Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function.

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

Rethinking Disparities in Minimally Invasive Myomectomy: Identifying Drivers of Disparate Surgical Approach to Myomectomy Between African American and White Women.

STUDY OBJECTIVE: To identify drivers of disparities among patients undergoing surgical management of myomas when stratified by self-identified patient race. DESIGN: This is a retrospective institutional review board-approved chart review of all patients who underwent a myomectomy at a large academic center. Surgical approach to myomectomy was classified as abdominal, laparoscopic, or robotic-assisted laparoscopic. Myoma burden was quantified preoperatively using uterine volume, intraoperatively by number of myomas listed on operative report, and postoperatively by myoma weight from pathology reports. SETTING: A large tertiary care hospital containing a comprehensive myoma treatment center. PATIENTS: A total of 265 white patients and 121 African American patients who underwent a myomectomy between January 2012 and October 2018 were included in the study population. INTERVENTIONS: Abdominal, laparoscopic, and robotic-assisted myomectomy. Laparoscopic and robotic-assisted myomectomy were classified as minimally invasive myomectomy. Multivariable logistic regression models and a propensity score matching algorithm were used to match African American (AA) women and white women for myoma burden. MEASUREMENTS AND MAIN RESULTS: A total of 386 women were included in the study. AA women (31%; n = 121) had higher myoma burden than white women by preoperative imaging (AA: 36% with 3 or more myomas; white: 19% with 3 or more myomas; p <.01) and operative report (>8 AA: 31% vs white 13%; p <.01). Despite this, AA women underwent minimally invasive myomectomy at similar rates as compared with white women when adjusted for myoma burden, body mass index, preoperative hematocrit, hypertension, and surgical indication (adjusted odds ratio 1.3; 95% confidence interval, 0.8-2.2 myomas; p <.01). Sensitivity analysis using propensity score matching found similar results. CONCLUSION: In this population, AA women had a higher myoma burden than white women. When matched for myoma burden, however, there was no statistically significant difference between rates of minimally invasive myomectomy and abdominal myomectomy. This finding was consistent when controlling for myoma burden measured by preoperative, intraoperative, or postoperative methods of measurement. Further studies are needed to better characterize this disparity at other hospitals and to investigate ways to increase access and equity among patients undergoing minimally invasive myomectomy.

Endometrial findings among transgender and gender nonbinary people using testosterone at the time of gender-affirming hysterectomy.

OBJECTIVE: To describe clinical characteristics and associated endometrial findings of transgender and gender nonbinary people using gender-affirming testosterone. DESIGN: Retrospective case series. SETTING: Academic medical center and public safety net hospital. PATIENT(S): Eighty-one patients using gender-affirming testosterone therapy undergoing hysterectomy for the indication of gender affirmation from 2000 to 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preoperative clinical characteristics and endometrium surgical pathology diagnoses. RESULT(S): Median age was 31 years (interquartile range [IQR] 27-40), and median body mass index 27 kg/m2 (IQR 24-30). Six patients (7%) were parous and 60 (74%) had amenorrhea. Thirty-three patients (40%) had proliferative and 40 (50%) atrophic endometrium. Endometrial polyps were found in nine patients (11%) of the sample. Endometrial findings were similar in the subgroup of 60 patients with preoperative amenorrhea. There were no cases of endometrial hyperplasia or malignancy. In bivariate analysis, those with proliferative endometrium were found to be, on average, 5.6 years younger than those with atrophic endometrium. There were no clinical factors associated with having proliferative versus atrophic endometrium in multivariable models. CONCLUSION(S): People using gender-affirming testosterone may have either proliferative or atrophic endometrium, including people who present with amenorrhea. Further study is needed to develop evidence-based guidelines for appropriate screening for endometrial hyperplasia or cancer in this population.

PROMISe trial: a pilot, randomized, placebo-controlled trial of magnetic resonance guided focused ultrasound for uterine fibroids.

