Consensus on Current Management of Endometriosis
Consensus on Current Management of Endometriosis
Study question: Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis?
Summary answer: It was possible to produce an international consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis.
What is known already: Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence.
Study design, size, duration: A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken.
Participants/materials, setting, methods: A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.
Main results and the role of chance: A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis.
Limitations, reasons for caution: This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements.
Wider implications of the findings: This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.
Study funding/competing interest(s): The World Endometriosis Society commissioned and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Full disclosures of all participants are presented herein.
Endometriosis is an inflammatory condition characterized by lesions of endometrial-like tissue outside of the uterus and is associated with pelvic pain and infertility (Giudice, 2010). It affects an estimated 176 million women of reproductive age worldwide (Adamson et al., 2010). It is widely assumed that lesions arise through retrograde endometrial tissue loss during menstruation, coelomic metaplasia and lymphatic spread in immunologically and genetically susceptible individuals. While its underlying cause is uncertain, it is likely to be multifactorial including genetic factors with possible epigenetic influences, perhaps promoted through environmental exposures. Endometriosis has elements of a pain syndrome with central neurological sensitization (and some hallmarks of a neurological disorder) (Stratton and Berkley, 2011), and is a proliferative, estrogen-dependent disorder (with growing evidence of progesterone resistance) (Pabona et al., 2012). There is overlap with other conditions characterized by pelvic–abdominal pain and infertility. Some symptomatic women with pelvic pain, who do not have diagnosed endometriosis or who are prior to diagnosis, may benefit from similar treatments.
Women with endometriosis typically have a range of pelvic–abdominal pain symptoms, including dysmenorrhoea, dyspareunia, heavy menstrual bleeding, non-menstrual pelvic pain, pain at ovulation, dyschezia and dysuria, as well as chronic fatigue (Kennedy et al., 2005; Nnoaham et al., 2011). Endometriosis lesions, particularly deep infiltrating lesions, are often innervated. The presence of endometriotic lesions, followed by denervation and re-innervation, may result in accompanying changes in the central nervous system (central sensitization), creating a chronic pain syndrome (Stratton and Berkley, 2011). Endometriosis is also associated with infertility, with a strong association between severity of disease and impact on fertility, probably due to impaired tubo-ovarian function, the presence of ovarian endometrioma, subclinical pelvic inflammation, possibly reduced oocyte quality and reduced endometrial receptivity to implantation (Lessey, 2011). Both endometriosis and adenomyosis (lesions occurring in the uterine intramural muscular layer) reduce the chance of success of assisted reproductive treatment (Barnhart et al., 2002; Maubon et al., 2010).
Symptoms of endometriosis contribute substantially to the burden of disease and add substantial cost to society through reduced economic and personal productivity (Simoens et al., 2007; Nnoaham et al., 2011; Simoens et al., 2012).
While symptoms and examination findings may suggest endometriosis (Nnoaham et al., 2011, 2012), the gold standard for making the diagnosis remains the laparoscopic visualization of lesions preferably with histologic confirmation (Kennedy et al., 2005). In the absence of histological sampling, the false-positive rate with laparoscopic visualization alone may approach 50% especially in women with minimal or mild endometriosis (Wykes et al., 2004). Laparoscopy also enables endometriosis to be staged by the revised American Society for Reproductive Medicine (r-ASRM, 1997) scoring system, the 'scoring' system most commonly in current use, objectively defining the disease as minimal (stage I), mild (stage II), moderate (stage III) or severe (stage IV) based on its laparoscopic appearance. It is recognized that the stage/extent of disease may not correlate with symptoms experienced, reproductive outcome or recurrence risk (Adamson, 2011). Much research has recently focused on serum biomarkers, including cancer antigen-125 (CA125), leptin, monocyte chemotactic protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF), although these have not been useful diagnostic predictors owing to poor sensitivity or specificity, small sample size or inadequate validation of their accuracy (May et al., 2010). Recent interest has focused on endometrial immunohistochemistry for nerve fibre density (Al-Jefout et al., 2009; Bokor et al., 2009) and on urinary markers (cytokeratin 19, urinary peptide 1.8 kDa) (May et al., 2010). These less invasive diagnostic tests require future formal and robust evaluation of their accuracy.
Several guidelines have been developed by a number of national and international bodies: the European Society for Human Reproduction and Embryology (http://guidelines.endometriosis.org/), the American Society of Reproductive Medicine: (http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Educational_Bulletins/endometriosis_and_infertility(1).pdf and http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Educational_Bulletins/Treatment_of_pelvic_pain(1).pdf), the Royal College of Obstetricians and Gynaecologists (http://www.rcog.org.uk/files/rcog-corp/GTG2410022011.pdf), the Society of Obstetrics and Gynecology of Canada (http://www.sogc.org/guidelines/documents/gui244CPG1007E.pdf) and the Cochrane Database of Systematic Reviews (http://thecochranelibrary.com), yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence.
The World Endometriosis Society (WES) has therefore developed a process to bring together representatives of national and international, medical and non-medical societies with an interest in endometriosis, aiming to derive a consensus on the management of endometriosis from a global perspective, in which the views of women with endometriosis were represented.
