Innie Chen

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 Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline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).

Expectant Management of Severe Preeclampsia Remote from Term: A Structured Systematic Review

Objective: To compare outcomes associated with expectant vs. interventionist care of severe preeclampsia in observational studies. Data Sources: Medline (01/1980–07/2007), bibliographies of retrieved papers, personal files, Cochrane Database of Systematic Reviews. Study Selection: Expectant or interventionist care of preeclampsia at <34 wk. Tabulation, Integration, Results: Data abstraction independently by two reviewers. Median [IQR] of clinical maternal/perinatal outcomes presented. Results: 72 publications, primarily from tertiary care centres in Dutch and developed world sites. Expectant care of severe preeclampsia <34 wk (39 cohorts, 4,650 women), for which 40% of women are eligible, is associated with pregnancy prolongation of 7–14 d, and few serious maternal complications (median <5%), similar to interventionist care (2 studies, 42 women). Complication rates are higher with HELLP <34wk (12 cohorts, 438 women) and severe preeclampsia <28wk (6 cohorts, 305 women), similar to interventionist care (6 cohorts, 467 women and 2 cohorts, 70 women, respectively). Expectant care of HELLP <34 wk (12 cohorts, 438 women) is associated with fewer days gained (median 5), but more serious maternal morbidity (e.g., eclampsia, median 15%). More than half of women have at least temporary improvement of HELLP. In the developed world, expectant (vs. interventionist) care of severe preeclampsia or HELLP <34 wk is associated with reduced neonatal death and complications. Stillbirth is higher in Dutch and developing world sites where viability thresholds are higher. For preeclampsia <24wk (4 cohorts), perinatal mortality is >80%. No predictors of adverse maternal/perinatal outcomes were identified (13 studies). Conclusions: Future research should establish the best maternal/fetal monito regimen and indications for delivery with expectant care. A definitive RCT is needed.

Gonadotropin-releasing hormone agonist in laparoscopic myomectomy: systematic review and meta-analysis of randomized controlled trials.

A systematic review and meta-analysis of randomized controlled trials was performed to estimate the effects on surgical outcomes of pretreatment with gonadotropin-releasing hormone (GnRH) agonist before laparoscopic myomectomy. The electronic bibliographic databases MEDLINE, EMBASE, Web of Knowledge, Scopus, and Cochrane Library, and reference lists from relevant articles were searched for English-language publications describing randomized controlled trials of GnRH agonist pretreatment vs placebo or no treatment before laparoscopic myomectomy. Three studies including 168 participants were identified. Pretreatment with GnRH agonist did not reduce operative time; however, intraoperative blood loss was statistically lowered (mean difference, 60 mL; 95% confidence interval [CI], 39-82). Statistical difference was also observed in postoperative hemoglobin concentration (mean difference, 1.15 g/dL; 95% CI, 0.46-1.83]) and red blood cell count (mean difference, 0.65 × 10(6) cells/mL; 95% CI, 0.16-1.14]) but not serum iron concentration. None of the patients in the studies experienced any major intraoperative or postoperative complications, and only 1 patient in each group required blood transfusion. This study does not show a difference in operative time with GnRH agonist pretreatment, which clarifies the previous conflicting reports on the effect of GnRH agonist therapy on the duration of laparoscopic myomectomy. Furthermore, despite previously reported decreased bleeding conferred by the laparoscopic approach compared with laparotomy, this meta-analysis demonstrates a further reduction in intraoperative blood loss with GnRH agonist pretreatment in patients undergoing laparoscopic myomectomy. Additional high-quality studies with appropriate power and follow-up are needed to corroborate these findings and to evaluate the treatment effects on short- and long-term outcomes such as perioperative complications and fertility.

