Nicholas Leyland

The Management of Uterine Leiomyomas

OBJECTIVES The aim of this guideline is to provide clinicians with an understanding of the pathophysiology, prevalence, and clinical significance of myomata and the best evidence available on treatment modalities. OPTIONS The areas of clinical practice considered in formulating this guideline were assessment, medical treatments, conservative treatments of myolysis, selective uterine artery occlusion, and surgical alternatives including myomectomy and hysterectomy. The risk-to-benefit ratio must be examined individually by the woman and her health care provider. OUTCOMES Implementation of this guideline should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options, and reviewed the risks and anticipated benefits. EVIDENCE Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2013, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to January 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. BENEFITS, HARMS, AND COSTS The majority of fibroids are asymptomatic and require no intervention or further investigations. For symptomatic fibroids such as those causing menstrual abnormalities (e.g. heavy, irregular, and prolonged uterine bleeding), iron defficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy is a definitive solution. However, it is not the preferred solution for women who wish to preserve fertility and/or their uterus. The selected treatment should be directed towards an improvement in symptomatology and quality of life. The cost of the therapy to the health care system and to women with fibroids must be interpreted in the context of the cost of untreated disease conditions and the cost of ongoing or repeat investigative or treatment modalities. VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Caadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. Uterine fibroids are common, appearing in 70% of women by age 50; the 20% to 50% that are symptomatic have considerable social and economic impact in Canada. (II-3) 2. The presence of uterine fibroids can lead to a variety of clinical challenges. (III) 3. Concern about possible complications related to fibroids in pregnancy is not an indication for myomectomy except in women who have had a previous pregnancy with complications related to these fibroids. (III) 4. Women who have fibroids detected in pregnancy may require additional maternal and fetal surveillance. (II-2) 5. Effective medical treatments for women with abnormal uterine bleeding associated with uterine fibroids include the levonorgestrel intrauterine system, (I) gonadotropin-releasing hormone analogues, (I) selective progesterone receptor modulators, (I) oral contraceptives, (II-2) progestins, (II-2) and danazol. (II-2) 6. Effective medical treatments for women with bulk symptoms associated with fibroids include selective progesterone receptor modulators and gonadotropin-releasing hormone analogues. (I) 7. Hysterectomy is the most effective treatment for symptomatic uterine fibroids. (III) 8. Myomectomy is an option for women who wish to preserve their uterus or enhance fertility, but carries the potential for further intervention. (II-2) 9. Of the conservative interventional treatments currently available, uterine artery embolization has the longest track record and has been shown to be effective in properly selected patients. (II-3) 10. Newer focused energy delivery methods are promising but lack long-term data. (III) Recommendations 1. Women with asymptomatic fibroids should be reassured that there is no evidence to substantiate major concern about malignancy and that hysterectomy is not indicated. (III-D) 2. Treatment of women with uterine leiomyomas must be individualized based on symptomatology, size and location of fibroids, age, need and desire of the patient to preserve fertility or the uterus, the availability of therapy, and the experience of the therapist. (III-B) 3. In women who do not wish to preserve fertility and/or their uterus and who have been counselled regarding the alternatives and risks, hysterectomy by the least invasive approach possible may be offered as the definitive treatment for symptomatic uterine fibroids and is associated with a high level of satisfaction. (II-2A) 4. Hysteroscopic myomectomy should be considered first-line conservative surgical therapy for the management of symptomatic intracavitary fibroids. (II-3A) 5. Surgical planning for myomectomy should be based on mapping the location, size, and number of fibroids with the help of appropriate imaging. (III-A) 6. When morcellation is necessary to remove the specimen, the patient should be informed about possible risks and complications, including the fact that in rare cases fibroid(s) may contain unexpected malignancy and that laparoscopic power morcellation may spread the cancer, potentially worsening their prognosis. (III-B) 7. Anemia should be corrected prior to proceeding with elective surgery. (II-2A) Selective progesterone receptor modulators and gonadotropin-releasing hormone analogues are effective at correcting anemia and should be considered preoperatively in anemic patients. (I-A) 8. Use of vasopressin, bupivacaine and epinephrine, misoprostol, peri-cervical tourniquet, or gelatin-thrombin matrix reduce blood loss at myomectomy and should be considered. (I-A) 9. Uterine artery occlusion by embolization or surgical methods may be offered to selected women with symptomatic uterine fibroids who wish to preserve their uterus. Women choosing uterine artery occlusion for the treatment of fibroids should be counselled regarding possible risks, including the likelihood that fecundity and pregnancy may be impacted. (II-3A) 10. In women who present with acute uterine bleeding associated with uterine fibroids, conservative management with estrogens, selective progesterone receptor modulators, antifibrinolytics, Foley catheter tamponade, and/or operative hysteroscopic intervention may be considered, but hysterectomy may become necessary in some cases. In centres where available, intervention by uterine artery embolization may be considered. (III-B).

