Continuous adaptation of conversation aids for uterine fibroids treatment options in a four-year multi-center implementation project.

BACKGROUND: Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred. METHODS: We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group with project stakeholders and user-testing interviews with eligible individuals with symptomatic uterine fibroids. We analyzed the results of the user-testing interviews using Morville's Honeycomb framework. Spanish translations of the conversation aids occurred in parallel with the English iterations. We documented the continuous adaptations of the conversation aids that occurred during the project using an expanded framework for reporting adaptations and modifications to evidence-based interventions (FRAME). RESULTS: The first iteration of the conversation aids was developed in December 2018. Focus group participants (n = 6) appreciated the brevity of the tools and suggested changes to the bar graphs and illustrations used in the picture-enhanced version. User-testing with interview participants (n = 9) found that both conversation aids were satisfactory, with minor changes suggested. However, during implementation, significant changes were suggested by patients, other stakeholders, and participating clinicians when they reviewed the content. The most significant changes required the addition or deletion of information about treatment options as newer research was published or as novel interventions were introduced into clinical practice. CONCLUSIONS: This multi-year project revealed the necessity of continuously adapting the uterine fibroids conversation aids so they remain acceptable in an implementation and sustainability context. Therefore, it is important to seek regular user feedback and plan for the need to undertake updates and revisions to conversation aids if they are going to be acceptable for clinical use.

Detection of endometrial cancer using tampon-based collection and methylated DNA markers.

OBJECTIVE: Alterations in DNA methylation are early events in endometrial cancer (EC) development and may have utility in EC detection via tampon-collected vaginal fluid. METHODS: For discovery, DNA from frozen EC, benign endometrium (BE), and benign cervicovaginal (BCV) tissues underwent reduced representation bisulfite sequencing (RRBS) to identify differentially methylated regions (DMRs). Candidate DMRs were selected based on receiver operating characteristic (ROC) discrimination, methylation level fold-change between cancers and controls, and absence of background CpG methylation. Methylated DNA marker (MDM) validation was performed using qMSP on DNA from independent EC and BE FFPE tissue sets. Women ≥45 years of age with abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB) or any age with biopsy-proven EC self-collected vaginal fluid using a tampon prior to clinically indicated endometrial sampling or hysterectomy. Vaginal fluid DNA was assayed by qMSP for EC-associated MDMs. Random forest modeling analysis was performed to generate predictive probability of underlying disease; results were 500-fold in-silico cross-validated. RESULTS: Thirty-three candidate MDMs met performance criteria in tissue. For the tampon pilot, 100 EC cases were frequency matched by menopausal status and tampon collection date to 92 BE controls. A 28-MDM panel highly discriminated between EC and BE (96% (95%CI 89-99%) specificity; 76% (66-84%) sensitivity (AUC 0.88). In PBS/EDTA tampon buffer, the panel yielded 96% (95% CI 87-99%) specificity and 82% (70-91%) sensitivity (AUC 0.91). CONCLUSION: Next generation methylome sequencing, stringent filtering criteria, and independent validation yielded excellent candidate MDMs for EC. EC-associated MDMs performed with promisingly high sensitivity and specificity in tampon-collected vaginal fluid; PBS-based tampon buffer with added EDTA improved sensitivity. Larger tampon-based EC MDM testing studies are warranted.

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids.

BACKGROUND: Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. OBJECTIVE: We examined differences in change from baseline to 1-, 2-, and 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. STUDY DESIGN: The COMPARE-UF registry is a multiinstitutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1384 women aged 31 to 45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy (n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1, 2, and 3 years posttreatment. We used the UFS-QoL (Uterine Fibroid Symptom and Quality of Life) questionnaire to ascertain symptom severity and health-related quality of life scores among participants. To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total health-related quality of life and symptom severity scores after enrollment with a repeated measures model. For this health-related quality of life tool, a specific minimal clinically important difference has not been determined, but on the basis of previous research, a difference of 10 points was considered as a reasonable estimate. Use of this difference was agreed upon by the Steering Committee at the time when the analysis was planned. RESULTS: At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared with those undergoing abdominal myomectomy or laparoscopic myomectomy (P<.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (standard deviation, 6.7; P<.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (Uterine Fibroids Symptom and Quality of Life: delta= [+] 49.2; symptom severity: delta= [-] 51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life (delta= [+]43.9, [+]32.9, [+]40.7, respectively) and symptom severity (delta= [-]41.4, [-] 31.5, [-] 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine-sparing procedures during second (Uterine Fibroids Symptom and Quality of Life: delta= [+]40.7, [+]37.4, [+]39.3 SS: delta= [-] 38.5, [-] 32.0, [-] 37.7 and third year (Uterine Fibroids Symptom and Quality of Life: delta= [+] 40.9, [+]39.9, [+]41.1 and SS: delta= [-] 33.9, [-]36.5, [-] 33.0, respectively), posttreatment intervals, however with a trend toward decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the Uterine Fibroids Symptom and Quality of Life, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. CONCLUSION: All treatment modalities were associated with significant improvements in health-related quality of life and symptom severity reduction 1-year posttreatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated a gradual decline in symptom improvement and health-related quality of life by third year after the procedure.