Relationship between interpregnancy interval and congenital anomalies

OBJECTIVE To assess the association between interpregnancy intervals and congenital anomalies. STUDY DESIGN A retrospective cohort study on women who had 2 consecutive singleton births from 1999-2007 was conducted using a linked dataset from the Alberta Perinatal Health Program, the Alberta Congenital Anomalies Surveillance System, and the Alberta Health and Wellness Database. Interpregnancy interval was calculated as the interval between 2 consecutive deliveries minus the gestational age of the second infant. The primary outcome of congenital anomaly was defined using the International Classification of Diseases. Maternal demographic and obstetric characteristics and interpregnancy intervals were included in multivariable logistic regression models for congenital anomalies. RESULTS The study included 46,243 women, and the overall rate of congenital anomalies was 2.2%. Both short and long interpregnancy intervals were associated with congenital anomalies. The lowest rate was for the 12-17 months category (1.9%, reference category), and increased rates were seen for both short intervals (2.5% for 0-5 months; adjusted odds ratio, 1.32; 95% confidence interval, 1.01-1.72) and long intervals (2.3% for 24-35 months; adjusted odds ratio, 1.25; 95% confidence interval, 1.02-1.52). Statistically significant associations were also observed for folate independent anomalies, but not for folate dependent anomalies. CONCLUSION The risk of congenital anomalies appears to increase with both short and long interpregnancy intervals. This study supports the limited existing studies in the literature, further explores the types of anomalies affected, and has implications for further research and prenatal risk assessment.

A National Survey of Endoscopic Practice Among Gynaecologists in Canada

OBJECTIVE To assess the current status of endoscopic gynaecological surgery in Canada, as well as the attitudes, perceptions, and educational preferences regarding endoscopy among Canadian obstetrician-gynaecologists. METHODS An electronic online survey was sent to 630 obstetrician-gynaecologists in Canada through the Society of Obstetricians and Gynaecologists of Canada electronic mailing list. Survey respondents were asked about demographic variables, level of training and current practice of endoscopic procedures, reasons for and barriers to performing endoscopy, and interest in continuing surgical education in laparoscopy and hysteroscopy. RESULTS A total of 178 responses (28.3%) were collected and 152 (85.4%) analyzed. The majority of respondents were general obstetrician-gynaecologists (78.0%). More gynaecologic surgeons performed abdominal (92.7%) and vaginal hysterectomies (89.7%) than laparoscopic (68.4%) and robotic hysterectomies (2.2%). Even though 93.2% of respondents selected the endoscopic approach as the preferred approach to surgery for their patients, 38.7% of respondents did not feel that they had adequate training during residency to perform endoscopy. Lack of operating room resources and lack of time and opportunity for further training were frequently selected as major barriers to performing endoscopy. Participants identified weekend continuing medical education courses and trained endoscopic surgeon outreach as preferred methods of acquiring endoscopic skills. CONCLUSION This survey provides a contemporary assessment of the current endoscopic practice patterns of Canadian obstetrician-gynaecologists, and it helps to identify some potentially modifiable factors hindering the practice of endoscopy and some possible solutions to overcoming these barriers.

Dienogest for the treatment of deep endometriosis: Case report and literature review

A 38‐year‐old woman was found to have a deep 3.3‐cm endometriotic nodule of the bladder, confirmed by cystoscopic resection and imaging. Ultrasound also confirmed a 2.6‐cm vaginal fornix implant with similar appearance to the bladder mass. The patients primary symptoms were mild dysmenorrhea, catamenial dysuria and hematuria. The patient conceived shortly after referral and 3 months post‐delivery was offered surgical management but declined in favor of medical management. Dienogest 2 mg once a day was started and after 16 months of treatment, more than 50% reduction in the size of the bladder nodule was seen (pretreatment: 3.3 × 3.0 × 2.7 cm, volume: 13.9 cm3; post‐treatment: 2.8 × 2.3 × 1.0 cm, volume: 6.4 cm3). The vaginal mass also decreased in size from a pretreatment value of 2.0 × 2.6 × 1.4 cm (3.8 cm3) to 1.1 × 1.4 × 0.5 mm (0.40 cm3) after the treatment. The patient remained asymptomatic with no significant adverse drug reaction during management. Dienogest may be one of the options for medical management of deep endometriosis in young women especially when surgical intervention is declined.

