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.

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.

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.

Professionalism in medicine: we should set the standard.

As military physicians we have a unique set of professional values that may differ from our civilian counterparts because we have both our professional responsibilities to our patients as well as our professional values as military officers. Our core military values provide a solid foundation to set the standard for professionalism in medicine. As educators for medical students, residents, and fellows we have an obligation to not only teach them the art of medicine but to mentor them as professional military officers. The objectives of this article are threefold: first to define professionalism, second to identify measurement tools, and finally to offer suggestions for documentation and remediation when problems of professionalism are identified among residents and fellows.

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.

Too little time to teach? Medical student education and the resident work-hour restriction.

OBJECTIVE: The purpose of this study was to examine the impact of the resident duty-hour restriction on medical student education through a survey of faculty, residents, and interns, with interns providing experience as students relative to implementation of work-hour restrictions. METHODS: A survey was performed at two (one military and one civilian) obstetrics and gynecology residency programs. Additional surveys were obtained from an Association of Professors of Gynecology and Obstetrics workshop, which included military and nonmilitary attendees. RESULTS: The majority of faculty reported spending 5 to 10 hours per week in medical education before and after implementation of the work-hour restriction. Residents reported less time teaching students after work-hour restrictions were instituted. Nearly all interns, responding about their clinical clerkship experience as students, believed their educational experience would have been improved if residents were more involved in teaching. CONCLUSION: This pilot study suggests residents are less involved in medical student education following implementation of the duty-hour restrictions.

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.

Cost and efficacy comparison of in vitro fertilization and tubal anastomosis for women after tubal ligation.

OBJECTIVE: To compare cost and efficacy of tubal anastomosis to in vitro fertilization (IVF) in women who desired fertility after a tubal ligation. DESIGN: Cost-effectiveness analysis. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cost per ongoing pregnancy. RESULT(S): Cost per ongoing pregnancy for women after tubal anastomosis ranged from $16,446 to $223,482 (2014 USD), whereas IVF ranged from $32,902 to $111,679 (2014 USD). Across maternal age groups <35 and 35-40, years tubal anastomosis was more cost effective than IVF for ongoing pregnancy. Sensitivity analyses validated these findings across a wide range of ongoing pregnancy probabilities as well as costs per procedure. CONCLUSION(S): Tubal anastomosis was the most cost-effective approach for most women less than 41 years of age, whereas IVF was the most cost-effective approach for women aged ≥41 years who desired fertility after tubal ligation. A model was created that can be modified based on cost and success rates in individual clinics for improved patient counseling.

Estimated economic impact of the levonorgestrel intrauterine system on unintended pregnancy in active duty women.

Unintended pregnancy is reportedly higher in active duty women; therefore, we sought to estimate the potential impact of the levonorgestrel-containing intrauterine system (LNG-IUS) could have on unintended pregnancy in active duty women. A decision tree model with sensitivity analysis was used to estimate the number of unintentional pregnancies in active duty women which could be prevented. A secondary cost analysis was performed to analyze the direct cost savings to the U.S. Government. The total number of Armed Services members is estimated to be over 1.3 million, with an estimated 208,146 being women. Assuming an age-standardized unintended pregnancy rate of 78 per 1,000 women, 16,235 unintended pregnancies occur each year. Using a combined LNG-IUS failure and expulsion rate of 2.2%, a decrease of 794, 1588, and 3970 unintended pregnancies was estimated to occur with 5%, 10% and 25% usage, respectively. Annual cost savings from LNG-IUS use range from $3,387,107 to $47,352,295 with 5% to 25% intrauterine device usage. One-way sensitivity analysis demonstrated LNG-IUS to be cost-effective when the cost associated with pregnancy and delivery exceeded $11,000. Use of LNG-IUS could result in significant reductions in unintended pregnancy among active duty women, resulting in substantial cost savings to the government health care system.

Cost-effectiveness analysis comparing continuation of assisted reproductive technology with conversion to intrauterine insemination in patients with low follicle numbers.

