Alicia Y. Armstrong

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

Racial and ethnic disparities in assisted reproductive technology outcomes in the United States

OBJECTIVE To evaluate ethnic differences in assisted reproductive technology (ART) outcomes in the United States. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) A total of 139,027 ART cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System online database for 2004-2006, limited to white, Asian, black, and Hispanic women. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Logistic regression was used to model the odds of pregnancy and live birth; among singletons and twins, the odds of preterm birth and fetal growth restriction. Results are presented as adjusted odds ratios, with white women as the reference group. RESULT(S) The odds of pregnancy were reduced for Asians (0.86), and the odds of live birth were reduced for all groups: Asian (0.90), black (0.62), and Hispanic (0.87) women. Among singletons, moderate and severe growth restriction were increased for all infants in all three minority groups (Asians [1.78, 2.05]; blacks [1.81, 2.17]; Hispanics [1.36, 1.64]), and preterm birth was increased among black (1.79) and Hispanic women (1.22). Among twins, the odds for moderate growth restriction were increased for infants of Asian (1.30) and black women (1.97), and severe growth restriction was increased among black women (3.21). The odds of preterm birth were increased for blacks (1.64) and decreased for Asians (0.70). CONCLUSION(S) There are significant disparities in ART outcomes according to ethnicity.

Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study

OBJECTIVE To evaluate the efficacy and tolerability of the P receptor modulator CDB-2914 (Ulipristal, CDB). DESIGN Randomized, placebo-controlled double-blind clinical trial. SETTING Clinical research center. PATIENT(S) Premenopausal women with symptomatic uterine fibroids. INTERVENTION(S) Once-daily oral CDB (10 or 20 mg) or placebo (PLC) for 12 weeks (treatment 1). A second 3-month treatment with CDB (treatment 2) was offered. A computer-generated blocked randomization was used. MAIN OUTCOME MEASURE(S) Magnetic resonance imaging (MRI)-determined total fibroid volume (TFV) change was the primary outcome; amenorrhea and quality of life (QOL) were secondary end points. RESULT(S) Treatment 1 TFV increased 7% in the PLC group, but decreased 17% and 24% in the CDB10 and CDB20 groups. The TFV decreased further in treatment 2 (-11%). Amenorrhea occurred in 20/26 women taking CDB and none on PLC. Ovulation resumed after CDB. Hemoglobin improved only with CDB (11.9 ± 1.5 to 12.9 ± 1.0 g/dL) as did the Fibroid QOL Questionnaire symptom severity, energy/mood, and concern subscores, and overall QOL scores. The CDB was well tolerated, with no serious adverse events. Adverse events were unchanged during treatments. CONCLUSION(S) Administration of CDB-2914 for 3-6 months controls bleeding, reduces fibroid size, and improves QOL.

A randomized, double-blind crossover trial of sertraline in women with chronic pelvic pain

The efficacy of antidepressants as analgesics for a range of chronic pain problems is well documented. However, a controlled trial of an antidepressant for women with chronic pelvic pain has not yet been published. We randomized 23 women from a general gynecology clinic to either double-blind sertraline or placebo. Measures of psychological function, pain, and functional disability were taken at baseline and 6 weeks. After a 2-week washout, the groups were crossed-over and the same measures were done over the next 6 weeks. There were no significant improvements in pain or functional disability noted on sertraline compared to placebo. Studies involving larger samples of patients are needed to confirm these findings.

Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System

OBJECTIVE To evaluate factors predictive of clinical pregnancy and of pregnancy loss from assisted reproductive technology (ART) using data from the Society for Assisted Reproductive Technology database for 2004-2006. DESIGN Retrospective cohort. SETTING Clinic-based data. PATIENT(S) The study population included 225,889 fresh embryo transfer cycles using autologous oocytes and partner semen. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Clinical intrauterine gestation (presence of gestational sac) and live birth (>or=22 weeks gestation and >or=300 g birth weight). RESULT(S) Increasing maternal age was significantly associated with a reduced odds of conception and increased fetal loss until 19 weeks gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection (ICSI), assisted hatching, and increasing number of embryos transferred had significant positive effects on the odds of conception and pregnancy continuation through the first trimester, but did not affect the risk of later loss. Blacks, Asians, and Hispanics had significantly lower odds of clinical pregnancy compared with whites. Also compared with whites, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a significantly greater risk of pregnancy loss in all trimesters. CONCLUSION(S) Certain demographic and ART treatment parameters influenced chance of conception and early pregnancy loss, whereas black race and Hispanic ethnicity were also significantly associated with late pregnancy loss in ART-conceived pregnancies.

