The study found a significant association (P ≤ 0.01)between endometriosis and selected SNPs of CYP17 gene, with the homozygous genotype conferring decreased risk. A highly significant difference (P ≤ 0.01) in CYP17 gene expression from women with versus without endometriosis and increased by 1.56-fold in women with endometriosis. These findings suggest that variation in or around CYP17 may be associated with endometriosis development in the Iraqi women.
Nair, Hareesh B.; Baker, Robert; Owston, Michael A.; Escalona, Renee; Dick, Edward J.; VandeBerg, John L.; Nickisch, Klaus J.
Endometriosis is a chronic estrogen-dependent disease that occurs in approximately 10% of reproductive age women. Baboons offer a clear benefit for studying the initiation and progression of endometriosis since baboon is very close to humans phylogenetically. Progestins are used in the treatment of endometriosis. The therapeutic window of progestins depends on the ratio of its affinity towards progesterone receptor agonism verses antagonism. The present study is to determine the role of pure antiprogestin in baboon endometriosis. We hypothesize that pure antiprogestin will induce unopposed estrogenicity and spontaneous endometriosis in baboons. The rate of endometrial invasion and attachment through modeled peritoneum in the presence and absence of progesterone and antiprogestin was evaluated in this study. A baboon model of endometriosis induced by unopposed estrogenicity using progesterone receptor antagonist (EC304) was used in this study. We observed EC304 has induced unopposed estrogenicity that deregulated proteins involved in attachment, invasion, cell growth, and steroid hormone receptors in this model. Our data suggest that depleting progesterone levels in the endometrium will increase estrogen hyper-responsiveness that leads to increased endometriotic lesion progression in the baboon (Papio anubis) model. This study reports a refined model of human endometriosis in baboons that could potentially be used to develop new diagnostic and therapeutic strategies for the benefit of women suffering from endometriosis. PMID:26908459
ZHANG, XIAO; MU, LIN
Recent studies have shown that macrophage migration inhibitory factor (MIF) has a possible role in endometriosis-related pain and infertility, yet it has not been explored whether the mRNA level of MIF is altered in endometrial tissues from patients with endometriosis. The aim of the present study was to compare the expression of MIF in endometrial tissues from women with and without endometriosis, and to analyze the association between endometrial MIF expression and 17β-estradiol (E2). The protein and mRNA expression of MIF in the human endometrial tissue was assessed by western blotting and reverse transcription-polymerase chain reaction analysis, respectively. The MIF expression of women with endometriosis was found to be significantly higher than that of the controls. A positive correlation was noted between the serum E2 level and MIF expression. In endometrial cells from women with endometriosis, the level of E2-induced MIF upregulation was significantly higher than that in cells from women without endometriosis. In conclusion, this study demonstrated a significant increase in MIF expression in the endometrial tissues of women with endometriosis and an association between MIF expression and E2 level. MIF expression in endometrial cells from patients with endometriosis showed an increased sensitivity to stimulation by E2. PMID:26622394
André, Gustavo M; Barbosa, Caio P; Teles, Juliana S; Vilarino, Fábia L; Christofolini, Denise M; Bianco, Bianca
To evaluate FOXP3 polymorphisms (rs3761549, rs3761548, rs2232368, rs2232366, and rs2280883) in a group of infertile women with and without endometriosis and controls. Case control study. Human Reproduction Outpatient Clinic of Faculdade de Medicina do ABC. The study groups were 177 infertile women with endometriosis, 71 women with idiopathic infertility, and 171 fertile women as controls. The FOXP3 polymorphisms were identified by TaqMan polymerase chain reaction (PCR). The results were analyzed statistically. Genotype distribution, allele frequency, and haplotype analysis of the FOXP3 polymorphisms. Single-marker analysis revealed that FOXP3 rs3761549 was significantly associated with endometriosis. In the infertile group without endometriosis, single-marker analysis revealed statistical difference for rs2280883 and rs2232368 FOXP3 polymorphisms. No associations were found with rs3761548 and rs2232366 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five FOXP3 polymorphisms identified a haplotype CTTGA associated with endometriosis and ACTAG associated with idiopathic infertility. This is the first study to report an association between FOXP3 polymorphisms and endometriosis and/or infertility. These findings require replication in other populations but suggest that the FOXP3 polymorphisms can be associated with risk of idiopathic infertility (rs2280883 and rs2232368) and endometriosis (rs3761549) in Brazilian women. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Endometriosis consists of the growth of endometrial tissue outside the uterus. A rat model of endometriosis is available to evaluate the potential for environmental chemicals to promote the disease but may he relatively insensitive for the evaluation of the hazard of certain comp...
Stratton, Pamela; Berkley, Karen J.
BACKGROUND Many clinicians and patients believe that endometriosis-associated pain is due to the lesions. Yet causality remains an enigma, because pain symptoms attributed to endometriosis occur in women without endometriosis and because pain symptoms and severity correlate poorly with lesion characteristics. Most research and reviews focus on the lesions, not the pain. This review starts with the recognition that the experience of pain is determined by the central nervous system (CNS) and focuses on the pain symptoms. METHODS Comprehensive searches of Pubmed, Medline and Embase were conducted for current basic and clinical research on chronic pelvic pain and endometriosis. The information was mutually interpreted by a basic scientist and a clinical researcher, both in the field of endometriosis. The goal was to develop new ways to conceptualize how endometriosis contributes to pain symptoms in the context of current treatments and the reproductive tract. RESULTS Endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the CNS. This engagement provides a mechanism by which the dynamic and hormonally responsive nervous system is brought directly into play to produce a variety of individual differences in pain that can, in some women, become independent of the disease itself. CONCLUSIONS Major advances in improving understanding and alleviating pain in endometriosis will likely occur if the focus changes from lesions to pain. In turn, how endometriosis affects the CNS would be best examined in the context of mechanisms underlying other chronic pain conditions. PMID:21106492
Brosens, Ivo; Brosens, Jan J; Benagiano, Giuseppe
The eutopic endometrium in women suffering from endometriosis is different in many ways from that of healthy controls. Both proliferative and secretory eutopic endometria exhibit changes in endometriosis with heterogeneous responses. In addition, nerve fibres appear in the endometrium and myometrium of these women. The endometrium is a rich source of pro-angiogenic factors and vascular events are often disrupted in endometriosis with an overall increase in angiogenesis. A number of investigations have shown that endometriosis is likely the most common cause of endometrial receptivity defects. Endometriosis is also associated with relative 17β-hydroxysteroid dehydrogenase type II deficiency and these molecular aberrations indicate that local oestrogen production sustains ectopic implants. Recently it has been shown that endometriosis, as a chronic inflammatory disorder, disrupts co-ordinated progesterone response throughout the reproductive tract, including the endometrium, leading to a condition of 'progesterone resistance'. Investigators have searched for biomarkers of endometriosis, but these investigations are fraught with methodological difficulties. In conclusion, molecular phenotyping of the endometrium is changing the disease paradigm, from being foremost an oestrogen-dependent disease to a disorder characterized primarily by progesterone resistance. In recent years, research on the pathogenesis of endometriosis has been focused on alterations in the uterus and particularly the eutopic endometrium. The eutopic endometrium in women suffering from endometriosis is different in many ways from that of healthy controls. Both proliferative and secretory eutopic endometria exhibit changes in endometriosis with heterogeneous responses. The endometrium is a rich source of pro-angiogenic factors and vascular events are often disrupted in endometriosis with an overall increase in angiogenesis. A number of investigations have shown that endometriosis is likely the most
Yamamoto, Ayae; Johnstone, Erica B; Bloom, Michael S; Huddleston, Heather G; Fujimoto, Victor Y
The purpose of the study was to determine whether diagnosis of endometriosis or endometriosis with endometrioma influences in vitro fertilization (IVF) outcomes in an ethnically diverse population. Women undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31, 2009, at a university-affiliated infertility clinic, were retrospectively assessed for an endometriosis diagnosis. Differences in prevalence of endometriosis by ethnicity were determined, as well as differences in IVF success by ethnicity, with a focus on country of origin for Asian women. A multivariate model was generated to assess the relative contributions of country of origin and endometriosis to chance of clinical pregnancy with IVF. Endometriosis was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of endometrioma. Endometriosis prevalence in Asian women was significantly greater than in Caucasians (15.7 vs. 5.8%, p < 0.01). Women of Filipino (p < 0.01), Indian (p < 0.01), Japanese (p < 0.01), and Korean (p < 0.05) origin specifically were more likely to have endometriosis than Caucasian women, although there was no difference in endometrioma presence by race/ethnicity. Oocyte quantity, embryo quality, and fertilization rates did not relate to endometriosis. Clinical pregnancy rates were significantly lower for Asian women, specifically in Indian (p < 0.05), Japanese (p < 0.05), and Korean (p < 0.05) women, compared to Caucasian women, even after controlling for endometriosis status. The prevalence of endometriosis appears to be higher in Filipino, Indian, Japanese, and Korean women presenting for IVF treatment than for Caucasian women; however, the discrepancy in IVF outcomes was conditionally independent of the presence of endometriosis. Future research should focus on improving pregnancy outcomes for Asian populations whether or not they are affected by endometriosis, specifically in the form of longitudinal studies where exposures can be
Jeung, In-Cheul; Chung, Youn-Jee; Chae, Boah; Kang, So-Yeon; Song, Jae-Yen; Jo, Hyun-Hee; Lew, Young-Ok; Kim, Jang-Heub; Kim, Mee-Ran
Background and Aim: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis Materials and Methods: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker. Results: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p = 0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p = 0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p = 0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p = 0.014) in stage III/IV. Conclusions: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results
Mannini, Luca; Sorbi, Flavia; Noci, Ivo; Ghizzoni, Viola; Perelli, Federica; Di Tommaso, Mariarosaria; Mattei, Alberto; Fambrini, Massimiliano
The main aim of this study was to evaluate the incidence of endometriosis and intrahepatic cholestasis (ICP) and induction of labor in pregnant women with endometriosis compared with women without endometriosis. The secondary aim was to confirm increased incidence of already known endometriosis-related pregnancy complications in these patients. This is a retrospective cohort study performed at a tertiary hospital between January 2009 and December 2014 to compare obstetrics outcome between women with endometriosis and women without endometriosis. Pregnant patients with endometriosis were included in the study group. Patients were divided in the following subgroups: patients with deep infiltrating endometriosis (DIE subgroup) and patients without deep infiltrating endometriosis (non-DIE subgroup); patients with singleton pregnancy and spontaneous conception (subgroup A) and patients with multiple pregnancy and/or patients who underwent assisted reproductive technology (subgroup B). To form a control group, for each patient with endometriosis, two patients without endometriosis were selected as the control group by means of matched sample. The study population included 262 pregnant women with endometriosis and 524 controls. Patients of the study population had significantly increased risks of placenta praevia (p < 0.05), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01). DIE patients had a significantly higher percentage only of preterm birth (p < 0.01), while in non-DIE group all complications had a higher incidence except for placenta praevia, which did not differ with control. Subgroup A had a statistically higher incidence of placenta praevia (p < 0.01), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01) compared to its control subgroup. There was no difference in distribution of pregnancy complications between subgroup B and control subgroup. Our results showed for the first time that women with
Arsenault, Frédéric; Turcotte, Éric
Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosis proliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.
Schipper, Erica; Nezhat, Camran
Endometriosis is a highly enigmatic disease with multiple presentations ranging from infertility to severe pain, often causing significant morbidity. Video-assisted laparoscopy (VALS) has now replaced laparotomy as the gold standard for the diagnosis and management of endometriosis. While imaging has a role in the evaluation of some patients, histologic examination is needed for a definitive diagnosis. Laboratory evaluation currently has a minor role in the diagnosis of endometriosis, although studies are underway investigating serum markers, genetic studies, and endometrial sampling. A high index of suspicion is essential to accurately diagnose this complex condition, and a multidisciplinary approach is often indicated. The following review discusses laparoscopic diagnosis of endometriosis from the pre-operative evaluation of patients suspected of having endometriosis to surgical technique for safe and adequate laparoscopic diagnosis of the condition and postsurgical care. PMID:22927769
Troncon, Júlia Kefalás; Zani, Ana Carolina Tagliatti; Vieira, Andrea Duarte Damasceno; Poli-Neto, Omero Benedicto; Nogueira, Antônio Alberto; Rosa-e-Silva, Júlio César
Objective. To report a case of Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) in which there were two nonfunctional rudimentary uteruses with the presence of ovarian endometrioma, corroborating that there are valid alternative theories to the existence of endometriosis, rather than Sampson's theory alone, such as the coelomic metaplasia theory. Design. A case report. Setting. A tertiary referral center, which is also a university hospital. Patient. A fifteen-year-old patient with MRKH syndrome and endometriosis. Intervention. Laparoscopic approach for diagnostic confirmation and treatment of the endometrioma. Results. Evidence of endometriosis in a patient with no functional uterus. Conclusions. This case report and a few others that are available in the literature reinforce the possibility that coelomic metaplasia could be the origin of endometriosis. Patients with müllerian agenesis and pelvic pain should be carefully evaluated, and the presence of pelvic endometriosis should not be excluded. PMID:25610677
Troncon, Júlia Kefalás; Zani, Ana Carolina Tagliatti; Vieira, Andrea Duarte Damasceno; Poli-Neto, Omero Benedicto; Nogueira, Antônio Alberto; Rosa-E-Silva, Júlio César
Objective. To report a case of Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) in which there were two nonfunctional rudimentary uteruses with the presence of ovarian endometrioma, corroborating that there are valid alternative theories to the existence of endometriosis, rather than Sampson's theory alone, such as the coelomic metaplasia theory. Design. A case report. Setting. A tertiary referral center, which is also a university hospital. Patient. A fifteen-year-old patient with MRKH syndrome and endometriosis. Intervention. Laparoscopic approach for diagnostic confirmation and treatment of the endometrioma. Results. Evidence of endometriosis in a patient with no functional uterus. Conclusions. This case report and a few others that are available in the literature reinforce the possibility that coelomic metaplasia could be the origin of endometriosis. Patients with müllerian agenesis and pelvic pain should be carefully evaluated, and the presence of pelvic endometriosis should not be excluded.
Rosina, Paolo; Pugliarello, Silvia; Colato, Chiara; Girolomoni, Giampiero
Umbilical endometriosis has an estimated incidence of 0.5%-1% of all patients with endometrial ectopia. It is a very rare disease, but should be considered on the differential diagnosis of umbilical lesions. We report on a case of spontaneous umbilical endometriosis in a 38-year-old woman, with a dark brown nodule periodically bleeding, associated with severe abdominal pain. There was no history of endometriosis and she had not been pregnant before. Laparoscopic visualization of pelvic cavity showed bilateral ovarian endometrioma (it was removed while sparing the ovaries). Surgical treatment proved effective. Cutaneous endometriosis could be a sign of internal endometriosis. Presentations may be atypical and pose diagnostic difficulty, mimicking other acute diseases, e.g., skin neoplasm, folliculitis, etc., but it should be suspected in any female presenting with a painful or bleeding mass close to the umbilicus or abdominal surgical scar.
Carvalho, Luiz; Abrão, Mauricio Simões; Deshpande, Abhishek; Falcone, Tommaso
This systematic review evaluates the role of robotics in the surgical treatment of endometriosis. Electronic database searches were conducted in MEDLINE, Scopus, and ISI Web of Knowledge for relevant studies over the past 10 years. Four published articles were found that used robotic assisted laparoscopy to perform endometriosis surgery. All four studies used the da Vinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). Three studies were case reports, and one was a cohort study. Robotics appears to be as effective as conventional laparoscopy in the management of endometriosis. There were no reports of any major complications. Few studies have been published and show us that robotic endometriosis surgery is feasible even in severe endometriosis cases without conversion. There is a lack of long-term outcome papers in the literature. Randomized controlled trials are necessary. Copyright © 2011 John Wiley & Sons, Ltd.
Burney, Richard O.; Behr, Barry; Milki, Amin A.; Westphal, Lynn M.; Lathi, Ruth B.
Purpose To investigate the hypothesis that surgical treatment of endometriosis in infertile patients may improve pregnancy rates by improving embryo quality. Methods We conducted a retrospective evaluation of 30 infertile patients treated with in vitro fertilization (IVF) before and after surgery for endometriosis. Patients served as their own controls and only cycles with similar stimulation protocols were compared. Results Using standard visual evaluation, embryo quality on day 3 was similar before and after surgical treatment of endometriosis. Fifty seven percent of patients had stage I–II endometriosis and 43% had stage III–IV disease. No patients had a live birth after the first IVF cycle and 43% of patients had a live birth with the IVF cycle after surgery. Conclusions Surgical treatment of endometriosis does not alter embryo quality in patients with infertility treated with IVF. PMID:19214735
Yu, Jie; Boicea, Anisoara; Barrett, Kara L; James, Christopher O; Bagchi, Indrani C; Bagchi, Milan K; Nezhat, Ceana; Sidell, Neil; Taylor, Robert N
Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell-cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/β-actin ratios=.4±1.5 in control and =1.2±0.3 in endometriosis biopsies (P<0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2±0.2- versus 1.7±0.4-fold, P<0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted.
Schuster, Mitchell W; Wheeler, Thomas L; Richter, Holly E
To compare the incidence of new-onset endometriosis after laparoscopic supracervical hysterectomy (LSH) with uterine morcellation to traditional routes. Single center case-control study (Canadian Task Force classification II-2) of hysterectomies performed from January 2006 through December 2008. Two hundred seventy-seven laparoscopic supracervical hysterectomies with morcellation (cases) and 187 transvaginal or abdominal hysterectomies without morcellation (controls) were performed from January 2006 through December 2008. A total of 464 women underwent hysterectomy, 277 cases via laparoscopic supracervical approach (LSH) with morcellation and 187 performed either transvaginally or abdominally without morcellation. Repeat operative procedures were performed for other benign indications on 16 of 464 (3.5%) patients who had undergone prior hysterectomy. One hundred two patients had endometriosis at the time of hysterectomy diagnosed by pathologic evaluation or gross visualization. In those without endometriosis, repeat operative procedures were performed for pain and bleeding in 3.3% (12/362). Sixty percent (3/5) of patients treated with LSH and 28.6% (2/7) of the control group were found to have newly diagnosed endometriosis, conferring a rate of 1.4% (3/217) in the LSH group and 1.4% (2/145) in the control subjects. In patients with endometriosis, repeat operative procedures for pain or bleeding occurred in 2.9% (3/102): 3/60 patients treated with LSH and none in the control group (0/42). Two of these 3 patients undergoing a second surgery had recurrent/continued endometriosis. Newly diagnosed endometriosis was noted in 1.4% of patients after hysterectomy, with a similar incidence between the LSH and control groups. Reoperation for those with endometriosis at the time of LSH with morcellation was infrequent, but endometriosis was usually found. Further research is needed to delineate risk factors for development of de novo endometriosis after hysterectomy. Copyright
Schuster, Mitchell W.; Wheeler, Thomas L.; Richter, Holly E.
