Does provision of antenatal care in Southern Asia improve neonatal survival? A systematic review and meta-analysis.

BACKGROUND: Southern Asia has one of the highest burdens of neonatal mortality worldwide (26/1000 live births). Ensuring that women receive antenatal care from a skilled provider may play an important role in reducing this burden. OBJECTIVE: This study aimed to determine whether antenatal care received from a skilled provider could reduce neonatal mortality in Southern Asia by systematically reviewing existing evidence. STUDY DESIGN: Seven databases were searched (MEDLINE, Embase, Cochrane Library, CINAHL, PubMed, PsycINFO, and International Bibliography of the Social Sciences [IBSS]). The key words included: "neonatal mortality," "antenatal care," and "Southern Asia." Nonrandomized comparative studies conducted in Southern Asia reporting on neonatal mortality in women who received antenatal care compared with those who did not were included. Two authors carried out the screening and data extraction. The Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was used to assess quality of studies. Results were reported using a random-effects model based on odds ratios with 95% confidence intervals. RESULTS: Four studies were included in a meta-analysis of adjusted results. The pooled odds ratio was 0.46 (95% confidence interval, 0.24 to 0.86) for neonatal deaths among women having at least 1 antenatal care visit during pregnancy compared with women having none. In the final meta-analysis, 16 studies could not be included because of lack of adjustment for confounders, highlighting the need for further higher-quality studies to evaluate the true impact. CONCLUSION: This review suggests that in Southern Asia, neonates born to women who received antenatal care have a lower risk of death in the neonatal period compared with neonates born to women who did not receive antenatal care. This should encourage health policy to strengthen antenatal care programs in Southern Asia.

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.

What Motivates Health Communication's Peer Reviewers to Review? A Survey of Our Scholarly Community.

The peer review process is a necessary, labor-intensive, and imperfect element of scientific research. Among the many issues identified by its critics, finding willing reviewers can be an arduous task for journal editors and is acknowledged as one of the primary factors holding up the publication process. In an attempt to better understand and serve Health Communication reviewers, we surveyed them and inquired about their motivations for reviewing a manuscript, including why they agree, decline, or disregard invitations to review submissions. According to responses from 380 reviewers, the most compelling reasons for agreeing to review reflected a dedication to performing scholarly service and loyalty to the journal. The primary reasons selected for declining to review included lack of time and insufficient expertise to evaluate the submission. The main reasons for failing to respond to requests to review were e-mail overload and indecision about whether to take on the review. Recognition for service was the most recommended suggestion offered to motivate reviewers to agree to take on more manuscripts. On the whole, reviewers feel a strong sense of duty to review manuscripts. However, time constraints, poor fit, and lack of recognition are roadblocks to agreeing.

90Y-Daclizumab (Anti-CD25), High-Dose Carmustine, Etoposide, Cytarabine, and Melphalan Chemotherapy and Autologous Hematopoietic Stem Cell Transplant Yielded Sustained Complete Remissions in 4 Patients with Recurrent Hodgkin's Lymphoma.

Background: Despite advances in therapy of Hodgkin's lymphoma (HL), a proportion of patients will not respond or relapse. The authors had previously identified CD25, IL-2Rα, as a target for systemic radioimmunotherapy of HL since most normal cells do not express CD25, but it is expressed by a minority of Hodgkin/Reed-Sternberg (HRS) cells and most Tregs rosetting around HRS cells. Study Design and Treatment: This was a single institution, nonrandomized, open-label phase I/II trial of radiolabeled 90Y-daclizumab, an anti-CD25 monoclonal antibody, BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning treatment followed by autologous hematopoietic stem cell transplant (ASCT). Four patients with refractory and relapsed HL were treated in this trial with 3 patients receiving a single dose of 564.6-574.6 MBq 90Y-daclizumab and the fourth patient receiving two doses of 580.9-566.1 MBq 90Y-daclizumab followed by high-dose chemotherapy and ASCT. Results: All 4 evaluable patients treated with 90Y-daclizumab obtained complete responses (CRs) that are ongoing 4.5-7 years following their stem cell transplant. The spectrum and severity of adverse events were mild and more importantly none of the patients, including several with multiple therapies before this treatment, developed the myelodysplastic syndrome. Discussion: Targeting by daclizumab was not directed primarily at tumor cells, but rather the nonmalignant CD25-expressing T cells adjacent to the HRS cells and 90Y-daclizumab provided strong enough ß emissions to kill CD25-negative tumor cells at a distance by a crossfire effect. Furthermore, the strong ß irradiation killed normal cells in the tumor microenvironment. Conclusions: 90Y-daclizumab (anti-CD25), high-dose BEAM chemotherapy and ASCT was well tolerated and yielded sustained complete remissions in all 4 patients with recurrent HL patients who completed their treatment. Significance: Despite advances, a proportion of patients with HL will not have a CR to their initial treatment, and some with CRs will relapse. They demonstrated that the addition of 90Y-daclizumab into the preconditioning regimen for refractory and relapsed HL patients with high-dose BEAM chemotherapy and ASCT provided sustained CRs in the 4 patients studied. Two of these patients were highly refractory to multiple prior treatments with bulky disease at entry into this study, including 1 patient who never entered a remission and had failed 6 different therapeutic regimens. Despite the small number of patients treated in this study, the sustained clinical benefit in these patients indicates a highly effective treatment. The daclizumab was directed primarily not at HRS cells themselves but toward nonmalignant T cells rosetting around malignant cells. 90Y provided strong ß emissions that killed antigen nonexpressing tumor cells at a distance by a crossfire effect. Furthermore, the strong ß radiation killed normal cells in the tumor microenvironment that nurtured the malignant cells in the lymphomatous mass. The present study supports expanded analysis of 90Y-daclizumab as part of the regimen of ASCT in patients with refractory and relapsed HL.

