Endometrial Effects of Prolonged Therapy with the Selective Progesterone Receptor Modulator Ulipristal Acetate: A Case Report.

BACKGROUND: Prolonged exposure to a selective progesterone receptor modulator (ulipristal acetate) in a patient with benign metastasizing leiomyoma did not result in endometrial hyperplasia or neoplasia. CASE: A woman with history of benign metastasizing leiomyoma underwent medical treatment for 5 years with ulipristal acetate. Endometrial biopsies were performed at established intervals to monitor for intraepithelial neoplasia or progesterone receptor modulator-associated endometrial changes (PAECs). The patient tolerated UPA therapy well; there was no evidence of hyperplasia or proliferative changes associated with progesterone-associated endometrial changes. CONCLUSION: In this case prolonged exposure to ulipristal acetate did not result in premalignant or malignant endometrial pathology.

Is Myomectomy Prior to Assisted Reproductive Technology Cost Effective in Women with Intramural Fibroids?

AIM: To evaluate the cost effectiveness of surgery to remove intramural (IM) fibroids prior to assisted reproductive technology (ART). METHODS: The decision tree mathematical model along with sensitivity analysis was performed to analyze cost effectiveness of: (1) myomectomy followed by ART or (2) ART with IM myoma(s) in situ. RESULTS: At the median ongoing pregnancy (OP) rate (OPR) reported in the literature for a fresh, autologous ART cycle with IM fibroids in situ vs. post-IM myomectomy, average cost per OP was $72,355 vs. 66,075, indicating a cost savings with myomectomy. Sensitivity analysis over the range of reported OPRs demonstrated that pre-ART IM myomectomy was always cost effective when OPR among women with in situ myomas was <15.4%. However, for OPRs ≥15.4%, pre-ART IM myomectomy was only cost effective if it increased OPR by at least 9.6%. At the high end of OPRs reported for patients with IM myomas in situ (31.4%), a 19.5% improvement in OPR was needed to justify IM myomectomy from a cost perspective. CONCLUSION: Myomectomy should be used sparingly in cases where the goal of surgery is to achieve improvement in the outcomes of ART.

Clinical management of leiomyoma.

Uterine leiomyoma, benign monoclonal tumors, afflict an estimated 60% of reproductive-aged women, with higher rates among African American women. Leiomyoma are associated with significant medical costs, impaired fertility potential, obstetric complications, and gynecologic morbidity. Currently, the effective clinical management of leiomyoma is limited by the fact that hysterectomy is the only cure. The purpose of this article is to provide the practitioner with a practical overview of the clinical management of this disease.

The health disparities of uterine fibroid tumors for African American women: a public health issue.

Uterine fibroid tumors (leiomyomas) are the most common benign pelvic tumors in women and are the major indication for hysterectomy. Fibroid tumors are more common and more severe among African American women. Although this disease disproportionately affects the African American population, we understand little about what causes the disparity. Fibroid tumors should be considered a public health issue, given the magnitude of the problem and the costs of health care for this disease. In this review, we examine the burden of disease from fibroid tumors in the African American population and review the natural history, diagnosis, and treatment of uterine fibroid tumors, with emphasis on how these can differ, depending on race. We also focus on the socioeconomic burden caused by the disease and describe the anticipated influence of new health care reforms and funding mechanisms for fibroid tumor research.

Biomarkers in uterine leiomyoma.

Biomarkers are biologic compounds that are easily accessible and reflect normal physiology or pathology. They are useful in a variety of clinical situations that involve detection of subclinical disease, risk stratification, preoperative planning, and monitoring treatment. A useful intervention needs to exist for a biomarker to be an effective tool. Many compounds have been investigated as potential biomarkers for the diagnosis and surveillance of uterine leiomyomas. Most of these compounds demonstrate subtle differences among patients when leiomyomas are compared with controls. The compounds investigated lack the diagnostic accuracy necessary to add any benefit to the current available modalities used to diagnose and monitor uterine leiomyomas.

Is anti-Müllerian hormone a marker of acute cyclophosphamide-induced ovarian follicular destruction in mice pretreated with cetrorelix?