OBJECTIVE: To evaluate the feasibility of a full-scale placebo-controlled trial of magnetic resonance-guided focused ultrasound for fibroids (MRgFUS) and obtain estimates of safety and efficacy. DESIGN: Pilot, randomized, placebo-controlled trial. SETTING: University medical center. PATIENT(S): Premenopausal women with symptomatic uterine fibroids. INTERVENTION(S): Participants randomized in a 2:1 ratio to receive MRgFUS or placebo procedure. PRIMARY OUTCOME: change in fibroid symptoms from baseline to 4 and 12 weeks after treatment assessed by the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QOL); secondary outcome: incidence of surgery or procedures for recurrent symptoms at 12 and 24 months. RESULT(S): Twenty women with a mean age of 44 years (±standard deviation 5.4 years) were enrolled, and 13 were randomly assigned to MRgFUS and 7 to placebo. Four weeks after treatment, all participants reported improvement in the UFS-QOL: a mean of 10 points in the MRgFUS group and 9 points in the placebo group (for difference in change between groups). By 12 weeks, the MRgFUS group had improved more than the placebo group (mean 31 points and 13 points, respectively). The mean fibroid volume decreased 18% in the MRgFUS group with no decrease in the placebo group at 12 weeks. Two years after MRgFUS, 4 of 12 women who had a follow-up evaluation (30%) had undergone another fibroid surgery or procedure. CONCLUSION(S): Women with fibroids were willing to enroll in a randomized, placebo-controlled trial of MRgFUS. A placebo effect may explain some of the improvement in fibroid-related symptoms observed in the first 12 weeks after MRgFUS. CLINICAL TRIAL REGISTRATION NUMBER: NCT01377519.

Use of medical, surgical and complementary treatments among women with fibroids.

OBJECTIVE: To examine the use of medical management, uterus-preserving surgery (UPS), and complementary treatments among women with uterine fibroids. STUDY DESIGN: Prospective cohort study of 933 premenopausal women ages 31-54 years with symptomatic fibroids who participated in the Study of Pelvic Problems, Hysterectomy, and Intervention Alternatives (SOPHIA) for an average of 4.3 years (SD 2.5 years). Incident use of fibroid treatments was determined through annual interviews. Linear regression models were used to compare changes in fibroid-related symptoms among women who underwent UPS versus those who did not undergo surgery. RESULTS: Participants were racially and ethnically diverse, with a mean age of 43 years. During study follow-up, 531 participants (57%) did not undergo UPS or hysterectomy, 250 (27%) had at least one UPS, and 152 (16%) underwent hysterectomy. Complementary and alternative treatments were commonly used, including exercise (45%), diet (34%), herbs (37%), and acupuncture (16%): participants reported significant symptom improvement and few side effects with these interventions. In multivariable linear regression models, women who did not undergo surgery during the study reported improvement in dyspareunia (p<.001), pelvic pain (p<.001), and menstrual cramps (p<.001). However, women who underwent UPS reported greater overall resolution of "pelvic problems" compared with women who did not have surgical treatment (difference in change score 1.18 on a four-point Likert scale, p<.001). CONCLUSION: UPS are effective treatments for women with fibroids, but many women use hormonal or complementary treatments and report significant symptom improvement without surgical intervention.

Contributions of hysterectomy and uterus-preserving surgery to health-related quality of life.

OBJECTIVE: To document the long-term effect of surgical interventions for noncancerous uterine conditions on health-related quality of life. METHODS: The Study of Pelvic Problems, Hysterectomy and Intervention Alternatives, conducted between 1998 and 2008, was a longitudinal study of 1,503 women with intact uteri experiencing abnormal uterine bleeding with or without leiomyomas, chronic pelvic pain, or pressure resulting from leiomyomas. Baseline and follow-up questionnaires included three condition-specific measures (Pelvic Problem Resolution, Pelvic Problem Impact Overall, and Pelvic Problem Impact on Sex) and five generic measures (Short Form-12 Mental and Physical Component Summaries, Current Health Utility, Feelings about Heath, and Satisfaction with Sex). We modeled changes over time in these patient-reported outcomes stratified by the most invasive treatment undergone (hysterectomy [13.7%], uterus-preserving surgery [9.0%], or nonsurgical therapy [77.3%]). RESULTS: Participants in all three groups reported significant improvement on all condition-specific measures and two of the five generic measures (Current Health Utility and Feelings about Health) from enrollment to final interview (all P values <.01). In general, greater improvements were experienced by women who had surgery. Trajectories modeled around the dates of surgery showed dramatic improvements after hysterectomy and, to a lesser degree, after uterus-preserving surgery. Although women who underwent uterus-preserving surgery tended to show immediate improvement, women who underwent hysterectomy experienced a 6-month delay in improvement in some outcomes with trajectories converging by 4 years postsurgery. CONCLUSION: Women seeking care for noncancerous uterine conditions can expect to experience improvement over time. Those who opt for surgery may experience most improvement. Understanding health-related quality-of-life trajectories may enhance counseling for women deciding between hysterectomy and alternative interventions. LEVEL OF EVIDENCE: II.