Study Objective To compare the incidence of new onset endometriosis after laparoscopic supracervical hysterectomy (LSH) with uterine morcellation to traditional routes. Design Single center case-control study Design Classification Canadian Task Force Classification II-2 Setting Single Center case-control study of hysterectomies from January, 2006 through December, 2008. Patients 277 laparoscopic supracervical hysterectomies with morcellation (cases) and 187 transvaginal or abdominal hysterectomies without morcellation (controls) performed from January, 2006 to December 2008. Interventions 464 women underwent hysterectomy, 277 cases via laparoscopic supracervical approach (LSH) with morcellation and 187 performed either transvaginally or abdominally without morcellation. Repeat operative procedures were performed for other benign indications on 16 of 464 (3.5%) prior hysterectomy patients. Measurements and Main Results 102 patients had endometriosis at the time of hysterectomy diagnosed by pathologic evaluation or gross visualization. In those without endometriosis, repeat operative procedures were performed for pain and bleeding in 3.3% (12/362). 60% (3/5) of LSH patients and 28.6% (2/7) of the control group were found to have newly diagnosed endometriosis conferring a rate of 1.4% (3/217) for the LSH group and 1.4% (2/145) in the controls. In patients with endometriosis, repeat operative procedures for pain and/or bleeding occurred in 2.9% (3/102); 3/60 of LSH patients and none in the control group (0/42). Two of these 3 patients undergoing a second surgery had recurrent/continued endometriosis. Conclusion Newly diagnosed endometriosis was noted in 1.4% of patients after hysterectomy with a similar incidence between the LSH and control groups. Reoperation for those with endometriosis at the time of LSH with morcellation was infrequent, but endometriosis was usually found. Further research is needed to delineate risk factors for development of de novo endometriosis
Bungum, Helle Folge; Vestergaard, Christian; Knudsen, Ulla Breth
Endometriosis is a chronic and debilitating disorder affecting up to 5-10% of women in reproductive age. Investigators have described deficiency in cellular immunity in women suffering from endometriosis, and in the recent years endometriosis has been linked to other diseases, allergic disease being one of them. The objective of this paper is to systematically review the existing literature on the possible association between endometriosis and allergic disease. This review is based on the recommendations by the preferred reporting of systematic reviews and meta-analysis (PRISMA) statement. PubMed and Embase were searched for studies on women diagnosed with endometriosis and with manifestations of allergic disease who were compared to a reference group. Out of 316 articles screened, 6 were reviewed and 5 ultimately met the inclusion criteria. Four out of the five studies reported a positive correlation between endometriosis and allergic manifestations, including hay fever, sinus allergic rhinitis, and food intolerance/sensitivities (food allergy). Investigators reported an odds ratio (OR) as high as 4.28 (95% CI: 2.93-6.27) for a positive history of allergy among women suffering from endometriosis. Equivocal results were found on asthma prevalence in women with endometriosis. Due to the heterogeneity of the included studies, no meta-analyses could be performed. The available literature clearly indicates that women with endometriosis are at an increased risk of allergic disorders compared to controls, but due to the lack of a concise definition of allergic disease and therefore diagnostic criteria, further studies are needed in order to draw firm conclusions on the association between endometriosis and allergic disease.
Harb, H M; Gallos, I D; Chu, J; Harb, M; Coomarasamy, A
Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. To explore the association between endometriosis and IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment. © 2013 RCOG.
Stratton, Pamela; Khachikyan, Izabella; Sinaii, Ninet; Ortiz, Robin; Shah, Jay
Objective To evaluate sensitization, myofascial trigger points, and quality of life in women with chronic pelvic pain with and without endometriosis. Methods A cross-sectional prospective study of women aged 18 to 50 with pain suggestive of endometriosis and healthy, pain-free volunteers without history of endometriosis. Patients underwent a physiatric neuro-musculoskeletal assessment of clinical signs of sensitization and myofascial trigger points in the abdominopelvic region. Pain symptoms, psychosocial, and quality-of-life measures were also assessed. All pain participants underwent laparoscopic excision of suspicious lesions to confirm endometriosis diagnosis by histologic evaluation. Results Patients included 18 with current, biopsy-proven endometriosis, 11 with pain only, and 20 healthy volunteers. The prevalence of sensitization as measured by regional allodynia and hyperalgesia was similar in both pain groups (83% and 82%) but much lower among healthy volunteers (15%, p<0.001). Nearly all women with pain had myofascial trigger points (94% and 91%). Adjusting for study group, those with high anxiety (OR=1.05, 95% CI:1.004–1.099; p=0.031) and depression (OR=1.06, 95% CI:1.005–1.113; p=0.032) scores were more likely to have sensitization. Pain patients with any history of endometriosis had the highest proportion of sensitization compared to the others (87% v 67% v 15%; p<0.001). Adjusting for any history of endometriosis, those with myofascial trigger points were most likely sensitized (OR=9.41, 95% CI:1.77–50.08, p=0.009). Conclusions Sensitization and myofascial trigger points were common in women with pain regardless of whether they had endometriosis at surgery. Those with any history of endometriosis were most likely to have sensitization. Traditional methods of classifying endometriosis-associated pain based on disease, duration, and anatomy are inadequate and should be replaced by a mechanism-based evaluation, as our study illustrates. PMID
Albertsen, Hans M; Ward, Kenneth
Endometriosis, defined by the presence of ectopic endometrial lesions, is a common disease in reproductive-age women that profoundly affects patients' quality of life. Various pathogenic models have been proposed, but the origin of endometriosis remains elusive. In this article, we propose that the mesothelial barrier, which protects the underlying stroma from endometrial transplants present in retrograde menstrual fluid, can be compromised by activation of the epithelial to mesenchymal transition (EMT) repair mechanism that lead to temporary loss of barrier integrity. Absent of the mesothelial barrier, endometrial cells can more readily adhere to the underlying peritoneal stroma and establish endometrial lesions. The hypothesis is based on the clinical and experimental observations that correlate the location of endometrial lesions with areas of mesothelial damage, together with genetic evidence that 4 genes associated with endometriosis are direct regulators of the actin-cytoskeleton, which coordinates mesothelial barrier integrity. It supports past observations that implicate the peritoneum in the pathogenesis of endometriosis and unifies previously disparate theories that endometriosis may be triggered by infection, mechanical damage, and inflammation since each of these mechanisms can induce EMT in the mesothelium. If the hypothesis is correct, inhibition of EMT in the mesothelial barrier provides a novel paradigm for the prevention and treatment of endometriosis.
Vercellini, Paolo; Buggio, Laura; Somigliana, Edgardo; Dridi, Dhouha; Marchese, Maria Antonietta; Viganò, Paola
Is the prevalence of blue eye colour higher in women with deep endometriosis? Blue eye colour is more common in women with deep endometriosis when compared with both women with ovarian endometriomas and women without a history of endometriosis. Recent and intriguing evidence suggests that women with deep endometriosis may have particular phenotypic characteristics including a higher prevalence of a light-colour iris. Available epidemiological evidence is however weak. Case-control study performed in a large academic department specializing in the study and treatment of endometriosis. Individual iris colour was evaluated in daylight and categorized in three grades, namely blue-grey (blue), hazel-green (green) and brown. One observer assessed iris colour. In addition, the women themselves were invited to indicate the colour of their eyes according to the same classification system. Cases with discordant eye colour determinations between the observer and the woman were excluded from the final analysis. Two hundred and twenty-three women with deep endometriosis (cases), 247 with ovarian endometriomas and 301 without a history of endometriosis were enrolled. After exclusion of 52 discordant cases, the proportions of brown, blue and green eye colours were, respectively, 61, 30 and 9% in the deep endometriosis group, 74, 16 and 10% in the endometrioma group and 75, 15 and 10% in the non-endometriosis group. Women in the deep endometriosis group had a statistically significant excess of blue eyes and a reduced proportion of brown eyes compared with the two control groups (P = 0.002 and P < 0.001, respectively). The proportion of blue eyes was almost identical in the ovarian endometrioma group and the non-endometriosis group, and that of green eyes was substantially similar in all study groups. The OR (95% CI) of having blue eyes in women with deep endometriosis compared with women with ovarian endometriosis and with those without endometriosis was, respectively, 2.2 (1
Sapkota, Yadav; Low, Siew-Kee; Attia, John; Gordon, Scott D.; Henders, Anjali K.; Holliday, Elizabeth G.; MacGregor, Stuart; Martin, Nicholas G.; McEvoy, Mark; Morris, Andrew P.; Takahashi, Atsushi; Scott, Rodney J.; Kubo, Michiaki; Zondervan, Krina T.; Montgomery, Grant W.; Nyholt, Dale R.
STUDY QUESTION Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk? SUMMARY ANSWER We found evidence for strong association between IL1A SNPs and endometriosis risk. WHAT IS KNOWN ALREADY Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis. STUDY DESIGN, SIZE, DURATION We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed. MAIN RESULTS AND THE ROLE OF CHANCE All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with
Kho, Kimberly A.; Morozov, Vadim
Background and Objectives: To report the feasibility and safety of the use of a novel energy source that uses an electrically neutral beam of pure argon plasma for the laparoscopic management of endometriosis. Methods: In this prospective pilot study, 20 patients undergoing laparoscopic treatment of endometriosis were included. Characteristic endometriotic lesions throughout the pelvis were vaporized or resected using neutral argon plasma. Specimens were evaluated for the presence of endometriosis and thermal effects on tissue. The bases of the treated lesions were biopsied to determine whether residual endometriosis was present. Results: Neutral argon plasma was used in 18 of the 20 patients for laparoscopic treatment of pelvic endometriosis. All biopsies confirmed complete vaporization or re-section with no residual endometriosis at the base. Endometriosis was identified on pathology in all lesions excised. Thermal effects did not interfere with histologic analysis in any of the lesions. No complications occurred. Conclusion: Neutral argon plasma can be utilized as a multi-functional device that has vaporization, coagulation, and superficial cutting capacities with minimal thermal spread and acceptable outcomes. The use of neutral argon plasma appears to be efficacious and safe for the complete treatment of endometriotic implants. PMID:20202387
Gui, Benedetta; Valentini, Anna Lia; Ninivaggi, Valeria; Miccò, Maura; Zecchi, Viola; Grimaldi, Pier Paolo; Cambi, Francesco; Guido, Maurizio; Bonomo, Lorenzo
Endometriosis is a disease distinguished by the presence of endometrial tissue outside the uterine cavity with intralesional recurrent bleeding and resulting fibrosis. The most common locations for endometriosis are the ovaries, pelvic peritoneum, uterosacral ligaments, and torus uterinus. Typical symptoms are secondary dysmenorrhea and cyclic or chronic pelvic pain. Unusual sites of endometriosis may be associated with specific symptoms depending on the localization. Atypical pelvic endometriosis localizations can occur in the cervix, vagina, round ligaments, ureter, and nerves. Moreover, rare extrapelvic endometriosis implants can be localized in the upper abdomen, subphrenic fold, or in the abdominal wall. Magnetic resonance imaging (MRI) represents a problem-solving tool among other imaging modalities. MRI is an advantageous technique, because of its multiplanarity, high contrast resolution, and lack of ionizing radiation. Our purpose is to remind the radiologists the possibility of atypical pelvic and extrapelvic endometriosis localizations and to illustrate the specific MRI findings. Endometriotic tissue with hemorrhagic content can be distinguished from adherences and fibrosis on MRI imaging. Radiologists should keep in mind these atypical localizations in patients with suspected endometriosis, in order to achieve the diagnosis and to help the clinicians in planning a correct and complete treatment strategy.
Gui, Benedetta; Valentini, Anna Lia; Ninivaggi, Valeria; Miccò, Maura; Zecchi, Viola; Grimaldi, Pier Paolo; Cambi, Francesco; Guido, Maurizio; Bonomo, Lorenzo
Endometriosis is a disease distinguished by the presence of endometrial tissue outside the uterine cavity with intralesional recurrent bleeding and resulting fibrosis. The most common locations for endometriosis are the ovaries, pelvic peritoneum, uterosacral ligaments, and torus uterinus. Typical symptoms are secondary dysmenorrhea and cyclic or chronic pelvic pain. Unusual sites of endometriosis may be associated with specific symptoms depending on the localization. Atypical pelvic endometriosis localizations can occur in the cervix, vagina, round ligaments, ureter, and nerves. Moreover, rare extrapelvic endometriosis implants can be localized in the upper abdomen, subphrenic fold, or in the abdominal wall. Magnetic resonance imaging (MRI) represents a problem-solving tool among other imaging modalities. MRI is an advantageous technique, because of its multiplanarity, high contrast resolution, and lack of ionizing radiation. Our purpose is to remind the radiologists the possibility of atypical pelvic and extrapelvic endometriosis localizations and to illustrate the specific MRI findings. Endometriotic tissue with hemorrhagic content can be distinguished from adherences and fibrosis on MRI imaging. Radiologists should keep in mind these atypical localizations in patients with suspected endometriosis, in order to achieve the diagnosis and to help the clinicians in planning a correct and complete treatment strategy. PMID:28703103
Coccia, Maria Elisabetta; Rizzello, Francesca; Gianfranco, Scarselli
Endometriosis is a common estrogen-dependent disease. The aim of this study was to assess whether controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART) was associated with an increased incidence in endometriosis recurrence as documented by transvaginal ultrasound (TV-US). In a retrospective cohort study of 592 patients submitted to laparoscopy for endometriosis, 177 with infertility-related endometriosis who underwent a periodic ultrasound follow-up after laparoscopy were selected. Women who started ART after laparoscopy (n = 90) were compared with the control group, who did not undergo ART (n = 87). Recurrence of endometriosis was defined as the presence of endometriotic lesions observed through TV-US. During a long-term TV-US follow-up (1-15 years), 40 (22.6%) recurrences were observed. Patients submitted to ART showed a cumulative recurrence rate similar to that of the control group (28.6% and 37.9% respectively, p = 0.471). Recurrent lesions were ovarian cysts (47.5%), ovarian nodules (37.5%), and rectovaginal disease (15%). The stratified analysis based on stages of endometriosis and pelvic pain did not show differences. Gonadotropin treatments do not seem to affect the natural history of endometriotic lesions. The most important prognostic factors in recurrent disease observed by TV-US seem to be the stage of endometriosis and the presence of pelvic pain at the time of the first laparoscopic treatment.
Vercellini, Paolo; Buggio, Laura; Somigliana, Edgardo; Barbara, Giussy; Viganò, Paola; Fedele, Luigi
To evaluate physical attractiveness in women with and without endometriosis. Case-control study. Academic hospital. Three hundred nulliparous women. Assessment of attractiveness by four independent female and male observers. A graded attractiveness rating scale. A total of 31 of 100 women in the rectovaginal endometriosis group (cases) were judged as attractive or very attractive, compared with 8 of 100 in the peritoneal and ovarian endometriosis group and 9 of 100 in the group of subjects without endometriosis. A higher proportion of cases first had intercourse before age 18 (53%, 39%, and 30%, respectively). The mean ± SD body mass index in women with rectovaginal endometriosis, in those with other disease forms, and in those without endometriosis was, respectively, 21.0 ± 2.5, 21.3 ± 3.3, and 22.1 ± 3.6. The median (interquartile range) waist-to-hip ratio and breast-to-underbreast ratio were, respectively, 0.75 (0.71-0.81), 0.76 (0.71-0.81), and 0.78 (0.73-0.83), and 1.15 (1.12-1.20), 1.14 (1.10-1.17), and 1.15 (1.11-1.18). Women with rectovaginal endometriosis were judged to be more attractive than those in the two control groups. Moreover, they had a leaner silhouette, larger breasts, and an earlier coitarche. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Setúbal, António; Sidiropoulou, Zacharoula; Torgal, Mariana; Casal, Ester; Lourenço, Carlos; Koninckx, Philippe
To review bowel complications caused by deep endometriosis during pregnancy or in vitro fertilization (IVF). Three case reports and a systematic review. A tertiary referral center for deep endometriosis surgery. Three case reports of bowel perforation or occlusion during pregnancy caused by deep endometriosis. A PubMed search was conducted to identify complications of deep endometriosis during pregnancy or IVF. The literature search identified 13 articles. According to these, 12 articles described 12 bowel complications caused by progression of deep endometriosis during pregnancy, and 1 article described six cases of bowel occlusion during IVF. In 12 of 15 women, complications occurred during the third trimester of pregnancy, whereas 3 of 15 women presented with complications in the postpartum period. All complications during IVF occurred during stimulation. No specific factors that could predict these complications were identified, leading to the conclusion that endometriosis complications that occur in pregnancy or in IVF patients are probably underreported. Bowel complications during pregnancy or IVF stimulation may occur in women with deep endometriosis. This suggests that the endocrine environment of pregnancy does not prevent progression, at least in some women. These complications are rare, although probably underreported. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Borahay, Mostafa A.; Lu, Fangxian; Ozpolat, Bulent; Tekedereli, Ibrahim; Gurates, Bilgin; Karipcin, Sinem; Kilic, Gokhan S.
Objective. To determine the effects of Mullerian inhibiting substance (MIS) treatment on endometriosis cells through study of apoptosis and autophagy. Design. Experimental in vitro study. Setting. University research laboratory. Cell Line. CRL-7566 endometriosis cell line. This line was established from a benign ovarian cyst taken from a patient with endometriosis. Interventions. In vitro treatment with MIS. Main Outcome Measures. The main outcome measures were cellular viability, proliferation, cell-cycle arrest, and induction of apoptosis and autophagy in endometriotic cells. Results. MIS treatment inhibited proliferation of endometriosis cells and induced apoptosis, as indicated by Annexin V staining, and induced caspase-9 cleavage and cell-cycle arrest, as evidenced by increased expression of p27 CDK-inhibitor. MIS treatment also induced autophagy in endometriosis cells as demonstrated by a significant increase in LC3-II induction, a hallmark of autophagy. Conclusions. MIS inhibits cell growth and induces autophagy, as well as apoptosis, in ectopic endometrial cell lines. Our results suggest that MIS may have a potential as a novel approach for medical treatment of endometriosis. Further studies may be needed to test the efficacy of MIS treatment in animal models and to develop MIS treatment specifically targeted to the endometriosis. PMID:23853725
Lin, Wu-Chou; Chang, Cherry Yin-Yi; Hsu, Yu-An; Chiang, Jen-Huai; Wan, Lei
Abstract Endometriosis results from the ectopic invasion of endometrial glands and stroma in the peritoneal cavity. The exact etiology of endometriosis is still unknown. It has, however, been shown that there are higher numbers of Escherichia coli in menstrual blood, and higher endotoxin levels in menstrual fluid, as well as, in the peritoneal fluid of patients with endometriosis. In this study, we aimed to determine whether lower genital tract infections could increase the risk of endometriosis. We used the Taiwan National Health Insurance database to conduct a population-based cohort study. We included patients diagnosed with inflammatory diseases of the cervix, vagina, and vulva, and a control group comprising patients matched by age, sex, and comorbidities but without inflammatory diseases of the cervix, vagina, or vulva. A total of 79,512 patients were included in the inflammatory disease group and an equal number of control individuals were selected. The incidence of endometriosis (hazard ratio, 2.01; 95% confidence interval, 1.91–2.12; P < 0.001) was higher among patients than controls. Cox proportional hazards models showed that irrespective of comorbidities, lower genital tract infection was an independent risk factor for endometriosis. Patients with lower genital tract infections exhibit a substantially higher risk for developing endometriosis. PMID:26962775
Vanhie, A.; Fassbender, A.; O, D.; Tomassetti, C.; Meuleman, C.; Peeraer, K.; Debrock, S.; D'Hooghe, Th.
Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women's lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis. PMID:26240823
Lukovich, Péter; Csibi, Noémi; Brubel, Réka; Tari, Krisztina; Csuka, Szilvia; Harsányi, László; Rigó, János; Bokor, Attila
In the treatment of colorectal endometriosis a multidisciplinary laparoscopic resection is suggested, for this reason the correct selection of bowel infiltration is essential before surgery. Between 2009 and 2015, 383 sigmoidoscopies were performed in patients with endometriosis. Where mucosal invasion was absent secondary signs (wall rigidity, impression, kinking, pain during the examination, suffusion) were analysed. In endoscopically confirmed cases multidisciplinary surgery was performed, the remaining patients were operated by a gynecologic team only. Endometriosis was endoscopically confirmed in 224 patients (58.49%), 108 of them underwent multidisciplinary operation, the negative 135 cases received gynaecological surgery. Bowel endometriosis was confirmed in 103 out of 108 cases intraoperatively, while in 8 cases of the sigmoidoscopically negative patients bowel infiltration was diagnosed intraoperatively by the gynaecological team. Complete sigmoidoscopy was performed in 43.47% of the cases. Intraluminal endometriosis was found in 4.91%, secondary signs as rigidity in 38.39%, impression in 45.54%, kinking in 57.14%, pain (in cases of examination without narcosis) in 26.06% and suffusion in 3.82% of the cases was found during sigmoidoscopy. Sigmoidoscopic examination has a 92.8% specificity and 96.2% sensitivity in cases of bowel endometriosis. Sigmoidoscopy performed by an experienced gastroenterologist is a highly sensitive examination for the diagnosis of bowel endometriosis. Orv. Hetil., 2017, 158(7), 264-269.
Tanbo, Tom; Fedorcsak, Peter
Endometriosis is a common condition in women of reproductive age. In addition to pain, endometriosis may also reduce fertility. The causes of infertility in women with endometriosis may range from anatomical distortions due to adhesions and fibrosis to endocrine abnormalities and immunological disturbances. In some cases, the various pathophysiological disturbances seem to interact through mechanisms so far not fully understood. Whether surgery should be offered as a treatment option in endometriosis-associated infertility has become controversial, partly due to its modest or undocumented effect. Medical or hormonal treatment alone has little or no effect and should only be used in conjunction with assisted reproductive technology (ART). Of the various methods of ART, intrauterine insemination, due to its simplicity, can be recommended in women with minimal or mild peritoneal endometriosis, even though insemination may yield a lower success rate than in women without endometriosis. In vitro fertilization (IVF) is an effective treatment option in less-advanced disease stages, and the success rates are similar to the results in other causes of infertility. However, women with more advanced stages of endometriosis have lower success rates with IVF. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.
Burghaus, Stefanie; Fasching, Peter A; Häberle, Lothar; Rübner, Matthias; Büchner, Kathrin; Blum, Simon; Engel, Anne; Ekici, Arif B; Hartmann, Arndt; Hein, Alexander; Beckmann, Matthias W; Renner, Stefan P
Several genetic variants have been validated as risk factors for ovarian cancer. Endometriosis has also been described as a risk factor for ovarian cancer. Identifying genetic risk factors that are common to the two diseases might help improve our understanding of the molecular pathogenesis potentially linking the two conditions. In a hospital-based case-control analysis, 12 single nucleotide polymorphisms (SNPs), validated by the Ovarian Cancer Association Consortium (OCAC) and the Collaborative Oncological Gene-environment Study (COGS) project, were genotyped using TaqMan® OpenArray™ analysis. The cases consisted of patients with endometriosis, and the controls were healthy individuals without endometriosis. A total of 385 cases and 484 controls were analyzed. Odds ratios and P values were obtained using simple logistic regression models, as well as from multiple logistic regression models with adjustment for clinical predictors. rs11651755 in HNF1B was found to be associated with endometriosis in this case-control study. The OR was 0.66 (95% CI, 0.51 to 0.84) and the P value after correction for multiple testing was 0.01. None of the other genotypes was associated with a risk for endometriosis. As rs11651755 in HNF1B modified both the ovarian cancer risk and also the risk for endometriosis, HNF1B may be causally involved in the pathogenetic pathway leading from endometriosis to ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.
Vicente-Muñoz, Sara; Morcillo, Inmaculada; Puchades-Carrasco, Leonor; Payá, Vicente; Pellicer, Antonio; Pineda-Lucena, Antonio
To evaluate potential variations in the plasma metabolomic profile of endometriosis patients as a consequence of pathophysiologic alterations associated with this disorder. Prospective study. For each subject, a plasma sample was collected after overnight fasting and before surgery. University medical center. The clinical cohort included 50 endometriosis patients, diagnosed at early (n = 6) and advanced (n = 44) stages of the disease, and 23 healthy women. All volunteers underwent diagnostic laparoscopy to visually confirm the presence or absence of endometriotic lesions. Metabolomic profiling of plasma samples based on (1)H-nuclear magnetic resonance (NMR) spectroscopy in combination with statistical approaches. Comparative identification of metabolites present in plasma from endometriosis patients and healthy women. The plasma metabolomic profile of endometriosis patients was characterized by increased concentration of valine, fucose, choline-containing metabolites, lysine/arginine, and lipoproteins and decreased concentration of creatinine compared with healthy women. Metabolic alterations identified in the plasma metabolomic profile of endometriosis patients correlate with pathophysiologic events previously described in the progression of this disease. The results highlight the potential of (1)H-NMR-based metabolomics to characterize metabolic alterations associated with endometriosis in plasma samples. This information could be useful to get a better understanding of the molecular mechanisms involved in the pathogenesis of endometriosis, thus facilitating the noninvasive diagnosis of this pathology at early stages. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Riccio, L G C; Baracat, E C; Chapron, C; Batteux, F; Abrão, M S
The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for "endometriosis", "B cells" and "B lymphocytes" in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells. Copyright © 2017 Elsevier B.V. All rights reserved.
Lo Turco, Edson Guimarães; Cordeiro, Fernanda Bertuccez; Lopes, Paula Helena de Carvalho; Gozzo, Fábio Cesar; Pilau, Eduardo Jorge; Soler, Thiesa Butterby; da Silva, Barbara Ferreira; Del Giudice, Paula Toni; Bertolla, Ricardo Pimenta; Fraietta, Renato; Cedenho, Agnaldo Pereira
Endometriosis is a gynecological disease that affects women of reproductive age. The protein profiles of women with endometriosis who were able or unable to achieve pregnancy and women without endometriosis who did achieve pregnancy were compared in this study. The follicular fluid was collected from 21 patients undergoing in vitro-fertilization treatment, according to the following groups: nine women in the control group (Group C), four women with endometriosis who achieved pregnancy (Group E.P), and eight women with endometriosis who did not achieve pregnancy (Group E.NP). Follicular fluid proteins were separated using 2D-electrophoresis, and their spots were compared, excised, and submitted to LC-ESI-MS/MS for proteins identification. The analysis showed 29 differentially expressed spots among the groups, and from these, 21 proteins were identified. Analysis showed some functional enrichment in the E.P group, including response to oxidative stress and apoptosis, while the E.NP group showed functions related to response to reactive oxygen species and positive regulation of apoptosis. These data suggest that endometriosis leads to differential protein expression in the follicular fluid, which can influences the outcome of pregnancy. These proteins may be potential targets for better diagnostics and new therapeutic intervention in affected women, as well as assisting in comprehending the physiopathologic mechanisms underlying endometriosis.
Xu, Bo; Guo, Nan; Zhang, Xiao-min; Shi, Wei; Tong, Xian-hong; Iqbal, Furhan; Liu, Yu-sheng
Endometriosis, a pathological condition in which the endometrium grows outside the uterus, is one of the most common causes of female infertility; it is diagnosed in 25–40% of infertile women. The mechanism by which endometriosis affects the fertility of females remains largely unknown. We examined the ultrastructure of oocytes from patients with minimal or mild endometriosis and control females undergoing in vitro fertilization (IVF) treatment by transmission electron microscopy (TEM) to investigate the physiological significance of oocyte quality for patients with minimal or mild endometriosis. The TEM results revealed that the oocytes from women with minimal or mild endometriosis exhibited abnormal mitochondrial structure and decreased mitochondria mass. Quantitative real time PCR analysis revealed that the mitochondrial DNA copy number was significantly reduced in the oocytes from women with minimal or mild endometriosis compared with those of the control subjects. Our results suggest that decreased oocyte quality because of impaired mitochondrial structure and functions probably an important factor affecting the fertility of endometriosis patients. PMID:26022105
De Conto, Emily; Matte, Úrsula; Bilibio, João Paolo; Genro, Vanessa Krebs; Souza, Carlos Augusto; Leão, Delva Pereira; Cunha-Filho, João Sabino
The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the - 482A G SNP in the AMHR2 gene were found to be unrelated.
Endometriosis is strongly associated with infertility. Endometrial polyps are prevalent in infertile women and they have similar pathological characteristics to endometriosis, suggesting a possible association. Uterine malformations as uterine septum and hypoplastic uterus are also linked to endometriosis. Hysterosalpingogram and transvaginal ultrasonography are used to diagnose endometrial lesions. Hysteroscopy can detect small lesions that might be missed. Recently, 4D ultrasonography is being used, but which is superior has not been established yet. We aim to compare 4D ultrasonography to office hysteroscopy in evaluating uterine cavity in cases with endometriosis; also we aim at correlating these findings with the stage of endometriosis. 50 cases of endometriosis diagnosed by laparoscopy were randomly selected from El Shatby fertility clinic, Alexandria University, Egypt, with exclusion of cases with any previous intrauterine surgery or any hormonal treatment. Transvaginal 4D ultrasonography and office hysteroscopy were done. 4D ultrasonography agreed with office hysteroscopy in diagnosing abnormal uterine findings in 14 cases and four additional cases were diagnosed by hysteroscopy alone. Conclusion. Endometrial polyps, septate uterus, and hypoplastic uterus are more prevalent among infertile women who happen to have endometriosis. 4D ultrasonography and office hysteroscopy are equally successful in assessing the uterine cavity. PMID:28638413
Karp, Barbara Illowsky; Sinaii, Ninet; Nieman, Lynnette K.; Silberstein, Stephen D.; Stratton, Pamela
Objective To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis. Design Prospective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria. Setting Clinical research hospital. Patient(s) 108 women in a clinical trial for chronic pelvic pain (NCT00001848). Intervention(s) Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches. Main Outcome Measure(s) Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis. Result(s) Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone. Conclusion(s) Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology. PMID:21145540
Tomassetti, C; Geysenbergh, B; Meuleman, C; Timmerman, D; Fieuws, S; D'Hooghe, T
Can the ability of the endometriosis fertility index (EFI) to predict non-assisted reproductive technology (ART) pregnancy after endometriosis surgery be confirmed by an external validation study? The significant relationship between the EFI score and the time to non-ART pregnancy observed in our study represents an external validation of this scoring system. The EFI was previously developed and tested prospectively in a single center, but up to now no external validation has been published. Our data provide validation of the EFI in an external fertility unit on a robust scientific basis, to identify couples with a good prognosis for spontaneous conception who can therefore defer ART treatment, regardless of their revised American Fertility Society (rAFS) endometriosis staging. Retrospective cohort study where the EFI was calculated based on history and detailed surgical findings, and related to pregnancy outcome in 233 women attempting non-ART conception immediately after surgery; all data used for EFI calculation and analysis of reproductive outcome had been collected prospectively as part of another study. The EFI score was calculated (score 0-10) for 233 women with all rAFS endometriosis stages (minimal-mild, n = 75; moderate-severe, n = 158) after endometriosis surgery (1 September 2006-30 September 2010) in a university hospital-based reproductive medicine unit with combined expertise in reproductive surgery and medically assisted reproduction. All participants attempted non-ART conception immediately after surgery by natural intercourse, ovulation induction with timed intercourse or intrauterine insemination (with or without ovulation induction or controlled ovarian stimulation). All analyses were performed for three different definitions of pregnancy [overall (any HCG >25 IU/l), clinical and ongoing >20 weeks]. Six groups were distinguished (EFI scores 1-3, 4, 5, 6, 7+8, 9+10), and Kaplan-Meier (K-M) estimates for cumulative pregnancy rate were calculated
Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong
Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (P<0.001) and deep infiltrating endometriotic lesions of uterosacral ligament (P = 0.028)compared with glandular epithelial cells of the endometrium from women with endometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (P<0.001, P<0.001, respectively). NFDs of Anti
Harris, Holly R.; Chavarro, Jorge E.; Malspeis, Susan; Willett, Walter C.; Missmer, Stacey A.
The etiology of endometriosis is poorly understood, and few modifiable risk factors have been identified. Dairy foods and some nutrients can modulate inflammatory and immune factors, which are altered in women with endometriosis. We investigated whether intake of dairy foods, nutrients concentrated in dairy foods, and predicted plasma 25-hydroxyvitamin D (25(OH)D) levels were associated with incident laparoscopically confirmed endometriosis among 70,556 US women in Nurses’ Health Study II. Diet was assessed via food frequency questionnaire. A score for predicted 25(OH)D level was calculated for each participant. During 737,712 person-years of follow-up over a 14-year period (1991–2005), 1,385 cases of incident laparoscopically confirmed endometriosis were reported. Intakes of total and low-fat dairy foods were associated with a lower risk of endometriosis. Women consuming more than 3 servings of total dairy foods per day were 18% less likely to be diagnosed with endometriosis than those reporting 2 servings per day (rate ratio = 0.82, 95% confidence interval: 0.71, 0.95; Ptrend = 0.03). In addition, predicted plasma 25(OH)D level was inversely associated with endometriosis. Women in the highest quintile of predicted vitamin D level had a 24% lower risk of endometriosis than women in the lowest quintile (rate ratio = 0.76, 95% confidence interval: 0.60, 0.97; Ptrend = 0.004). Our findings suggest that greater predicted plasma 25(OH)D levels and higher intake of dairy foods are associated with a decreased risk of endometriosis. PMID:23380045
Wu, Yan; Strawn, Estil; Basir, Zainab; Halverson, Gloria; Guo, Sun-Wei
The physiological effects of progesterone (P) are mediated by two isoforms of progesterone receptors (PRs): PR-A and PR-B. Progestins have long been used in the treatment of endometriosis but unfortunately the relief of pain is relatively short-term. In addition, about nine percent of women with endometriosis simply do not respond to progestin therapy due to unknown reasons. In fact, a general tendency for relative progesterone resistance within eutopic and ectopic endometrium of women with endometriosis and also the downregulation of PR-B, but not PR-A, in endometriosis have been noted. Since promoter hypermethylation is well-documented to be associated with transcriptional silencing, we sought to determine the methylation status of the PR-A and PR-B promoter regions in the epithelial component of endometriotic implants using a combination of laser capture microdissection (LCM), methylation specific PCR, and bisulfite sequencing. We found that the promoter region of PR-B, but not PR-A, is hypermethylated in endometriosis as compared with controls. In addition, the PR-B expression was significantly reduced in the ectopic endometrium. Our finding suggests that progesterone resistance in endometriosis in general and the down regulation of PR-B, but not PR-A, in particular, are a result of promoter hypermethylation of PR-B, but not PR-A. This, in conjunction with our reported aberrant methylation of HOXA10 in the eutopic endometrium of women with endometriosis, strongly suggests that endometriosis is an epigenetic disease. This perspective should potentially open up new avenues for the delineation of pathogenesis of endometriosis, and might also lead to novel ways to treat the disease through reversing aberrant methylation via pharmacological means.
Naqvi, Hanyia; Mamillapalli, Ramanaiah; Krikun, Graciela; Taylor, Hugh S
The mechanisms that lead to the altered uterine gene expression in women with endometriosis are poorly understood. Are these changes in gene expression mediated by proximity to endometriotic lesions or is endometriosis a systemic disease where the effect is independent of proximity to the uterus? To answer this question, we created endometriosis in a murine model either in the peritoneal cavity (proximal) or at a subcutaneous remote site (distal). The expression of several genes that are involved in endometrial receptivity (homeobox A10 [Hoxa10], homeobox A11 [Hoxa11], insulin-like growth factor binding protein 1 [Igfbp1], Kruppel-like factor 9 [Klf9], and progesterone receptor [Pgr]) was measured in the eutopic endometrium of mice transplanted with either proximal or distal endometriosis lesions. Decreased expression of Hoxa10, Igfbp1, Klf9, and total Pgr genes was observed in the eutopic endometrium of mice with peritoneal endometriosis. In the mice with distal lesions, overall expression of these genes was not as severely affected, however, Igfbp1 expression was similarly decreased and the effect on Pgr was more pronounced. Endometriosis does have a systemic effect that varies with distance to the end organ. However, even remote disease selectively and profoundly alters the expression of genes such as Pgr. This is the first controlled experiment demonstrating that endometriosis is not simply a local peritoneal disease. Selective alteration of genes critical for endometrial receptivity and endometriosis propagation may be systemic. Similarly, systemic effects of endometriosis on other organs may also be responsible for the widespread manifestations of the disease.