Maternal morbidity and perinatal outcomes among women in rural versus urban areas

Background: Most studies examining geographic barriers to maternity care in industrialized countries have focused solely on fetal and neonatal outcomes. We examined the association between rural residence and severe maternal morbidity, in addition to perinatal mortality and morbidity. Methods: We conducted a retrospective population-based cohort study of all women who gave birth in British Columbia, Canada, between Jan. 1, 2005, and Dec. 31, 2010. We compared maternal mortality and severe morbidity (e.g., eclampsia) and adverse perinatal outcomes (e.g., perinatal death) between women residing in areas with moderate to no metropolitan influence (rural) and those living in metropolitan areas or areas with a strong metropolitan influence (urban). We used logistic regression analysis to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: We found a significant association between death or severe maternal morbidity and rural residence (adjusted OR 1.15, 95% CI 1.03–1.28). In particular, women in rural areas had significantly higher rates of eclampsia (adjusted OR 2.70, 95% CI 1.79–4.08), obstetric embolism (adjusted OR 2.16, 95% CI 1.14–4.07) and uterine rupture or dehiscence (adjusted OR 1.96, 95% CI 1.42–2.72) than women in urban areas. Perinatal mortality did not differ significantly between the study groups. Infants in rural areas were more likely than those in urban areas to have a severe neonatal morbidity (adjusted OR 1.14, 95% CI 1.02–1.29), to be born preterm (adjusted OR 1.06, 95% CI 1.01–1.11), to have an Apgar score of less than 7 at 5 minutes (adjusted OR 1.24, 95% CI 1.13–1.31) and to be large for gestational age (adjusted OR 1.14, 95% CI 1.10–1.19). They were less likely to be small for gestational age (adjusted OR 0.90, 95% CI 0.85–0.95) and to be admitted to an neonatal intensive care unit (NICU) (adjusted OR 0.36, 95% CI 0.33–0.38) compared with infants in urban areas. Interpretation: Compared with women in urban areas, those in rural areas had higher rates of severe maternal morbidity and severe neonatal morbidity, and a lower rate of NICU admission. Maternity care providers in rural regions need to be aware of potentially life-threatening maternal and perinatal complications requiring advanced obstetric and neonatal care.

Relationship Between Interpregnancy Interval and Adverse Perinatal and Neonatal Outcomes in Northern Alberta

BACKGROUND Birth outcomes are known to be associated with birth spacing, but there are population differences. The purpose of this study was to examine the association between interpregnancy intervals and perinatal and neonatal outcomes in a Canadian population during the era of mandatory folate fortification of food. METHODS We conducted a study of 46 243 women who had two consecutive singleton births in northern Alberta between 1999 and 2007, using a linked provincial dataset. Perinatal outcomes of interest were preterm birth, low birth weight (LBW), small for gestational age, and perinatal death. Neonatal outcomes were low Apgar score, low arterial blood gas pH, need for neonatal resuscitation or admission to NICU, and neonatal death. Multivariable logistic regression was used to control for maternal demographic and obstetrical characteristics. RESULTS The risk of preterm birth was increased for multiple interpregnancy intervals: for an interval of 0 to 5 months, the adjusted odds ratio (aOR) was 1.37 (95% CI 1.18 to 1.59), for 6 to 11 months the aOR was 1.18 (95% CI 1.04 to 1.34), for 24 to 35 months the aOR was 1.16 (95% CI 1.02 to 1.31), and for 36+ months the aOR was 1.36 (95% CI 1.20 to 1.53), compared with the reference interval of 12 to 17 months. The risk of LBW was increased with interpregnancy intervals of 0 to 5 months (aOR 1.48; 95% CI 1.23 to 1.80), 6 to 11 months (aOR 1.21; 95% CI 1.03 to 1.42), 24 to 35 months (aOR 1.21; 95% CI 1.03 to 1.41) and 36+ months (aOR 1.48; 95% CI 1.27 to 1.73). The risk of SGA was increased with intervals 0 to 5 months (aOR 1.29; 95% CI 1.09 to 1.52), 24 to 35 months (aOR 1.15; 95% CI 1.01 to 1.31), and 36+ months (aOR 1.26; 95% CI 1.11 to 1.44). The risk of perinatal death was increased with an interval of 36+ months (aOR 1.60; 95% CI 1.06 to 2.43). Similar associations were also observed for neonatal outcomes. CONCLUSION This study suggests that both short and long interpregnancy intervals are associated with adverse perinatal and neonatal outcomes, and it provides risk estimates for a Canadian population in the era of folate fortification of food.

