Corifollitropin alfa vs recombinant FSH for controlled ovarian stimulation in women aged 35-42 years with a body weight ≥50 kg: a randomized controlled trial.

STUDY QUESTION: Is corifollitropin alfa 150 µg equivalent to follitropin beta 300 IU/day for controlled ovarian hyperstimulation (COS) in older women weighing ≥50 kg undergoing IVF and/or ICSI in Vietnam? SUMMARY ANSWER: Corifollitropin alfa 150 µg was equivalent to follitropin beta 300 IU/day with respect to the number of oocytes retrieved, the ongoing, cumulative and live birth rates and obstetric outcomes. WHAT IS KNOWN ALREADY: Corifollitropin alfa is a recombinant FSH (rFSH) preparation with slow absorption and a long half-life allowing administration of a single dose for COS lasting 7 days. Several randomized, controlled clinical trials have reported that COS with corifollitropin alfa is associated with similar outcomes compared with COS using daily rFSH. However, limited data are available in Asian patients. STUDY DESIGN SIZE DURATION: This randomized controlled trial was conducted at a single large IVF centre in Vietnam from June 2015 to August 2016. A total of 400 patients were included, 200 in each treatment group. The primary outcome measure was the number of oocytes retrieved. Patients were followed for 1 year after randomization. PARTICIPANTS /MATERIALS SETTING METHODS: Participants aged 35-42 years with a body weight ≥50 kg who were undergoing an IVF cycle were randomized to undergo COS with a single dose of corifollitropin alfa 150 µg on Day 2 or 3 of the menstrual cycle, or follitropin beta 300 IU/day for 7 days starting on Day 2 or 3 of the menstrual cycle. All underwent ICSI according to standard institutional protocols. A beta hCG test was performed 17 days after ovum pick-up, and positive tests were confirmed on vaginal and/or abdominal ultrasound at 5-6 weeks after embryo transfer (clinical pregnancy) and at ≥10 weeks (ongoing pregnancy). Rates of ovarian hyperstimulation syndrome, and maternal and foetal outcomes after one cycle of ICSI were monitored over 12 months. MAIN RESULTS AND THE ROLE OF CHANCE: Patients in the corifollitropin alfa and follitropin beta groups were well matched at baseline (mean age 37.5 ± 1.9 vs 37.7 ± 2.0 years, mean body weight 53.7 ± 5.4 vs 52.5 ± 4.8 kg). There was no significant difference between the corifollitropin alfa and follitropin beta groups in the number of oocytes retrieved (11.4 ± 5.9 vs 10.8 ± 5.8; P = 0.338). The ongoing pregnancy rate (31.5 vs 32.0%; P = 0.99) and live birth rate (30.5 vs 32.0%; P = 0.83) (both per initiated cycle at 12 months after randomization) were also similar in the two treatment groups. Complication rates were low and similar in the corifollitropin alfa and follitropin beta groups, and there were no significant between-group differences in obstetric outcomes. LIMITATIONS REASONS FOR CAUTION: This study had an open-label design, and therefore, the potential for bias cannot be excluded. The findings are only applicable to patient populations with similar characteristics to those enroled in the study. WIDER IMPLICATIONS OF THE FINDINGS: This study adds to the body of evidence supporting the equivalence of corifollitropin alfa and follitropin beta for COS in a variety of patients undergoing IVF and/or ICSI. The ability to provide COS with corifollitropin alfa has the potential to reduce the burden of treatment for patients. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Merck Sharp and Dohme. The authors state that they have no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: The trial was registered with clinicaltrials.gov (NCT02466204). TRIAL REGISTRATION DATE: 2 June 2015. DATE OF FIRST PATIENT'S ENROLMENT: 19 June 2015.

Recombinant follicle-stimulating hormone and recombinant luteinizing hormone versus recombinant follicle-stimulating hormone alone during GnRH antagonist ovarian stimulation in patients aged ≥35 years: a randomized controlled trial.