A systematic review on the use of artificial intelligence in gynecologic imaging - Background, state of the art, and future directions.

OBJECTIVE: Machine learning, deep learning, and artificial intelligence (AI) are terms that have made their way into nearly all areas of medicine. In the case of medical imaging, these methods have become the state of the art in nearly all areas from image reconstruction to image processing and automated analysis. In contrast to other areas, such as brain and breast imaging, the impacts of AI have not been as strongly felt in gynecologic imaging. In this review article, we: (i) provide a background of clinically relevant AI concepts, (ii) describe methods and approaches in computer vision, and (iii) highlight prior work related to image classification tasks utilizing AI approaches in gynecologic imaging. DATA SOURCES: A comprehensive search of several databases from each database's inception to March 18th, 2021, English language, was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Ovid Cochrane Database of Systematic Reviews and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We performed an extensive literature review with 61 articles curated by three reviewers and subsequent sorting by specialists using specific inclusion and exclusion criteria. TABULATION, INTEGRATION, AND RESULTS: We summarize the literature grouped by each of the three most common gynecologic malignancies: endometrial, cervical, and ovarian. For each, a brief introduction encapsulating the AI methods, imaging modalities, and clinical parameters in the selected articles is presented. We conclude with a discussion of current developments, trends and limitations, and suggest directions for future study. CONCLUSION: This review article should prove useful for collaborative teams performing research studies targeted at the incorporation of radiological imaging and AI methods into gynecological clinical practice.

Quantifying procedural pain associated with office gynecologic tract sampling methods.

OBJECTIVE: Emerging technologies may enable detection of endometrial cancer with methods that are less invasive than standard biopsy methods. This study compares patient pain scores among 3 office gynecologic tract sampling methods and explores their potential determinants. METHODS: A prospective study including 3 sampling methods (tampon, Tao brush (TB), endometrial biopsy (EB)) was conducted between December 2015 and August 2017 and included women ≥45 years of age presenting with abnormal uterine bleeding, postmenopausal bleeding, or thickened endometrial stripe. Patients rated pain after each sampling procedure using a 100-point visual analog scale (VAS). RESULTS: Of 428 enrolled, 190 (44.39%) patients underwent all 3 sampling methods and reported a VAS score for each. Nearly half were postmenopausal (n = 93, 48.9%); the majority were parous (172, 90.5%) of which 87.8% had at least one vaginal delivery. Among the 190 patients, the median (IQR) pain score was significantly lower for sampling via tampon (0 [0,2]) compared to TB (28 [12, 52]) or EB (32 [15, 60]) (both p < 0.001, Wilcoxon signed rank test). Among women who underwent tampon sampling, age and pain scores showed a weak positive correlation (Spearman rank correlation, r = 0.14; p = 0.006); EB sampling was associated with a weak inverse correlation between parity and pain scores (r = -0.14; p = 0.016). CONCLUSION: Gynecologic tract sampling using a tampon had significantly lower pain than both EB and TB. Pain with tampon sampling was positively correlated with age and pain with EB sampling was inversely correlated with parity. Pain scores for TB and EB were not significantly related to age, menopausal status, or BMI.