Neonatal outcomes in women with sonographically identified uterine leiomyomata.

OBJECTIVE: We sought to compare perinatal outcomes between women with and without leiomyomata. STUDY DESIGN: This is a retrospective cohort study comparing neonatal outcomes in women with and without uterine leiomyomata discovered at routine second trimester obstetric ultrasonography, all of whom delivered at a single institution. Potential confounders such as maternal age, parity, race, ethnicity, medical insurance, previous uterine surgery, fetal presentation, length of labor, mode of delivery, presence of placenta previa, placental abruption, chorioamnionitis, and epidural use were controlled for using multivariable logistic regression. RESULTS: From 1993 to 2003, 15,104 women underwent routine second trimester prenatal ultrasonography, with 401 (2.7%) women identified with at least one leiomyoma. By univariate and multivariable analyses, the presence of leiomyomata was associated with statistically significant increased risks for preterm delivery at <34 weeks [adjusted odds ratio (AOR) 1.7, 95% confidence interval (CI) 1.1-2.6], <32 weeks (AOR 1.9, 95% CI 1.2-3.2), and <28 weeks (AOR 2.0, 95% CI 1.1-3.8). An association with increased risk for intrauterine fetal demise (IUFD) was also demonstrated (AOR 2.7, 95% CI 1.0-6.9). When IUFD was examined before and after 32 weeks' gestation, the finding only persisted at earlier gestational ages (<32 weeks: AOR 4.2, 95% CI 1.2-14.7 vs. >32 weeks: AOR 0.82, 95% CI 0.1-6.2). CONCLUSION: Regardless of maternal age, ethnicity, and parity, pregnant women with leiomyomata are at increased risk for preterm birth and IUFD. This did not translate to lower birth weight outcomes among term patients, suggesting that LBW is more likely due to preterm birth than growth restriction. These results may be useful for preconception and prenatal counseling of women with leiomyomata.

Symptom resolution after hysterectomy and alternative treatments for chronic pelvic pain: does depression make a difference?

OBJECTIVE: The purpose of this study was to determine whether depression influences treatment outcomes and to identify predictors of symptom resolution among women with chronic pelvic pain (CPP). STUDY DESIGN: Analysis of 701 women with CPP in the Study of Pelvic Problems, Hysterectomy and Intervention Alternatives prospective cohort study, which included 153 women (22%) with depression. We conducted multivariable analyses to evaluate the influence of depression on pre-/posttreatment differences in symptoms and health-related quality of life and to identify other predictors of symptom improvement. RESULTS: CPP treatments included hysterectomy (9%), other surgical treatments (9%), hormonal medications (50%), narcotic analgesics (47%), physical therapy (12%), and nonprescription medications (93%). Depression predicted lower gains in health perception (P < .05) but not in symptom resolution, sexual functioning, or other aspects of health-related quality of life. Symptom resolution was predicted by hysterectomy (P < .001), entering menopause (P < .001), and pretreatment satisfaction with sex (P = .039). CONCLUSION: Depression does not influence substantially treatment-related gains in CPP symptom resolution and health-related quality of life. Coexisting depression should not delay treatment for CPP.

Success of uterus-preserving treatments for abnormal uterine bleeding, chronic pelvic pain, and symptomatic fibroids: age and bridges to menopause.

OBJECTIVE: The purpose of this study was to determine whether age at first uterus-preserving treatment (UPT) predicts symptom resolution among women with common pelvic problems. STUDY DESIGN: We conducted an analysis of 557 participants in the Study of Pelvic Problems, Hysterectomy and Intervention Alternatives cohort who reported having undergone a UPT. We performed multivariable regression modeling age at first UPT, hysterectomy, menopause, and other covariates to predict symptom resolution. RESULTS: Mean ± SD age at enrollment was 42.7 ± 4.7 years; mean follow-up time was 4.4 ± 2.7 years. Sixteen percent of the women underwent hysterectomy; 37% of the women entered menopause. Hysterectomy was a strong predictor of symptom resolution (P < .001). Compared with women who were younger (first UPT at age <40 years), older women reported greater symptom resolution, even after the data were controlled for hysterectomy use and menopausal status (P = .028). CONCLUSION: Women who are ≥40 years old when they undergo their first uterus-preserving treatment experience greater symptom resolution than younger women. Framing UPTs as hysterectomy alternatives may be accurate only for a subset of women who are >40 years old.