Yeung, Patrick; Sinervo, Ken; Winer, Wendy; Albee, Robert B
To determine long-term outcomes after complete laparoscopic excision done at a tertiary referral center in a teenager population, who were not specifically advised to take postoperative hormonal suppression. Prospective observational case series (Canadian Task Force II-3). A tertiary referral center that specializes in the laparoscopic treatment of endometriosis. Teenagers with symptoms suspicious for endometriosis who consented and were prospectively recruited to participate in the study. All patients underwent diagnostic laparoscopy and complete excision of all areas of abnormal peritoneum with typical and atypical endometriosis. Patients were not specifically advised to take postoperative hormonal suppression. Rate of recurrent (or persistent) endometriosis. Twenty teenagers underwent complete laparoscopic excision of all areas of abnormal peritoneum with typical and atypical endometriosis. Seventeen patients had endometriosis confirmed by histology at initial surgery. Follow-up was up to 66 months (average 23.1 months). There was a statistically significant improvement in most pain symptoms, including bowel-related symptoms, during this time period. The rate of repeat surgery was 8 of 17 patients (47.1%), but the rate of endometriosis (diagnosed visually or histologically) found at surgery was zero. Only one-third of patients took postoperative hormonal suppression for any length of time. Complete laparoscopic excision of endometriosis in teenagers--including areas of typical and atypical endometriosis--has the potential to eradicate disease. These results do not depend on postoperative hormonal suppression. These data have important implications in the overall care of teenagers, regarding pain management, but also potentially for fertility. Further large comparative trials are needed to verify these results. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Trabert, Britton; Peters, Ulrike; De Roos, Anneclaire J; Scholes, Delia; Holt, Victoria L
Diet plausibly has a role in the aetiology of endometriosis through effects on steroid hormone levels; however, few published studies have examined the diet and endometriosis risk. We evaluated dietary risk factors for endometriosis in a population-based case-control study. Cases were 284 Group Health (GH) enrollees aged 18-49 years with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001. Controls were 660 randomly selected age-matched female GH enrollees without a history of endometriosis. Nutrients and selected food groups were assessed using the Women's Health Initiative FFQ. OR of endometriosis risk associated with dietary exposures were estimated using unconditional logistic regression and adjusted for identified covariates. Increased total fat consumption was associated with decreased endometriosis risk (fourth quartile v. lowest: OR 0·5, 95% CI 0·2, 1·0, P-trend = 0·12). Increased β-carotene consumption and servings/d of fruit were associated with increased risk (β-carotene third quartile v. lowest: OR 1·7, 95% CI 1·1, 2·6; fourth quartile v. lowest: OR 1·6, 95% CI 1·0, 2·5, P-trend 0·16; fruit >2 servings/d v. < 1: OR 1·5, 95% CI 1·0, 2·3, P-trend = 0·04). We also found a suggestion of decreased endometriosis risk associated with the consumption of dairy products (2 servings/d v. ≤ 1: OR 0·6, >2 servings/d v. ≤ 1: OR 0·7), but this association was not statistically significant for the highest tertile. The present study suggests that specific dietary components may be associated with endometriosis risk.
Teng, Sen-Wen; Horng, Huann-Cheng; Ho, Chi-Hong; Yen, Ming-Shyen; Chao, Hsiang-Tai; Wang, Peng-Hui
Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities. Copyright © 2016. Published by Elsevier Taiwan LLC.
Ruiz, A; Rockfield, S; Taran, N; Haller, E; Engelman, R W; Flores, I; Panina-Bordignon, P; Nanjundan, M
In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis.
Ruiz, A; Rockfield, S; Taran, N; Haller, E; Engelman, R W; Flores, I; Panina-Bordignon, P; Nanjundan, M
In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis. PMID:26775710
Pellicer, A; Albert, C; Mercader, A; Bonilla-Musoles, F; Remohí, J; Simón, C
To assess the endocrine, paracrine, and autocrine milieu in patients with endometriosis on the basis of the measurement of several cytokines in serum and follicular fluid (FF) and in vitro culture of granulosa luteal cells. Case-control study. In vitro fertilization program at the Instituto Valenciano de Infertilidad. Twenty patients with laparoscopically documented endometriosis and 18 controls. Fifteen subjects were studied in a natural cycle and 23 were investigated in a stimulated cycle while undergoing IVF. Individual follicle aspiration, oocyte isolation, FF storage, and preparation of luteinized granulosa cell cultures. Diagnostic laparoscopy in natural cycles. Serum (day of ovum pick-up or laparoscopy) and FF measurement of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF). Secretion of IL-1beta, IL-6, and VEGF in the cell-conditioned medium. Results were compared between patients with endometriosis and controls. Interleukin-6 levels in serum were increased in the natural cycles of patients with endometriosis and modulated by ovarian stimulation, showing a significant decrease in hMG- and FSH-stimulated cycles and a significant increase after hCG administration. In addition, IL-6 levels were increased in the FF of patients with endometriosis and released in higher amounts by their granulosa luteal cells. Vascular endothelial growth factor was accumulated in lesser concentrations in the FF of patients with endometriosis. Interleukin-1beta levels did not show significant changes. Implantation rates were decreased significantly in patients with endometriosis who were undergoing IVF. The data demonstrate that cytokines are regulated differently in patients with endometriosis, who have increased IL-6 production, and suggest that fine hormonal modulation of this cytokine occurs at the systemic and local (ovarian) levels. These changes show that the endocrine, paracrine, and autocrine milieu is different in patients with endometriosis and
Wiegand, Kimberly C.; Shah, Sohrab P.; Al-Agha, Osama M.; Zhao, Yongjun; Tse, Kane; Zeng, Thomas; Senz, Janine; McConechy, Melissa K.; Anglesio, Michael S.; Kalloger, Steve E.; Yang, Winnie; Heravi-Moussavi, Alireza; Giuliany, Ryan; Chow, Christine; Fee, John; Zayed, Abdalnasser; Prentice, Leah; Melnyk, Nataliya; Turashvili, Gulisa; Delaney, Allen D.; Madore, Jason; Yip, Stephen; McPherson, Andrew W.; Ha, Gavin; Bell, Lynda; Fereday, Sian; Tam, Angela; Galletta, Laura; Tonin, Patricia N.; Provencher, Diane; Miller, Dianne; Jones, Steven J.M.; Moore, Richard A.; Morin, Gregg B.; Oloumi, Arusha; Boyd, Niki; Aparicio, Samuel A.; Shih, Ie-Ming; Mes-Masson, Anne-Marie; Bowtell, David D.; Hirst, Martin; Gilks, Blake; Marra, Marco A.; Huntsman, David G.
BACKGROUND Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.) PMID:20942669
Wiegand, Kimberly C; Shah, Sohrab P; Al-Agha, Osama M; Zhao, Yongjun; Tse, Kane; Zeng, Thomas; Senz, Janine; McConechy, Melissa K; Anglesio, Michael S; Kalloger, Steve E; Yang, Winnie; Heravi-Moussavi, Alireza; Giuliany, Ryan; Chow, Christine; Fee, John; Zayed, Abdalnasser; Prentice, Leah; Melnyk, Nataliya; Turashvili, Gulisa; Delaney, Allen D; Madore, Jason; Yip, Stephen; McPherson, Andrew W; Ha, Gavin; Bell, Lynda; Fereday, Sian; Tam, Angela; Galletta, Laura; Tonin, Patricia N; Provencher, Diane; Miller, Dianne; Jones, Steven J M; Moore, Richard A; Morin, Gregg B; Oloumi, Arusha; Boyd, Niki; Aparicio, Samuel A; Shih, Ie-Ming; Mes-Masson, Anne-Marie; Bowtell, David D; Hirst, Martin; Gilks, Blake; Marra, Marco A; Huntsman, David G
Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).
Bendifallah, Sofiane; Roman, Horace; Mathieu d'Argent, Emmanuelle; Touleimat, Salma; Cohen, Jonathan; Darai, Emile; Ballester, Marcos
To compare the impact of first-line assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI]-IVF) and first-line colorectal surgery followed by ART on fertility outcomes in women with colorectal endometriosis-associated infertility. Retrospective matched cohort study using propensity score (PS) matching (PSM) analysis. University referral centers. A total of 110 women were analyzed from January 2005 to June 2014. A PSM was generated using a logistic regression model based on the age, antimüllerian hormone (AMH) serum level, and presence of adenomyosis to compare the treatment strategy. First-line surgery group followed by ART versus exclusive ART with in situ colorectal endometriosis. After PSM, pregnancy rates (PRs), live-birth rates (LBRs), and cumulative rates (CRs) were estimated. After PSM, in the whole population, the total LBR and PR were 35.4% (39/110) and 49% (54/110), respectively. The specific cumulative LBR at the first ICSI-IVF cycle in the first-line surgery group compared with the first-line ART was, respectively, 32.7% versus 13.0%; at the second cycle, 58.9% versus 24.8%; and at the third cycle, 70.6% versus 54.9%. The cumulative LBRs were significantly higher for women who underwent first-line surgery followed by ART compared with first-line ART in the subset of women with good prognosis (age ≤ 35 years and AMH ≥ 2 ng/mL and no adenomyosis) and women with AMH serum level < 2 ng/mL. First-line surgery may be a good option for women with colorectal endometriosis-associated infertility. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Socolov, Razvan; Socolov, Demetra; Sindilar, Allia; Pavaleanu, Ioana
Endometriosis is a disease that affects 7-10% of reproductive-age women. When its diagnosis is delayed, its management becomes more difficult. Both for earlier detection and for therapeutic follow-up, discovering noninvasive biological markers with good specificity for this disease is a promising aspect of its research. We analyzed the recent data in the literature regarding these markers to determine which were worth following. This literature review focused on medical data reported in the last 6 years (2011-2016). After identifying articles in PubMed, an analysis of the type of data and level of evidence provided was performed. The selected articles were compared and conclusions regarding the specific markers addressed. Of the 255 articles identified that reported human studies, we had access to the full text for 169 of them. We selected 71 prospective studies to include in our analysis. The studies were divided based on the primary marker studied: 22 analyzed inflammatory and immunological markers, 9 adhesivity and migration markers, 18 genetic polymorphisms, 7 oxidative stress, 4 micro-RNA circulating fragments, and 11 other biological markers (hormonal receptors, leukocytes, and others). CA 125 remains the most recommended marker for suspicion of endometriosis and follow-up. Other markers, such as CA 19-9, CA 72-4, and endometrial cells in peripheral blood, have more value for differentiating endometriosis from other pathologies, while circulating micro-RNA could help clarify the endometrial stem cell's implication in its pathogeny. Finally, other new urinary markers could be used in early diagnostic and screening strategies.
D'Amora, Paulo; Maciel, Thiago Trovati; Tambellini, Rodrigo; Mori, Marcelo A.; Pesquero, João Bosco; Sato, Helio; Girão, Manoel João Batista Castello; Guerreiro da Silva, Ismael Dale Cotrim; Schor, Eduardo
Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype. PMID:19497994
D'Amora, Paulo; Maciel, Thiago Trovati; Tambellini, Rodrigo; Mori, Marcelo A; Pesquero, João Bosco; Sato, Helio; Girão, Manoel João Batista Castello; Guerreiro da Silva, Ismael Dale Cotrim; Schor, Eduardo
Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype.
Lund, Iréne; Lundeberg, Thomas
Introduction Endometriosis is a multifactorial, estrogen-dependent, inflammatory gynecological condition – often with long-lasting visceral pelvic pain of different origin, and infertility among women. Current management options for patients’ are often inadequate, with side effects for many for whom acupuncture techniques could be an alternative. Earlier studies have discussed the efficacy of acupuncture, but not its methodological aspects. Objectives To summarize the documented clinical effects of acupuncture on rated visceral pelvic endometriosis-related pain, and associated variables among individuals, within and between studied groups, and to discuss the methodological treatment aspects. Methods Published full text clinical studies, case reports, and observational studies with abstracts written in English were searched by using the keywords “Acupuncture and Endometriosis” in databases such as PubMed, Web of Science, and CINAHL. The reporting guidelines, Standards for Reporting Interventions in Clinical Trials of Acupuncture was used for the methodological report. Results Three studies were found including 99 women, 13–40 years old, with diagnosed endometriosis. The studies were different in research design, needle stimulation techniques, and evaluation instruments. Methodological similarities were seven to12 needle insertions per subject/session, and 15–25 minutes of needle retention time. The needles were placed in lower back/pelvic-abdominal area, in the shank, feet, and hands. Treatment numbers varied from nine to 16 and patients received one to two treatments per week. Similarity in reported treatment effects in the quoted studies, irrespective of research design or treatment technique, was reported decrease of rated pain intensity. Discussion Meta-analysis is the standard procedure for the evaluation of evidence of treatment effects, ie, on a group level, usually without analysis of the individual responses even with obvious spread in the
Chettier, Rakesh; Ward, Kenneth; Albertsen, Hans M.
Endometriosis is a complex gynecological condition that affects 6–10% of women in their reproductive years and is defined by the presence of endometrial glands and stroma outside the uterus. Twin, family, and genome-wide association (GWA) studies have confirmed a genetic role, yet only a small part of the genetic risk can be explained by SNP variation. Copy number variants (CNVs) account for a greater portion of human genetic variation than SNPs and include more recent mutations of large effect. CNVs, likely to be prominent in conditions with decreased reproductive fitness, have not previously been examined as a genetic contributor to endometriosis. Here we employ a high-density genotyping microarray in a genome-wide survey of CNVs in a case-control population that includes 2,126 surgically confirmed endometriosis cases and 17,974 population controls of European ancestry. We apply stringent quality filters to reduce the false positive rate common to many CNV-detection algorithms from 77.7% to 7.3% without noticeable reduction in the true positive rate. We detected no differences in the CNV landscape between cases and controls on the global level which showed an average of 1.92 CNVs per individual with an average size of 142.3 kb. On the local level we identify 22 CNV-regions at the nominal significance threshold (P<0.05), which is greater than the 8.15 CNV-regions expected based on permutation analysis (P<0.001). Three CNV's passed a genome-wide P-value threshold of 9.3×10−4; a deletion at SGCZ on 8p22 (P = 7.3×10−4, OR = 8.5, Cl = 2.3–31.7), a deletion in MALRD1 on 10p12.31 (P = 5.6×10−4, OR = 14.1, Cl = 2.7–90.9), and a deletion at 11q14.1 (P = 5.7×10−4, OR = 33.8, Cl = 3.3–1651). Two SNPs within the 22 CNVRs show significant genotypic association with endometriosis after adjusting for multiple testing; rs758316 in DPP6 on 7q36.2 (P = 0.0045) and rs4837864 in ASTN2 on 9q33.1 (P = 0.0002). Together
Hirsch, Martin; Duffy, James M N; Kusznir, Jennie O; Davis, Colin J; Plana, Maria N; Khan, Khalid S
We reviewed the outcomes and outcome measures reported in randomized controlled trials and their relationship with methodological quality, year of publication, commercial funding, and journal impact factor. We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase, and (3) MEDLINE from inception to November 2014. We included all randomized controlled trials evaluating a surgical intervention with or without a medical adjuvant therapy for the treatment of endometriosis symptoms. Two authors independently selected trials, assessed methodological quality (Jadad score; range, 1-5), outcome reporting quality (Management of Otitis Media with Effusion in Cleft Palate criteria; range, 1-6), year of publication, impact factor in the year of publication, and commercial funding (yes or no). Univariate and bivariate analyses were performed using Spearman Rh and Mann-Whitney U tests. We used a multivariate linear regression model to assess relationship associations between outcome reporting quality and other variables. There were 54 randomized controlled trials (5427 participants), which reported 164 outcomes and 113 outcome measures. The 3 most commonly reported primary outcomes were dysmenorrhea (10 outcome measures; 23 trials), dyspareunia (11 outcome measures; 21 trials), and pregnancy (3 outcome measures; 26 trials). The median quality of outcome reporting was 3 (interquartile range 4-2) and methodological quality 3 (interquartile range 5-2). Multivariate linear regression demonstrated a relationship between outcome reporting quality with methodological quality (β = 0.325; P = .038) and year of publication (β = 0.067; P = .040). No relationship was demonstrated between outcome reporting quality with journal impact factor (Rho = 0.190; P = .212) or commercial funding (P = .370). Variation in outcome reporting within published endometriosis trials prohibits comparison, combination, and synthesis of data. This limits the usefulness of
Hernández Quijano, Tomás; Hernández Valencia, Marcelino; Zárate Treviño, Arturo; Pérez Figueroa, Eduardo
Endometriosis syndrome affects 5% to 35% of women in reproductive age. Many theories have been suggested, but the true importance is the survival mechanism of endometriotic tissue, which seems to be related to a defect of the immunological vigilance from macrophages, which are responsible for secretion of a variety of biochemical substances such as cytokines, prostaglandins and growth factors, which through different ways stimulates the growth of the endometrial cells. This has been observed for the clear interrelation between the homeostasis of the body and the evident association of the hormonal factors with the processes of the immunological system, in whose field many steps are unknown.
Eliassen, A Heather; Tamimi, Rulla M; Spiegelman, Donna; Michels, Karin B; Missmer, Stacey A
Objective To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women. Design Prospective cohort study. Setting Nurses’ Health Study II, 1989-2011. Participants 72 394women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea. Main outcome measures Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis. Results Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100 000 person years compared with 184 cases/100 000 person years in women who reported a lifetime total of ≥36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P<0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P<0.001 for trend). Women who breastfed for ≥36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced
Filali Adib, Abdelhai; Bezad, Rachid
Endometriosis is defined by the presence and growth of ectopic functional endometrial tissue outside the uterus. Scar endometriosis has been described following obstetrical and gynecological surgery. It is a rare condition, though probably on the rise, due to the considerable increase of cesarean sections performed worldwide. Its physiopathology is complex; its symptomatology is rich and diverse but thorough clinical examination along with ultrasound imaging and potentially pretherapeutic cytologic evaluation are usually efficient in diagnosing the condition. Treatment is mostly surgical. We report the case of a cesarean section scar endometriosis, managed at a tertiary level center and emphasize the diagnosis and treatment options. PMID:28326210
Hughes, C. L.; Foster, W. G.
In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women's health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan. PMID:26064879
Mutrynowski, Andrzej; Zabielska, Renata; Smolarczyk, Roman
The study aimed at evaluating the success rate of the operative laparoscopy assisted by electrocoagulation and laser as well as danazol and lynestrenol in the endometriosis treatment. One-hundred-ninety women with the recognized endometriosis were included into the study. In the I degree(s) endometriosis the operative or hormonal therapy was applied, in the II-IV degree(s) the combined therapy was used. The complete cure was achieved in 159 of the patients (84%): 28 women conceived, in 131 of the cases remission was recognized during the second laparoscopy. Eighteen women found improvement (9%) while 13 women (7%) reported the lack of improvement.
Gerlinger, Christoph; Faustmann, Thomas; Hassall, Jeffrey J; Seitz, Christian
Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG) versus gonadotropin-releasing hormone (GnRH) analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology.
Haruki, Tomohiro; Fujioka, Shinji; Adachi, Yoshin; Miwa, Ken; Taniguchi, Yuji; Nakamura, Hiroshige
Pulmonary endometriosis is a disease in which uterine endometrial cells with stromal components grow in the pulmonary parenchymal tissues or pleura. Surgical resection is considered an effective and radical treatment for pulmonary endometriosis to avoid the adverse effects of long-term hormone therapy in young women of childbearing years with a localized abnormal lesion. We report a case of pulmonary endometriosis with catamenial hemoptysis, an uncommon result of this disease, which was diagnosed histologically and treated successfully by video-assisted thoracic surgery.