Endometriosis: Diagnosis and Management

OBJECTIVE To improve the understanding of endometriosis and to provide evidence-based guidelines for the diagnosis and management of endometriosis. OUTCOMES OUTCOMES evaluated include the impact of the medical and surgical management of endometriosis on womens experience of morbidity and infertility. METHODS Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of both location in Canada and type of practice, as well as subspecialty expertise along with general gynaecology background. The committee reviewed all available evidence in the English and French medical literature and available data from a survey of Canadian women. Recommendations were established as consensus statements. The final document was reviewed and approved by the Executive and Council of the SOGC. RESULTS This document provides a summary of up-to-date evidence regarding diagnosis, investigations, and medical and surgical management of endometriosis. The resulting recommendations may be adapted by individual health care workers when serving women with this condition. CONCLUSIONS Endometriosis is a common and sometimes debilitating condition for women of reproductive age. A multidisciplinary approach involving a combination of lifestyle modifications, medications, and allied health services should be used to limit the impact of this condition on activities of daily living and fertility. In some circumstances surgery is required to confirm the diagnosis and provide therapy to achieve the desired goal of pain relief or improved fecundity. Women who find an acceptable management strategy for this condition may have an improved quality of life or attain their goal of successful pregnancy. EVIDENCE Medline and Cochrane databases were searched for articles in English and French on subjects related to endometriosis, pelvic pain, and infertility from January 1999 to October 2009 in order to prepare a Canadian consensus guideline on the management of endometriosis. VALUES The quality of evidence was rated with use of the criteria described by the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described by the Task Force. See Table 1. BENEFITS, HARMS, AND COSTS Implementation of the guideline recommendations will improve the care of women with pain and infertility associated with endometriosis.

Substance Use in Pregnancy

OBJECTIVE To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. OPTIONS This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy. OUTCOMES Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. EVIDENCE Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). BENEFITS, HARMS, AND COSTS This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care leads to reduced health care costs and decreased maternal and neonatal morbidity and mortality. RECOMMENDATIONS 1. All pregnant women and women of childbearing age should be screened periodically for alcohol, tobacco, and prescription and illicit drug use. (III-A) 2. When testing for substance use is clinically indicated, urine drug screening is the preferred method. (II-2A) Informed consent should be obtained from the woman before maternal drug toxicology testing is ordered. (III-B) 3. Policies and legal requirements with respect to drug testing of newborns may vary by jurisdiction, and caregivers should be familiar with the regulations in their region. (III-A) 4. Health care providers should employ a flexible approach to the care of women who have substance use problems, and they should encourage the use of all available community resources. (II-2B) 5. Women should be counselled about the risks of periconception, antepartum, and postpartum drug use. (III-B) 6. Smoking cessation counselling should be considered as a first-line intervention for pregnant smokers. (I-A) Nicotine replacement therapy and/or pharmacotherapy can be considered if counselling is not successful. (I-A) 7. Methadone maintenance treatment should be standard of care for opioid-dependent women during pregnancy. (II-IA) Other slow-release opioid preparations may be considered if methadone is not available. (II-2B) 8. Opioid detoxification should be reserved for selected women because of the high risk of relapse to opioids. (II-2B) 9. Opiate-dependent women should be informed that neonates exposed to heroin, prescription opioids, methadone, or buprenorphine during pregnancy are monitored closely for symptoms and signs of neonatal withdrawal (neonatal abstinence syndrome). (II-2B) Hospitals providing obstetric care should develop a protocol for assessment and management of neonates exposed to opiates during pregnancy. (III-B) 10. Antenatal planning for intrapartum and postpartum analgesia may be offered for all women in consultation with appropriate health care providers. (III-B) 11. The risks and benefits of breastfeeding should be weighed on an individual basis because methadone maintenance therapy is not a contraindication to breastfeeding. (II-3B).