STUDY QUESTION: Does luteinizing hormone (LH) supplementation improve live birth rate after in vitro fertilization (IVF) in patients aged ≥35 years receiving a gonadotrophin-releasing hormone (GnRH) antagonist protocol? SUMMARY ANSWER: There was no difference in live birth rate with use of LH during IVF in patients aged ≥35 years undergoing IVF treatment using a GnRH antagonist protocol. WHAT IS KNOWN ALREADY: Use of GnRH analogues as part of a controlled ovarian hyperstimulation protocol during IVF treatment cycles decreases the amount of LH available to developing follicles. The role of LH supplementation for improving outcomes in patients undergoing controlled ovarian hyperstimulation as part of assisted reproduction treatments, particularly those involving a GnRH antagonist protocol, is unclear. It has been suggested that higher risk patients (e.g. age ≥35 years, poor ovarian reserve) may benefit from LH supplementation. STUDY DESIGN, SIZE, DURATION: This single-centre, randomized controlled trial was conducted from 1 October 2012 to 30 June 2014. A total of 240 women aged ≥35 years undergoing IVF received ovarian stimulation using a GnRH antagonist protocol, with recombinant follicle-stimulating hormone (r-FSH; Gonal-F(®)) starting from cycle day 2 or 3. GnRH antagonist (Cetrotide(®)) was administered on Day 5 of r-FSH administration. On Day 6, patients in the LH supplementation group were switched to r-FSH/r-LH (Pergoveris(®)) 150/75 IU/day. Randomization to study treatments was performed in blocks of 4 via a computer-generated random number list. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 240 patients randomized to treatment, 120 received r-FSH/r-LH and 120 received r-FSH. Patients were recruited from the IVFAS, An Sinh Hospital, Ho Chi Minh City, Vietnam. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rate did not differ significantly (P > 0.05) between r-FSH/r-LH and r-FSH recipients (16.7 versus 17.5%; between-group difference 0.8, 95% confidence interval [CI] -9.5, 11.2). In addition, there were no significant differences between the r-FSH/r-LH and r-FSH groups with respect to the number of oocytes retrieved, implantation rate, miscarriage rate and clinical pregnancy rate. LIMITATIONS, REASONS FOR CAUTION: The open-label design could have introduced bias, and the relatively small sample size may have allowed detection of only the most common adverse events. In addition, the study was likely to be underpowered based on differences between the response rate assumptions used in the sample size calculation and the actual response rate during the study. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study found no additional benefit from adding LH supplementation to ovarian stimulation with a GnRH antagonist protocol in women aged ≥35 years, and add to the body of evidence in this area. However, findings across studies are still inconsistent and additional research is needed before any clear recommendations for clinical practice can be made. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Research Center for Genetics and Reproductive Health, School of Medicine, Vietnam National University HCMC. The authors state that they have no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: The trial was registered with clinicaltrials.gov (NCT02244866).

Evaluation of corneal sensitivity to mechanical and chemical stimuli after LASIK: a pilot study.

PURPOSE: To evaluate the effect of laser in situ keratomileusis (LASIK) on corneal sensitivity, nerve morphology, and tear film characteristics. METHODS: A cross-sectional study design was used. Eighteen patients (eight men and 10 women with a mean age of 36.9 +/- 11.2 years) who had undergone bilateral LASIK for low myopia within 18 months of the study and 28 control subjects (16 men and 12 women with a mean age of 27.2 +/- 7.7 years) were enrolled. Central and inferior corneal thresholds to mechanical (air) and chemical (air plus carbon dioxide) stimuli were determined by using a staircase technique. Stimuli of a 1-second duration at 34 degrees C were delivered with a CRCERT-Belmonte aesthesiometer. Images of subbasal nerves in the central cornea were captured with confocal microscopy. Nerve morphology was classified as no nerves, short nerves (<175 microm), or long nerves (>175 microm), with or without interconnections. Noninvasive tear break up time was measured. The phenol red thread test was used to indicate basal tear secretion. Differences between groups were evaluated with analysis of variance, and associations between variables were evaluated with parametric or nonparametric correlation, when appropriate. RESULTS: Central corneal mechanical sensitivity was significantly reduced in the post-LASIK group compared with the control subjects (P < 0.001). Nerve morphology was associated with mechanical threshold. Nerve morphology, mechanical sensitivity, and tear breakup time improved during the first 1 to 3 months after surgery, with little change thereafter. Chemical sensitivity was associated with tear secretion (P < 0.05). CONCLUSIONS: Central corneal mechanical sensitivity is reduced in patients after LASIK, with partial recovery seen 3 months after surgery. A similar recovery trend is seen for nerve morphology.