Smuc, Tina; Hevir, Neli; Ribic-Pucelj, Martina; Husen, Bettina; Thole, Hubert; Rizner, Tea Lanisnik
Endometriosis is a very common disease in pre-menopausal women, where defective metabolism of steroid hormones plays an important role in its development and promotion. In the present study, we have examined the expression of 11 estrogen and progesterone metabolizing enzymes and their corresponding receptors in samples of ovarian endometriomas and control endometrium. Expression analysis revealed significant up-regulation of enzymes involved in estradiol formation (aromatase, sulfatase and all reductive 17beta-hydroxysteroid dehydrogenases) and in progesterone inactivation (AKR1C1 and AKR1C3). Among the estrogen and progesterone receptors, ERalpha was down-regulated, ERbeta was up-regulated, and there was no significant difference in expression of progesterone receptors A and B (PRAB). Our data indicate that several enzymes of estrogen and progesterone metabolism are aberrantly expressed in endometriosis, which can lead to increased local levels of mitogenic estradiol and decreased levels of protective progesterone. Changes in estrogen receptor expression suggest that estradiol may also act via non-estrogen receptor-mediated pathways, while expression of progesterone receptors still needs further investigation.
Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Petraglia, Felice
Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induced a chronic inflammatory reaction. The data collected from Italy showed that around 3 million women are affected by endoemtriosis and the condition was predominantly found in women of reproductive age (50% of women were in the 29-39 age range), only 25% of women were asymptomatic. The associated symptoms can create an impact in general physical, mental, and social well-being. Endometriosis is associated with severe dysmenorrhea, deep dyspareunia, chronic pelvic pain, ovulation pain, cyclical, or perimenstrual symptoms, with or without abnormal bleeding, infertility, and chronic fatigue. The annual cost for hospital admission can be estimated to be in a total around 54 million euros. The average time for right diagnosis is around 9 years still today and it follows a long and expensive diagnostic search. Therapies can be useful to relieve and sometimes solve the symptoms, encourage fertility, eliminate endometrial lesions, and restore the anatomy of the pelvis. For medical therapy, several different preparations (oral contraceptives, progestogenics, gestrinone, danazol, and GnRHa) and new options (GnRH antagonists, aromatase inhibitors, estrogen receptor beta agoinist, progesterone receptor modulators, angiogenesis inhibitors, and COX-2 selective inhibitors) are available.
Costa, Marta; Bento, Ana; Batista, Hamilton; Oliveira, Fernando
Appendicular intussusception is an uncommon entity, with a reported incidence of 0.01%. The diagnosis is difficult and often only performed at the time of surgery. Intussusception has multiple causes including tumours, foreign bodies and polyps. The definitive treatment is surgical, and the extent of resection is determined by the underlying pathology and degree of invagination. Endometriosis is a rare cause of appendicular intussusception, with 194 cases described in the English literature. We report a case of a 42-year-old woman who presented with chronic abdominal pain in the lower right quadrant. A mass at the caecum was identified during investigations for renal stones by CT. Colonoscopy showed a polypoid lesion, with presumed origin in the appendix. Ileocaecal resection was performed because an appendicular tumour was suspected. Pathological examination identified endometriosis of the appendix and associated peritoneum with invagination of the caecum. The patient was discharged 7 days after surgery and is currently asymptomatic. 2014 BMJ Publishing Group Ltd.
Sheveleva, T; Bejenar, V; Komlichenko, E; Dedul, A; Malushko, A
Endometriosis is a chronic, progressive, relapsing estrogen-dependent disorder characterized by the growth of tissue structure and function similar to the endometrium outside the normal mucosa of the uterine cavity localization. Endometriosis is found in 10-15% of women in reproductive age and it is one of the main causes of pelvic pain syndrome and infertility. Mechanisms of the development of endometriosis and related pathological pain impulses are still poorly understood and therapeutic approaches do not always have a sufficient effect; in this connection, the study of the pathogenesis of endometriosis and endometriosis-associated pain currently is perspective. Identification of significant factors of angiogenesis, lymphangiogenesis, and neurogenesis in the external genital endometriosis will promote the development of non-invasive early diagnosis and pathogenetic therapy.
Guerrero Hernández, Antonio; Oropeza Rechy, Guillermo; Gómez García, Elisabeth
Endometriosis no ectopic endometrial stroma and glands. Have different risk factors. Four theories explain it: the theory of coelomic metaplasia, embryonic cell debris, deployment and immunological. Clinical data are pain and infertility. For the American Fertility Society (AFS) is divided into minimal, mild, moderate and severe. Diagnostic studies are antigen Ca 125, Magnetic Resonance, and abdominal ultrasound. The ideal method is direct visualization with histological confirmation. The medical and surgical treatment. To determine the risk factors, diagnosis of Endometriosis and effectiveness of treatments used in clinical Endometriosis Gynecology Unit at the General Hospital of Mexico OD. A descriptive, longitudinal and retrospective duration of 2 years 6 months in 30 patients diagnosed with endometriosis in the clinical treatment of Endometriosis General Hospital of Mexico OD. The most affected age group was 21 to 25 years, the risk factors are Gesta 1, a resident of Mexico, Mullerian malformation. The symptom was dysmenorrhea. In 16 were diagnosed as a surgical finding and laparoscopically diagnosed. It is important to study the risk factors. The diagnosis is made using clinical data, quantification of CA125 antigen and imaging studies. Medical treatment is indicated both in the preoperative as well as postoperative surgical treatment and seeks to eradicate the lesions.
Giacomelli, L; Pulcini, A; Leone, L; Fabrizio, G; Granai, A V; Messinetti, S
The Authors report a case of ovarian endometriosis causing an "Ab extrinseco" sigmoid stenosis. The histogenesis as well as different possibilities of treatment, i.e. medical and surgical, are discussed.
Wu, Ling-Ling; Pang, Rui-Ping; Yin, Yu-Zhu; Shen, Kai-Feng; Zhang, Pei-Zhen
To investigate whether and how human chorionic gonadotropin (HCG) treatment ameliorates endometriosis in an endometriotic rat model. Twenty-four endometriosis rats were established and were randomly divided into four groups, and then the rats were treated with 19.4, 25.8, and 51.6 IU/100 g weight/day of HCG, respectively. The control group was treated with 0.9% NaCl. After 15 days (3 estrous cycles), the ectopic lesion volume and the expression of leptin protein in eutopic and ectopic endometrium were investigated. After HCG treatment, the volumes of endometriotic lesions were significantly smaller than those before treatment. During endometriosis development, the expression of leptin protein in eutopic and ectopic endometrium was remarkably increased. HCG administration reversed leptin upregulation in endometriotic tissues. HCG therapy appears to be an effective treatment for endometriosis in rats through down-regulation of leptin expression in eutopic and ectopic endometrium. © 2015 S. Karger AG, Basel.
Camargo-Kosugi, Cíntia M; da Silva, Ismael D C G; Sato, Hélio; D'Amora, Paulo; Carvalho, Cristina V; Nogueira-de-Souza, Naiara C; Girão, Manoel J C B; Schor, Eduardo
To investigate the prevalence of the p27 gene polymorphism in women with endometriosis. Transversal case-control study. Genomic DNA was extracted from cells collected from buccal swabs. The p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population. We analysed the 104 patients and 109 control subjects. The distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p=0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR=1.9; 95% CI, 1.120-3.343). The polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development.
Bruner-Tran, K L; Herington, J L; Duleba, A J; Taylor, H S; Osteen, K G
Progesterone action normally mediates the balance between anti-inflammatory and proinflammatory processes throughout the female reproductive tract. However, in women with endometriosis, endometrial progesterone resistance, characterized by alterations in progesterone responsive gene and protein expression, is now considered a central element in disease pathophysiology. Recent studies additionally suggest that the peritoneal microenvironment of endometriosis patients exhibits altered physiological characteristics that may further promote inflammation-driven disease development and progression. Within this review, we summarize our current understanding of the pathogenesis of endometriosis with an emphasis on the role that inflammation plays in generating not only the progesterone-resistant eutopic endometrium but also a peritoneal microenvironment that may contribute significantly to disease establishment. Viewing endometriosis from the emerging perspective that a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment are biologically linked risk factors for disease development provides a novel mechanistic framework to identify new therapeutic targets for appropriate medical management.
Szczepańska, Malgorzata; Mostowska, Adrianna; Wirstlein, Przemyslaw; Skrzypczak, Jana; Misztal, Matthew; Jagodziński, Paweł P
Data suggests that dopamine receptor DRD2 gene variants may contribute to hyperprolactinemia and that they may be risk factors for endometriosis-related infertility. The purpose of the present study was to determine whether nucleotide variants of the DRD2 gene may be associated with infertility related to endometriosis. Five DRD2 SNPs, rs1800497, rs6277, rs2283265, rs4245146 and rs4648317, which are located in different blocks of linkage disequilibrium, were studied in 151 cases and 381 controls. No significant differences between DRD2 rs1800497, rs6277, rs2283265, rs4245146 and rs4648317 genotype, allele nor haplotype frequencies were observed in women with endometriosis-related infertility compared with the control group. The present results did not confirm DRD2 gene variants to be genetic risk factors for endometriosis-related infertility.
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Chmaj-Wierzchowska, Karolina; Pieta, Beata; Czerniak, Tomasz; Opala, Tomasz
Endometriosis is an estrogen-dependent, chronic disease consisting in implantation and hyperplasia of the endometrium outside of the uterine cavity Endometriosis in post-laparoscopic scars applies to approx. 0.5-7% of the extraorganic locations of the disease. The purpose of the paper was to describe medical management and literature review for endometriosis in a post-laparoscopic scar. Two lesions located near the insertion site for the lower trocars were removed along with the border of healthy tissue. At the time of publication of this paper the patient did not report any complaints. In conclusion, each limited lesion in the subcutaneous tissue, with pain intensifying during menstruation, should suggest an initial diagnosis of scar endometriosis, regardless of patient age and type of surgery
Bruner-Tran, Kaylon L.; Herington, Jennifer L.; Duleba, Antoni J.; Taylor, Hugh S.; Osteen, Kevin G.
Progesterone action normally mediates the balance between anti-inflammatory and pro-inflammatory processes throughout the female reproductive tract. However, in women with endometriosis, endometrial progesterone resistance, characterized by alterations in progesterone responsive gene and protein expression, is now considered a central element in disease pathophysiology. Recent studies additionally suggest that the peritoneal microenvironment of endometriosis patients exhibits altered physiological characteristics that may further promote inflammation-driven disease development and progression. Within this review, we summarize our current understanding of the pathogenesis of endometriosis with an emphasis on the role that inflammation plays in generating not only the progesterone-resistant eutopic endometrium but also a peritoneal microenvironment that may contribute significantly to disease establishment. Viewing endometriosis from the emerging perspective that a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment are biologically linked risk factors for disease development provides a novel mechanistic framework to identify new therapeutic targets for appropriate medical management. PMID:23598784
Mirkin, David; Murphy-Barron, Carrieann; Iwasaki, Kosuke
Endometriosis is a painful, chronic disease affecting 5.5 million women and girls in the United States and Canada and millions more worldwide. The usual age range of women diagnosed with endometriosis is 20 to 45 years. Endometriosis has an estimated prevalence of 10% among women of reproductive age, although estimates of prevalence vary greatly. Endometriosis is the most common gynecological cause of chronic pelvic pain, but published information on its associated medical care costs is scarce. The aim of this study was to determine (1) the prevalence of endometriosis in the United States, (2) the amount of health care services used by women coded with endometriosis in a commercial medical claims database during 1999 to 2003, and (3) the endometriosis-related costs for 2003, the most recent data available at the time the study was performed. This study was a retrospective review of administrative data for commercial payers, which included enrollment, eligibility, and claims payment data contained in the Medstat Marketscan database for approximately 4 million commercial insurance members. All claims and membership data were extracted for each woman aged 18 to 55 years who had at least 1 medical or hospital claim with a diagnosis code for endometriosis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 617.00-617.99) for 1999 through 2003. Claims data from 1999 through 2003 were used to determine prevalence and health care resource utilization (i.e., annual admission rate, annual surgical rate, distribution of endometriosis-related surgeries, and prevalence of comorbid conditions). The cost analysis was based on claims from 2003 only. Cost was defined as the payer-allowed charge, which equals the net payer cost plus member cost share. The prevalence of women with medical claims (inpatient and/or outpatient) containing ICD-9-CM codes for endometriosis was 1.1% for the age band of 30 to 39 years and 0.7% over the entire
Blanchot, J; Jacquemard, F; Letoquart, J P; Marcorelles, P; Mambrini, A; Giraud, J R
The authors report 5 cases of intestinal endometriosis which required resection. They review the pathological characteristics and attempt to define the while accepting that the indications for resection should be extremely limited from both gynecological and intestinal viewpoints.
Vietri, Maria Teresa; Molinari, Anna Maria; Iannella, Iolanda; Cioffi, Michele; Bontempo, Paola; Ardovino, Mario; Scaffa, Cono; Colacurci, Nicola; Cobellis, Luigi
p53 codon 72 polymorphism in Italian women have a minor role in determining genetic susceptibility to endometriosis. The racial differences, in association with other risk factors, might be underlined in endometriotic disease.
Hajhosseini, Babak; King, Louise P.
Background: Endometriosis commonly affects the pelvic organs but can also affect organs outside the pelvis and is then termed extragenital endometriosis. Cases: Successful robotically assisted laparoscopic management of extragenital endometriosis, specifically, endometriosis of the bowel, bladder, and ureter in 5 patients. Conclusion: A substantial body of evidence supports the laparoscopic approach as the preferred method for many procedures; yet, a majority of procedures today still are performed by laparotomy. This preference for open procedures is likely due to the lack of trained endoscopic surgeons, the difficulty in obtaining proper instruments, and the long learning curve of operative laparoscopy. The recent advent of computer-enhanced technology may provide the bridge necessary for more surgeons to incorporate laparoscopic surgery in the treatment of complex cases. PMID:21985730
Rosales Delgado, J A; González-Sicilia Cotter, E; Aedo Ocaña, O
Laparoscopy was performed on patients with dysmenorrhea, sterility and pelvic pain in order to evaluate the prevalence of endometriosis in our environment therefore considering the population of female beneficiary patients of reproductive age of the ISSSTE hospital in the city of Veracruz, Ver. in México. The percentages of endometriosis were similar to the reports published in the international journals with the exception of the dysmenorrhea where our results were higher. In all the cases the same variables were analyzed; age, active sexual life (V.S.A.), birth control method, menarche (men), menstrual cycle, childbirths and abortions, as well as other laparoscopic detections. Each of the endometriosis cases were classified according to the revised American Fertility Society classification of 1985 (R.A.F.S.) for endometriosis.
Prescott, J.; Farland, L.V.; Tobias, D.K.; Gaskins, A.J.; Spiegelman, D.; Chavarro, J.E.; Rich-Edwards, J.W.; Barbieri, R.L.; Missmer, S.A.
STUDY QUESTION Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76–2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46–2.14; multivariate HR 35–39 years = 1.20, 95% CI = 0.94–1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION We did not have information on participants
Missmer, Stacey A.; Bove, Geoffrey M.
Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain. PMID:21665106
Missmer, Stacey A; Bove, Geoffrey M
Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain.
Huang, Miaomaio; Li, Xuqing; Guo, Peipei; Yu, Zhaojuan; Xu, Yuting; Wei, Zhaolian
The junctional zone (JZ), also called as the endometrial-myometrial junction, is related to peristaltic-like movements in the non-pregnant uterus. Hyperperistalsis and dysperistalsis of uterus constructions might underlie many important disorders such as dysmenorrhea, infertility, endometriosis, implantation failure. The major proteins for uterine contraction of the non-pregnant uterus may be Oxytocin (OT) and oxytocin receptor (OTR). The objective of this study was to inspect the expression of OTR in isthmic and mid-fundal parts of the uterine junctional zone at different stages of the follicular cycle in patients with and without endometriosis. Uterine biopsies containing endometrium and junctional zone were collected from the isthmic and mid-fundal parts of the anterior wall after hysterectomy. The OTR expression was evaluated by immunohistochemistry. In the control uterus, OTR expression in the isthmic region was significantly higher than in the fundal region in the proliferative phase (p < 0.05) but significantly lower in the secretory phase (p < 0.05). And the expression of OTR in the proliferative phase was significantly higher than that in the secretory phase in both isthmic and fundal regions (p = 0.000 and 0.049, respectively). However, in endometriosis uteri, OTR expression in the isthmic region showed no significant difference with that in the fundal region in both proliferative and secretory phases (p = 0.597 and 0.736, respectively). In both isthmic and fundal regions, OTR expression was not significantly different between the proliferative phase and secretory phase (p = 0.084 and 0.222, respectively). OTR expression in fundal regions of revised ASRM I and II endometriosis were lower than that of revised ASRM III and IV (p = 0.049). In the fundal region of JZ, the expression of OTR in ovarian endometriosis was significantly lower than that in deep infiltrating endometriosis (p = 0.046). The expression level of OTR in the
De Roos, Anneclaire J.; Thompson, Mary Lou; Sathyanarayana, Sheela; Scholes, Delia; Barr, Dana Boyd; Holt, Victoria L.
Background: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. Objective: We investigated endometriosis risk in relation to environmental exposure to OCPs. Methods: We conducted the present analyses using data from the Women’s Risk of Endometriosis (WREN) study, a population-based case–control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Results: Our data suggested increased endometriosis risk associated with serum concentrations of β-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum β-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). Conclusions: In our case–control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of β-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women. Citation: Upson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, Holt VL. 2013
Poole, Elizabeth M; Lin, Wayne T; Kvaskoff, Marina; De Vivo, Immaculata; Terry, Kathryn L; Missmer, Stacey A
Endometriosis is associated with ovarian cancer, but the relation with endometrial cancer is unclear. Prior studies generally were retrospective and had potential limitations, including use of self-reported endometriosis, failure to account for delays between symptom onset and endometriosis diagnosis, and changes in risk factors post-endometriosis diagnosis. We evaluated whether these limitations obscured a weak association with endometrial cancer and the extent to which these limitations impacted associations with ovarian cancer. Cox proportional hazards regression models were used to assess associations between endometriosis and cancer risk, evaluating the impacts of self-reported vs. laparoscopically confirmed endometriosis, delayed diagnosis, and post-endometriosis diagnosis changes in risk factor exposures on relative risk estimates. Over 18 years of follow-up, we identified 228 ovarian and 166 endometrial cancers among 102,025 and 97,109 eligible women, respectively. Self-reported endometriosis was associated with ovarian cancer [relative risk (RR): 1.81; 95% confidence interval (CI): 1.26-2.58]; this association was stronger for laparoscopically confirmed endometriosis (HR: 2.14; 95% CI 1.45-3.15). No association was observed with endometrial cancer (self-report RR: 0.78; 95% CI 0.42-1.44; laparoscopic-confirmation RR: 0.76; 95% CI 0.35-1.64). Accounting for diagnosis delays or post-endometriosis diagnosis changes in risk factors had a little impact. This study adds to the evidence that endometriosis is not strongly linked to endometrial cancer risk and that the association with ovarian cancer is robust to misclassification, diagnostic delay, and changes in exposures post-endometriosis diagnosis. Our analysis suggests that confounding and misclassification do not obscure a weak association for endometrial cancer risk, although our results should be replicated.