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.

Perinatal Natural History of the Ts1Cje Mouse Model of Down Syndrome: Growth Restriction, Early Mortality, Heart Defects, and Delayed Development.

BACKGROUND: The Ts1Cje model of Down syndrome is of particular interest for perinatal studies because affected males are fertile. This permits affected pups to be carried in wild-type females, which is similar to human pregnancies. Here we describe the early natural history and growth profiles of Ts1Cje embryos and neonates and determine if heart defects are present in this strain. METHODS: Pups were studied either on embryonic (E) day 15.5, or from postnatal (P) day 3 through weaning on P21. PCR amplification targeting the neomycin cassette (present in Ts1Cje) and Sry (present in males) was used to analyze pup genotypes and sex ratios. Body weights and lengths, as well as developmental milestones, were recorded in Ts1Cje mice and compared to their wild-type (WT) littermates. Histological evaluations were performed at E15.5 to investigate the presence or absence of heart defects. Pups were divided into two groups: Ts1Cje-I pups survived past weaning and Ts1Cje-II pups died at some point before P21. RESULTS: Ts1Cje mouse embryos showed expected Mendelian ratios (45.8%, n = 66 for Ts1Cje embryos; 54.2%, n = 78 for WT embryos). Histological analysis revealed the presence of ventricular septal defects (VSDs) in 21% of Ts1Cje E15.5 embryos. After weaning, only 28.2% of pups were Ts1Cje (185 Ts1Cje out of 656 total pups generated), with males predominating (male:female ratio of 1.4:1). Among the recovered dead pups (n = 207), Ts1Cje (63.3%, n = 131, p<0.01) genotype was found significantly more often than WT (36.7%, n = 76). Retrospective analysis of Ts1Cje-II (pre-weaning deceased) pups showed that they were growth restricted compared to Ts1Cje-I pups (post-weaning survivors). Growth restriction correlated with statistically significant delays in achieving several neonatal milestones between P3 and P21 compared to Ts1Cje-I (post-weaning survivors) neonates and WT littermates. CONCLUSIONS: Ts1Cje genotype is not associated with increased early in utero mortality. Cardiac defects, specifically VSDs, are part of the phenotype in this strain. There is increased neonatal mortality in Ts1Cje pups, with sex differences observed. Ts1Cje mice that died in the neonatal period were more likely to be growth restricted and delayed in achieving neonatal developmental milestones.

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome.

Human fetuses with Down syndrome demonstrate abnormal brain growth and reduced neurogenesis. Despite the prenatal onset of the phenotype, most therapeutic trials have been conducted in adults. Here, we present evidence for fetal brain molecular and neonatal behavioral alterations in the Ts1Cje mouse model of Down syndrome. Embryonic day 15.5 brain hemisphere RNA from Ts1Cje embryos (n = 5) and wild type littermates (n = 5) was processed and hybridized to mouse gene 1.0 ST arrays. Bioinformatic analyses were implemented to identify differential gene and pathway regulation during Ts1Cje fetal brain development. In separate experiments, the Fox scale, ultrasonic vocalization and homing tests were used to investigate behavioral deficits in Ts1Cje pups (n = 29) versus WT littermates (n = 64) at postnatal days 3-21. Ts1Cje fetal brains displayed more differentially regulated genes (n = 71) than adult (n = 31) when compared to their age-matched euploid brains. Ts1Cje embryonic brains showed up-regulation of cell cycle markers and down-regulation of the solute-carrier amino acid transporters. Several cellular processes were dysregulated at both stages, including apoptosis, inflammation, Jak/Stat signaling, G-protein signaling, and oxidoreductase activity. In addition, early behavioral deficits in surface righting, cliff aversion, negative geotaxis, forelimb grasp, ultrasonic vocalization, and the homing tests were observed. The Ts1Cje mouse model exhibits abnormal gene expression during fetal brain development, and significant neonatal behavioral deficits in the pre-weaning period. In combination with human studies, this suggests that the Down syndrome phenotype manifests prenatally and provides a rationale for prenatal therapy to improve perinatal brain development and postnatal neurocognition.

Antenatal noninvasive DNA testing: clinical experience and impact.