Predictors of hysterectomy use and satisfaction.

OBJECTIVE: To identify static and time-varying sociodemographic, clinical, health-related quality-of-life and attitudinal predictors of use and satisfaction with hysterectomy for noncancerous conditions. METHODS: The Study of Pelvic Problems, Hysterectomy, and Intervention Alternatives (SOPHIA) was conducted from 1998 to 2008. English-, Spanish-, or Chinese-speaking premenopausal women (n=1,420) with intact uteri who had sought care for pelvic pressure, bleeding, or pain from an academic medical center, county hospital, closed-panel health maintenance organization, or one of several community-based practices in the San Francisco Bay area were interviewed annually for up to 8 years. Primary outcomes were use of and satisfaction with hysterectomy. RESULTS: A total of 207 women (14.6%) underwent hysterectomy. In addition to well-established clinical predictors (entering menopause, symptomatic leiomyomas, prior treatment with gonadotropin-releasing hormone agonist, and less symptom resolution), greater symptom impact on sex (P=.001), higher 12-Item Short Form Health Survey mental component summary scores (P=.010), and higher scores on an attitude measure describing "benefits of not having a uterus" and lower "hysterectomy concerns" scores (P<.001 for each) were predictive of hysterectomy use. Most participants who underwent hysterectomy were very (63.9%) or somewhat (21.4%) satisfied in the year after the procedure, and we observed significant variations in posthysterectomy satisfaction across the clinical sites (omnibus P=.036). Other determinants of postsurgical satisfaction included higher pelvic problem impact (P=.035) and "benefits of not having a uterus" scores (P=.008) before surgery and greater posthysterectomy symptom resolution (P=.001). CONCLUSION: Numerous factors beyond clinical symptoms predict hysterectomy use and satisfaction. Providers should discuss health-related quality of life, sexual function, and attitudes with patients to help identify those who are most likely to benefit from this procedure.

Prevalence and incidence of urinary incontinence in a diverse population of women with noncancerous gynecologic conditions.

OBJECTIVE: To determine the prevalence and incidence of urinary incontinence (UI) in a diverse cohort of women presenting with noncancerous gynecologic conditions and to assess factors associated with UI prevalence and incidence. METHODS: We conducted a secondary analysis of data from SOPHIA (Study of Pelvic Problems, Hysterectomy and Intervention Alternatives), a longitudinal study of women with noncancerous gynecologic conditions (bleeding, pelvic pain, and symptomatic fibroids). UI was defined as incontinence in the last 4 weeks as reported on interviewer-administered annual questionnaires. We also evaluated the type of UI: stress (SUI), urge (UUI) or mixed incontinence (MUI). RESULTS: The study population of 907 women was 40.8% White, 28.0% African American, 17.3% Latina and 8.1% Asian. The mean age was 44.1 ± 5.4 years and 48.5% had an annual household income of ≤$50,000. The overall prevalence of any UI was 51.1%. At baseline, SUI was the most common at 39.4% followed by UUI at 23.7% and MUI at 18.9%. The average annual incidence for any UI was 4.2%. 13% of the women who underwent hysterectomy developed incident UI after their surgery. In multivariable logistic regression analysis, prevalent UI was associated with the following: age in decades (OR 1.6, 95% CI 1.2, 2.2), Latina race/ethnicity compared to white (OR 2.1, 95% CI 1.3, 3.3), and parity (OR 1.7, 95% CI 1.2, 2.4). None of the factors evaluated were associated with incidence of UI. CONCLUSION: Urinary incontinence is very common in women seeking care for noncancerous gynecologic conditions, particularly among older, parous Latinas.

Nationwide use of laparoscopic hysterectomy compared with abdominal and vaginal approaches.