OBJECTIVE: To define whether anti-Müllerian hormone (AMH) may be a marker of acute cyclophosphamide (CTX)-induced germ cell destruction in mice pretreated with the GnRH antagonist, cetrorelix. DESIGN: Controlled, experimental study. SETTING: Research laboratory in a federal research facility. ANIMAL(S): Balb/c female mice (6 weeks old). INTERVENTION(S): Mice were treated with GnRH antagonist (cetrorelix) or saline for 15 days followed by 75 mg/kg or 100 mg/kg of CTX or saline control on day 9. MAIN OUTCOME MEASURE(S): Number of primordial follicles (PMF), DNA damage, AMH protein expression, and AMH serum levels. RESULT(S): Ovaries in mice pretreated with cetrorelix had significantly more PMFs and reduced DNA damage compared with those exposed to CTX alone. Immunohistochemical staining for AMH expression and serum AMH levels did not differ significantly between treatment groups. CONCLUSION(S): Cetrorelix protected PMFs and reduced DNA damage in follicles of mice treated with CTX, but AMH levels in tissue and serum did not correlate with germ cell destruction. Further research is needed to determine the mechanism responsible for the protective effects on PMF counts observed with cetrorelix.

Are there ethnic differences in pregnancy rates in African-American versus white women undergoing frozen blastocyst transfers?

OBJECTIVE: To determine whether frozen-thawed blastocyst transfer pregnancy rates (PR) are lower in African-American compared with white women. DESIGN: Retrospective review of frozen blastocyst cycles. SETTING: University-based assisted reproductive technology (ART) program. PATIENT(S): All patients who underwent a frozen blastocyst transfer between 2003 and 2008. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): One hundred sixty-nine patients underwent transfer of a frozen-thawed blastocyst. African-American women had a higher incidence of leiomyoma (40% vs. 10%) and tubal and uterine factor infertility. There was no difference in the live birth rate for African-American patients (28.0%) compared with white patients (30.2%). Of the patients who underwent a frozen-thawed blastocyst transfer, 58% (n=98) had their fresh, autologous IVF cycle, which produced the cryopreserved blastocyst, at Walter Reed Medical Center. A higher peak serum E2 level was noted in African-American patients (5,355 pg/mL) compared with white patients (4,541 pg/mL). During the fresh cycle, the live birth rates between African-American and white patients were significantly different at 16.7% versus 39.7%, respectively. CONCLUSION(S): Live birth rates after frozen blastocyst transfer are not different between African-American and white women despite a fourfold higher incidence of leiomyomas in African-American women.

Use of F 18-fluoro-D-glucose-positron emission tomography-computed tomography to localize a hilar cell tumor of the ovary.

OBJECTIVE: To describe provocative testing and alternative imaging strategies used to localize an androgen-producing tumor in a 58-year-old woman with severe hirsutism. DESIGN: Case report. SETTING: Clinical Research Center. PATIENT(S): A 58-year-old woman who was seen for evaluation of severe hirsutism. INTERVENTION(S): Serum androgen levels were measured at baseline, 4 hours after administration of 2000 IU of hCG, and 11 days after administration of 3.75 mg of leuprolide acetate (LA). Magnetic resonance imaging and F 18-fluoro-D-glucose-positron emission tomography-computed tomography (FDG-PET/CT) were performed. MAIN OUTCOME MEASURE(S): Description of preoperative provocative testing and imaging. RESULT(S): In response to hCG, T rose from 243 to 288 ng/dL then decreased to 233 ng/dL after LA administration. The FDG-PET/CT scan demonstrated focal hypermetabolism in the right pelvis, corresponding to a soft-tissue density on the noncontrast CT scan. Magnetic resonance images were correlated with the PET/CT, and the right ovary was identified. Right salpingo-oophorectomy was performed, and final pathologic examination revealed a hilar cell tumor with ovarian cortical hyperplasia. CONCLUSION(S): This case demonstrates the utility of provocative testing in the evaluation of a patient with severe hirsutism and illustrates the value of FDG-PET/CT when traditional imaging is nondiagnostic.

CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial.

OBJECTIVE: To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms. METHODS: Premenopausal women with symptomatic uterine leiomyomata were randomly assigned to CDB-2914 at 10 mg (T1) or 20 mg (T2) daily or to placebo (PLC) for 3 cycles or 90-102 days if no menses occurred. The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy. Secondary outcomes included the proportion of amenorrhea, change in hemoglobin and hematocrit, ovulation inhibition, and quality-of-life assessment. RESULTS: Twenty-two patients were allocated, and 18 completed the trial. Age and body mass index were similar among groups. Leiomyoma volume was significantly reduced with CDB-2914 administration (PLC 6%; CDB-2914 -29%; P=.01), decreasing 36% and 21% in the T1 and T2 groups, respectively. During treatment, hemoglobin was unchanged, and the median estradiol was greater than 50 pg/mL in all groups. CDB-2914 eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles: CDB-2914, 20%; PLC, 83%; P=.001). CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality-of-life subscale (P=.04). One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported. CONCLUSION: Compared with PLC, CDB-2914 significantly reduced leiomyoma volume after three cycles, or 90-102 days. CDB-2914 treatment resulted in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment. In this small study, CDB-2914 was well-tolerated without serious adverse events. Thus, there may be a role for CDB-2914 in the treatment of leiomyomata. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,www.clinicaltrials.gov, NCT00290251 LEVEL OF EVIDENCE: I.