Consensus Guidelines for the Management of Chronic Pelvic Pain

OBJECTIVE To improve the understanding of chronic pelvic pain (CPP) and to provide evidence-based guidelines of value to primary care health professionals, general obstetricians and gynaecologists, and those who specialize in chronic pain. BURDEN OF SUFFERING: CPP is a common, debilitating condition affecting women. It accounts for substantial personal suffering and health care expenditure for interventions, including multiple consultations and medical and surgical therapies. Because the underlying pathophysiology of this complex condition is poorly understood, these treatments have met with variable success rates. OUTCOMES Effectiveness of diagnostic and therapeutic options, including assessment of myofascial dysfunction, multidisciplinary care, a rehabilitation model that emphasizes achieving higher function with some pain rather than a cure, and appropriate use of opiates for the chronic pain state. EVIDENCE Medline and the Cochrane Database from 1982 to 2004 were searched for articles in English on subjects related to CPP, including acute care management, myofascial dysfunction, and medical and surgical therapeutic options. The committee reviewed the literature and available data from a needs assessment of subjects with CPP, using a consensus approach to develop recommendations. VALUES The quality of the evidence was rated using the criteria described in the Report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice were ranked according to the method described in that report (Table 1). RECOMMENDATIONS The recommendations are directed to the following areas: (a) an understanding of the needs of women with CPP; (b) general clinical assessment; (c) practical assessment of pain levels; (d) myofascial pain; (e) medications and surgical procedures; (f) principles of opiate management; (g) increased use of magnetic resonance imaging (MRI); (h) documentation of the surgically observed extent of disease; (i) alternative therapies; (j) access to multidisciplinary care models that have components of physical therapy (such as exercise and posture) and psychology (such as cognitive-behavioural therapy), along with other medical isciplines, such as gynaecology and anesthesia; (k) increased attention to CPP in the training of health care professionals; and (l) increased attention to CPP in formal, high-calibre research. The committee recommends that provincial ministries of health pursue the creation of multidisciplinary teams to manage the condition. CHAPTER 7: MYOFASCIAL DYSFUNCTION: 1. Health care providers should become more aware of myofascial dysfunction as a cause of chronic pelvic pain (CPP) and the available treatment options (IB). 2. Patients should participate in the management of CPP due to myofascial dysfunction by actively using a home stretching and exercise program (ll-2B). CHAPTER 8: MEDICAL THERAPY--EVIDENCE ON EFFECTIVENESS: 1. Opioid therapy can be considered for pain control under adequate supervision (II-3B). 2. Hormonal treatment of chronic pelvic pain of gynaecologic origin, including oral contraceptives, progestins, danazol, and gonadotropin-releasing hormone agonists, has been studied extensively and should be considered as the first line for many women, especially those with endometriosis (I and II-1A). 3. Adjuvant medications, such as antidepressants and antibiotics, can be of supporting help in specific situations (II-3B). CHAPTER 9: SURGERY-EVIDENCE ON EFFECTIVENESS: 1. The lack of robust clinical trials of the surgical management of chronic pelvic pain should be addressed. The use of alternative epidemiologic models, including case-controlled and cohort-controlled trials, should be considered (III-A). 2. Further delineation of the role of appendectomy and of presacral neurectomy appears warranted in the management of endometriosis-related pain (III-A). CHAPTER 11: MULTIDISCIPLINARY CHRONIC PAIN MANAGEMENT: 1. Multidisciplinary chronic pain management should be available for women with chronic pelvic pain within the publicly funded health care system in each province and territory of Canada (III-B). CHAPTER 14: FUTURE DIRECTIONS 1. The curriculum for professional development should be expanded to include theory and techniques in the management of myofascial dysfunction (A). 2. Research into CPP should be encouraged, particularly in the areas of the impact of CPP on the use of health services, the pathophysiology of myofascial dysfunction, and gene therapy. Because randomized trials for qualitative outcomes are exceedingly difficult, alternative robust models, such as case-controlled or cohort-controlled trials, should be pursued (A). 3. Methods of improving interaction with patients should be explored. They might include formal contractual approaches to managing pain with opiates and efforts to better appreciate the patients perceived needs (A).