Factors that influence special care nursery admissions to a district hospital in South-western Sydney.

OBJECTIVES: To explore the socio-demographic factors and maternal characteristics that influence special care nursery (SCN) admission for infants of more than 34 weeks' gestation. Particularly, this paper aims (i) to estimate the incidence of SCN admission by various mothers' socio-demographic factors; and (ii) to investigate the relationship between SCN admission and mothers' socio-demographic and obstetric and gynaecological factors. METHODS: This was a cohort study of 10,148 pregnant women who accessed the birthing unit within a public district hospital in south-western Sydney in New South Wales, between 1998 and 2001. The main outcome measure was risk factors for SCN admission. RESULTS: The incidence of SCN admission was 11.7%. Multivariate analysis revealed that the risk factors for SCN admission were diabetes, gestational diabetes, high parity, pregnancy induced hypertension, living in suburbs with low education and occupation index, and no private health insurance status. CONCLUSIONS: The results from this large population-based study suggest that, apart from clinical/medical factors, admission to a special care nursery at a District Hospital was significantly affected by maternal insurance status and level of education and occupation.

A novel antigenic variant of Canine parvovirus from a Vietnamese dog.

Nine isolates of Canine parvovirus (CPV) were obtained from Vietnamese dogs and cats. One canine isolate showed a unique antigenic property which indicates a novel antigenic variant of CPV-2b when examined with hemagglutination inhibition tests using our monoclonal antibodies, 21C3 and 19D7, which were recently developed. This isolate had an amino acid substitution of residue 426, Asp to Glu, and the same substitution has recently been found in CPV from Italian dogs. This study first showed that such substitution caused an antigenic difference demonstrable by monoclonal antibodies and that a similar evolution may have occurred in CPV in Vietnam.

Risk factors for low birth weight in a socio-economically disadvantaged population: parity, marital status, ethnicity and cigarette smoking.

Low birth weight (LBW) is a public health problem, because it is associated with increased risk of morbidity and mortality. The principal aim of this study was to assess risk factors for LBW in a large multi-ethnic and socio-economically disadvantaged population. Data from 3242 mothers, who attended the Well Baby Clinic (Southwestern Sydney, Australia) for the first time, were analysed in relation to their demographic characteristics and socio-economic indices. The overall birthweight was 3377 +/- 577 g (mean +/- SD). In multiple linear regression analysis, smoking during pregnancy, marital status, parity, and country of birth were independently associated with birth weight. According to this analysis, lower birth weight was associated with mothers who had smoked during pregnancy (by 215.2 +/- 18.6 g), who were single (46.9 +/- 21 g), and of Asian background (108.5 +/- 38.2 g). However, higher parity was associated with significantly higher birth weight. The presence of each factor was coded as 1 and the absence, 0. A 'risk score' was then derived by summing up the individual scores. When birth weight was classified as 'low birth weight' (defined as those with birth weight being less than 2500 g) or normal birth weight, the overall prevalence of LBW was 1.9%. Each unit increase in the risk score was associated with a 1.9-fold (95% confidence interval: 1.5-2.6) increase in the risk of LBW. These data suggest that apart from marital status, ethnicity and parity, maternal smoking is the single most important preventable risk factors for LBW.

[The value of repeated determinations of brain natriuretic peptide for the diagnosis of unstable angina]. / Intérêt des dosages répétés du brain natriuretic peptide pour le diagnostic d'angor instable.