Abdominal Ice after Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To assess the impact of abdominal ice packs on opioid use and pain control after laparoscopic hysterectomy DESIGN: Randomized controlled trial. SETTING: Academic tertiary care medical center. PATIENTS: Total of 142 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy were randomized to control (n = 69) or intervention (n = 73). Exclusion criteria included preoperative opioid use, planned intensive care unit admission or same-day discharge, an incision ≥4 cm, and regional anesthesia use. INTERVENTIONS: Subjects in the intervention group had a large ice pack placed directly on the lower abdomen before leaving the operating room. The ice pack was maintained continuously for 12 hours postoperation, as desired thereafter until discharge, and continued use encouraged after discharge for up to 48 hours. MEASUREMENTS AND MAIN RESULTS: Total opioids administered postoperatively, while inpatient and after dismissal, were assessed in morphine milligram equivalents. Postoperative pain, as well as analgesia acceptability and side effects, were assessed using validated measures: Brief Pain Inventory and Overall Benefit of Analgesia Score. Median morphine milligram equivalent was lower in the intervention group than the controls from inpatient stay on the floor to completion of opioid use as an outpatient (22.5 vs 26.2) but was not statistically significant (p = .79). There was no significant difference between the groups in Brief Pain Inventory assessment of postoperative pain severity (p = .80) or pain interference (p = .36) or Overall Benefit of Analgesia Score total score (p = .88). Most patients in the intervention group were very satisfied with ice pack use (n = 51, 79.7%) and very likely to recommend it to friends or family (n = 54, 83.1%). There were no adverse events related to ice pack use. CONCLUSION: There was no significant difference in postoperative opioid use or pain assessment with ice pack use after laparoscopic hysterectomy. However, most of the subjects expressed high satisfaction specific to ice pack use and would recommend its use to others, suggesting potential desirability as adjunct therapy in postoperative pain control.

A prospective clinical cohort study of women at increased risk for endometrial cancer.

OBJECTIVE: To evaluate endometrial cancer (EC) risk assessment and early detection strategies in high-risk populations, we designed a large, prospective cohort study of women undergoing endometrial evaluation to assess risk factors and collect novel biospecimens for future testing of emerging EC biomarkers. Here we report on the baseline findings of this study. METHODS: Women aged ≥45 years were enrolled at the Mayo Clinic from February 2013-June 2018. Risk factors included age, body mass index (BMI), smoking, oral contraceptive and hormone therapy use, and parity. We collected vaginal tampons, endometrial biopsies, and Tao brush samples. We estimated mutually-adjusted odds ratios (OR) and 95% confidence intervals (CI) using multinomial logistic regression; outcomes included EC, atypical hyperplasia, hyperplasia without atypia, disordered proliferative endometrium, and polyps, versus normal endometrium. RESULTS: Subjects included 1205 women with a mean age of 55 years; 55% were postmenopausal, and 90% had abnormal uterine bleeding. The prevalence of EC was 4.1% (n = 49), predominantly diagnosed in postmenopausal women (85.7%). Tampons and Tao brushings were obtained from 99% and 68% of women, respectively. Age (OR 1.14, 95% CI 1.1-1.2) and BMI (OR 1.39, 95% CI 1.1-1.7) were positively associated with EC; atypical hyperplasia (OR 1.07, 95% CI 1.0-1.1; OR 2.00, 95% CI 1.5-2.6, respectively), and polyps (OR 1.06, 95% CI 1.0-1.1; OR 1.17, 95% CI 1.0-1.3, respectively); hormone therapy use and smoking were inversely associated with EC (OR 0.42, 95%, 0.2-0.9; OR 0.43, 95% CI, 0.2-0.9, respectively). Parity and past oral contraception use were not associated with EC. CONCLUSIONS: Well-established EC risk factors may have less discriminatory accuracy in high-risk populations. Future analyses will integrate risk factor assessment with biomarker testing for EC detection.

Short-term quality of life after myomectomy for uterine fibroids from the COMPARE-UF Fibroid Registry.