Maffione, Anna Margherita; Panzavolta, Riccardo; Lisato, Laura Camilla; Ballotta, Maria; D'Isanto, Mariangela Zanforlini; Rubello, Domenico
Endometriosis is a frequent and clinically relevant problem in young women. Laparoscopy is still the gold standard for the diagnosis of endometriosis, but frequently both morphologic and functional imaging techniques are involved in the diagnostic course before achieving a conclusive diagnosis. We present a case of a patient affected by infiltrating retroperitoneal endometriosis falsely interpreted as a malignant mass by contrast-enhanced magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography. PMID:26097425
Eskenazi, Brenda; Mocarelli, Paolo; Warner, Marcella; Samuels, Steven; Vercellini, Paolo; Olive, David; Needham, Larry L; Patterson, Donald G; Brambilla, Paolo; Gavoni, Nicoletta; Casalini, Stefania; Panazza, Stefania; Turner, Wayman; Gerthoux, Pier Mario
Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis. PMID:12117638
Eskenazi, Brenda; Mocarelli, Paolo; Warner, Marcella; Samuels, Steven; Vercellini, Paolo; Olive, David; Needham, Larry L; Patterson, Donald G; Brambilla, Paolo; Gavoni, Nicoletta; Casalini, Stefania; Panazza, Stefania; Turner, Wayman; Gerthoux, Pier Mario
Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis.
Brüggmann, Dörthe; Elizabeth-Martinez, Alexandra; Klingelhöfer, Doris; Quarcoo, David; Jaque, Jenny M; Groneberg, David A
Endometriosis is one of the most common gynecological diseases. It is still a chameleon in many aspects and urges intense research activities in the fields of diagnosis, therapy and prevention. Despite the need to foster research in this area, no in-depth analysis of the global architecture of endometriosis research exists yet. We here used the NewQIS platform to conduct a density equalizing mapping study, using the Web of Science as database with endometriosis related entries between 1900 and 2009. Density equalizing maps of global endometriosis research encompassing country-specific publication activities, and semi-qualitative indices such as country specific citations, citation rates, h-Indices were created. In total, 11,056 entries related to endometriosis were found. The USA was leading the field with 3705 publications followed by the United Kingdom (952) and Japan (846). Concerning overall citations and country-specific h-Indices, the USA again was the leading nation with 74,592 citations and a modified h-Index of 103, followed by the UK with 15,175 citations (h-Index 57). Regarding the citation rate, Sweden and Belgium were at top positions with rates of 22.46 and 22.26, respectively. Concerning collaborative studies, there was a steep increase in numbers present; analysis of the chronological evolution indicated a strong increase in international collaborations in the past 10 years. This study is the first analysis that illustrates the global endometriosis research architecture. It shows that endometriosis research is constantly gaining importance but also underlines the need for further efforts and investments to foster research and ultimately improve endometriosis management on a global scale.
Johnson, M Cecilia; Pinto, Claudio; Alves, Alessandra; Palomino, Alberto; Fuentes, Ariel; Boric, M Angélica; Vega, Margarita
Endometriosis, a common gynecologic disorder characterized by endometrial glands and stroma outside the uterus, is diagnosed by direct visualization of peritoneal and ovarian implants during laparoscopy. To study the estrogenic microenvironment in eutopic endometria of women with and without endometriosis. Eutopic endometria, obtained during laparoscopy from 23 women with endometriosis and 20 fertile cyclic women undergoing tubal sterilization, was studied. P450Arom mRNA expression (RT-PCR) was measured. Also, P450Arom activity was assessed measuring testosterone conversion to estradiol and the concentration of this last hormone in cultured endometrial explants. Age and body mass index was similar in both groups studied. Seventy nine percent of endometria from women with endometriosis and in 29.4% from control group expressed P450Arom mRNA (p <0.01). The intensity of the band was higher in secretory endometria from women with endometriosis when compared to controls (p <0.01), but it was similar during the proliferative phase. Estradiol secretion to the culture media by proliferative endometria explants from women with endometriosis was 3-fold higher than secretory endometria (p <0.01) and endometria from control women in both phases. P450Arom activity, in the presence of testosterone, was 7-fold higher in endometrial cultures from women with endometriosis, when compare with the basal culture (p <0.01). However, in endometrial explant cultures from control women, this activity was not statistical different. These results indicate that in women with endometriosis, the microenvironment in the endometria is estrogenic as a consequence of an increased expression and activity of the P450Arom.
Fazleabas, Asgerally T.; Braundmeier, Andrea; Parkin, Kirstin
Endometriosis is a gynecological disorder which is associated with alterations in the immune system that contributes to its pathology as well as its associated infertility. This brief report summarizes our findings related to the changes in T regulatory cells (Tregs) which may affect the uterine environment and impact the fertility of women and non-human primates with endometriosis. Targeted therapies that could reduce Tregs within the reproductive tract may have a potential as long-lasting or permanent contraception. PMID:26086573
Sánchez Justicia, Carlos; Granero Peiró, Lucia; Arabe Paredes, Jorge Ali
Anisakiasis and endometriosis is rare cause of intestinal obstruction and even perforation, the latter being extremely rare. We report the case of a patient with intestinal obstruction that progress to perforation and whose differential diagnosis is complex. The interest in this clinical case lies in the unexpected histology of the surgical specimen after the intervention of the patient, because the intestinal endometriosis as intestinal anisakiasis are rare entities that make diagnosis difficult.
Jørgensen, Hilde; Hill, Abby S; Beste, Michael T; Kumar, Manu P; Chiswick, Evan; Fedorcsak, Peter; Isaacson, Keith B; Lauffenburger, Douglas A; Griffith, Linda G; Qvigstad, Erik
Our aim was to characterize peritoneal cytokine profiles in patients with infertility, with and without endometriosis, to illuminate potential differences in immune profiles that may reflect mechanistic differences between these two patient populations. Cross-sectional study. University hospital and research center. Women undergoing laparoscopy for infertility investigation (n = 107). Peritoneal fluid was collected during surgery. Clinical characteristics were registered preoperatively. We determined the concentration of 48 different cytokines from the peritoneal fluid with multiplex immunoassays. Associations between cytokines and clinical findings were assessed with logistic regression and partial least squares discriminant analyses (PLS-DA). Concentrations of SCGF-β, IL-8, HGF, and MCP-1 were significantly higher, while IL-13 was significantly lower in the endometriosis group compared with the group without endometriosis. Multiple stepwise logistic regression identified a combination of SCGF-β, IL-13, and G-CSF concentrations that predicted the presence of endometriosis with 86% sensitivity and 67% specificity. PLS-DA identified a class of 11 cytokines (SCGF-β, HGF, IL-13, MCP-1, CTACK, MCP-3, M-CSF, LIF, IL-5, IL-9, and IFN-a2) that were more characteristic of endometriosis than nonendometriosis patients. By combining univariate and multivariate analyses, profiles of cytokines more likely to be enriched or depleted in infertility patients with endometriosis compared with those without endometriosis were identified. These findings may inform future analyses of pathophysiological mechanisms of endometriosis in infertile patients, including dysregulated Th1/Th2 response and mobilization and proliferation of hematopoietic stem cells. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Uppal, Jaya; Sobotka, Stanislaw; Jenkins, Arthur L
Multiple causes outside the spine can mimic spinal back pain. Endometriosis is an important gynecologic disorder, which commonly affects the lower region of the female pelvis and less frequently the spine and soft tissues. The lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Therefore symptoms of endometriosis include severe reoccurring pain in the pelvic area as well as lower back and abdominal pain. We report on a 39-year-old gymnast with cyclic sciatica and back pain, whose initial presentation initially led to a spinal fusion at L4/5 and L5/S1, but that procedure did not change her symptoms. Her diagnosis of endometriosis was not made until 2 years after her spinal fusion. Ultimately, once diagnosed with endometriosis of the retroperitoneal spinal and neural elements, her back and leg pain responded completely to hormonal therapy and then to a hysterectomy and a bilateral salpingo-oophorectomy. Because her true diagnosis of endometriosis was unknown and she had some degenerative changes in her spine, she underwent a spinal fusion that would probably not have been done if the diagnosis of endometriosis had been suggested. It is critical for any clinician who deals with back pain to at least consider the diagnosis of endometriosis in female patients who have a history of pelvic pain. The diagnosis of endometriosis should be considered in candidate patients by asking whether there is a significant hormonal cyclic nature to the symptoms, to prevent such unnecessary surgical adventures. Copyright © 2016 Elsevier Inc. All rights reserved.
Burghaus, S.; Fehm, T.; Fasching, P. A.; Blum, S.; Renner, S. K.; Baier, F.; Brodkorb, T.; Fahlbusch, C.; Findeklee, S.; Häberle, L.; Heusinger, K.; Hildebrandt, T.; Lermann, J.; Strahl, O.; Tchartchian, G.; Bojahr, B.; Porn, A.; Fleisch, M.; Reicke, S.; Füger, T.; Hartung, C.-P.; Hackl, J.; Beckmann, M. W.; Renner, S. P.
Introduction: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. Material and Methods: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. Results: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. Conclusion: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers. PMID:27582581
Ailawadi, Radhika K; Jobanputra, Smeeta; Kataria, Meera; Gurates, Bilgin; Bulun, Serdar E
To determine the role of an aromatase inhibitor, letrozole, in the treatment of reproductive-age women with endometriosis and associated chronic pelvic pain. Phase 2, open-label, nonrandomized proof-of-concept study. Outpatient tertiary-care center. Ten patients with endometriosis, all previously treated both medically and surgically, with unsatisfactory results. Endometriosis was diagnosed by biopsy and scored from an initial diagnostic laparoscopy performed within 1 month before treatment was begun. Oral administration of letrozole (2.5 mg), the progestin norethindrone acetate (2.5 mg), calcium citrate (1,250 mg), and vitamin D (800 IU) was done daily for 6 months. Within 1-2 months after completion of the treatment, a second-look laparoscopy was performed to score and biopsy endometriosis. Changes in American Society for Reproductive Medicine (ASRM) scores for endometriosis, pelvic pain assessed by visual analog scale, serum hormone levels (FSH, LH, E(2), and estrone [E(1)]), and bone density (DEXA scan). No histologically demonstrable endometriosis was present in any patient during the second-look laparoscopy. ASRM and pelvic pain scores decreased significantly in response to treatment. Overall, no significant change in bone density was detected. Gonadotropin levels were not significantly altered by treatment, and although circulating E(2) and E(1) levels were reduced, the decrease was not statistically significant. The combination of letrozole and norethindrone acetate achieved marked reduction of laparoscopically visible and histologically confirmed endometriosis in all 10 patients and significant pain relief in nine out of 10 patients who had not responded previously to currently available treatments. On this basis, letrozole should be a candidate for the medical management of endometriosis.
Da Ines, David; Bourdel, Nicolas; Charpy, Cécile; Montoriol, Pierre François; Petitcolin, Virginie; Canis, Michel; Garcier, Jean-Marc
Abdominal wall endometriosis is unusual and mostly occurs in scars following Cesarean section. Although malignant transformation is rare, it must be recognized in order to benefit from radical resection. We report a very rare case of mixed endometrioid and serous carcinoma developing in a Cesarean section endometriosis scar and the way we managed it using surgery and chemotherapy. 18-FDG PET-CT imaging was performed to correctly stage the disease.
Gonçalves-Filho, Rubens P; Brandes, Ariel; Christofolini, Denise M; Lerner, Tatiana G; Bianco, Bianca; Barbosa, Caio P
To evaluate PAI-1 genotypes in a group of infertile women with or without endometriosis and control subjects. Case-control study. Human Reproduction Center of Medicina do ABC Faculty. One hundred and forty infertile women with endometriosis, 64 women with idiopathic infertility and 148 fertile women as control subjects. The PAI-1 4G/5G polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. Genotype distribution and allele frequency of the 4G/5G polymorphism of the PAI-1 gene. The frequencies of genotypes 4G/4G, 4G/5G and 5G/5G of the PAI-1 gene in the infertile women with endometriosis were 38.6, 37.1 and 24.3%, respectively, and in the control group 24.3, 33.8 and 41.9%, respectively (p=0.003). When the infertile women with endometriosis were divided according to their endometriosis stage, genotypes 4G/4G, 4G/5G and 5G/5G were identified, respectively, in 36.7, 32.9 and 30.4% of the patients with minimal/mild endometriosis (p=0.102) and in 41.0, 42.6 and 16.4% of the patients with moderate/severe endometriosis (p=0.001); in the women with idiopathic infertility, these genotypes were found at a frequency of 29.7, 34.3 and 36%, respectively (p=0.637). The data suggest that, in Brazilian women, the PAI-1 4G/5G polymorphism may be associated with a risk of endometriosis-associated infertility. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.
Burghaus, S; Fehm, T; Fasching, P A; Blum, S; Renner, S K; Baier, F; Brodkorb, T; Fahlbusch, C; Findeklee, S; Häberle, L; Heusinger, K; Hildebrandt, T; Lermann, J; Strahl, O; Tchartchian, G; Bojahr, B; Porn, A; Fleisch, M; Reicke, S; Füger, T; Hartung, C-P; Hackl, J; Beckmann, M W; Renner, S P
Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.
Lusine, Aghajanova; Signe, Altmäe; Sergo, Kasvandik; Andres, Salumets; Anneli, Stavreus-Evers; Giudice Linda, C
Objective To determine expression of stanniocalcin-1 (STC1) in human endometrium with and without endometriosis and its regulation by steroid hormones. Design Laboratory study. Setting University. Patients 19 women with endometriosis and 33 control women. Intervention(s) Endometrial biopsy and fluid sampling Main Outcome Measure(s) Analysis of early secretory (ESE) and mid-secretory (MSE) endometrial secretomes from fertile women with nano-LC/MS/MS; real-time Q-PCR and immunohistochemistry for STC1 and its receptor CASR mRNA and proteins in endometrium with and without endometriosis; evaluation of STC1 and CASR mRNA expression in endometrial stromal fibroblasts (eSF) from women with and without endometriosis decidualized with E2P4 or 8-bromo-cAMP. Results STC1 protein was strongly upregulated (p=0.0004) in MSE versus ESE in endometrial fluid of fertile women. STC1 mRNA significantly increased in MSE from women with, but not without endometriosis, compared to proliferative endometrium (PE) or ESE, with no significant difference throughout the menstrual cycle between groups. STC1 mRNA in eSF from control women increased >230-fold upon decidualization with cAMP versus 45-fold from women with endometriosis, which was not seen upon decidualization with E2/P4. CASR mRNA did not exhibit significant differences in any condition, and was not expressed in isolated eSF. STC1 protein immunoexpression in eSF was significantly lower in women with endometriosis compared to controls. Conclusions STC1 protein is significantly upregulated in MSE endometrial fluid, and is dysregulated in eutopic endometrial tissue from women with endometriosis. It is likely regulated by cAMP and may be involved in the pathogenesis of decidualization defects. PMID:27322879
Wang, Jayson; Strauss, Dirk C; Messiou, Christina; Thway, Khin
While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens.
Hamdan, Mukhri; Omar, Siti Z; Dunselman, Gerard; Cheong, Ying
To investigate the association of endometriosis on assisted reproductive technology (ART) outcomes and to review if surgical treatment of endometriosis before ART affects the outcomes. We searched studies published between 1980 and 2014 on endometriosis and ART outcome. We searched MEDLINE, PubMed, ClinicalTrials.gov, and Cochrane databases and performed a manual search. A total of 1,346 articles were identified, and 36 studies were eligible to be included for data synthesis. We included published cohort studies and randomized controlled trials. Compared with women without endometriosis, women with endometriosis undertaking in vitro fertilization and intracytoplasmic sperm injection have a similar live birth rate per woman (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.84-1.06, 13 studies, 12,682 patients, I=35%), a lower clinical pregnancy rate per woman (OR 0.78, 95% CI 0.65-0.94), 24 studies, 20,757 patients, I=66%), a lower mean number of oocyte retrieved per cycle (mean difference -1.98, 95% CI -2.87 to -1.09, 17 studies, 17,593 cycles, I=97%), and a similar miscarriage rate per woman (OR 1.26, 95% CI (0.92-1.70, nine studies, 1,259 patients, I=0%). Women with more severe disease (American Society for Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy rate, and mean number of oocytes retrieved when compared with women with no endometriosis. Women with and without endometriosis have comparable ART outcomes in terms of live births, whereas those with severe endometriosis have inferior outcomes. There is insufficient evidence to recommend surgery routinely before undergoing ART.
Fourquet, Jessica; Gao, Xin; Zavala, Diego; Orengo, Juan C.; Abac, Sonia; Ruiz, Abigail; Laboy, Joaquín; Flores, Idhaliz
NARRATIVE ABSTRACT The objective of this study was to assess the burden of endometriosis by obtaining Patient Reported Outcome (PRO) data describing the experience of living with this disease. Survey data from one hundred and seven women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work and daily life. PMID:19926084
Fourquet, Jessica; Gao, Xin; Zavala, Diego; Orengo, Juan C; Abac, Sonia; Ruiz, Abigail; Laboy, Joaquín; Flores, Idhaliz
The objective of this study was to assess the burden of endometriosis by obtaining patient-reported outcome data describing the experience of living with this disease. Survey data from 107 women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work, and daily life. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Araujo, F.M.; Meola, J.; Rosa-e-Silva, J.C.; Paz, C.C.P.; Ferriani, R.A.; Nogueira, A.A.