The diagnosis of unstable angina (troponine undetectable) is often difficult in the absence of electrocardiographic changes after suggestive chest pains. The object of this study was to analyse the kinetics of Brain Natiuretic Peptide (BNP) during acute coronary syndromes (ACS) without ST elevation. Plasma BNP was measured every 6 hours for 48 hours in 65 patients admitted for suspicion of ACS without ST elevation and without clinical, radiological or echocardiographic signs of left ventricular dysfunction. The results of BNP measurements were masked until the final diagnosis was established on the usual investigations (ECG changes, troponine I values, myocardial scintigraphy, coronary angiography). These investigations identified 3 groups of patients: non-Q wave infarction (group A: 19 patients), unstable angina (group B: 21 patients) and non-coronary chest pain (group C: 25 patients). The peak BNP was significantly higher in groups A (210 +/- 172 pg/ml) and B (152 +/- 159 pg/ml) than in group C (16 +/- 14 pg/ml). However, the BNP was normal or only slightly increased (< 50 pg/ml) in 25% of cases of ACS. Analysis of the kinetics of BNP was much more discriminating: early increase after the pain, peak between the 14th and 24th hours (19th hour on average), followed by a progressive decrease. The kinetics were identical in Groups A and B, contrasting with the flat profile of the curve in group C. A change of > 20 pg/ml in BNP was a better criterion of ACS with a diagnostic accuracy > 90% than increased troponine (group A) or undetectable troponine (group B). The authors conclude that BNP kinetics is a new and reliable diagnostic marker of unstable angina when the usual criteria of ACS are not present (notably a normal ECG and undetectable troponine).

[Mobile right heart thrombus with minimal pulmonary embolism. A case report]. / Thrombus mobile intracavitaire droit associé à une embolie pulmonaire minime. A propos d'un cas.

The generalisation of the use of transthoracic echocardiography in the investigation of pulmonary embolism leads to the diagnosis of mobile right heart thrombus in about 5% of cases. A review of the literature shows that this association is mainly observed in clinically severe pulmonary embolism. The presence of a mobile right heart thrombus is associated with a poor prognosis and emergency treatment is based on thrombolytic therapy or surgical embolectomy. In minimal or infraclinical pulmonary embolism, the finding of a mobile right heart thrombus is rare and there is no consensus about its treatment. The authors report the case of a 61 year old man admitted to hospital for bilateral deep vein thrombosis with no symptoms of pulmonary embolism in whom investigations revealed a mobile right heart thrombus with minimal pulmonary embolism. The outcome was favourable with progressive resolution of the right heart thrombus with oral anticoagulation after three weeks of heparin therapy.

[Localization of isolated atrial involvement of cardiac sarcoidosis]. / Localisation auriculaire isolée d'une sarcoïdose cardiaque. A propos d'un cas.

The authors report the first case of cardiac sarcoidosis involving only the interatrial septum and the atrioventricular node in a 30 year old man with known lymph node sarcoidosis. The diagnosis was suspected after the finding of an apparently innocent 1st degree atrioventricular block and confirmed by transoesophageal echocardiography and by IMATRON computerised tomography. Isolated atrial involvement of sarcoidosis is rare in the absence of any left ventricular disease. This explains the negative findings at transthoracic echocardiography and radio-isotopic investigations usually recommended for diagnosing cardiac sarcoidosis.

Genetic analyses of feline foamy virus isolates from domestic and wild feline species in geographically distinct areas.

To know the genetic diversities and phylogenetic relationship among feline foamy virus (FeFV) isolates from domestic cats (Felis catus) and FeFV-related viruses from the Iriomote cats (Felis iriomotensis) and leopard cats (Felis bengalensis) in geographically distinct areas, we sequenced a partial gag-pol region of 17 strains and a partial env region of nine strains, and the U3 region of long terminal repeat of three strains of the viruses. FeFV-related viruses from the feral cats were quite similar to the FeFV from domestic cats in the sequenced regions. In the partial gag region, the identities of nucleotide sequences among the isolates were from 94 to 99%. In the partial env gene, the isolates were divided into two distinct genotypes (F17- and FUV-types) as reported by Winkler et al. (Virology 247 (1999) 144-151). More than 94% nucleotide identities were observed in the env region within a particular env genotype and about 75% nucleotide identities were noted between the two genotypes.

A framework for monitoring maternal and infant health status.