BACKGROUND: Uterine fibroids may decrease quality of life in a significant proportion of affected women. Myomectomy offers a uterine-sparing treatment option for patients with uterine fibroids that can be performed abdominally, laparoscopically (with or without robotic assistance), and hysteroscopically. Quality of life information using validated measures for different myomectomy routes, especially hysteroscopic myomectomy, is limited. OBJECTIVE: To compare women's perception of their short-term health-related quality of life measures and reported time to return to usual activities and return to work for different routes of myomectomy. MATERIALS AND METHODS: Comparing Options for Management: Patient-centered Results for Uterine Fibroids (COMPARE-UF) is a prospective nationwide fibroid registry that enrolled premenopausal women seeking treatment for uterine fibroids at 8 clinical sites. For this analysis, we included women undergoing hysteroscopic, abdominal, or laparoscopic myomectomy who completed the postprocedure questionnaire scheduled between 6 and 12 weeks after surgery. Health-related quality of life outcomes, such as pain, anxiety, and return to usual activitie, were assessed for each route. The hysteroscopic myomectomy group had large differences in demographics, fibroid number, and uterine size compared to the other groups; thus, a direct comparison of quality of life measures was performed only for abdominal and laparoscopic approaches after propensity weighting. Propensity weighting was done using 24 variables that included demographics, quality of life baseline measures, and fibroid and uterine measurements. RESULTS: A total of 1206 women from 8 COMPARE-UF sites underwent myomectomy (338 hysteroscopic, 519 laparoscopic, and 349 abdominal). All women had substantial improvement in short-term health-related quality of life and symptom severity scores, which was not different among groups. Average symptom severity scores decreased about 30 points in each group. Return to usual activities averaged 0 days (interquartile range, 0-14 days) for hysteroscopic myomectomy, 21 days (interquartile range, 14-28 days) for laparoscopic myomectomy, and 28 days (interquartile range, 14-35 days) for abdominal myomectomy. After propensity adjustment, quality of life outcomes in the laparoscopic and abdominal myomectomy groups were similar except for more anxiety in the laparoscopic myomectomy group and slightly more pain in the abdominal myomectomy group. After propensity weighting, return to usual activities favored laparoscopic compared to abdominal procedures; median time was the same at 21 days, but the highest quartile of women in the abdominal group needed an additional week of recovery (interquartile range,14.0-28.0 for laparoscopic versus 14.0-35.0 for abdominal, P < .01). Time to return to work was also longer in the abdominal arm (median, 22 days; interquartile range, 14-40 days, versus median, 42; interquartile range, 27-56). CONCLUSION: Women who underwent myomectomy had substantial improvement in health-related quality of life, regardless of route of myomectomy. After propensity weighting, abdominal myomectomy was associated with a nearly 2-week longer time to return to work than laparoscopic myomectomy.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms.

BACKGROUND: Most endometrial cancer cases are preceded by abnormal uterine bleeding, offering a potential opportunity for early detection and cure of endometrial cancer. Although clinical guidelines exist for diagnostic workup of abnormal uterine bleeding, consensus is lacking regarding optimal management for women with abnormal bleeding to diagnose endometrial cancer. OBJECTIVE: We report the baseline data from a prospective clinical cohort study of women referred for endometrial evaluation at the Mayo Clinic, designed to evaluate risk stratification in women at increased risk for endometrial cancer. Here, we introduce a risk-based approach to evaluate diagnostic tests and clinical management algorithms in a population of women with abnormal bleeding undergoing endometrial evaluation at the Mayo Clinic. STUDY DESIGN: A total of 1163 women aged ≥45 years were enrolled from February 2013 to May 2019. We evaluated baseline absolute risks and 95% confidence intervals of endometrial cancer and endometrial intraepithelial neoplasia according to clinical algorithms for diagnostic workup of women with postmenopausal bleeding (assessment of initial vs recurrent bleeding episode and endometrial thickness measured through transvaginal ultrasound). We also evaluated risks among women with postmenopausal bleeding according to baseline age (<60 vs 60+ years) as an alternative example. For this approach, biopsy would be conducted for all women aged 60+ years and those aged <60 years with an endometrial thickness of >4 mm. We assessed the clinical efficiency of each strategy by estimating the percentage of women who would be referred for endometrial biopsy, the percentage of cases detected and missed, and the ratio of biopsies per case detected. RESULTS: Among the 593 women with postmenopausal bleeding, 18 (3.0%) had endometrial intraepithelial neoplasia, and 47 (7.9%) had endometrial cancer, and among the 570 premenopausal women with abnormal bleeding, 8 (1.4%) had endometrial intraepithelial neoplasia, and 7 (1.2%) had endometrial cancer. Maximum risk was noted in women aged 60+ years (17.7%; 13.0%-22.3%), followed by those with recurrent bleeding (14.7%; 11.0%-18.3%). Among women with an initial bleeding episode for whom transvaginal ultrasound was recommended, endometrial thickness did not provide meaningful risk stratification: risks of endometrial cancer and endometrial intraepithelial neoplasia were nearly identical in women with an endometrial thickness of >4 mm (5.8%; 1.3%-10.3%) and ≤4 mm (3.6%; 0.9%-8.6%). In contrast, among those aged <60 years with an endometrial thickness of >4 mm, the risk of endometrial cancer and endometrial intraepithelial neoplasia was 8.4% (4.3%-12.5%), and in those with an endometrial thickness of ≤4 mm, the risk was 0% (0.0%-3.0%; P=.01). The most efficient strategy was to perform biopsy in all women aged 60+ years and among those aged <60 years with an endometrial thickness of >4 mm, with the lowest percentage referred to biopsy while still detecting all cases. CONCLUSION: Existing clinical recommendations for endometrial cancer detection in women with abnormal bleeding are not consistent with the underlying risk. Endometrial cancer risk factors such as age can provide important risk stratification compared with the assessment of recurrent bleeding. Future research will include a formal assessment of clinical and epidemiologic risk prediction models in our study population as well as validation of our findings in other populations.