Laparoscopic Versus Abdominal Myomectomy: Practice Patterns and Health Care Use in British Columbia

OBJECTIVE To examine the relative frequency and surgical outcomes of laparoscopic myomectomy compared with abdominal myomectomy in British Columbia. METHODS A linked database containing hospital admission, operating room, and emergency room data from 2007 to 2011 from eight Vancouver Coastal Health and Providence Health Region hospitals in British Columbia was used to conduct a retrospective cohort study of women who had myomectomy for uterine fibroids. All consecutive women who had abdominal or laparoscopic myomectomy at five hospitals were included in the study. Patients who had submucosal fibroids or hysteroscopic procedures were excluded. Abdominal and laparoscopic myomectomies were contrasted in terms of patient characteristics and surgical outcomes. Statistical significance was assessed using t tests, Wilcoxon, chi-square, and Fisher exact test; a two-sided P value < 0.05 was considered significant. RESULTS Of eight hospitals offering gynaecologic surgery, myomectomies were performed at five hospitals located in metropolitan areas. Of 436 women undergoing myomectomy, 88 cases (20.2%) were laparoscopic, 342 (78.4%) were abdominal, and 6 (1.38%) were laparoscopic with conversion to laparotomy. Women who had laparoscopic rather than abdominal myomectomies were slightly older (mean 38.7 vs. 37.4 years, respectively, P < 0.05). No significant difference was observed in median operative time (106 vs. 95 min), but length of stay was decreased for laparoscopic myomectomies (median 1 vs. 2 days, P < 0.01). No significant differences were observed between laparoscopic and abdominal routes in the rates of admission to intensive care, prolonged hospitalization (> 3 days), or rehospitalization. CONCLUSION Myomectomies are performed in urban, metropolitan areas in British Columbia, and a significant fraction of myomectomies are performed by laparoscopy. Compared with abdominal myomectomies, laparoscopic myomectomies in pre-selected patients are associated with decreased length of stay and comparable perioperative surgical outcomes.

Incorporating ulipristal acetate in the care of symptomatic uterine fibroids: a Canadian cost-utility analysis of pharmacotherapy management

Objective To present a Canadian economic evaluation on the cost-utility of ulipristal acetate (5 mg orally daily) compared to leuprolide acetate (3.75 mg intramuscular monthly) in the treatment of moderate-to-severe symptoms of uterine fibroids in women eligible for surgery. Methods A probabilistic decision tree was constructed to model the pre-operative pharmacological management of uterine fibroids under the primary perspective of the Ontario public payer. The model parameterized data from clinical trials, observational studies, and public costing databases. The outcome measure was the incremental cost-utility ratio. Uncertainty in the model was explored through sensitivity and scenario analyses. Results Ulipristal was associated with faster control of excessive menstrual bleeding, fewer symptoms of hot flashes and lower health care resource consumption. The ulipristal strategy dominated leuprolide as it provided patients with more quality-adjusted life years (0.177 versus 0.165) at a lower cost (