Adhesion Prevention in Gynaecological Surgery

OBJECTIVES To review the etiology and incidence of and associative factors in the formation of adhesions following gynaecological surgery. To review evidence for the use of available means of adhesion prevention following gynaecological surgery. OPTIONS Women undergoing pelvic surgery are at risk of developing abdominal and/or pelvic adhesive disease postoperatively. Surgical technique and commercial adhesion prevention systems may decrease the risk of postoperative adhesion formation. OUTCOMES The outcomes measured are the incidence of postoperative adhesions, complications related to the formation of adhesions, and further intervention relative to adhesive disease. EVIDENCE Medline, EMBASE, and The Cochrane Library were searched for articles published in English from 1990 to March 2009, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, cohort studies, and meta-analyses specifically addressing postoperative adhesions, adhesion prevention, and adhesive barriers. Searches were updated on a regular basis and incorporated in the guideline to March 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care SUMMARY STATEMENTS: 1. Meticulous surgical technique is a means of preventing adhesions. This includes minimizing tissue trauma, achieving optimal hemostasis, minimizing the risk of infection, and avoiding contaminants (e.g., fecal matter) and the use of foreign materials (e.g., talcum powder) when possible. (II-2). 2. The risk of adhesions increases with the total number of abdominal and pelvic surgeries performed on one patient; every surgery needs to be carefully considered in this context. (II-2). 3. Polytetrafluoroethylene (Gore-Tex) barrier is more effective than no barrier or oxidized regenerated cellulose in preventing adhesion formation. (I). 4. Oxidized regenerated cellulose (Interceed) adhesion barrier is associated with a reduced incidence of pelvic adhesion formation at both laparoscopy and laparotomy when complete hemostasis is achieved. Oxidized regenerated cellulose may increase the risk of adhesions if optimal hemostasis is not achieved. (II-2). 5. Chemically modified sodium hyaluronate/carboxymethylcellulose (Seprafilm) is effective in preventing adhesion formation, especially following myomectomies. There is insufficient evidence on the effect of sodium hyaluronate/carboxymethylcellulose on long-term clinical outcomes such as fertility, chronic pelvic pain or small bowel obstruction. (II-2). 6. No adverse effects have been reported with the use of oxidized regenerated cellulose, polytetrafluoroethylene, or sodium hyaluronate/carboxymethylcellulose. (II-1). 7. Various pharmacological agents have been marketed as a means of preventing adhesions. None of these agents are presently available in Canada. There is insufficient evidence for the use of pharmacological agents in preventing adhesions. (III-C). RECOMMENDATIONS 1. Surgeons should attempt to perform surgical procedures using the least invasive method possible in order to decrease the risk of adhesion formation. (II-1B ). When feasible, for example, a laparoscopic surgical approach is preferable to an abdominal approach, and a vaginal or laparoscopic hysterectomy is preferable to an abdominal hysterectomy. 2. Precautions should be taken at surgery to minimize tissue trauma in order to decrease the risk of postoperative adhesions. These precautions include limiting packing, crushing, and manipulating of tissues to what is strictly required for safe completion of the procedure. (III-B). 3. Surgeons could consider using an adhesion barrier for patients who are at high risk of forming clinically significant adhesions (i.e., patients who have endometriosis or pelvic inflammatory disease or who are undergoing a myomectomy). If there is a risk of ongoing bleeding from the surgical site, oxidized regenerated cellulose (Interceed) should not be used as it may increase the risk of adhesions in this situation. (II-2B).