Incidence of sarcoma in patients undergoing hysterectomy for benign indications: a population-based study.

BACKGROUND: Minimally invasive hysterectomy may require the use of morcellation to remove the uterus. In the presence of unexpected sarcoma, morcellation risks disseminating malignant cells and worsening survival outcomes. As a consequence, in 2014 the US Food and Drug Administration issued a black box warning against the use of power morcellator for the treatment of uterine fibroids. However, the proportion of unexpected sarcoma at the time of hysterectomy for presumed benign indication remains unclear. OBJECTIVE: The objective of the study was to estimate the incidence of sarcoma among women undergoing hysterectomy for benign indication in Olmsted County, MN, between 1999 and 2013. STUDY DESIGN: We conducted a population-based study including all hysterectomies performed for benign indication in Olmsted County women between Jan. 1, 1999, and Dec. 31, 2013. Cases were identified using the medical records-linkage system of the Rochester Epidemiology Project, and data were abstracted by a gynecologist who reviewed the complete medical records of each woman who underwent hysterectomy. An expert pathologist reviewed the pathologic slides of each sarcoma to ensure the accuracy of the diagnosis. Incidences of sarcoma (overall and by type of sarcoma) were estimated both overall and stratified by menopausal status, indication for surgery, and uterine weight as a rate per 100 persons. RESULTS: A total of 4232 hysterectomies were performed during the study period. Among them, we identified 16 sarcomas, of which 11 (69%) were suspected preoperatively and 5 (31%) were unexpected. Of the total number of hysterectomies, 3759 (88.8%) were performed for benign indication. Among those, the incidence of unexpected sarcoma was 0.13% (5 per 3759 [95% confidence interval, 0.04-0.31%]). Uterine fibroids comprised 27.3% of all hysterectomies for benign indication (n = 1025) and was the indication most commonly associated with diagnosis of unexpected sarcoma. The incidence of unexpected sarcoma among surgeries for uterine fibroids was 0.35% (3 of 851) for premenopausal women and 0.57% (1 of 174) for peri/postmenopausal, and all 4 unexpected sarcomas were leiomyosarcoma. The incidence of unexpected sarcoma progressively increased with higher uterine weight with an incidence of 0.03% (1 of 2993) among women with a uterine weight <250 g vs 15.4% (2 of 13) with a uterine weight ≥2000 g. CONCLUSION: Unexpected uterine sarcoma was low in all women undergoing hysterectomy for benign indication (0.13% or 1 in 752 surgeries) while it was increased in women with uterine fibroids (0.39% or 1 in 256 surgeries). Peri/postmenopausal women, women with large uteri, and age ≥45 years were risk factors for sarcoma.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile.

BACKGROUND: Vaginal diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption. AIM: To determine the pharmacokinetic and adverse event profile of diazepam vaginal suppositories. METHODS: We used a prospective pharmacokinetic design with repeated assessments of diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods. RESULTS: The mean peak diazepam concentration (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and nordiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants. CLINICAL IMPLICATIONS: Serum plasma concentrations of vaginally administered diazepam are low; however the half-life is prolonged. STRENGTHS & LIMITATIONS: Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal diazepam in lieu of performing a pure pharmacokinetic study with healthy participants. CONCLUSION: Vaginal administration of diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with diazepam's long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763-766.

Non-surgical Management of Myomas.