Endometriosis is a benign, estrogen-dependent disease with symptoms such as pelvic pain and infertility, and it is characterized by the ectopic distribution of endometrial tissue. The expression of the ID2, PRELP and SMOC2 genes was compared between the endometrium of women without endometriosis in the proliferative phase of their menstrual cycle and the eutopic and ectopic endometrium of women with endometriosis in the proliferative phase. Paired tissue samples from 20 women were analyzed: 10 from endometrial and peritoneal endometriotic lesions and 10 from endometrial and ovarian endometriotic lesions. As controls, 16 endometrium samples were collected from women without endometriosis in the proliferative phase of menstrual cycle. Analysis was performed by real-time polymerase chain reaction (PCR). There was no significant difference between gene expression in the endometrium of women with and without endometriosis. The ID2 gene expression was increased in the most advanced stage of endometriosis and in ovarian endometriomas, the PRELP was more expressed in peritoneal lesions, and the SMOC2 was highly expressed in both peritoneal and endometrioma lesions. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue. PMID:28678915
Cuevas, Marielly; Flores, Idhaliz; Thompson, Kenira J.; Ramos-Ortolaza, Dinah L.; Torres-Reveron, Annelyn
Women with endometriosis have significant emotional distress; however, the contribution of stress to the pathophysiology of this disease is unclear. We used a rat model of endometriosis to examine the effects of stress on the development of this condition and its influence on inflammatory parameters. Female Sprague-Dawley rats were subjected to swim stress for 10 consecutive days prior to the surgical induction of endometriosis by suturing uterine horn implants next to the intestinal mesentery (endo-stress). Sham-stress animals had sutures only, and an endo-no stress group was not subjected to the stress protocol. At the time of sacrifice on day 60, endometriotic vesicles were measured and colons assessed for macroscopic and microscopic damage. Colonic tissue and peritoneal fluid were collected for inflammatory cell analysis. Endometriosis, regardless of stress, produced a decrease in central corticotropin-releasing factor immunoreactivity, specifically in the CA3 subregion of the hippocampus. Prior exposure to stress increased both the number and severity of vesicles found in animals with endometriosis. Stress also increased colonic inflammation, motility, myeloperoxidase levels, and numbers of mast cells. In summary, prior stress may contribute to the development and severity of endometriosis in this animal model through mechanisms involving cell recruitment (eg, mast cells), release of inflammatory mediators, and deregulation of hypothalamic–pituitary axis responses in the hippocampus. PMID:22527982
Berlanda, Nicola; Frattaruolo, Maria Pina; Aimi, Giorgio; Farella, Marilena; Barbara, Giussy; Buggio, Laura; Vercellini, Paolo
Despite higher costs for robotic-assisted laparoscopy (RAL) than standard laparoscopy (SL), RAL treatment of endometriosis is performed without established indications. PubMed/MEDLINE was searched for 'robotic surgery' and 'endometriosis' or 'gynaecological benign disease' from January 2000 to December 2016. Full-length studies in English reporting original data were considered. Among 178 articles retrieved, 17 were eligible: 11 non-comparative (RAL only) and six comparative (RAL versus SL). Non-comparative studies included 445 patients. Mean operating time, blood loss and hospital stay were 226 min, 168 ml and 4 days. Major complications and laparotomy conversions were 3.1% and 1.3%. Eight studies reported pain improvement at 15-month follow-up. Comparative studies were all retrospective; 749 women underwent RAL and 705 SL. Operating time was longer for RAL in five studies. Major complications and laparotomy conversions for RAL and SL were 1.5% versus 0.3% and 0.3% versus 0.5%. One study reported pain reduction for RAL at 6-month follow-up. RAL treatment of endometriosis did not provide benefits over SL, overall and among subgroups of women with severe endometriosis, peritoneal endometriosis and obesity. Available evidence is low-quality, and data regarding long-term pain relief and pregnancy rates are lacking. RAL treatment of endometriosis should be performed only within controlled studies. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Kurisu, Yoshitaka; Tsuji, Motomu; Shibayama, Yuro; Yamada, Takashi; Ohmichi, Masahide
Multicystic mesothelioma was described as a benign neoplasm in most reports. But, whether it is neoplastic or reactive is still controversial. Although multicystic mesothelioma is often accompanied by endometriosis, histologic findings of the lesion with endometriosis have not been well documented. In this report, 2 cases of multicystic mesothelioma with endometriosis were studied histologically. The first lesion consisted of multiple cysts having thin walls lined with single-layered cuboidal mesothelia, and in the cystic walls, small foci of endometriosis were found. The second lesion was next to the endometriotic cysts in the pelvic space. These histologic findings suggest that endometriosis greatly contributes to the origin of the lesions. In addition, from the review of the literature, cystic mesothelioma was divided into 2 categories, that is, neoplastic or non-neoplastic lesions. Differentiation of both disorders might be possible by the following: size of the lesion, macroscopic and microscopic solid proliferation, features of adenomatoid tumor, and common mesothelioma-like histology. In conclusion, multicystic mesothelioma accompanied by endometriosis is thought to be a secondary non-neoplastic lesion induced by adhesion or inflammation rather than a neoplasm.
Meresman, G F; Vighi, S; Buquet, R A; Contreras-Ortiz, O; Tesone, M; Rumi, L S
To evaluate and compare spontaneous apoptosis and Bcl-2 and Bax expression in eutopic endometrium from women with and without endometriosis. Apoptosis and Bcl-2 and Bax expression were examined in eutopic endometrium from women with and without endometriosis. Instituto de Biología y Medicina Experimental-CONICET, Department of Gynecology and Department of Gynecological Pathology, Clínicas University Hospital, Buenos Aires, Argentina. Women with untreated endometriosis (n = 14) and controls (n = 16). Collection of endometrial samples during diagnostic or therapeutic laparoscopy. Apoptotic cells were detected with use of the dUTP nick-end labeling (TUNEL) assay; Bcl-2 and Bax expressions were assessed with use of immunohistochemical techniques. Spontaneous apoptosis was significantly lower in eutopic endometrium from patients with endometriosis, compared with healthy controls (2.26 +/- 0.53 and 9.37 +/- 1.69 apoptotic cells/field, respectively) and was independent of cycle phase. An increased expression of Bcl-2 protein was found in proliferative eutopic endometrium from patients with endometriosis. Bax expression was absent in proliferative endometrium, whereas there was an increase in its expression in secretory endometrium from both patients and controls. Women with endometriosis show decreased number of apoptotic cells in eutopic endometrium. The abnormal survival of endometrial cells may result in their continuing growth into ectopic locations.
Rozsnyai, Francisc; Resch, Benoit; Dugardin, Fabrice; Berrocal, Juan; Descargues, Gérôme; Schmied, Remi; Boukerrou, Malik; Marpeau, Loïc
Objectives: To report the outcomes of surgical management of urinary tract endometriosis and discuss the choice between conservative and radical surgery. Materials and Methods: We reviewed data concerning women managed for ureteral or bladder deep infiltrating endometriosis in 5 surgical departments participating in the CIRENDO prospective database. Preoperative data, surgical procedure data, and postoperative outcomes were analyzed. Results: Data from 30 women pooled in the database showed 15 women presenting with ureteral endometriosis, 14 women with bladder nodules, and 1 with both types of lesions. Ureterolysis was performed in 14 cases; the ureter was satisfactorily freed in 10 of these. In 4 women over 40 years old, who were undergoing definitive amenorrhea, moderate postoperative ureteral stenosis was tolerated and later improved in 3 cases, while the fourth underwent secondary ureteral resection and ureterocystoneostomy. Primary ureterectomy was carried out in 4 women. Two cases of intrinsic ureteral endometriosis were found in 5 ureter specimens. Four complications were related to surgical procedures on ureteral nodules, and 2 complications followed the removal of bladder endometriosis. Delayed postoperative outcomes were favorable with a significant improvement in painful symptoms and an absence of unpleasant urinary complaints, except for one patient with prolonged bladder denervation. Conclusion: Conservative surgery, in association with postoperative amenorrhea, can be proposed in a majority of cases of urinary tract endometriosis. Although the outcomes are generally favorable, the risk of postoperative complications should not be overlooked, as surgery tends to be performed in conjunction with other complex procedures such as colorectal surgery. PMID:22643496
Wölfler, Monika Martina; Küppers, Mareike; Rath, Werner; Buck, Volker Uwe; Meinhold-Heerlein, Ivo; Classen-Linke, Irmgard
Recent data implicate an altered expression of progesterone receptor isoform A (PR-A) and B (PR-B) in the endometrium of endometriosis patients. This prospective exploratory study aimed to precisely determine the PR-A and PR-B expression using immunohistochemical techniques in eutopic endometrium of women with endometriosis compared with disease-free women throughout the menstrual cycle. All symptomatic patients underwent laparoscopy for the diagnosis of endometriosis and histological confirmation of the disease (EO) whereas controls were proven disease-free (CO). In CO samples (n=10) an increased expression of PR-A and PR-B during the proliferative to early secretory phase and a decreased expression of both receptor isoforms during the mid to late secretory phase was ascertained in accordance with previous studies. In patients with endometriosis (n=16) no cycle dependent pattern of PR-A and PR-B expression was identified in contrast to patients without endometriosis. Moreover, in EO samples a huge variety of inter- and intra-individual differences in PR-A and PR-B expression were detected. These data provide further evidence that dysregulation of the PR-A and PR-B expression might contribute to the pathophysiology of endometriosis.
Xiong, Wenqian; Zhang, Ling; Yu, Lan; Xie, Wei; Man, Yicun; Xiong, Yao; Liu, Hengwei; Liu, Yi
Endometriosis is an estrogen-dependent disease that involves the adhesion, invasion, and angiogenesis of endometrial tissues outside of the uterine cavity. We hypothesized that a link exists between estrogen and beta-catenin (β-catenin) signaling in the pathogenesis of endometriosis. Human endometrial stromal cells (HESCs) were separated from eutopic endometrial tissues that were obtained from patients with endometriosis. β-catenin expression and cells invasiveness ability were up-regulated by 17β-estradiol (E2) in an estrogen receptor (ESR)-dependent manner, whereas β-catenin siRNA abrogated this phenomenon. Moreover, co-immunoprecipitation and dual immunofluorescence studies confirmed ESR1, β-catenin, and lymphoid enhancer factor 1/T cell factor 3 co-localization in the nucleus in HESCs after E2 treatment. To determine the role of β-catenin signaling in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium from endometriosis patients into ovariectomized severe combined immunodeficiency mice. The implantation of the endometrium was suppressed by β-catenin siRNA. Collectively, studies regarding β-catenin signaling are critical for improving our understanding of the pathogenesis of estrogen-induced endometriosis, which can translate into the development of treatments and therapeutic strategies for endometriosis. PMID:26432349
Kim, Seul Ki; Park, Jung Yeon; Jee, Byung Chul; Suh, Chang Suk; Kim, Seok Hyun
To evaluate the association between the severity of endometriosis and the preoperative neutrophil-to-lymphocyte ratio (NLR) and serum level of cancer antigen 125 (CA 125). Data were obtained from the medical records of 419 patients who underwent laparoscopic conservative surgery for ovarian endometrioma between April 2005 and March 2013. Each patient's preoperative complete blood count was recorded and the endometriosis score was assessed. The endometriosis score was not associated with either the NLR or the serum level of CA 125. The endometriosis score was negatively related to preoperative hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The only positive association was between NLR and the patients' age. NLR and preoperative serum anti-Müllerian hormone level were found to be negatively related. The severity of endometriosis was not associated with the serum level of CA 125 or the NLR. The presence of a negative correlation between the severity of endometriosis and red blood cell dynamics needs further investigation.
Yang, H; Yin, J; Ficarrotta, K; Hsu, S H; Zhang, W; Cheng, C
To investigate the role and potential molecular mechanism of Galectin-3 (Gal-3) in the etiology of endometriosis-associated infertility. We detected Gal-3 expression in eutopic endometrium from women with endometriosis-associated infertility and healthy women without endometriosis or infertility. We then evaluated Gal-3 expression in endometrial glandular epithelial cells (EECs) and endometrial stromal cells (ESCs) and investigated its response to hormone stimulation in EECs and ESCs from both groups of women. Results of real-time PCR and western blot analysis showed Gal-3 expression in both proliferative and secretory stages of the menstrual cycle decreased significantly in women with endometriosis-associated infertility compared to healthy women. The changes in expression of Gal-3 were more dramatic in EECs than ESCs. Moreover, estrogen (E2) and progesterone (P4) induced Gal-3 expression in EECs of healthy groups, and P4 was more significant than E2 and combined E2 and P4 (E2P4). However, in the endometriosis group, P4 failed to induce a similar increase in Gal-3 expression. Our results suggest that aberrant expression of Gal-3 might contribute to infertility in patients with endometriosis due to progesterone resistance.
Berlanda, Nicola; Somigliana, Edgardo; Frattaruolo, Maria Pina; Buggio, Laura; Dridi, Dhouha; Vercellini, Paolo
Deep endometriosis, occurring approximately in 1% of women of reproductive age, represents the most severe form of endometriosis. It causes severe pain in the vast majority of affected women and it can affect the bowel and the urinary tract. Hormonal treatment of deep endometriosis with progestins, such as norethindrone acetate or dienogest, or estroprogestins is effective in relieving pain in more than 90% of women at one year follow up. Progestins and estroprogestins can be safely administered in the long-term, may be not expensive and are usually well tolerated. Therefore, they should represent the first-line treatment of deep endometriosis associated pain in women not seeking natural conception. However, hormonal treatment is ineffective or not tolerated in about 30% of women, the most common side effects being erratic bleeding, weight gain, decreased libido and headache. Surgical excision of deep endometriosis is mandatory in presence of symptomatic bowel stenosis, ureteral stenosis with secondary hydronephrosis, and when hormonal treatments fail. Surgical treatment is similarly effective as compared to hormonal treatment in relieving dismenorhea, dyspareunia and dyschezia at one year follow up in more than 90% of women with deep endometriosis. Surgical removal of the nodules may require resection of the bowel, ureter or bladder, with possible severe complications such as rectovaginal or ureterovaginal fistula and anastomotic leakage. A thorough counsel with the patient is necessary in order to pursue a therapeutic plan centered not on the endometriotic lesions, but on the patient's symptoms, priorities and expectations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Lin, Shih-Chieh; Lee, Hsiu-Chi; Hou, Pei-Chi; Fu, Jhao-Lin; Wu, Meng-Hsing; Tsai, Shaw-Jenq
Endometriosis is a highly prevalent gynaecological disease that severely reduces women's health and quality of life. Ectopic endometriotic lesions have evolved mechanisms to survive in the hypoxic peritoneal microenvironment by regulating the expression of a significant subset of genes. However, the master regulator controlling these genes remains to be characterized. Herein, by using bioinformatics analysis and experimental verification, we identified yes-associated protein 1 (YAP1) as a master regulator of endometriosis. Nuclear localization and transcriptional activity of YAP1 were up-regulated by hypoxia via down-regulation of LATS1, a kinase that inactivates YAP1. Disruption of hypoxia-induced YAP1 signalling by siRNA knockdown or inhibitor treatment abolished critical biological processes involved in endometriosis development such as steroidogenesis, angiogenesis, inflammation, migration, innervation, and cell proliferation. Treatment with a YAP1 inhibitor caused the regression of endometriotic lesions without affecting maternal fertility or the growth rate of offspring in the mouse model of endometriosis. Taken together, we identify hypoxia/LATS1/YAP1 as a novel pathway for the pathogenesis of endometriosis and demonstrate that targeting YAP1 might be an alternative approach to treat endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Izumi, Gentaro; Koga, Kaori; Takamura, Masashi; Makabe, Tomoko; Nagai, Miwako; Urata, Yoko; Harada, Miyuki; Hirata, Tetsuya; Hirota, Yasushi; Fujii, Tomoyuki; Osuga, Yutaka
To characterize peritoneal dendritic cells (DCs) in endometriosis and to clarify their role in its etiology. Experimental. University hospital. Sixty-three women (35 patients with endometriosis and 28 control women) who had undergone laparoscopic surgery. Peritoneal DCs from endometriosis and control samples were analyzed for the expression of cell surface markers. Monocyte-derived dendritic cells (Mo-DCs) were cultured with dead endometrial stromal cells (dESCs) to investigate changes in phagocytic activity and cytokine expression. Cell surface markers and cytokine expression and identification with the use of flow cytometry or reverse-transcription polymerase chain reaction (RT-PCR). Changes in cytokine expression and phagocytic activity of Mo-DCs cultured with dESCs and d-mannan were measured with the use of flow cytometry and RT-PCR. The proportion of mannose receptor (MR)-positive myeloid DC type 1 was higher in endometriosis samples than in control samples. The blocking of MR reduced phagocytosis of dESCs by Mo-DCs. Mo-DCs cultured with dESCs expressed higher levels of interleukin (IL) 1β and IL-6 than control samples. Peritoneal DCs in endometriosis tissue express high levels of MR, which promotes phagocytosis of dead endometrial cells and thereby contributes to the etiology of endometriosis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Vyas, Monika; Wong, Serena; Zhang, Xuchen
Endometriosis of the appendix can be an incidental finding or a cause of appendicitis, intussusception, perforation or retention mucocele. Intestinal metaplasia of appendiceal endometriosis may occur, which can lead to a misdiagnosis of low-grade appendiceal mucinous neoplasm. On a retrospective search of the pathology database from 2001 to 2015, we identified 78 appendiceal endometriosis cases and intestinal metaplasia was present in 10/78 (13%) cases. In most of the cases (90%), the foci of intestinal metaplasia were mainly localized close to the mucosa. Intestinal and endometrial hybrid glands were present in 9/10 (90%) cases. These cases were often associated with marked appendiceal distortion, luminal obliteration and mass formation, causing concern for a mucinous neoplasm clinically and pathologically. Our findings indicate that intestinal metaplasia in appendiceal endometriosis is not an uncommon phenomenon, which can be mistaken for a mucinous neoplasm. Endometriosis should be kept in mind when a diagnosis of appendiceal mucinous neoplasm is made, especially in a young woman with a clinical history of endometriosis.
Nasiri, Nahid; Moini, Ashraf; Eftekhari-Yazdi, Poopak; Karimian, Leila; Salman-Yazdi, Reza; Arabipoor, Arezoo
Objective This study aimed to evaluate the levels of two oxidative stress (OS) markers including lipid peroxide (LPO) and total antioxidant capacity (TAC) in both serum and follicular fluid (FF) of women with endometriosis after puncture. Materials and Methods In this cross-sectional study, a total number of sixty-three women younger than 40 years old with laparoscopy (gold standard for endometriosis diagnosis) indication underwent in vitro fertilization (IVF) program in the Royan Institute, Tehran, Iran from September 2013 to October 2014. About forty-three patients were diagnosed with endometriosis after laparoscopy. Blood and FF from the leading follicle in each stimulated ovary were obtained at the time of egg retrieval; samples were centrifuged and frozen until assessment. At the time of sample assessment, serum and FF samples were evaluated for the levels of LPO and TAC on spectrophotometery. Results We observed that women with endometriosis had significantly higher LPO and lower TAC levels in the serum and FF as compared with the control group (P<0.05). Conclusion It has observed that FF of women with endometriosis, regardless of disease stage, increases the proliferation power of endometrial cells in vitro, we presume that inflammatory reactions-induced OS in ovary may be responsible for proliferation induction ability in FF obtained from women with endometriosis. PMID:28042542
Cordeiro, Fernanda Bertuccez; Cataldi, Thais Regiani; Perkel, Kayla Jane; do Vale Teixeira da Costa, Lívia; Rochetti, Raquel Cellin; Stevanato, Juliana; Eberlin, Marcos Nogueira; Zylbersztejn, Daniel Suslik; Cedenho, Agnaldo Pereira; Turco, Edson Guimarães Lo
The aim of the present study was to analyze the lipid profile of follicular fluid from patients with endometriosis and endometrioma who underwent in vitro fertilization treatment (IVF). The control group (n = 10) was composed of women with tubal factor or minimal male factor infertility who had positive pregnancy outcomes after IVF. The endometriosis group consisted of women with endometriosis diagnosed by videolaparoscopy (n = 10), and from the same patients, the endometriomas fluids were collected, which composed the endometrioma group (n = 10). From the follicular fluid and endometriomas, lipids were extracted by the Bligh and Dyer method, and the samples were analyzed by tandem mass spectrometry. We observed phosphatidylglycerol phosphate, phosphatidylcholine, phosphatidylserine, and phosphatidylnositol bisphosphate in the control group. In the endometriosis group, sphingolipids and phosphatidylcholines were more abundant, while in the endometrioma group, sphingolipids and phosphatidylcholines with different m/z from the endometriosis group were found in high abundance. This analysis demonstrated that there is a differential representation of these lipids according to their respective groups. In addition, the lipids found are involved in important mechanisms related to endometriosis progress in the ovary. Thus, the metabolomic approach for the study of lipids may be helpful in potential biomarker discovery.