BACKGROUND: Nearly two decades ago, the discovery of circulating cell-free fetal DNA in maternal blood created a paradigm shift in prenatal testing. Recent advances in DNA sequencing technology have facilitated the rapid translation of DNA-based testing into clinical antenatal care. CONTENT: In this review, we summarize the technical approaches and current clinical applications of noninvasive testing using cell-free DNA in maternal plasma. We discuss the impact of these tests on clinical care, outline proposed integration models, and suggest future directions for the field. SUMMARY: The use of cell-free DNA in maternal blood for the detection of fetal rhesus D antigen status, fetal sex, and common whole chromosomal aneuploidies is now well established, although testing for aneuploidy is still considered screening and not diagnostic. Further advances in technology and bioinformatics may see future clinical applications extend to the noninvasive detection of fetal subchromosomal aneuploidy, single gene disorders, and the entire fetal genome.

Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction.

No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10(7) to 5.8 × 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10(9) vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.

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.

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.

Functional imaging of SDHx-related head and neck paragangliomas: comparison of 18F-fluorodihydroxyphenylalanine, 18F-fluorodopamine, 18F-fluoro-2-deoxy-D-glucose PET, 123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetreotide scintigraphy.

RATIONALE: Accurate diagnosis of head and neck paragangliomas is often complicated by biochemical silence and lack of catecholamine-associated symptoms, making accurate anatomical and functional imaging techniques essential to the diagnostic process. METHODS: Ten patients (seven SDHD, three SDHB), with a total of 26 head and neck paragangliomas, were evaluated with anatomical and functional imaging. This study compares five different functional imaging techniques [(18)F-fluorodihydroxyphenylalanine ((18)F-FDOPA) positron emission tomography (PET), (18)F-fluorodopamine ((18)F-FDA) PET/computed tomography (CT), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT, (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy, and (111)In-pentetreotide scintigraphy] in the localization of head and neck paragangliomas. RESULTS: Prospectively (18)F-FDOPA PET localized 26 of 26 lesions in the 10 patients, CT/magnetic resonance imaging localized 21 of 26 lesions, (18)F-FDG PET/CT localized 20 of 26 lesions, (111)In-pentetreotide scintigraphy localized 16 of 25 lesions, (18)F-FDA PET/CT localized 12 of 26 lesions, and (123)I-MIBG scintigraphy localized eight of 26 lesions. Differences in imaging efficacy related to genetic phenotype, even in the present small sample size, included the negativity of (18)F-FDA PET/CT and (123)I-MIBG scintigraphy in patients with SDHB mutations and the accuracy of (18)F-FDG PET/CT in all patients with SDHD mutations, as compared with the accuracy of (18)F-FDG PET/CT in only one patient with an SDHB mutation. CONCLUSION: Overall, (18)F-FDOPA PET proved to be the most efficacious functional imaging modality in the localization of SDHx-related head and neck paragangliomas and may be a potential first-line functional imaging agent for the localization of these tumors.

Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis.

OBJECTIVE: To estimate the rate of wound complications associated with protocol-driven postcesarean enoxaparin thromboprophylaxis. METHODS: After implementing an Institutional Clinical Practice Guideline for postoperative cesarean delivery thromboprophylaxis among at-risk gravid women (older than 35 years of age, body mass index greater than 30 kg/m2, or both), data on all cesarean deliveries over the first 23 months of guideline implementation were extracted and analyzed. Primary (wound hematoma, separation, or dehiscence) and secondary (venous thromboembolism) outcomes were compared in stratified and multivariable models controlling for potential confounders. RESULTS: Over 23 months, 2,509 cesarean deliveries were performed. A total of 1,677 (68%) gravid women met criteria for thromboprophylaxis; 653 received enoxaparin per protocol ("cases"), and, at the discretion of the ordering physician, 1,024 did not (at-risk, protocol-noncompliant "controls"). Cases differed significantly by virtue of maternal age, body mass index, and diabetic status. Univariable analysis subsequently revealed a higher rate of wound separation (6.8% compared with 3.6%, P=.003), rehospitalization (2.1% compared with 0.8%, P=.017) and composite score (8.9% compared with 4.8%, P=.002) among protocol-compliant cases, but no increased risk of wound hematoma (P>.06). In multivariable analysis, adjusted odds ratios continued to reveal an association between enoxaparin use and wound separation (OR 1.66, P=.04) as well as higher composite score (OR 1.69, P=.01). However, among the protocol-noncompliant controls, a nonsignificant increase in the rate of venous thromboembolism occurred. CONCLUSION: In our series, prophylactic enoxaparin use among at-risk gravid women undergoing cesarean delivery was accompanied by an increased risk of wound separation. LEVEL OF EVIDENCE: II.

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.

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.

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.

Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations.

We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[(18)F]-fluorodopamine ([(18)F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) PET (76%), and scintigraphy with [(123/131)I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [(18)F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [(18)F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [(18)F]-FDG PET is highly recommended in SDHB mutation patients, whereas [(18)F]-FDA PET is recommended in patients without the mutation.