Uterine myomas are a common condition and the leading cause of hysterectomy. Clinically, myomas can be challenging because they range from asymptomatic to causing severe, debilitating symptoms and occur in many women before childbearing is complete. Thus, women often seek uterine-conserving and nonsurgical management of their myomas. In this review the available uterine-conserving treatment options from medical management through minimally invasive procedures are discussed. To the extent of research available, the sustainability of symptom improvement and the effects on future fertility are reviewed. Future research may lead to therapies that reduce the risks of major surgery, decrease side effects, and offer primary or secondary prevention options.

Periprocedural outcomes comparing fibroid embolization and focused ultrasound: a randomized controlled trial and comprehensive cohort analysis.

BACKGROUND: Uterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. OBJECTIVE: The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. RESULTS: Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P <.001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self-rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median [interquartile range], 5 [1-7] vs 1 [1-4]; P = .002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < .001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < .001) and to have a longer median (interquartile range) recovery time (days off work, 8 [6-14] vs 4 [2-7]; P < .001; days until return to normal, 15 [10-29] vs 10 [10-15]; P = .02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities (P < .001 for each). Results were similar when restricted to the randomized controlled trial. CONCLUSION: Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.

Clinical Manifestations and Outcomes in Surgically Managed Gartner Duct Cysts.

STUDY OBJECTIVE: Gartner duct cysts (GDCs) are rare embryological remnants of the mesonephric duct with the majority of cases discovered incidentally in asymptomatic patients. The largest prior published series evaluating the surgical management of GDCs included 4 patients. The present study aimed to determine the manifestations and outcomes of surgically managed patients with GDCs with important implications for surveillance, monitoring, and management. DESIGN: A retrospective chart review (Canadian Task Force classification III). SETTING: A tertiary care center. PATIENTS: All women diagnosed with GDCs from January 1994 to April 2014 at our institution were identified. Patients were included if they underwent surgical management and had GDCs confirmed by pathology. One hundred twenty-four charts were manually reviewed, and 29 patients were included in the analysis. INTERVENTIONS: All patients underwent surgical management, which included vaginal excision or marsupialization. MEASUREMENTS AND MAIN RESULTS: A total of 29 patients met the inclusion criteria for this study. The median age of the patients included in the analysis was 36 years old. Eleven patients were asymptomatic at the time of diagnosis (37.9%). The reason for surgical intervention was not available in 9 of these patients. Surgical intervention was performed in 2 of the 11 asymptomatic patients because of an increasing size of the lesion during observation. Presenting symptoms included dyspareunia or pain with tampon placement (37.9%), pelvic pain or pressure (24.1%), pelvic mass or bulge (17.2%), and urinary incontinence (6.9%). Preoperative imaging studies were obtained in 62% of patients; ultrasound was used in 44.4%, computed tomographic scanning in 22.2%, magnetic resonance imaging in 16.7%, and multiple modalities in 16.7%. Approximately 10% were found to have other genitourinary anomalies, including a bladder cyst, urethral diverticulum, and a solitary right kidney with uterine didelphis and septate vagina. The average cyst size was 3.5 cm (±1.8 cm). Surgical excision of GDCs was performed in all except for 3 cases of marsupialization. No intraoperative complications occurred. The median follow-up was 82 months (range, 0-246 months). One patient had possible recurrence with dyspareunia and protruding tissue diagnosed 14 months postoperatively. There were no other postoperative complications in the follow-up period. CONCLUSION: GDCs are rare pelvic masses that are often asymptomatic but may present with dyspareunia, pelvic pain or pressure, pelvic mass or bulge, or urinary symptoms. Excision or marsupialization is successful in the majority of cases without significant morbidity.

Soy-based Infant Formula Feeding and Heavy Menstrual Bleeding Among Young African American Women.