OBJECTIVE: To examine factors associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy or vaginal hysterectomy. METHODS: This is a cross-sectional analysis of the 2005 Nationwide Inpatient Sample. All women aged 18 years or older who underwent hysterectomy for a benign condition were included. Multivariable analyses were used to examine demographic, clinical, and health-system factors associated with each hysterectomy route. RESULTS: Among 518,828 hysterectomies, 14% were laparoscopic, 64% abdominal, and 22% vaginal. Women older than 35 years had lower rates of laparoscopic than abdominal (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.77-0.94 for age 45-49 years) or vaginal hysterectomy (OR 0.61, 95% CI 0.540.69 for age 45-49 years). The odds of laparoscopic compared with abdominal hysterectomy were higher in the West than in the Northeast (OR 1.77, 95% CI 1.2-2.62). African-American, Latina, and Asian women had 40-50% lower odds of laparoscopic compared with abdominal hysterectomy (P<.001). Women with low income, Medicare, Medicaid, or no health insurance were less likely to undergo laparoscopic than either vaginal or abdominal hysterectomy (P<.001). Women with leiomyomas (P<.001) and pelvic infections (P<.001) were less likely to undergo laparoscopic than abdominal hysterectomy. Women with leiomyomas (P<.001), endometriosis (P<.001), or pelvic infections (P<.001) were more likely to have laparoscopic than vaginal hysterectomy. Laparoscopic hysterectomy had the highest mean hospital charges ($18,821, P<.001) and shortest length of stay (1.65 days, P<.001). CONCLUSION: In addition to age and clinical diagnosis, nonclinical factors such as race/ethnicity, insurance status, income, and region appear to affect use of laparoscopic hysterectomy compared with abdominal hysterectomy and vaginal hysterectomy. LEVEL OF EVIDENCE: III.

Effect of noncancerous pelvic problems on health-related quality of life and sexual functioning.

OBJECTIVE: To assess the effect of abnormal uterine bleeding and pelvic pain and pressure on health-related quality of life and sexual functioning and assess treatment satisfaction. METHODS: This is a cross-sectional study of 1,493 sociodemographically diverse women who were seeking care for noncancerous pelvic problems and who had not undergone hysterectomy. Participants were asked about symptoms, attitudes, health-related quality of life, sexual functioning, and treatment satisfaction. Preference for current health was measured using the time tradeoff metric, which asked respondents to estimate the number of years of life they would be willing to trade off to not have a uterine condition. Multivariable logistic regression was used to identify determinants of treatment satisfaction. RESULTS: Most (82.7%) participants reported a complete lack of or only partial symptom resolution, and 42.3% reported that their pelvic problems interfered with their ability to have and enjoy sex. Mean Short Form-12 Physical (43-49) and Mental (41-44) Component Summary scores were substantially lower than population norms for women aged 40-49 years. Mean current health time tradeoff scores ranged from 0.78 to 0.88. Satisfaction with Western medicines ranged from 31.3% (progestin intrauterine device) to 58.2% (opiates) and with uterine-preserving surgery from 20.0% (dilation and curettage) to 51.0% (myomectomy); 27.7 % of the women who used acupuncture were satisfied. Participants with lower educational attainment, greater symptom resolution, and less interference of pelvic problems with sex were more likely to be satisfied. CONCLUSION: Noncancerous pelvic problems are associated with serious decrements in health-related quality of life and sexual functioning and low rates of treatment satisfaction. LEVEL OF EVIDENCE: II.

Ultrasound interstitial thermal therapy (USITT) for the treatment of uterine myomas.

Uterine myomas (fibroids) are the most common pelvic tumors occurring in women, and are the leading cause of hysterectomy. Symptoms can be severe, and traditional treatments involve either surgical removal of the uterus (hysterectomy), or the fibroids (myomectomy). Interstitial ultrasound technologies have demonstrated potential for hyperthermia and high temperature thermal therapy in the treatment of benign and malignant tumors. These ultrasound devices offer favorable energy penetration allowing large volumes of tissue to be treated in short periods of time, as well as axial and angular control of heating to conform thermal treatment to a targeted tissue, while protecting surrounding tissues from thermal damage. The goal of this project is to evaluate interstitial ultrasound for controlled thermal coagulation of fibroids. Multi-element applicators were fabricated using tubular transducers, some of which were sectored to produce 180° directional heating patterns, and integrated with water cooling. Human uterine fibroids were obtained after routine myomectomies, and instrumented with thermocouples spaced at 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 cm from the applicator. Power levels ranging from 8-15 W per element were applied for up to 15 minute heating periods. Results demonstrated that therapeutic temperatures >50° C and cytotoxic thermal doses (t43) extended beyond 2 cm radially from the applicator (>4 cm diameter). It is anticipated that this system will make a significant contribution toward the treatment of uterine fibroids.

Obstetric outcomes in women with sonographically identified uterine leiomyomata.