The Mother and Infant Network (MINET) Program was established in South Western Sydney Area Health Service (SWSAHS) in 1997. MINET developed and implemented an integrated clinical data network as a key strategy to support and inform a Continuum of Care comprising hospital and community based services. There are good data sources within the MINET program. Its scope spans care for mothers and children, which begins with the first antenatal attendance and ends at school entry. This paper has three interrelated aims: to describe the development of the MINET program; to demonstrate the benefits of a sustainable Information Culture which can assist an Area Health Services in adopting a health outcomes based approach to service delivery; and to describe how MINET has the capacity to support Health Services Research.

Quality of health services and early postpartum discharge: results from a sample of non-English-speaking women.

Few studies have explored the knowledge, perceptions and satisfaction of ethnic women in relation to early obstetric discharge. The aim of this study was to form a profile of Vietnamese mothers who opt for early postpartum discharge, and to identify factors associated with those decisions. Focus group discussions, in-depth interviews and survey questionnaires were utilized to collect information from a sample of 160 mothers. Sixty mothers (38%) opted for early discharge (< 48 h). Factors strongly associated with early discharge were poor comprehension of English (OR=6.58, 95% CI=1.81, 24.02), very low level of education (OR=3.10, 95% CI=1.55, 6.20) and first time mother (OR=2.70, 95% CI=1.15, 4.27). The in-depth interviews identified further factors driving early discharge, including fear and anxiety when having to approach staff for assistance, and perceptions of disempowerment within culturally unfamiliar hospital surroundings. The findings in this study ought to alert administrators and clinicians to possible negative drivers for the choice of early postpartum discharge by Vietnamese mothers.

Occupational exposure and chronic respiratory symptoms--a population based study in Vietnam.

In order to investigate the relationship between occupational exposure to dust/chemicals (toxic gases/fumes) and chronic respiratory symptoms in Vietnam, the questionnaire standardized by the American Thoracic Society was applied to 368 subjects living in Ha Thai district of Vietnam. According to the results of multiple logistic regression analyses, the odds ratios of chronic respiratory symptoms by occupational exposure are over unity, except for the relationship between chronic cough and occupational exposure to chemicals. Especially for chronic breathlessness, significantly higher odds ratios are observed among people with a history of occupational exposure to dust or chemicals: 2.925 (95% CI: 1.130-7.574) for dust, and 3.721 (95% CI: 1.412-9.803) for chemicals. As for the interaction between occupational exposure to dust and cigarette smoking, it is considered that occupational exposure leads to an increase in chronic respiratory symptoms independent of the effects of cigarette smoking.

Tissue and cellular distribution of the extended family of protein kinase C isoenzymes.

Polyclonal isoenzyme-specific antisera were developed against four calcium-independent protein kinase C (PKC) isoenzymes (delta, epsilon, epsilon', and zeta) as well as the calcium-dependent isoforms (alpha, beta I, beta II, and gamma). These antisera showed high specificities, high titers, and high binding affinities (3-370 nM) for the peptide antigens to which they were raised. Each antiserum detected a species of the predicted molecular weight by Western blot that could be blocked with the immunizing peptide. PKC was sequentially purified from rat brain, and the calcium-dependent forms were finally resolved by hydroxyapatite chromatography. Peak I reacted exclusively with antisera to PKC gamma, peak II with PKC beta I and -beta II, and peak III with PKC alpha. These same fractions, however, were devoid of immunoreactivity for the calcium-independent isoenzymes. The PKC isoenzymes demonstrated a distinctive tissue distribution when evaluated by Western blot and immunocytochemistry. PCK delta was present in brain, heart, spleen, lung, liver, ovary, pancreas, and adrenal tissues. PKC epsilon was present in brain, kidney, and pancreas, whereas PKC epsilon' was present predominantly in brain. PKC zeta was present in most tissues, particularly the lung, brain, and liver. Both PKC delta and PKC zeta showed some heterogeneity of size among the different tissues. PKC alpha was present in all organs and tissues examined. PKC beta I and -beta II were present in greatest amount in brain and spleen. Although the brain contained the most PKC gamma immunoreactivity, some immunostaining was also seen in adrenal tissue. These studies provide the first evidence of selective organ and tissue distributions of the calcium-independent PKC isoenzymes.

