Cost analysis of abdominal, laparoscopic, and robotic-assisted myomectomies.

STUDY OBJECTIVE: To perform a cost-minimization analysis of abdominal, traditional laparoscopic and robotic-assisted myomectomy. DESIGN: Cost analysis (Canadian Task Force Classification III). SETTING: Academic medical center. PATIENTS: Women undergoing myomectomy by various surgical approaches. INTERVENTIONS: We developed a decision model to compare the costs ($2009) of different approaches to myomectomy from a healthcare system perspective. The model included operative time, conversion risk, transfusion risk, and length of stay (LOS) for each modality. Baseline estimates and ranges were based on reported values extracted from existing literature. We analyzed two different models: #1) Existing Robot model and #2) Robot Purchase model. MEASUREMENTS AND MAIN RESULTS: In the baseline analysis for the Existing Robot model, abdominal myomectomy (AM) was the least expensive at $4937 compared with laparoscopic myomectomy (LM) at $6219 and robotic-assisted laparoscopic myomectomy (RM) at $7299. The abdominal route remained the least expensive when varying all parameters and costs except for two cases in which LM became least expensive: 1) If AM length of stay was greater than 4.6 days, and 2) If the surgeon's fee for AM was greater than $2410. When comparing LM to RM, the cost of RM was consistently higher unless the robotic disposable equipment costs were less than $1400. In the Robot Purchase model, only the RM costs increased while AM and LM costs remained the same. CONCLUSION: In this cost-minimization analysis, abdominal myomectomy is the least expensive approach when compared to laparoscopy and robotic-assisted laparoscopy.

Spontaneous pregnancy reaches viability after low first trimester serum progesterone: a case report.

BACKGROUND: Progesterone is produced by the corpus luteum until completion of the luteal-placental shift at approximately 6-10 weeks following last menstruation. Studies have shown that first trimester progesterone levels are predictive of pregnancy viability, and some authors support a level of 5 ng/mL as an absolute threshold to indicate viability. CASE: A 47-year-old woman with recurrent pregnancy loss was noted to have a very low first trimester progesterone level (1.2 ng/mL), but the pregnancy progressed to viability. She unfortunately delivered an intrauterine fetal demise at 27 weeks and 3 days' gestation. CONCLUSION: A single serum progesterone level of < 5 ng/mL is suggestive, but not diagnostic, of a nonviable pregnancy. Routine uterine curettage during the evaluation of a pregnancy of unknown location using this level as an absolute cutoff may result in the interruption of a desired, viable pregnancy.

Validation study of the Access antimüllerian hormone assay for the prediction of poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma. DESIGN: Prospective cohort study. SETTING: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). PATIENT(S): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. RESULT(S): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4). CONCLUSION(S): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible.

Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells.

The effects of progesterone on breast epithelial cells remain poorly defined with observations showing both proliferative and antiproliferative effects. As an example, progesterone levels correlate with increased epithelial cell proliferation, but there is discordance between the dividing cells and the cells with nuclear progesterone receptor expression. The release of paracrine growth factors from nuclear receptor-positive cells has been postulated as a mechanism, since in vitro studies show a lack of growth effect by progesterone in breast epithelial cells lacking nuclear receptors. This study examined possible nongenomic effects of progesterone in breast epithelia by using MCF-10A cells known to lack nuclear progesterone receptor expression. Treatment for 30-60 min with progesterone or the progestin, R5020, increased mitochondrial activity as shown by an increase in mitochondrial membrane potential (hyperpolarization) with a concordant increase in total cellular ATP. The reaction was inhibited by a specific progesterone receptor antagonist and not affected by the translation inhibitor cycloheximide. Progestin treatment inhibited apoptosis induced by activation of the FasL pathway, as shown by a decrease in sub-G(1) cell fraction during fluorescence-activated cell sorting and a decrease in caspase 3/7 levels. Progestin treatment did not alter the cell cycle over 48 h. Our study demonstrates a nongenomic action of progesterone on benign breast epithelial cells, resulting in enhanced cellular respiration and protection from apoptosis.

Pilot survey of oncologists regarding treatment-related infertility and fertility preservation in female cancer patients.

OBJECTIVE: To conduct a quantitative survey that focuses on oncologists' practice patterns and attitudes surrounding treatment-related infertility and fertility preservation, specifically among women of reproductive age. STUDY DESIGN: A 19-item survey was emailed to medical, pediatric, radiation and surgical oncologists at Duke University. Descriptive statistics were used. RESULTS: Most oncologists (61%) who responded always or usually discuss the impact treatment will have on fertility. Nearly half (45%) never refer women to reproductive specialists. Respondents who attended an educational session on fertility preservation were more likely to consider a patient's desire for fertility when planning her treatment than those who did not attend (45% vs. 33%). More than half (55%) of attendees were willing to consider a less aggressive regimen to preserve fertility, compared with 29% of those who did not attend. CONCLUSION: While most oncologists recognize the importance of discussing infertility risks, many do not discuss fertility preservation routinely. Reasons for this discrepancy included poor prognosis and emergent need to start therapy. Increasing awareness through educational events may influence current practice patterns and increase collaboration between reproductive endocrinologists and oncologists.

Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved. DESIGN: Prospective cohort study. SETTING: Thirteen private and academic fertility centers in the United States. PATIENTS(S): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15. RESULT(S): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%. CONCLUSION(S): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes.

Eligibility and accessibility of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of uterine leiomyomas.