OBJECTIVE: To examine the association between leiomyomata and complications during pregnancy, delivery, and the puerperium. METHODS: We conducted a retrospective cohort study comparing pregnancy outcomes in women with and without uterine leiomyomata who underwent routine second trimester obstetric ultrasonography and delivered viable infants at a single institution. Potential confounding variables, including maternal age, weight, ethnicity, parity, gestational age, epidural use, and labor induction, were controlled for using multivariate logistic regression techniques. RESULTS: From 1993 to 2003, 15,104 women underwent routine second trimester prenatal ultrasonography, and 401 (2.7%) women were identified with at least 1 leiomyoma. By univariate and multivariate analyses, the presence of leiomyomata was associated with increased risks for cesarean delivery (adjusted odds ratio [AOR] 1.57, 95% confidence interval [CI] 1.16-2.13), breech presentation (AOR 1.64, 95% CI 1.11-2.40), malposition (AOR 1.59, 95% CI 1.18-2.15), preterm delivery (AOR 1.45, 95% CI 1.08-1.96), placenta previa (AOR 1.86, 95% CI 1.02-3.39), and severe postpartum hemorrhage (AOR 2.57, 95% CI 1.54-4.27). Premature rupture of membranes, operative vaginal delivery, chorioamnionitis, and endomyometritis were not associated with leiomyomata. Median length of labor was not different between the 2 groups. When compared with leiomyomata less than 10 cm in size, leiomyomata 10 cm or larger were associated with rates of cesarean delivery that were not statistically different (25% compared with 31%, P = .49). CONCLUSION: Pregnant women with leiomyomata are at increased risk for cesarean delivery, breech presentation, malposition, preterm delivery, placenta previa, and severe post partum hemorrhage. Women with leiomyomata 10 cm or larger achieve a vaginal delivery rate of nearly 70%. These results are useful for preconception and prenatal counseling of women with leiomyomata. LEVEL OF EVIDENCE: II-2.

Systematic review of mifepristone for the treatment of uterine leiomyomata.

OBJECTIVE: To systematically review the effect of mifepristone on uterine leiomyoma size and symptoms and to summarize its adverse effects. DATA SOURCES: A computerized search in MEDLINE, EMBASE, LILACS, and Cochrane databases from 1985 to 2002 and hand searches of conference proceedings from 1995 to 2002 were performed with the search terms "mifepristone" and "leiomyomata" and publication type "clinical trial." METHODS OF STUDY SELECTION: Titles and abstracts were reviewed by 2 authors; there were no areas of disagreement. Inclusion criteria were clinical trials of daily mifepristone for uterine leiomyomata that measured uterine or leiomyoma volume before and after treatment. TABULATION, INTEGRATION, AND RESULTS: Data from each article were abstracted by 2 reviewers. The search identified 6 before-and-after clinical trials involving a total of 166 women with symptomatic uterine leiomyomata. The subjects received 5 to 50 mg/d of mifepristone for 3 to 6 months. No study was placebo-controlled or blinded. Meta-analytic techniques were not performed due to variation in outcome and mifepristone dose. Daily treatment with all doses of mifepristone resulted in reductions in uterine and leiomyoma volumes ranging from 27% to 49% and 26% to 74%, respectively. Mifepristone treatment reduced the prevalence and severity of dysmenorrhea, menorrhagia, and pelvic pressure. Rates of amenorrhea ranged from 63% to 100%. Transient elevations in transaminases occurred in 4%. Endometrial hyperplasia was detected in 10 (28%) of 36 women screened by endometrial biopsy. CONCLUSION: Published trials of mifepristone showed reduction in leiomyoma size and improvement in symptoms. A notable adverse effect of mifepristone was development of endometrial hyperplasia.

Coil embolization of a tuboovarian anastomosis before uterine artery embolization to prevent nontarget particle embolization of the ovary.

Uterine artery embolization (UAE) is being used more frequently as a primary treatment for uterine leiomyoma. Performing UAE in women who desire future fertility is controversial because of the risks of premature menopause and the undetermined effects on pregnancy. The etiology of ovarian failure after UAE is not yet clearly defined, but one of the leading possibilities is nontarget embolization of the ovaries. In this case report, the authors describe a technique of selective coil embolization of a uterine artery-to-ovarian artery communication before UAE performed specifically to protect the ovary from nontarget embolization.

Reversal of flow in the ovarian artery during uterine artery embolization.

Uterine artery embolization (UAE) is gaining increasing recognition as an effective treatment alternative to hysterectomy in select patients. As interventional radiologists gain more experience in the treatment of fibroids, new interest is being directed toward arterial communications between the uterine arteries and ovarian arteries. This case report focuses on the potentially serious complication of flow reversal up the ovarian artery into the aorta during UAE.