Abnormal Uterine Bleeding in Pre-Menopausal Women

BACKGROUND Abnormal uterine bleeding is the direct cause of a significant health care burden for women, their families, and society as a whole. Up to 30% of women will seek medical assistance for this problem during their reproductive years. This guideline replaces previous clinical guidelines on the topic and is aimed to enable health care providers with the tools to provide the latest evidence-based care in the diagnosis and the medical and surgical management of this common problem. OBJECTIVE To provide current evidence-based guidelines for the diagnosis and management of abnormal uterine bleeding (AUB) among women of reproductive age. OUTCOMES Outcomes evaluated include the impact of AUB on quality of life and the results of interventions including medical and surgical management of AUB. METHODS Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of location in Canada, type of practice, subspecialty expertise, and general gynaecology background. The committee reviewed relevant evidence in the English medical literature including published guidelines. Recommendations were established as consensus statements. The final document was reviewed and approved by the Executive and Council of the SOGC. RESULTS This document provides a summary of up-to-date evidence regarding diagnosis, investigations, and medical and surgical management of AUB. The resulting recommendations may be adapted by individual health care workers when serving women with this condition. CONCLUSIONS Abnormal uterine bleeding is a common and sometimes debilitating condition in women of reproductive age. Standardization of related terminology, a systematic approach to diagnosis and investigation, and a step-wise approach to intervention is necessary. Treatment commencing with medical therapeutic modalities followed by the least invasive surgical modalities achieving results satisfactory to the patient is the ultimate goal of all therapeutic interventions. EVIDENCE Published literature was retrieved through searches of MEDLINE and the Cochrane Library in March 2011 using appropriate controlled vocabulary (e.g. uterine hemorrhage, menorrhagia) and key words (e.g. menorrhagia, heavy menstrual bleeding, abnormal uterine bleeding). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1999 to March 2011. Searches were updated on a regular basis and incorporated in the guideline to February 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). BENEFITS, HARMS, AND COSTS Implementation of the guideline recommendations will improve the health and well-being of women with abnormal uterine bleeding, their families, and society. The economic cost of implementing these guidelines in the Canadian health care system was not considered.

Consensus Guidelines for the Management of Chronic Pelvic Pain. This guideline was developed by the Chronic Pelvic Pain Working Group and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada

OBJECTIVE To improve the understanding of chronic pelvic pain (CPP) and to provide evidence-based guidelines of value to primary care health professionals, general obstetricians and gynaecologists, and those who specialize in chronic pain. BURDEN OF SUFFERING: CPP is a common, debilitating condition affecting women. It accounts for substantial personal suffering and health care expenditure for interventions, including multiple consultations and medical and surgical therapies. Because the underlying pathophysiology of this complex condition is poorly understood, these treatments have met with variable success rates. OUTCOMES Effectiveness of diagnostic and therapeutic options, including assessment of myofascial dysfunction, multidisciplinary care, a rehabilitation model that emphasizes achieving higher function with some pain rather than a cure, and appropriate use of opiates for the chronic pain state. EVIDENCE Medline and the Cochrane Database from 1982 to 2004 were searched for articles in English on subjects related to CPP, including acute care management, myofascial dysfunction, and medical and surgical therapeutic options. The committee reviewed the literature and available data from a needs assessment of subjects with CPP, using a consensus approach to develop recommendations. VALUES The quality of the evidence was rated using the criteria described in the Report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice were ranked according to the method described in that report (Table 1). RECOMMENDATIONS The recommendations are directed to the following areas: (a) an understanding of the needs of women with CPP; (b) general clinical assessment; (c) practical assessment of pain levels; (d) myofascial pain; (e) medications and surgical procedures; (d) principles of opiate management; (f) increased use of magnetic resonance imaging (MRI); (g) documentation of the surgically observed extent of disease; (h) alternative therapies; (i) access to multidisciplinary care models that have components of physical therapy (such as exercise and posture) and psychology (such as cognitive-behavioural therapy), along with other medical disciplines, such as gynaecology and anesthesia; (j) increased attention to CPP in the training of health care professionals; and (k) increased attention to CPP in formal, high-calibre research. The committee recommends that provincial ministries of health pursue the creation of multidisciplinary teams to manage the condition.

Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist

Background Endometriosis is a chronic, estrogen‐dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin‐releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. Methods We performed two similar, double‐blind, randomized, 6‐month phase 3 trials (Elaris Endometriosis I and II [EM‐I and EM‐II]) to evaluate the effects of two doses of elagolix — 150 mg once daily (lower‐dose group) and 200 mg twice daily (higher‐dose group) — as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis‐associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. Results A total of 872 women underwent randomization in Elaris EM‐I and 817 in Elaris EM‐II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM‐I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower‐dose elagolix group and 75.8% in the higher‐dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM‐II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM‐I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower‐dose elagolix group and 54.5% in the higher‐dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM‐II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. Conclusions Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6‐month period in women with endometriosis‐associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM‐I and EM‐II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670.)