Impact of obesity on women's health

OBJECTIVE To review the impacts of obesity on womens reproductive health and fertility. DESIGN Literature review. SETTING Academic medical center. PATIENT(S) Forty articles are referenced. The number of patients evaluated in each of the studies varies from 33 to 213,208. INTERVENTION(S) Articles were identified from an Ovid/Medline search using the search terms obesity, dysfunctional uterine bleeding, contraception, miscarriage, infertility, and weight loss. MAIN OUTCOME MEASURE(S) The impacts of obesity on reproductive health and fertility. RESULT(S) Obesity is associated with early puberty, aberrant menstrual patterns, decreased contraceptive efficacy, ovulatory disorders, an increased miscarriage rate, and worse assisted reproductive technology outcomes. Losing weight can ameliorate many of these problems. CONCLUSION(S) Obesity is one of the most significant causes of morbidity and mortality in the U.S. Providers must educate patients about the impacts of obesity on reproductive health and fertility.

Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes.

OBJECTIVE To systematically review the reporting of race/ethnicity in Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) publications. DESIGN Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of literature published in PubMed on race/ethnicity that includes data from SART CORS. SETTING Not applicable. PATIENT(S) Not applicable. INTERVENTION(S) In vitro fertilization cycles reported to SART. MAIN OUTCOME MEASURE(S) Any outcomes reported in SART CORS. RESULT(S) Seven publications were identified that assessed racial/ethnic disparities in IVF outcomes using SART data. All reported a racial/ethnic disparity. However, more than 35% of cycles were excluded from analysis because of missing race/ethnicity data. CONCLUSION(S) Review of current publications of SART data suggests significant racial/ethnic disparities in IVF outcomes. However, the potential for selection bias limits confidence in these findings, given that fewer than 65% of SART reported cycles include race/ethnicity. Our understanding of how race/ethnicity influences ART outcome could be greatly improved if information on race/ethnicity was available for all reported cycles.

Do U.S. Medical Licensure Examination Step 1 Scores Correlate with Council on Resident Education in Obstetrics and Gynecology In-Training Examination Scores and American Board of Obstetrics and Gynecology Written Examination Performance?

OBJECTIVE The purpose of this study was to assess the possible association between scores of >200 on U.S. Medical Licensure Examination (USMLE) step 1 and the Council on Resident Education in Obstetrics and Gynecology (CREOG) in-training examinations and the pass rate on the American Board of Obstetrics and Gynecology (ABOG) written examination. METHODS The USMLE step 1 and postgraduate year 1 to 4 CREOG in-training examination scores for the graduating chief residents in eight accredited obstetrics and gynecology residency programs were obtained. Performance on USMLE step 1 was correlated with ABOG examination performance and CREOG in-training examination scores. The correlations between USMLE step 1 and CREOG in-training examination scores and ABOG examination performance were analyzed by using the Spearman correlation coefficient. RESULTS USMLE step 1 scores were significantly correlated with CREOG in-training examination scores (p < 0.000). None of the residents who scored >200 on USMLE step 1 and a mean of >200 on the CREOG in-training examinations failed the ABOG written examination. CONCLUSION Program directors have used USMLE step 1 to identify trainees who are likely to perform well on the CREOG in-training examination. The CREOG in-training examination has been used to identify residents who are likely to pass the ABOG written examination. The results of this study document the strength of these associations.

Modulation of endometrial steroid receptors and growth regulatory genes by tamoxifen.

Objective We investigated tamoxifens effects on the expression of growth regulatory genes in the endometrium to identify the mechanism by which tamoxifen induces proliferation. Methods Using immunohistochemical techniques, we analyzed 39 endometrial specimens for expression of Ki-67, lactoferrin, transforming growth factor-α, tumor necrosis factor receptor-II, adrenomedullin, estrogen receptors, and progesterone receptors. Twenty specimens were obtained from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months to include two endometrial adenocarcinoma specimens. Five secretory phase, three proliferative phase, and seven atrophic endometrial specimens were used as controls. In addition, four endometrial adenocarcinoma specimens were reviewed from patients not treated with tamoxifen. Intensity of immunostaining was quantified using digitized imaging techniques. Results Overexpression of both estrogen receptors and progesterone receptors, and an elevated proliferative index were the most consistent effects observed in benign endometrial specimens from tamoxifen-treated patients compared with atrophic controls (P < .003). This staining pattern was also evident in adenocarcinomas from patients who received tamoxifen. Benign endometrium from tamoxifen-treated patients also expressed transforming growth factor-α, tumor necrosis factor receptor-II, lactoferrin, and adrenomedullin at levels comparable with those found in proliferative endometrial specimens. Conclusion These data provide further documentation that the uterotropic effects of tamoxifen may be due, at least in part, to the induction of estrogen receptors and progesterone receptors, as well as other genes associated with the proliferative phase. Furthermore, analysis of estrogen receptors, progesterone receptors, and Ki-67 may be useful in identifying postmenopausal individuals on tamoxifen, who are at increased risk for developing endometrial cancer.

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.