Hirsch, Martin; Duffy, James M N; Barker, Claire; Hummelshoj, Lone; Johnson, Neil P; Mol, Ben; Khan, Khalid S; Farquhar, Cindy
Introduction Endometriosis is a common gynaecological disease characterised by pain and subfertility. Randomised controlled trials evaluating treatments for endometriosis have reported many different outcomes and outcome measures. This variation restricts effective data synthesis limiting the usefulness of research to inform clinical practice. To address these methodological concerns, we aim to develop, disseminate and implement a core outcome set for endometriosis engaging with key stakeholders, including healthcare professionals, researchers and women with endometriosis. Methods and analysis An international steering group has been established, including healthcare professionals, researchers and patient representatives. Potential outcomes identified from a systematic review of the literature will be entered into a modified Delphi method. Key stakeholders will be invited to participate including healthcare professionals, researchers and women with endometriosis. Participants will be invited to score individual outcomes on a nine-point Likert scale anchored between 1 (not important) and 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group converge towards consensus, ‘core’, outcomes. High-quality outcome measures will be associated with core outcomes. Ethics and dissemination The implementation of a core outcome set for endometriosis within future clinical trials, systematic reviews and clinical guidelines will enhance the availability of comparable data to facilitate evidence-based patient care. This study was prospectively registered with Core Outcome Measures in Effectiveness Trials Initiative; number: 691. PMID:28003300
Somigliana, Edgardo; Garcia-Velasco, Juan Antonio
Deep endometriosis is a demanding condition that is associated with infertility. However, evidence supporting a direct link between deep endometriosis and infertility is weak. In fact, infertility in affected patients is more likely to be explained by the strong association between deep endometriosis and adhesions, superficial endometriotic implants, ovarian endometriomas, and adenomyosis. The purported beneficial effects of surgery on infertility are mainly based on the 40%-42% pregnancy rate (PR) after surgery observed in published case series. However, this level of evidence is questionable and overestimates the benefits of the intervention. Even if comparative studies are lacking, IVF may be a valid alternative. The procedure may be less effective in affected women compared with other indications and it is not without additional deep endometriosis-related risks. Some case reports suggest that lesions might progress during IVF causing ureteral or intestinal complications or can decidualize during pregnancy causing intestinal perforation, pneumothorax, and pelvic vessels rupture. Finally, in the decision-making process, physicians should also consider that women with a history of deep endometriosis may face an increased risk of pregnancy complications. In conclusion, clear recommendation for the management of infertile women with deep endometriosis cannot be extrapolated from the literature. The therapeutic decision should be based on a comprehensive evaluation that includes clinical history, instrumental findings, pain symptoms, risks of pregnancy complications, and the woman's wishes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Shigetomi, Hiroshi; Higashiura, Yumi; Kajihara, Hirotaka; Kobayashi, Hiroshi
The roles of molecular alteration such as genomic instability and cell survival are debated aspects of the pathogenesis of endometriosis. To review the contemporary literature on potential factors and their signaling pathways that support prolonged survival of endometriotic cells. This article reviews the English-language literature for molecular, pathogenetic, and pathophysiological studies on endometriosis. This review is focused on the association of hepatocyte nuclear factor (HNF)-1β with endometriosis. The iron-induced oxidative stress plays a fundamental role for the pathogenesis of endometriosis. Oxidative stress, secondary to influx of iron during retrograde menstruation, modifies lipids and proteins, leading to cell and DNA damage. Recent studies demonstrated HNF-1β overexpression in endometriotic foci. HNF-1β increases the survival of endometriotic cells under iron-induced oxidative stress conditions possibly through the activation of forkhead box (FOX) transcription factors and/or endometriosis-specific expression of microRNAs. Endometriotic cells expressing HNF-1β also display cell cycle checkpoint pathways required to survive DNA damaging events. HNF-1β in endometriosis might be a factor that controls the cell cycle and DNA damage checkpoints.
Zhao, Yuechao; Gong, Ping; Chen, Yiru; Nwachukwu, Jerome C.; Srinivasan, Sathish; Ko, CheMyong; Bagchi, Milan K.; Taylor, Robert N.; Korach, Kenneth S.; Nettles, Kendall W.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.
Estrogenic and inflammatory components play key roles in a broad range of diseases including endometriosis, a common estrogen-dependent gynecological disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, causing pelvic pain and reduced fertility. Current medical therapies focus primarily on reducing systemic levels of estrogens, but these are of limited effectiveness and have considerable side effects. We developed estrogen receptor (ER) ligands, chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS), which showed strong ER-dependent anti-inflammatory activity in a preclinical model of endometriosis that recapitulates the estrogen dependence and inflammatory responses of the disease in immunocompetent mice and in primary human endometriotic stromal cells in culture. Estrogen-dependent phenomena, including cell proliferation, cyst formation, vascularization, and lesion growth, were all arrested by CLI or OBHS, which prevented lesion expansion and also elicited regression of established lesions, suppressed inflammation, angiogenesis, and neurogenesis in the lesions, and interrupted crosstalk between lesion cells and infiltrating macrophages. Studies in ERα or ERβ knockout mice indicated that ERα is the major mediator of OBHS effectiveness and ERβ is dominant in CLI actions, implying involvement of both ERs in endometriosis. Neither ligand altered estrous cycling or fertility at doses that were effective for suppression of endometriosis. Hence, CLI and OBHS are able to restrain endometriosis by dual suppression of the estrogen-inflammatory axis. Our findings suggest that these compounds have the desired characteristics of preventive and therapeutic agents for clinical endometriosis and possibly other estrogen-driven and inflammation-promoted disorders. PMID:25609169
Guo, Sun-Wei; Ding, Ding; Liu, Xishi
In light of recent findings showing that platelets play important roles in the development of endometriosis in general and in fibrogenesis in particular, this study investigated the efficacy of Ozagrel, a TXA2 synthase inhibitor, in a murine model of endometriosis. In addition, another mouse experiment was conducted to evaluate the effect of timing of platelet depletion and of sequential depletion of platelets and macrophages on the development of endometriosis. It was found that both the Ozagrel treatment and different platelet depletion schemes resulted in significant reduction in lesion growth (all P-values <0.01) along with improved hyperalgesia in mice with induced endometriosis. They also significantly reduced the expression of markers of proliferation, angiogenesis, inflammation and fibrosis as well as decreased macrophage infiltration in endometriotic lesions (all P-values <0.05). Compared with untreated mice, pre-emptive depletion of platelets as well as platelet depletion after induction resulted in significant reduction in lesion weight (both P-values <0.001), while sequential depletion of platelets and macrophages yielded similar reduction. These results, in conjunction with other roles that platelets play in the development of endometriosis, strongly argue for the potential of anti-platelet therapy in treating endometriosis. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Near, Aimee M.; Wu, Anna H.; Templeman, Claire; Van Den Berg, David J.; Doherty, Jennifer A.; Rossing, Mary Anne; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Fridley, Brooke L.; Chenevix-Trench, Georgia; Webb, Penelope M.; Kjær, Susanne Krüger; Hogdall, Estrid; Gayther, Simon A.; Ramus, Susan J.; Menon, Usha; Gentry-Maharaj, Aleksandra; Schildkraut, Joellen M.; Moorman, Patricia G.; Palmieri, Rachel T.; Ness, Roberta B.; Moysich, Kirsten; Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.; Pike, Malcolm C.; Berchuck, Andrew; Pearce, Celeste Leigh
Objective To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism (SNP) and the PROGINS allele. Design Control subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies. Setting An international ovarian cancer consortium including studies from the Australia, Europe and the United States, Patients 5,812 White female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies. Interventions None. Main Outcome Measures Genotypes for the +331C/T SNP and PROGINS allele and a history of endometriosis. Results The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (OR=0.65; 95% CI: 0.43–0.98, p=0.042), whereas there was no association between the PROGINS allele and endometriosis (OR=0.94, 95% CI 0.76, 1.16). Conclusions Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced PR-A to PR-B ratio and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease. PMID:20719308
Fritzer, N; Hudelist, G
Dyspareunia, a common symptom of endometriosis and may severely affect quality of sex life in affected patients. The objective of the present work was to review the effect of surgical resection of endometriosis on pain intensity and quality of sex life. MEDLINE and EMBASE databases were searched for papers investigating the outcome after surgical endometriosis resection on dyspareunia and quality of sex life measured via VAS/NAS respectively via standardized measuring instruments. However, data did not permit a meaningful meta-analysis according to current standards. However, out of 69 papers, four studies fulfilled the predefined inclusion criteria involving 321 patients with endometriosis and dyspareunia preoperatively. All included studies showed a significant postoperative reduction of dyspareunia after a follow-up period of 10 up to 60 months. Sex life as well as predominantly evaluated parameters like quality of life and mental health improved significantly. We therefore conclude that surgical excision of endometriosis is a feasible and good treatment option for pain relief and improvement of quality of sex life in symptomatic women with endometriosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Mansour, Gihan; Sharma, Rakesh K; Agarwal, Ashok; Falcone, Tommaso
To examine the effect of peritoneal fluid (PF) of patients with endometriosis on the cytoskeleton of metaphase II oocytes and correlate the results with the stage of endometriosis and the duration of infertility. Prospective-controlled study. Center for reproductive medicine at a tertiary-care hospital. Women with endometriosis (n=23) and tubal ligation/reversal (n=15). Peritoneal fluid obtained from 38 women (23 with endometriosis and 15 tubal ligation/reversal) after laparoscopy. Four hundred metaphase II oocytes were used: 165 frozen metaphase II oocytes were incubated in the PF of patients with endometriosis, 135 oocytes incubated in the PF of nonendometriosis patients (control subjects) and 100 oocytes incubated in human tubal fluid (HTF) media. Spindle abnormalities (microtubule and chromosomal) were evaluated by confocal imaging. In the endometriosis group, the cytoskeleton had a higher frequency of abnormal meiotic spindle and chromosomal misalignment (score ≥3), indicating severe damage compared with the control groups. The proportions of abnormalities in microtubule and chromosome alterations in endometriosis (67.9% and 63.6%, respectively) were significantly higher than for oocytes incubated with PF of the nonendometriosis group (24.4% and 14.8%) as well as the HTF group (13% and 13%). Oocyte cytoskeleton damage positively correlated with the duration of infertility and the stage of endometriosis. Alteration of oocyte cytoskeleton might be one of the causes of poor oocyte quality in patients with endometriosis. Copyright © 2010. Published by Elsevier Inc.
Barbara, Giussy; Facchin, Federica; Meschia, Michele; Berlanda, Nicola; Frattaruolo, Maria P; VercellinI, Paolo
Endometriosis is associated with an increased risk of dyspareunia, therefore this chronic gynecologic disease should be considered as a major cause of sexual dysfunctions. The aims of this study were to review the literature on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning, and to provide suggestions for future treatment strategies. We followed the PRISMA guidelines to conduct this systematic review, which involved an electronic database search of studies on the association between endometriosis and sexuality published between 2000 and 2016. As a result of the screening process, 22 studies were included in this systematic review. The 22 studies included were divided into two categories: (a) surgical intervention studies (n = 17), examining postoperative sexual outcomes of surgery for endometriosis; (b) pharmacological intervention studies (n = 5), evaluating the effects of pharmacological endometriosis treatments on sexual functioning. The studies considered showed that overall surgical and pharmacological interventions for endometriosis can lead to medium-/long-term improvement, but not necessarily to a definitive resolution of female sexual dysfunctions due to endometriosis. Sexual functioning is a multidimensional phenomenon and the ideal treatment for endometriosis-related sexual dysfunctions should be conducted by a multidisciplinary team that involves not only gynecologists, but also sexologists and psychologists/psychotherapists. Improving global sexual functioning, and not just reducing pain at intercourse, should be considered as a major clinical goal of endometriosis treatment. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.
Abrão, Mauricio Simões; Petraglia, Felice; Falcone, Tommaso; Keckstein, Joerg; Osuga, Yutaka; Chapron, Charles
Deep endometriosis invading the bowel constitutes a major challenge for the gynecologist. In addition to the greater impact on pain, the high incidence of surgical morbidity involved with bowel endometriosis poses a therapeutic dilemma for the surgeon. Intestinal involvement by deep endometriotic nodules has been estimated to occur in 8-12% of women with endometriosis. Individual and clinical factors, pre-operative morphologic characteristics from imaging, surgical considerations and impact on quality of life are critical variables that should be considered in determining the best therapeutic strategy for a patient with deep endometriosis involving the sigmoid and/or the rectum. Pre-operative planning is fundamental for defining the optimal therapeutic strategy; patient counseling of treatment options, and when surgery is indicated, involvement of a multidisciplinary surgical team is required. The PubMed and Cochrane database were searched for all original and review articles published in English, French and Italian, until June 2014. Search terms included 'deep endometriosis', 'surgical and clinical approach', 'bowel disease', 'quality of life', 'management of deep endometriosis'. Special attention was paid to articles comparing features of discoid and segmental resection. The rationale for the best therapeutic options for patients with deep endometriosis has been shown and an evidence-based treatment algorithm for determining when and which surgical intervention may be required is proposed. In deciding the best treatment option for patients with deep endometriosis involving the sigmoid and rectum, it is important to understand how the different clinical factors and pre-operative morphologic imaging affect the algorithm. Surgery is not indicated in all patients with deep endometriosis, but, when surgery is chosen, a complete resection by the most appropriate surgical team is required in order to achieve the best patient outcome. In women with deep endometriosis
Facchin, F; Barbara, G; Dridi, D; Alberico, D; Buggio, L; Somigliana, E; Saita, E; Vercellini, P
What factors affect the mental health of women with endometriosis? Not only pelvic pain, but also individual characteristics (i.e. self-esteem, body esteem and emotional self-efficacy), time from diagnosis and intimate relationship status influence the psychological health of endometriosis patients. The negative impact of endometriosis on mental health has been widely demonstrated by the research literature, along with the fact that presence and severity of pelvic pain are associated with anxiety and depression. However, endometriosis is a complex multidimensional disease and factors other than pelvic pain, including individual differences, may contribute to explain the variability in women's mental health. This cross-sectional study was conducted between 2015 and 2017 at an Italian academic department of obstetrics and gynaecology. A total of 210 consecutive endometriosis patients (age: 36.7 ± 7.0 years) were included. Demographic and endometriosis-related information was collected. Individual differences were assessed using validated measures evaluating self-esteem, body esteem and emotional self-efficacy. The Hospital Anxiety and Depression Scale (HADS) and the Ruminative Response Scale (RRS) were used to evaluate mental health. Based on the extant literature, we identified three categories of putative predictors (demographic variables, endometriosis-related factors and individual differences i.e. 'self'), whose psychological impact was examined using a hierarchical multiple regression approach. Being in a stable relationship (coded 1 ['yes'] or 0 ['no']) was associated with decreased rumination (RRS: β = -0.187; P = 0.002). A shorter time from diagnosis was associated with greater anxiety (HADS-A: β = -0.177; P = 0.015). Pelvic pain severity and 'self' were associated with all mental health variables (Ps < 0.01). Greater self-esteem, body esteem, and emotional self-efficacy were correlated with better psychological outcomes (Ps < 0.01). Sexual functioning
Rizk, B.; Turki, R.; Lotfy, H.; Ranganathan, S.; Zahed, H.; Freeman, A.R.; Shilbayeh, Z.; Sassy, M.; Shalaby, M.; Malik, R.
Objective: Surgery remains the mainstay in the diagnosis and management of endometriosis. The number of surgeries performed for endometriosis worldwide is ever increasing, however do we have evidence for improvement of infertility after the surgery and do we exaggerate the magnitude of effect of surgery when we counsel our patients? The management of patients who failed the surgery could be by repeat surgery or assisted reproduction. What evidence do we have for patients who fail assisted reproduction and what is their best chance for achieving pregnancy? Material and methods: In this study we reviewed the evidence-based practice pertaining to the outcome of surgery assisted infertility associated with endometriosis. Manuscripts published in PubMed and Science Direct as well as the bibliography cited in these articles were reviewed. Patients with peritoneal endometriosis with mild and severe disease were addressed separately. Patients who failed the primary surgery and managed by repeat or assisted reproduction technology were also evaluated. Patients who failed assisted reproduction and managed by surgery were also studied to determine of the best course of action. Results: In patients with minimal and mild pelvic endometriosis, excision or ablation of the peritoneal endometriosis increases the pregnancy rate. In women with severe endometriosis, controlled trials suggested an improvement of pregnancy rate. In women with ovarian endometrioma 4 cm or larger ovarian cystectomy increases the pregnancy rate, decreases the recurrence rate, but is associated with decrease in ovarian reserve. In patients who have failed the primary surgery, assisted reproduction appears to be significantly more effective than repeat surgery. In patients who failed assisted reproduction, the management remains to be extremely controversial. Surgery in expert hands might result in significant improvement in pregnancy rate. Conclusion: In women with minimal and mild endometriosis, surgical
Mumford, Sunni L; Weck, Jennifer; Kannan, Kurunthachalam; Buck Louis, Germaine M
Phytoestrogens have been associated with subtle hormonal changes, but their effects on endometriosis are largely unknown. We assessed the association between urinary concentrations of phytoestrogens and incident endometriosis. We included an operative sample of 495 premenopausal women aged 18-44 y undergoing laparoscopies and laparotomies at 14 clinical sites between 2007 and 2009 and a general population sample of 131 women from the same geographic area who were matched on age and menstruation status. Endometriosis in the surgical sample was assessed by surgical visualization (clinical gold standard), whereas disease in the general population sample was assessed with the use of a pelvic MRI. Urine concentrations of genistein, daidzen, O-desmethylangolensin, equol, enterodiol, and enterolactone were measured at baseline. Poisson regression with robust error variance was used to estimate the risk of an endometriosis diagnosis for each sample after adjusting for age and body mass index (in kg/m(2)). Separate models were run for each phytoestrogen. Overall geometric mean urine concentrations of phytoestrogens wer