BACKGROUND: Phytoestrogen exposure from soy formula feeding during infancy may disrupt reproductive system development, resulting in altered menstrual bleeding in adulthood. METHODS: We investigated this relationship in a cohort of 1,696 young African American women using enrollment data from the Study of Environment, Lifestyle, & Fibroids (2010-2012). Questionnaire data on soy formula feeding were available for 1,553 participants, 89% based on mother's report. Menstrual bleeding outcomes including those indicative of heavy menstrual bleeding were ascertained by interview. We estimated relative risks (RRs) and 95% confidence intervals (CI) for associations between soy formula feeding and menstrual bleeding outcomes using log-binomial regression and log-multinomial regression, comparing participants ever fed and never fed soy formula. RESULTS: We observed associations between soy formula feeding and variables indicating a history of heavy menstrual bleeding, including ever experiencing heavy, gushing-type bleeding (RR: 1.2, 95% CI: 1.0, 1.4), ever use of nonsteroidal anti-inflammatory drugs for heavy bleeding (RR: 1.3, 95% CI: 1.0, 1.6), and ever use of a contraceptive method for heavy bleeding (RR: 1.2, 95% CI, 0.9, 1.6). Among the subset of participants with menses in the past year who did not use medication that may alter menstrual flow (n = 762), our data suggested that soy formula feeding was associated with heavier flow and the adverse impact of menstrual bleeding on quality of life, but CIs were wide. CONCLUSIONS: Our data suggested that soy formula feeding is associated with heavy menstrual bleeding. Our results support the idea that infancy is a susceptible developmental window for female reproductive function.

Staging for low malignant potential ovarian tumors: a global perspective.

OBJECTIVE: We describe current evidence for staging low malignant potential ovarian tumors and their conformity to current consensus guidelines and practice from an international perspective. DATA SOURCES: A search of MEDLINE, EMBASE, and SCOPUS databases was conducted for articles published between January 1990 and April 2015. STUDY ELIGIBILITY CRITERIA: Studies on low malignant potential ovarian tumors that evaluated the prognostic value of disease stage, staging vs no staging, complete vs incomplete staging, or discrete components of staging were eligible. Studies that described only crude survival rates were excluded. STUDY APPRAISAL AND SYNTHESIS METHODS: Eligible studies were categorized according to their outcome (disease stage, staging procedure, or discrete staging elements). Data were abstracted using a standard form. Inconsistencies on data abstraction were resolved by consensus among the authors. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Of 1116 studies, 702 were excluded for irrelevance and 364 for not meeting inclusion criteria. Nine studies were excluded for describing crude survival rates without a comparative conclusion. We found that studies supporting the value of defining disease stage or staging procedures (mostly conducted in northern Europe) included more patients than studies that did not find disease stage or staging useful (predominantly from North America, 4072 vs 3951). Disease stage correlated with survival in 13 of 25 studies, whereas none of the studies that evaluated the value of staging found it beneficial (9 studies, 1979 patients). Studies that evaluated isolated components of staging found no benefit to these procedures. Regional guidelines and consensus reviews drew conclusions based on a limited number of studies that generally originated from the same region. CONCLUSIONS: Although the correlation of stage with survival was mixed, performing staging procedures for low malignant potential ovarian tumors is not supported by the best available evidence. Guidelines in support of staging based their recommendations on a few regional studies and conflict with better-quality data that do not support staging procedures. An international consensus statement is needed to standardize the surgical management of low malignant potential ovarian tumors.

Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial.

BACKGROUND: Uterine fibroids are an important source of morbidity for reproductive-aged women. Despite an increasing number of alternatives, hysterectomies account for about 75% of all fibroid interventional treatments. Evidence is lacking to help women and their health care providers decide among alternatives to hysterectomy. Fibroid Interventions: Reducing Symptoms Today and Tomorrow (NCT00995878, clinicaltrials.gov) is a randomized controlled trial to compare the safety, efficacy, and economics of 2 minimally invasive alternatives to hysterectomy: uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery. Although randomized trials provide the highest level of evidence, they have been difficult to conduct in the United States for interventional fibroid treatments. Thus, contemporaneously recruiting women declining randomization may have value as an alternative strategy for comparative effectiveness research. OBJECTIVE: We sought to compare baseline characteristics of randomized participants with nonrandomized participants meeting the same enrollment criteria and to determine whether combining the 2 cohorts in a comprehensive cohort design would be useful for analysis. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seeking interventional therapy at 3 US academic medical centers were randomized (1:1) in 2 strata based on calculated uterine volume (<700 and ≥700 cc(3)) to undergo embolization or focused ultrasound surgery. Women who met the same inclusion criteria but declined randomization were offered enrollment in a parallel cohort. Both cohorts were followed up for a maximum of 36 months after treatment. The measures addressed in this report were baseline demographics, symptoms, fibroid and uterine characteristics, and scores on validated quality-of-life measures. RESULTS: Of 723 women screened, 57 were randomized and 49 underwent treatment (27 with focused ultrasound and 22 with embolization). Seven of the 8 women randomized but not treated were assigned to embolization. Of 34 women in the parallel cohort, 16 elected focused ultrasound and 18 elected embolization. Compared with nonrandomized participants, randomized participants had higher mean body mass index (28.7 vs 25.3 kg/m(2); P = .01) and were more likely to be gravid (77% vs 47%; P = .003) and smokers (42% vs 12%; P = .003). Age, race, uterine volume, number of fibroids, and baseline validated measures of general and disease-specific quality of life, pain, depression, and sexual function did not differ between the groups. When we performed a comprehensive cohort analysis and analyzed by treatment arm, the only baseline difference observed was a higher median McGill Pain Score among women undergoing focused ultrasound (10.5 vs 6; P = .03); a similar but nonsignificant trend was seen in visual analog scale scores for pain (median, 39.0 vs 24.0; P = .06). CONCLUSION: Using a comprehensive cohort analysis of study data could result in additional power and greater generalizability if results are adjusted for baseline differences.

