A cost-effectiveness analysis of using umbilical cord blood pH for the diagnosis and management of neonatal asphyxia in term high-risk pregnancy.

OBJECTIVE: The objective was to evaluate the cost-effectiveness of using umbilical cord blood pH (UC-pH) in combination with APGAR score for neonatal asphyxia, in terms of high-risk pregnancies, compared to using the APGAR score only. Neonatal outcomes and the proportions of patients admitted to the neonatal intensive care unit (NICU) were evaluated. METHODS: A cost-effectiveness ambispective analysis study was carried out, comparing (i) UC-pH combined with APGAR score and (ii) APGAR score only in 399 term pregnancies with a high risk for neonatal asphyxia. Costs included implementation, medical, and admission costs. Incremental cost-effectiveness ratios (ICER) were calculated. The proportions of patients admitted to the NICU were evaluated. RESULTS: UC-pH combined with APGAR score demonstrated a cost-effective outcome (3990.64 USD vs 5545.11 USD) and an ICER shown as saving 103.66 USD compared to the APGAR score alone. The need for NICU admission was less in the umbilical cord blood collection group (18 vs 33 cases). CONCLUSION: A combination of UC-pH with APGAR score assessment for neonatal asphyxia in a high-risk term pregnancy can effectively reduce costs and requirement for NICU admission.

Direct cord blood LAMP colorimetric phenol red assay for detecting α0-thalassemia (SEA deletion); the validation and post-natal screening in Thailand.

Post-natal or newborn screening for thalassemia and hemoglobinopathies is useful for genetic counseling and managing thalassemia in children. We characterized thalassemia genotypes in newborns from the eastern part of Thailand. The results demonstrated a high heterogeneity of thalassemia and hemoglobinopathies with seventeen genotypes. We focused on α0- thalassemia (Southeast Asian [SEA] deletion) in this study. We developed and validated the loop-mediated isothermal amplification (LAMP) colorimetric assay for detecting α0- thalassemia (SEA deletion) using simple direct cord blood sampling compared to genomic DNA. A total of 160 cord blood samples were evaluated with the LAMP assay. The sensitivity and specificity of the LAMP colorimetric assay for α0-thalassemia (SEA deletion) using direct cord blood showed 100% (6/6 x 100) and 98.05% (151/154 x 100) whereas, genomic DNA showed 100% (6/6 x 100) and 100% (154/154 x 100), respectively. Moreover, we demonstrated other simple screening tools for α0-thalassemia with %Hb Bart's, MCV, and MCH values and found that these parameters were not diagnostic in our samples. The direct cord blood with colorimetric LAMP assay is simple, rapid, and does not require a post-LAMP step compared to conventional PCR. These techniques could be applied in post-natal or large population screening for α0-thalassemia (SEA deletion). Finally, this could support early prevention of complications, early management, genetic counseling for α-thalassemia disease in children, or a long-term prevention and control program of severe thalassemia in Thailand.

Student Competency for Midtrimester Obstetrics Scan upon Completion of the Master's Degree in Medical Sonography.

Objectives: To evaluate the competency of medical sonographer students who have completed training to estimate the gestational age (GA) and perform fetal biometric measurements compared to obstetricians. Methods: We conducted a cross-sectional observational study at the end of the medical sonographer students' practice sessions. In total, 80 midtrimester (18-28 weeks) pregnant women were recruited, and an ultrasound was performed according to the International Society of Sonography in Obstetrics and Gynecology (ISUOG) guideline. Estimated GA calculated from fetal biometric measurements was compared between medical sonographer students and qualified obstetricians. Subsequently, images were randomly evaluated by maternal-fetal medicine specialists to assess the measurement performance. Results: There was no significant difference in the estimated GA between the medical sonographer students and obstetricians (mean difference, 0.01 ± 2.92 day, p = 0.89). However, there was a significant difference in the measurement of the head circumference (HC) and abdominal circumference (AC) (p < 0.001). The overall image quality of the fetal head, abdomen, and femur was considered a good to excellent score (77.5%-80%). There was a perfect and nearly perfect agreement regarding the presence of the placenta previa, adequacy of amniotic fluid, and position of the placenta (k = 0.9-1.0). Conclusions: The medical sonographer students demonstrated competency in GA estimation by fetal biometry measurement similar to obstetricians. However, the quality of the acquired images, according to the ISUOG recommendation, needs improvement, and this should be emphasized in the sonography course curriculum. The results suggest that medical sonographers can relieve obstetricians' workload for ultrasound screening in midtrimester pregnancies.