[Dispersion of biochemical analysis results in Dakar: preliminary results]. / Etude de la dispersion des résultats d'analyses biochimiques à Dakar: résultats préliminaires.

Now and then, the conflicting character of results of some analyses is prejudicial to patients (financial and particullary psychological repercussions), to the laboratories (renown) and to the practitioners (difficulties of interpreting). After a study of the dispersion of some analyses results, the authors propose a creation of an Interlaboratory Quality Control in Clinical Biochemistry in Senegal.

Multicentre evaluation of the Boehringer Mannheim/Hitachi 717 analysis system.

We conducted an European multicentre trial to assess the performance of the new Boehringer Mannheim/Hitachi 717 analysis system. The photometer response was linear up to an absorbance of 2.8. The maximal CV of photometric imprecision was 0.5% for the wavelength pair 340/405 nm within the absorbance range 0.9 to 2.4. For the 13 analytes in our study, mean within-run imprecision was less than 2%, and mean between-day imprecision less than 2.5%. The results obtained with the Hitachi 717 instrument correlated closely with those of comparison instruments. Linearity for the various tests was high and exceeded the manufacturer's claims. No drift was detected during an 8-hour work period; carry over could not be detected under the chosen experimental conditions. The new instrument was readily accepted by the evaluators because of its ease of handling and simple daily maintenance.

Genetically determined alcohol preference and cyclic AMP binding proteins in mouse brain.

Free-choice consumption of alcohol by mice with differing phenotypic alcohol preferences caused uniformly large decreases in brain cyclic AMP-dependent protein kinase activity toward an exogenous substrate (histone 2b) but the effect of alcohol on brain cyclic AMP binding activity was strain-specific. Furthermore, particulate kinase phosphorylating activity toward an endogenous protein (kinase regulatory subunit, RII) was altered by alcohol consumption in a strain-specific manner. The changes in cyclic AMP binding and phosphorylating activity appeared to result from phenotypic differences in the brain's response to alcohol. Thus, low preference animals were sensitive to alcohol and showed a large decrease in cyclic AMP binding and an increase in phosphorylation of regulatory subunit in response to alcohol. In contrast, high preference strain had only a small decrease in cyclic AMP binding and a decrease in phosphorylation, even though these animals consumed a significantly larger dose of alcohol. These data suggest that changes in cyclic AMP binding and/or phosphorylation of kinase regulatory subunit may be phenotypic markers of alcohol preference in inbred mice.

A multicentre evaluation of the Boehringer Mannheim/Hitachi 704 analysis system.

The selective multitest Boehringer Mannheim/Hitachi 704 analysis system was examined according to the ECCLS guidelines in a multicentre evaluation involving four laboratories. Ten routine parameters, covering most of the application settings of the instrument, were measured in the respective laboratory at temperatures 25, 30 or 37 degrees C. The trial lasted four months and gave more than 40,000 data. It yielded the following results: 1. Within the four laboratories the mean coefficients of variation for three control sera at different concentrations were found to be equal to or better than 1.6% for the within-run imprecision and 2.8% or better for the between-day imprecision. 2. No drift was observed during eight hours. 3. Because of the high linear measuring range a re-run analysis was seldom necessary. 4. Sample-related carry-over was not seen. Reagent-dependent carry-over was measured from cholesterol to uric acid and from triacylglycerols to lipase. Through modification of the cholesterol and triacylglycerol reagents, the carry-over effect was practically eliminated. 5. The recovery of the assigned values of control sera showed average values between 99 and 104%. For bilirubin, creatinine, creatine kinase and alanine aminotransferase some control sera showed deviations greater than 10%. 6. In all cases, regression analysis of the results obtained in comparisons of the present instrument with the Hitachi 705 or 737 yielded slopes close to unity with extreme values of 0.95 and 1.06. 7. During the entire evaluation period there was no malfunction or breakdown of the instruments. The evaluators came to the conclusion that the analytical performance as well as the reliability and practicability of the Hitachi 704 can be rated as excellent.