OBJECTIVE: To evaluate patient eligibility and accessibility of magnetic resonance-guided focused ultrasound (MRgFUS) for women with symptomatic uterine leiomyomas who desire conservative therapy. DESIGN: Retrospective analysis of 169 patients referred for minimally invasive treatment of leiomyomas between November 2007 and February 2009. Clinical eligibility for MRgFUS was determined by Food and Drug Administration-based treatment guidelines. All patients underwent pretreatment pelvic imaging to determine candidacy for the procedure. PATIENT(S): Premenopausal women with symptomatic uterine leiomyomas. SETTING: Academic medical center. MAIN OUTCOME MEASURE(S): Eligibility for MRgFUS based on clinical and anatomic patient criteria. RESULT(S): Forty-seven percent of patients (80/169) were determined clinically eligible for the procedure. Of these, 16% of patients (27/169) were found to be eligible for MRgFUS based on imaging results. Overall, the main reasons for ineligibility were very large leiomyomas (8%; 14/169), cost (12%; 21/169), and desired fertility (14%; 23/169). An additional 48% of patients declined MRgFUS for unstated reasons, often after obtaining financial and insurance coverage information. CONCLUSION(S): Currently, many women with leiomyomas are unable to obtain MRgFUS treatment for multiple reasons, including uterine size, desire for fertility, and, most commonly, financial limitations. With increasing clinical experience, further research, and broadened insurance coverage, it may be possible to increase accessibility and expand eligibility criteria for this minimally invasive therapy.

A nationwide survey of oncologists regarding treatment-related infertility and fertility preservation in female cancer patients.

OBJECTIVE: To survey oncologists regarding their knowledge and practice patterns concerning fertility preservation for female cancer patients. DESIGN: An online survey was sent to oncologists at cancer centers ranked by U.S. News & World Report. SETTING: Oncologists who treat women of reproductive age at academic medical centers. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Counseling and referral practices of oncologists regarding fertility risks among young women with cancer. RESULTS: Most (95%) of the 249 responding oncologists routinely discuss a treatment's impact on fertility; 1,701 surveys were sent. Although 82% have referred patients to reproductive endocrinologists, more than half rarely refer. When planning treatment, 30% rarely consider a woman's desire for fertility. Gynecologic oncologists were more likely to routinely consider fertility compared with other oncologists (93% vs. 60%). Gynecologic oncologists also were more likely to provide a less effective regimen to better preserve fertility (61% vs. 37%). Most oncologists (86%) would be willing to sacrifice less than a 5% reduction in disease-free survival if a regimen offered better fertility outcomes; 36% felt patients would be willing to sacrifice >5%. CONCLUSION(S): Although most oncologists at academic medical centers discuss the risk of infertility with female patients, referrals to reproductive endocrinologists are rare. Gynecologic oncologists may be more likely than others to consider modifying treatment to preserve fertility. According to oncologists, patients may be willing to sacrifice more in survival than they would.

Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis.

PURPOSE: Treatment with cyclophosphamide (CYC) confers up to a 40% risk of ovarian failure in women of reproductive age. The use of GnRH agonists (GnRHa) to preserve ovarian function has been investigated in several small studies. We performed a systematic review of studies examining whether a GnRHa administered during chemotherapy is protective of ovarian function and fertility. METHODS: We searched the English-language literature (1966-April 2007) using MEDLINE and meeting abstracts and included studies that reported an association between GnRHa and ovarian preservation in women receiving chemotherapy. Studies without a control group were excluded. Ovarian preservation was defined as the resumption of menstrual cycles and a premenopausal follicle-stimulating hormone (FSH) after chemotherapy. Fertility was determined by a woman's ability to become pregnant. We estimated the summary relative risk (RR) and associated 95% confidence intervals (95% CI) using a random-effects model. RESULTS: Nine studies included 366 women. Three studies included women with autoimmune disease receiving CYC; six included women with hematologic malignancy receiving combination chemotherapy. In total, 178 women were treated with GnRHa during chemotherapy, 93% of whom maintained ovarian function. Of the 188 women not treated with GnRHa, 48% maintained ovarian function. The use of a GnRHa during chemotherapy was associated with a 68% increase in the rate of preserved ovarian function compared with women not receiving a GnRHa (summary RR = 1.68, 95% CI 1.34-2.1). Among the GnRHa-treated women, 22% achieved pregnancy following treatment compared with 14% of women without GnRHa therapy (summary RR = 1.65, CI 1.03-2.6). CONCLUSIONS: Based on the available studies, GnRHa appear to improve ovarian function and the ability to achieve pregnancy following chemotherapy. Several randomized trials are underway to define the role and mechanism of GnRHa in ovarian function preservation. In the meantime, premenopausal women facing chemotherapy should be counseled about ovarian preservation options, including the use of GnRHa therapy.

Thrombospondin-1 and thrombospondin-2 mRNA and TSP-1 and TSP-2 protein expression in uterine fibroids and correlation to the genes COL1A1 and COL3A1 and to the collagen cross-link hydroxyproline.

Uterine fibroids are composed of altered collagen fibrils and represent an arrested response to injury-initiating fibrosis. In many tissues, TSP-1 is secreted by adult macrophages and monocytes upon wounding and is involved in the activation of transforming growth factor beta. In the absence of TSP-1, the orchestrated process of wound healing is impaired. The authors obtained tissue from the edge and center of fibroids at the time of hysterectomy and compared them with adjacent myometrium. The pattern of TSP-1 and TSP-2 expression was correlated to that of COL1A1 and COL3A1. Collagen and hydroxyproline were increased in fibroids. Thrombospondin-1 was consistently underexpressed in both the edge and center of the fibroids, while COL1A1 and COL3A1 were consistently overexpressed. However, TSP-2 was inconsistently expressed. These findings lead to the conclusion that the underexpression of TSP-1 may contribute to the overall development of uterine fibroids.