Semi-automated morphometric analysis of human embryos can reveal correlations between total embryo volume and clinical pregnancy

what is known already: Morphometric analysis of a large group of embryos has revealed the potential to optimize algorithms for image-analysis systems for the grading of embryos and predicting pregnancy outcomes. study design, size, duration: Oocytes and embryos were obtained from 458 patients who underwent single embryo transfer on Day 3 after IVF/ICSI, between September 2006 and December 2010 at the Leuven University Fertility Center, Belgium. In total, the data set contained 2796 embryos including 458 embryos that were transferred on Day 3. Ongoing pregnancy was defined as the presence of at least one intrauterine gestational sac at 20 weeks. participants/materials, setting, methods: Patients included in this study were younger than 36 years, entering their first (n ¼ 375) or second (n ¼ 83) IVF/ICSI cycle and were only included once. Patients were excluded if the cycle included biopsy for PGD or if donor sperm/donor oocytes were used. Based on the 26 sequential images of the same embryo taken at one time point in different planes, the software calculates the total cytoplasmic volume for each time point, from which any reduction or change in the volume with time can be assessed (which helps interpret the degree of fragmentation) and the size of blastomeres. The diameter of the smallest and largest blastomere and the total volume of each embryo were extracted from the computer-assisted scoring system database and the coefficient of diversity was calculated for Days 1, 2 and 3. A logistic regression analysis was performed to determine the range of embryo volume associated with an increased chance of pregnancy. main results and the role of chance: On Day 3, blastomeres of 8-cell stage embryos were less divergent in size than those of 6-, 7-, 9-cell stage embryos. Although, the coefficients of diversity (ratio of the largest:smallest blastomeres) of implanted embryos tended to be lower than for non-implanted embryos, the difference was only significant for 6-cell stage embryos (P ¼ 0.02). After logistic regression, an association between total embryo volume and pregnancy was observed which had a quadratic nature: both lower and higher volumes were associated with a lower probability of successful pregnancy. A significant association was identified between total embryo volume and pregnancy rate on both Days 2 (P ¼ 0.003) and 3 (P ¼ 0.0003). Diagnostic measures (sensitivity, specificity, positive predictive value, accuracy and c-statistics) of the defined volume range were relatively poor. However, results showed a good negative predictive value [76.86% (95% confidence interval 71.03-82.02) on Day 3]. limitations, reasons for caution: A general disadvantage of studies evaluating the impact of a characteristic on the implantation potential of an embryo is the fact that the best embryo is chosen for transfer. No comparisons can therefore be made with the other embryos. Moreover, the decision process is currently based on a non-automated, standard scoring system, which means that a 'bias' in the selection process is always present. wider implications of the findings: Our results are an important step towards the development of an automated computer-assisted scoring system for the morphological characteristics of human embryos to improve embryo selection for optimizing implantation potential. Total embryo volume appears to be one of the objective characteristics that should be included. study funding/competing interest(s): None. trial registration number: Not applicable

A blended preconception lifestyle programme for couples undergoing IVF:lessons learned from a multicentre randomized controlled trial

Study question: What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition?Summery answer:This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes.What is know already:Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF.Study design, size, duration:A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid-19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy).Participants/materials, setting, methods:Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)-programme in addition to standard care. The PreLiFe-programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was 'time to ongoing pregnancy'. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat.Main results and the role of chance:A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness).Limitations, reasons for caution:The findings of this RCT should be considered exploratory, as the Covid-19 pandemic limited its power and the actual use of the mobile application was low.Wider implications of the findings:This is the first multicentre RCT evaluating the effect of a blended preconception lifestyle programme for women and their partners undergoing IVF on both reproductive and lifestyle outcomes. This exploratory RCT highlights the need for further studies into optimal intervention characteristics and actual use of preconception lifestyle programmes, as well as RCTs evaluating effectiveness.Study fonding/competing intrest(s):Supported by the Research foundation Flanders (Belgium) (FWO-TBM; reference: T005417N). No competing interests to declare.Trial registration number:ClinicalTrials.gov Identifier: NCT03790449TRIAL REGISTRATION DATE 31 December 2018DATE OF FIRST PATIENT'S ENROLMENT 2 January 201

Intra- and inter-observer analysis in the morphological assessment of early-stage embryos

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the intra- and inter-observer variability in the evaluation of embryo quality. Multilevel images of embryos on day 1, day 2 and day 3, were analysed using different morphological parameters.</p> <p>Methods</p> <p>Multilevel images of embryos on day 1, day 2 and day 3, were analysed using a standard scoring system. The kappa coefficient was calculated to measure intra- and inter-observer variability before and after training sessions.</p> <p>Results</p> <p>Good to excellent intra-observer agreement was present for most parameters exceptions being scoring the position of pronuclei and the presence of a cytoplasmic halo on day 1, multinucleation on day 2 and the size of fragments on day 3. Inter-observer agreement was only good to excellent for the number of blastomeres on day 2 and day 3 and the orientation of the cleavage axes on day 2. Training sessions had a positive impact on inter-observer agreement.</p> <p>Conclusion</p> <p>In conclusion, assessment of morphological characteristics of early stage embryos using multilevel images was marked by a high intra-observer and a moderate inter-observer agreement. Training sessions were useful to increase inter-observer agreement.</p

Non-human primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate

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Patterns of Safe Collaboration

When practicing secure programming, it is important to understand the restrictive influence programmed entities have on the propagation of authority in a program. To precisely model authority propagation in patterns of interacting entities, we present a new formalism Knowledge Behavior Models (KBM). To describe such patterns, we present a new domain specific declarative language SCOLL (Safe Collaboration Language), which semantics are expressed by means of KBMs. To calculate the solutions for the safety problems expressed in SCOLL, we have built SCOLLAR: a model checker and solver based on constraint logic programming. SCOLLAR not only indicates whether the safety requirements are guaranteed by the restricted behavior of the relied-upon entities, but also lists the different ways in which their behavior can be restricted to guarantee the safety properties without precluding their required functionality and (re-)usability. How the tool can help programmers to build reliable components that can safely interact with partially or completely untrusted components is shown in elaborate examples

Tutorial in biostatistics: The self-controlled case series method

The self-controlled case series method was developed to investigate associations between acute outcomes and transient exposures, using only data on cases, that is, on individuals who have experienced the outcome of interest. Inference is within individuals, and hence fixed covariates effects are implicitly controlled for within a proportional incidence framework. We describe the origins, assumptions, limitations, and uses of the method. The rationale for the model and the derivation of the likelihood are explained in detail using a worked example on vaccine safety. Code for fitting the model in the statistical package STATA is described. Two further vaccine safety data sets are used to illustrate a range of modelling issues and extensions of the basic model. Some brief pointers on the design of case series studies are provided. The data sets, STATA code, and further implementation details in SAS, GENSTAT and GLIM are available from an associated websit