Proline-based solution maintains cell viability and stemness of canine adipose-derived mesenchymal stem cells after hypothermic storage.

Transportation of mesenchymal stem cells (MSCs) under hypothermic conditions in 0.9% normal saline solution (NSS) might increase cell death and alter the stemness of MSCs. The present study aimed to evaluate the effect of proline-based solution (PL-BS) on cell viability and the stemness of newly established canine adipose-derived mesenchymal stem cells (cAD-MSCs) under hypothermic conditions. Characterized cAD-MSCs were stored in 1, 10, and 100 mM PL-BS or NSS at 4°C for 6, 9, and 12 hours prior to an evaluation. The results demonstrated that storage in 1 mM PL-BS for 6 hours decreased cell apoptosis and proliferation ability, but improved cell viability and mitochondrial membrane potential. cAD-MSCs maintained their high expression of CD44 and CD90, but had a low expression of CD34 and MHC class II. Trilineage differentiation ability of cAD-MSCs was not affected by storage in 1 mM PL-BS. Gene expression analysis demonstrated that immunomodulatory genes, including IDO, HGF, PGE-2, and IL-6, were upregulated in cAD-MSCs stored in 1 mM PL-BS. In conclusion, PL-BS can be effectively applied for storing cAD-MSCs under hypothermic conditions. These findings provide a new solution for effective handling of cAD-MSCs which might be promising for clinical applications.

Efficacy of Dehydroepiandrosterone (DHEA) to overcome the effect of ovarian ageing (DITTO): A proof of principle double blinded randomized placebo controlled trial.

OBJECTIVE: To evaluate the effect of DHEA supplementation on In-Vitro Fertilisation (IVF) outcome as assessed by ovarian response, oocyte developmental competence and live birth rates in women predicted to have poor ovarian reserve (OR). The feasibility of conducting a large trial is also assessed by evaluating the recruitment rates and compliance of the recruited participants with DHEA/placebo intake and follow-up rates. STUDY DESIGN: A single centre, double blinded, placebo controlled, randomized trial was performed over two years with 60 women undergoing in-vitro fertilisation (IVF). Subjects were randomized, based on a computer-generated pseudo-random code to receive either DHEA or placebo with both capsules having similar colour, size and appearance. 60 women with poor OR based on antral follicle count or anti-Mullerian hormone thresholds undergoing IVF were recruited. They were randomised to receive DHEA 75mg/day or placebo for at-least 12 weeks before starting ovarian stimulation. They had long protocol using hMG 300 IU/day. Data analysed by "intention to treat". Ovarian response, live birth rates and molecular markers of oocyte quality were compared between the study and control groups. RESULTS: The recruitment rate was 39% (60/154). A total of 52 participants (27 versus 25 in the study and placebo groups) were included in the final analysis after excluding eight. While the mean (standard deviation) DHEA levels were similar at recruitment (9.4 (5) versus 7.5 (2.4) ng/ml; P=0.1), the DHEA levels at pre-stimulation were higher in the study group than in the controls (16.3 (5.8) versus 11.1 (4.5) ng/ml; P<0.01). The number (median, range) of oocytes retrieved (4, 0-18 versus 4, 0-15 respectively; P=0.54) and live birth rates (7/27, 26% versus 8/25, 32% respectively; RR (95% CI): 0.74 (0.22-2.48) and mRNA expression of developmental biomarkers in granulosa and cumulus cells were similar between the groups. CONCLUSION: Pre-treatment DHEA supplementation, albeit statistical power in this study is low, did not improve the response to controlled ovarian hyperstimulation or oocyte quality or live birth rates during IVF treatment with long protocol in women predicted to have poor OR.

Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol.