Intraoperative Predictors of Long-term Outcomes After Radiofrequency Endometrial Ablation.

STUDY OBJECTIVE: To identify intraoperative predictors of radiofrequency ablation (RFA) failure after adjusting for clinical risk factors. DESIGN: A cohort study (Canadian Task Force II-2). SETTING: An academic institution in the Upper Midwest. PATIENTS: Data were retrospectively collected from medical records of women who underwent RFA and who had a postprocedure gynecologic assessment between April 1998 and December 2011. INTERVENTIONS: RFA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was RFA failure, which was defined as hysterectomy, repeat ablation, synechiolysis, or treatment with gonadotropin-releasing hormone analogue for postablation pain or bleeding. Cox proportional hazards regression was used to test the predictability of intraoperative variables on RFA failure with adjustment for baseline predictors. We created an RFA index to capture the procedure duration divided by the uterine surface area. One thousand one hundred seventy-eight women were eligible. The median age at ablation was 44 years (interquartile range, 40-48 years), and the median parity was 2 (interquartile range, 2-3). Dysmenorrhea and prior tubal ligation were reported in 37.1% and 37.2% of women, respectively. After adjustment for baseline characteristics, intraoperative predictors of failure were uterine sounding length >10.5 cm (adjusted hazard ratio [HR] = 2.58; 95% confidence interval [CI], 1.31-5.05), uterine cavity length >6 cm (adjusted HR = 2.06; 95% CI, 1.30-3.27), uterine width >4.5 cm (adjusted HR = 2.06; 95% CI, 1.29-3.28), surface area >25 cm(2) (adjusted HR = 2.02; 95% CI, 1.26-3.23), procedure time <93 seconds (adjusted HR = 2.61; 95% CI, 1.25-5.47), and RFA index <3.6 (adjusted HR = 3.14; 95% CI, 1.70-5.77). CONCLUSION: Intraoperative parameters are predictive of long-term adverse outcomes of RFA independent of patient clinical characteristics. Uterine length, procedure duration, and RFA index are associated with unfavorable outcomes and thus could be used to optimize postprocedure patient counseling.

Hysteroscopic Morcellation Versus Resection for the Treatment of Uterine Cavitary Lesions: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis compares hysteroscopic morcellation with electrosurgical resection to treat uterine cavitary lesions. A search of Ovid MEDLINE, Ovid Embase, Scopus, and Web of Science was conducted through August 18, 2015, for randomized controlled trials (RCTs) and prospective and retrospective studies, regardless of surgical indication and study language or sample size. Seven studies were eventually included (4 RCTs and 3 retrospective observational studies), enrolling 650 women. The meta-analysis showed that the total procedure time was significantly shorter for morcellation than for resection (weighted mean difference = 9.36 minutes; 95% confidence interval [CI], -15.08 to -3.64). When reviewing RCTs only, intrauterine morcellation was associated with a smaller fluid deficit and lower odds of incomplete lesion removal. This difference was not statistically significant in observational studies. There was no significant difference in the odds of surgical complications (odds ratio = 0.72; 95% CI, 0.20-2.57) or the number of insertions (weighted mean difference = -3.04; 95% CI, -7.86-1.78). In conclusion, compared with hysteroscopic resection, hysteroscopic morcellation is associated with a shorter operative time and possibly lower odds of incomplete lesion removal. The certainty in evidence was limited by heterogeneity and the small sample size.