Compensatory alterations in energy homeostasis characterized in uterine tumors from hereditary leiomyomatosis and renal cell cancer.

OBJECTIVE: To determine the molecular alterations that maintain energy homeostasis in hereditary leiomyomatosis and renal cell cancer (HLRCC) uterine tumors with disrupted fumarate hydratase, compared with nonsyndromic uterine tumors. DESIGN: Laboratory study. SETTING: Tertiary academic university hospital. PATIENT(S): Eleven nonsyndromic leiomyoma-myometrium pairs and three HLRCC leiomyoma-myometrium pairs were obtained from patients who were recruited at national and military research centers in the United States. INTERVENTION(S): Molecular analysis. MAIN OUTCOME MEASURE(S): Hereditary leiomyomatosis and renal cell cancer and nonsyndromic leiomyomas were compared with patient-matched myometrium for relative glycolysis and Krebs cycle gene expression. RESULT(S): By microarray analysis, we confirmed that fumarate hydratase messenger RNA (mRNA) was underexpressed in HLRCC fibroids, compared with matched myometrium. Consistent with the possibility that alterations in fumarate hydratase represented a change to a more anaerobic state, we found that HLRCC fibroids overexpressed genes such as phosphofructokinase, aldolase, phosphoglycerate kinase, enolase, and pyruvate kinase. Expression of these genes was not altered in nonsyndromic leiomyomas. Furthermore, there were no overt changes in expression of Krebs cycle enzyme gene expression, with the exception of fumarate hydratase. CONCLUSION(S): Our findings demonstrate that alterations in fumarate hydratase are compensated for by increases in glycolysis enzyme expression in HLRCC.

Comparison of assisted reproductive technology utilization and outcomes between Caucasian and African American patients in an equal-access-to-care setting.

OBJECTIVE: Racial disparity in assisted reproductive technology (ART) outcomes has been reported but remains controversial. Reasons for the disparity are unclear, and access to care has been suggested as a causative factor. In this study, we sought to examine minority utilization of ART in the Department of Defense (DoD) compared with minority utilization in the U.S. ART population. Outcomes from ART were compared between Caucasian (Cau) and African American (AA) patients, and etiologies of disparity were examined. DESIGN: Retrospective cohort study. SETTING: University-based ART program. PATIENT(S): A total of 1,457 patients undergoing first-cycle fresh, nondonor ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate, implantation rate, spontaneous abortion rate. RESULT(S): Within the DoD population, AA women had a fourfold increase in utilization of ART services relative to the U.S. ART population. In this equal-access-to-care setting, AA women experienced a clinically significant decrease in live birth rate that did not reach statistical significance (29.6% vs. 35.8%, risk ratio [RR] 0.83, 95% confidence interval [CI] 0.67-1.02) and a statistically significant increase in spontaneous abortions compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be explained, in part, by a higher prevalence of uterine leiomyomas in AA women (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women, the presence of fibroids at baseline ultrasound was associated with reductions in clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR 0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%, RR 0.63, 95% CI 0.44-0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98). CONCLUSION(S): Utilization of ART services among AA women increased when access to care was improved. A clinically significant reduction in live birth rate and statistically significant increase in spontaneous abortion rate was observed in AA women compared with Cau women. Leiomyomas were three times more prevalent in AA women and reduced ART success, regardless of race. The persistence of racial differences in an equal-access-to-care environment might be explained, in part, by the increased prevalence of leiomyomas in AA women.

Assessment of resident competency in the performance of sonohysterography: does the level of training impact the accuracy?

OBJECTIVE: The objective of this study was to examine the true-positive rates by level of training of the operator and to determine whether the accuracy of the procedure differed by the level of education after formalized training. STUDY DESIGN: This was a retrospective analysis. The records of patients who underwent surgery for the indication of an abnormal saline sonohysterography were reviewed from January 2001 to April 2003 (n=73 patients). The nature of the saline sonohysterography abnormality, the intraoperative findings, and the level of training of the provider were recorded. Findings at saline sonohysterography were compared with findings at hysteroscopy or surgery. Statistical significance was determined by chi(2) test. RESULTS: The overall true-positive rate was 86.3% (63/73 patients). The true-positive rates for nurse practitioners, second- and fourth-year residents, and fellows were 84%, 80%, 90%, and 89%, respectively. There was no significant difference among providers (P=.96). CONCLUSION: The true-positive rates for saline hysterography were comparable among different provider levels.