Abstract and Introduction
Abstract
Study question: Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis?
Summary answer: It was possible to produce an international consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis.
What is known already: Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence.
Study design, size, duration: A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken.
Participants/materials, setting, methods: A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.
Main results and the role of chance: A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis.
Limitations, reasons for caution: This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements.
Wider implications of the findings: This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.
Study funding/competing interest(s): The World Endometriosis Society commissioned and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Full disclosures of all participants are presented herein.
Introduction
Endometriosis is an inflammatory condition characterized by lesions of endometrial-like tissue outside of the uterus and is associated with pelvic pain and infertility (Giudice, 2010). It affects an estimated 176 million women of reproductive age worldwide (Adamson et al., 2010). It is widely assumed that lesions arise through retrograde endometrial tissue loss during menstruation, coelomic metaplasia and lymphatic spread in immunologically and genetically susceptible individuals. While its underlying cause is uncertain, it is likely to be multifactorial including genetic factors with possible epigenetic influences, perhaps promoted through environmental exposures. Endometriosis has elements of a pain syndrome with central neurological sensitization (and some hallmarks of a neurological disorder) (Stratton and Berkley, 2011), and is a proliferative, estrogen-dependent disorder (with growing evidence of progesterone resistance) (Pabona et al., 2012). There is overlap with other conditions characterized by pelvic–abdominal pain and infertility. Some symptomatic women with pelvic pain, who do not have diagnosed endometriosis or who are prior to diagnosis, may benefit from similar treatments.
Women with endometriosis typically have a range of pelvic–abdominal pain symptoms, including dysmenorrhoea, dyspareunia, heavy menstrual bleeding, non-menstrual pelvic pain, pain at ovulation, dyschezia and dysuria, as well as chronic fatigue (Kennedy et al., 2005; Nnoaham et al., 2011). Endometriosis lesions, particularly deep infiltrating lesions, are often innervated. The presence of endometriotic lesions, followed by denervation and re-innervation, may result in accompanying changes in the central nervous system (central sensitization), creating a chronic pain syndrome (Stratton and Berkley, 2011). Endometriosis is also associated with infertility, with a strong association between severity of disease and impact on fertility, probably due to impaired tubo-ovarian function, the presence of ovarian endometrioma, subclinical pelvic inflammation, possibly reduced oocyte quality and reduced endometrial receptivity to implantation (Lessey, 2011). Both endometriosis and adenomyosis (lesions occurring in the uterine intramural muscular layer) reduce the chance of success of assisted reproductive treatment (Barnhart et al., 2002; Maubon et al., 2010).
Symptoms of endometriosis contribute substantially to the burden of disease and add substantial cost to society through reduced economic and personal productivity (Simoens et al., 2007; Nnoaham et al., 2011; Simoens et al., 2012).
While symptoms and examination findings may suggest endometriosis (Nnoaham et al., 2011, 2012), the gold standard for making the diagnosis remains the laparoscopic visualization of lesions preferably with histologic confirmation (Kennedy et al., 2005). In the absence of histological sampling, the false-positive rate with laparoscopic visualization alone may approach 50% especially in women with minimal or mild endometriosis (Wykes et al., 2004). Laparoscopy also enables endometriosis to be staged by the revised American Society for Reproductive Medicine (r-ASRM, 1997) scoring system, the 'scoring' system most commonly in current use, objectively defining the disease as minimal (stage I), mild (stage II), moderate (stage III) or severe (stage IV) based on its laparoscopic appearance. It is recognized that the stage/extent of disease may not correlate with symptoms experienced, reproductive outcome or recurrence risk (Adamson, 2011). Much research has recently focused on serum biomarkers, including cancer antigen-125 (CA125), leptin, monocyte chemotactic protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF), although these have not been useful diagnostic predictors owing to poor sensitivity or specificity, small sample size or inadequate validation of their accuracy (May et al., 2010). Recent interest has focused on endometrial immunohistochemistry for nerve fibre density (Al-Jefout et al., 2009; Bokor et al., 2009) and on urinary markers (cytokeratin 19, urinary peptide 1.8 kDa) (May et al., 2010). These less invasive diagnostic tests require future formal and robust evaluation of their accuracy.
Several guidelines have been developed by a number of national and international bodies: the European Society for Human Reproduction and Embryology (http://guidelines.endometriosis.org/), the American Society of Reproductive Medicine: (http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Educational_Bulletins/endometriosis_and_infertility(1).pdf and http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Educational_Bulletins/Treatment_of_pelvic_pain(1).pdf), the Royal College of Obstetricians and Gynaecologists (http://www.rcog.org.uk/files/rcog-corp/GTG2410022011.pdf), the Society of Obstetrics and Gynecology of Canada (http://www.sogc.org/guidelines/documents/gui244CPG1007E.pdf) and the Cochrane Database of Systematic Reviews (http://thecochranelibrary.com), yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence.
The World Endometriosis Society (WES) has therefore developed a process to bring together representatives of national and international, medical and non-medical societies with an interest in endometriosis, aiming to derive a consensus on the management of endometriosis from a global perspective, in which the views of women with endometriosis were represented.
Source...