No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis.

STUDY QUESTION: What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)? SUMMARY ANSWER: The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone. WHAT IS KNOWN ALREADY: Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer. STUDY DESIGN, SIZE, DURATION: This IPD MA included all existing RCTs (n = 4) in which embryo selection by morphology was compared with embryo selection by morphology and the use of NIR spectroscopy of spent embryo culture medium by the Viametrics-E(™). PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of PubMed, the Cochrane Library and the WHO International Clinical Trials Registry were conducted and the sole manufacturer of the Viametrics-E(™) was consulted to identify clinics where an RCT comparing embryo selection by morphology to embryo selection by morphology and the use of the Viametrics-E(™) (NIR viability score) was performed. A total of 20 citations were potentially eligible for inclusion, two of which met the inclusion criteria. The manufacturer of the Viametrics-E(™) provided two additional clinical sites of use. In total, four RCTs were identified as eligible for inclusion. The IPD MA was based on a fixed effect model due to the lack of heterogeneity between included studies. Differences between study groups were tested and reported using logistic regression models adjusted for significant confounders. The pooled analysis of the primary outcome led to a total sample size of 924 patients: 484 patients in the control group (embryo selection by morphology alone) and 440 patients in the treatment group (embryo selection by morphology plus NIR spectroscopy). MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates in the control group and the NIR group were 34.7% (168 of 484) and 33.2% (146 of 440), respectively. The pooled odds ratio (OR) was 0.98 [95% confidence interval (CI) 0.74-1.29], indicating no difference in live birth rates between the two study groups. The data of the four studies showed no significant heterogeneity (I(2) = 26.2% P = 0.26). The multivariate regression analysis including all confounders show that maternal age (OR 0.90, 95% CI 0.87-0.94) and the number of previous IVF cycles (OR 0.83, 95% CI 0.71-0.96) were significantly related to live birth. The study group (i.e. embryo selection by morphology or embryo selection by morphology plus NIR) was not related to live birth (OR 0.97, 95% CI 0.73-1.29). LIMITATIONS AND REASONS FOR CAUTION: The availability of at least two similar best quality embryos as an inclusion criterion prior to transfer in the two largest RCTs might have caused a selection bias towards a better prognosis patient group. WIDER IMPLICATIONS OF THE FINDINGS: There is at present no evidence that NIR spectroscopy of spent embryo culture media in its current form can be used in daily practice to improve live birth rates.

Isolation and characterization of microsatellite markers from the Mediterranean fruit fly, Ceratitis capitata: cross-species amplification in other Tephritidae species reveals a varying degree of transferability.

The Mediterranean fruit fly, Ceratitis capitata, is a pest of major economic importance and has become a model for the development of SIT control programs for insect pests. Significant information has been accumulated on classical and population genetics of this species during the past 2 decades. However, the availability of molecular markers is limited. Here, we present the isolation and characterization of 159 microsatellite clones and the development of 108 polymorphic microsatellite markers for this insect pest. Mapping by in situ hybridization to polytene chromosomes of 21 microsatellite clones enriched the cytogenetic map that was previously constructed by our group. The enriched map provides a large number of STSs for future genome mapping projects. Cross-species amplification of these microsatellite loci in 12 Tephritidae species and sequence analysis of several amplification products indicated a varying degree of transferability and their possible usefulness as molecular and genetic markers in these species where genetic and molecular tools are limited.

Analysis of the evolution of chromosome abnormalities in human embryos from Day 3 to 5 using CGH and FISH.

The use of interphase fluorescent in situ hybridization (FISH) has shown that a large number of human embryos exhibit chromosomal abnormalities in vitro. The most common abnormality is mosaicism which is seen in up to 50% of preimplantation embryos at all stages of development. In this study, comparative genomic hybridization (CGH) was used to analyse 1-2 cells biopsied on Day 3 of development while the rest of the embryo was cultured until Day 5. Embryos were spread on Day 5 and analysed by FISH using probe combinations that varied depending on the CGH result, to investigate the progress of any abnormalities detected on Day 3. A total of 37 frozen-thawed embryos were analysed in this study. One gave no CGH or FISH results and was excluded from analysis. Six embryos failed to give any FISH result as they were degenerating on Day 5. Thirty embryos provided results from both techniques. According to the CGH results, the embryos were divided into two groups; Group 1 had a normal CGH result (13 embryos) and Group 2 an abnormal CGH result (17 embryos). For Group 1, three embryos showed normal CGH and FISH results, while 10 embryos were mosaic after FISH analysis, with various levels of abnormalities. For Group 2, FISH showed that all embryos were mosaic or completely chaotic. The combination of CGH and FISH enabled the thorough investigation of the evolution of mosaicism and of the mechanisms by which it is generated. The main two mechanisms identified were whole or partial chromosome loss and gain. These were observed in embryos examined on both Day 3 and 5.

Bilateral non-contemporary fractures of the proximal femur.

Ninety-seven bilateral non-contemporary fractures of the upper end of the femur were analysed retrospectively. They were collected from among a total of 1333 fractures treated in a 5-year period in two clinics, one in Athens and one in Geneva. The incidence of bilateral non-contemporary fractures was about 7.5 per cent of the total. The interval between the two fractures was shorter in males than in females, but a preponderance of females with bilateral fractures was evident. There was a significantly higher percentage of symmetrical fractures in the bilateral groups (70 per cent). No difference in the age, habits and general condition was found between the control (unilateral) and the bilateral fracture groups.

Correlation study of arterial blood pressure level to the amplitude of the pressure pulse waveform.

Automated blood pressure measurements are usually characterized by poor operational reliability and a considerable degree of complexity in performing the measurement. This paper introduces a new technique for the indirect measurement of the systolic and diastolic blood pressure of an individual. The technique is based upon a statistically consistent relationship between the amplitude of the pulsative pressure waveform at the systolic and diastolic points, and the amplitude of pulse signals detected when the artery is fully occluded. Clinical testing and statistical analysis techniques are used to derive appropriate numerical values for these relationship. The proposed procedure thus incorporates an adaptive measurement philosophy achieving minimum observer involvement and consequently high instrument accuracy. Overall measurement errors are maintained well within proposed standards for automated sphygmomanometers.

Slow evolution of chronic myeloid leukaemia relapsing after BMT with T-cell depleted donor marrow.

Thirty-three patients with Philadelphia positive (Ph+) chronic myeloid leukaemia (CML) treated in chronic phase by bone marrow transplantation (BMT) with T-cell depleted HLA-identical sibling marrow were evaluable for relapse at a median follow up of 41 months (range 16-59 months). Twenty-six (78%) had Ph+ marrow metaphases demonstrated at some time post BMT. The subsequent pattern of disease was variable. In 15 of these cases haematological relapse occurred within 24 months of BMT. Four patients proceeded to haematological relapse more slowly. Seven patients had only cytogenetic evidence of relapse. Of the 19 patients with haematological relapse, five received second transplants and two survive; 13 of the other 14 survive in chronic phase at median times from allografting and from recognition of haematological relapse of 41 months (range 25-59 months) and 18 months (range 5-36 months) respectively. For these 13 patients disease progression after relapse seems to be relatively indolent. In the four patients we could study, blood lymphocytes were almost all of donor origin. We suggest that even in patients with cytogenetic or haematological evidence of relapse after T-cell depleted BMT, leukaemic cell proliferation may still be restrained to some extent by a graft-versus-leukaemia effect mediated by donor-derived lymphoid cells.