INTRODUCTION: Dehydroepiandrosterone (DHEA) has been proposed to improve pregnancy rates in women with diminished ovarian reserve undergoing in vitro fertilisation (IVF) treatment. However, evidence regarding its efficacy is supported by a limited number of randomised controlled trials (RCTs). This double-blinded RCT aims to measure the effect of DHEA supplementation prior to and during controlled ovarian hyperstimulation on ovarian response prior to IVF treatment in women predicted to have poor ovarian reserve. METHODS AND ANALYSIS: Sixty women with ovarian antral follicle count ≤10 and serum anti-Mullerian hormone ≤5 pmol/L undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment at the Nurture fertility clinic, Nottingham will be recruited. They will be randomised to either receive DHEA capsule 75 mg/day or placebo for at least 12 weeks before egg collection. All participants will undergo standard long down regulation protocol using human menopausal gonadotropin 300 IU/day. Serum samples and follicular fluids at the time of egg collection will be collected for hormonal immunoassays. For ICSI participants, cumulus cells stripped from oocyte will be collected for cumulus gene expression analyses regarding oocyte competence. Microdrops of oocyte culture media before the time of ICSI will be assessed for glucose, pyruvate and lactate utilisation. Embryo transfer will be performed on day 2, 3 or 5 based on the number and quality of the embryos available. Pregnancy will be defined as urine pregnancy test positive (biochemical pregnancy) and 6-8 weeks ultrasound scan with fetal heart beat (clinical pregnancy) and live birth. It is planned to perform the molecular and nutritional fingerprint analyses in batches after finishing the clinical phase of the study. ETHICS AND DISSEMINATION: The approval of the study was granted by the NHS Research Ethics Committee (Ref number NRES 12/EM/0002), the Medicines and Healthcare products Regulatory Agency (MHRA), and the Nottingham University Hospitals Trust Research and Development department. All participants shall provide written informed consent before being randomised into allocated treatment groups. TRIAL REGISTRATION NUMBER: Protocol V.2.0; EudraCT number: 2011-002425-21; http://www.clinicaltrials.gov; NCT01572025; CTA reference: 03057/0053/001-0002.

Efficacy of dehydroepiandrosterone to improve ovarian response in women with diminished ovarian reserve: a meta-analysis.

Women with diminished ovarian reserve often respond poorly to controlled ovarian stimulation resulting in retrieval of fewer oocytes and reduced pregnancy rates. It has been proposed that pre-IVF Dehydroepiandrosterone (DHEA) adjuvant therapy may improve ovarian response and pregnancy rates in women with diminished ovarian reserve. This meta-analysis aims to investigate efficacy of DHEA as an adjuvant to improve ovarian response and IVF outcome in women with diminished ovarian reserve. Electronic databases were searched under the following terms: (DHEA) and (diminished ovarian reserve) and/or (poor response). Studies were included if they reported at least one of the following outcomes; clinical pregnancy rate, number of oocytes retrieved, miscarriage rate. We identified 22 publications determining effects of DHEA in clinical trials. Only 3 controlled studies were eligible for meta-analysis. There was no significant difference in the clinical pregnancy rate and miscarriage rates between women pre-treated with DHEA compared to those without DHEA pre-treatment (RR 1.87, 95% CI 0.96-3.64; and RR 0.59, 95% CI 0.21-1.65, respectively). The number of oocytes retrieved (WMD -1.88, 95% CI -2.08, 1.67; P < 0.001) was significantly lower in the DHEA group. In conclusion, based on the limited available evidence from a total of approximately 200 IVF cycles, there are insufficient data to support a beneficial role of DHEA as an adjuvant to controlled ovarian stimulation in IVF cycle. Well-designed, randomised controlled trials as well as more exact knowledge about DHEA mechanisms of action are needed to support use of DHEA in standard practice for poor-responders.

D-dimer as a tumor marker in pre-operative assessment of adnexal masses.

OBJECTIVE: To determine the sensitivity, specificity, and predictive value ofserum D-dimer testing in preoperative assessment of adnexal masses. MATERIAL AND METHOD: D-dimer levels were measured pre-operatively in 200 women diagnosed with adnexal masses who underwent surgical treatment at Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital between June 2007 and May 2008. The CA-125 level was also recorded RESULTS: When using cut-off value at 500 ng/ml, D-dimer has 91.8% sensitivity, 71.9% specificity, 58.9% PPV and 95.2% NPV of the tests in differentiating benign from malignant adnexal masses, compared with CA-125, which had 75.4%, 73.0%, 59.7%, and 84.8% respectively (cut-off 65 U/ml). Furthermore, the likelihood ratio to be negative ofD-dimer test is high at 0.11. In patients with epithelial ovarian cancer, D-dimer is increased in 83% of early stage (stage 1) ovarian cancer while only 39% of early stage patients have CA-125 level above cut-off value. CONCLUSION: D-dimer could be a useful test in pre-operative assessment of adnexal masses. In this study D-dimer seems to be better than CA-125 in diferentiating benign from malignant adnexal tumors.