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).

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.

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.

[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.

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.

Direct enzymatic determination of urea in plasma and urine with a centrifugal analyzer.

A direct enzymatic micromethod (sample volume, 3mul) has been adapted to the centrifugal analyzer (ENI-GEMSAEC) for measurement of urea in plasma and urine. The method is based on urease (urea amidohydrolase, EC3.5.1.5)/glutamate dehydrogenase [l-glutamate:NAD(P)+oxidoreductase (deaminating), EC1.41.3] coupled reactions, and uses a two-point fixed-time (t(1)=20s,t(2)=50s)kinetic scheme for monitoring the rate of comsumption of NADH at 340 nm. Sensitivity and precision of the method are excellent,and results compare well with those from a commonly used continuous-flow method.