Single-incision laparoscopy in gynecologic surgery: a systematic review and meta-analysis.

OBJECTIVE: To evaluate surgical outcomes for gynecologic surgery performed by single-incision laparoscopy compared with conventional multi-incision laparoscopy. DATA SOURCES: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through August 2012. We also screened reference lists of retrieved articles and manually searched abstracts from conference proceedings. METHODS OF STUDY SELECTION: We included randomized control trials (RCTs) and high-quality observational studies that compared outcomes for single-incision laparoscopy and conventional laparoscopy for gynecologic surgery in patients. Included studies met predefined quality criteria and reported, at minimum, on complications, conversions, and operative time. TABULATION, INTEGRATION, RESULTS: Six RCTs and 15 observational studies met inclusion criteria, with a total of 2,085 patients (899 single-incision laparoscopies and 1,186 conventional laparoscopies). In the pooled analysis, there was no significant difference in the risk of total complications between single-incision laparoscopy and conventional laparoscopy groups (relative risk 1.01, 95% confidence interval [CI] 0.72–1.40; P=.97, random effects model). The meta-analysis was powered to detect a 5% difference in complications (power=0.8, alpha=0.05). Mean operative time for adnexal surgery performed by single-incision laparoscopy was 6.97 minutes longer than conventional laparoscopy (95% CI 0.16–13.77; P=.045; I2=47.2; random effects based on three RCTs). There was no significant difference in mean operative time for hysterectomy procedures performed by single-incision laparoscopy (8.29 minutes, 95% CI −5.85 to 22.43; P=.251; I2=83.6; random effects based on three RCTs). Clinical outcomes of postoperative pain, change in hemoglobin, length of hospital stay, and scar cosmesis could not be pooled because of paucity of data and lack of uniform reporting. CONCLUSION: There was no difference in the risk of complications between single-incision laparoscopy and conventional laparoscopy approaches in gynecologic surgery. Studies with imprecise effect sizes suggest that single-incision laparoscopy may have longer operative time for adnexal surgery, but not for hysterectomy. Effects on other surgical outcomes remain uncertain.

Female Genital Cosmetic Surgery

OBJECTIVE To provide Canadian gynaecologists with evidence-based direction for female genital cosmetic surgery in response to increasing requests for, and availability of, vaginal and vulvar surgeries that fall well outside the traditional realm of medically-indicated reconstructions. EVIDENCE Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2011 and 2012 using appropriate controlled vocabulary and key words (female genital cosmetic surgery). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2012. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Recommendations 1. The obstetrician and gynaecologist should play an important role in helping women to understand their anatomy and to respect individual variations. (III-A) 2. For women who present with requests for vaginal cosmetic procedures, a complete medical, sexual, and gynaecologic history should be obtained and the absence of any major sexual or psychological dysfunction should be ascertained. Any possibility of coercion or exploitation should be ruled out. (III-B) 3. Counselling should be a priority for women requesting female genital cosmetic surgery. Topics should include normal variation and physiological changes over the lifespan, as well as the possibility of unintended consequences of cosmetic surgery to the genital area. The lack of evidence regarding outcomes and the lack of data on the impact of subsequent changes during pregnancy or menopause should also be discussed and considered part of the informed consent process. (III-L) 4. There is little evidence to support any of the female genital cosmetic surgeries in terms of improvement to sexual satisfaction or self-image. Physicians choosing to proceed with these cosmetic procedures should not promote these surgeries for the enhancement of sexual function and advertising of female genital cosmetic surgical procedures should be avoided (III-L) 5. Physicians who see adolescents requesting female genital cosmetic surgery require additional expertise in counselling adolescents. Such procedures should not be offered until complete maturity including genital maturity, and parental consent is not required at that time. (III-L) 6. Non-medical terms, including but not restricted to vaginal rejuvenation, clitoral resurfacing, and G-spot enhancement, should be recognized as marketing terms only, with no medical origin; therefore they cannot be scientifically evaluated. (III-L).