OBJECTIVE: To compare the cost effectiveness of proceeding with oocyte retrieval vs. converting to intrauterine insemination (IUI) in patients with ≤4 mature follicles during assisted reproductive technology (ART) cycles. DESIGN: Probabilistic decision analysis. The cost effectiveness of completing ART cycles in poor responders was compared to that for converting the cycles to IUI. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Cost-effectiveness analysis. MAIN OUTCOME MEASURE(S): Cost effectiveness, which was defined as the average direct medical costs per ongoing pregnancy. RESULT(S): In patients with 1-3 mature follicles, completing ART was more cost effective if the cost of a single ART cycle was between $10,000 and $25,000. For patients with 4 mature follicles, if an ART cycle cost<$18,025, it was more cost effective to continue with oocyte retrieval than to convert to IUI. CONCLUSION(S): In patients with ≤4 mature follicles following ovarian stimulation in ART cycles, it was on average more cost effective to proceed with oocyte retrieval rather than convert to IUI. However, important factors, such as age, prior ART failures, other fertility factors, and medications used in each individual case need to be considered before this analysis model can be adapted by individual practices.

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.

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.

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.

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.

2009 H1N1 influenza prevention and treatment: counseling infertility patients.

It is known that pregnant women are at high risk for complications from the 2009 H1N1 influenza virus. Reproductive endocrinologists often have the opportunity to evaluate patients before conception and are able to counsel them before they become part of this high-risk obstetrics group. The 2009 H1N1 vaccine data and the current recommendations by the Centers for Disease Control and Prevention, American College of Obstetrics and Gynecology, and American Society of Reproductive Medicine are discussed. There is universal agreement in recommending vaccination for all pregnant women and all women attempting conception. Patients should be counseled regarding the vaccine and consider delaying conception until the immunization has been received.

Cost analysis model of outpatient management of ovarian hyperstimulation syndrome with paracentesis: "tap early and often" versus hospitalization.

OBJECTIVE: To compare the cost of two treatment regimens for moderate to severe ovarian hyperstimulation syndrome (OHSS): conservative inpatient versus outpatient management with paracentesis. DESIGN: A decision-tree mathematical model comparing conservative inpatient versus outpatient management of moderate to severe OHSS was created. The common final pathway of either management was resolution of OHSS. Sensitivity analyses were performed over the range of variables. MAIN OUTCOME MEASURE(S): Total management cost of OHSS. RESULT(S): The cost of conservative therapy including first-tier complications was $10,099 (range $9,655-$15,044). The cost of outpatient management with paracentesis was $1954 (range $788-$12,041). This resulted in an estimated cost savings of $8145 with outpatient management with paracentesis. One-way sensitivity analyses were performed. Varying the probability of admission after outpatient treatment still indicated that outpatient treatment was the most cost-effective (probability = 1.0, cost = $6110). Varying the duration of hospitalization with primary inpatient treatment was equal to outpatient treatment costs only at a stay of 0.71 days or shorter. CONCLUSION(S): Our model suggests early outpatient paracentesis for moderate to severe OHSS is the most cost-effective management plan when compared with traditional conservative inpatient therapy. The cost savings for outpatient management persisted throughout a variety of outcome probabilities.

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.

Will decreasing assisted reproduction technology costs improve utilization and outcomes among minority women?

OBJECTIVE: To evaluate assisted reproduction technology (ART) usage and outcomes in minority women seeking care at enhanced access, military ART programs. DESIGN: Retrospective cohort. SETTING: Federal ART programs. PATIENT(S): Two thousand fifty women undergoing first cycle, fresh, nondonor ART from 2000 to 2005. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rate of ART use, clinical pregnancy rate, live birth rate. RESULT(S): African American women had an almost fourfold increased use of ART and Hispanic women had decreased use. Clinical pregnancy rates were significantly lower for African American women compared with white women (46.1% vs. 52.6%, relative risk [RR] 0.88; 95% confidence interval [CI], 0.78-0.99) as were live birth rates (33.7%. vs. 45.7%, RR 0.74; 95% CI, 0.63-0.91). CONCLUSION(S): Economics appear to influence ART use by African American women but not Hispanic women. Despite increased use by African American women, outcomes in this group were worse when compared with Caucasian women. Improving access through decreased cost may increase use by some but not all minority groups. Improved access may not translate into improved outcomes in some ethnic groups.

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.