Non invasive assessment of human oocytes and embryos in assisted reproduction: Review on present practices and future trends

Oocyte and embryo grading is one of the most important steps in assisted reproductive technology to identify the best among cultured embryos for transfer or vitrification. The most commonly used non-invasive method is morphological assessment of gametes and embryos using a microscope. This method despite being simple and cost-effective has interobserver and intraobserver variability and subjectivity and has little to offer about the physiological state of embryos. This review sourced research articles and reviews pertaining to other non-invasive assessment methodologies from Medline and PubMed to collate latest technologies in vogue and identify novel methodologies of the future. The review assesses the current understanding in oocyte and embryo grading and touches upon novel non-invasive techniques and potential biomarkers to identify the best embryo. The latest available literature on time-lapse imaging, hierarchical algorithms, omics (consisting of proteomics and secretomes), miRNAs, mitochondrial RNAs and artificial intelligence has been accessed to summarize the enormous information available, to identify gaps in current interpretations, to identify emerging technologies and to provide direction for future research. This review will greatly benefit anyone practicing assisted reproduction and clinical embryology.     

The infant health effects of starting universal child benefits in pregnancy: Evidence from England and Wales

Child benefits are typically paid from birth. This paper asks whether starting universal child benefits in pregnancy leads to improvements in infant health. Leveraging administrative birth registry and hospital microdata from England and Wales, I study the effects of the Health in Pregnancy Grant, a universal conditional cash transfer equivalent to three months of child benefit (190 GBP) as a lump sum to pregnant mothers from 2009 to 2011. I exploit quasi-experimental variation in eligibility with a regression discontinuity design in the date of birth of the baby. I find that the policy increased birth weight by 8–12 grams on average, reduced low birth weight ($<$2500 g) by 3-6 percent and decreased prematurity by 9–11 percent. Younger mothers, particularly those living in deprived areas, benefit the most. I present evidence that the mechanisms are unlikely to be antenatal care, nutrition or smoking, with reductions in stress remaining a possible explanation.     

Evaluación del desarrollo psicomotor hasta los 3 años de edad de niños españoles concebidos por técnicas de reproducción asistida (FIV/ICSI): estudio prospectivo de cohorte controlado

IntroductionMore than five million children have been conceived by assisted reproductive techniques (ART) around the world. Most authors agree that there are no differences in psychomotor development in comparison to naturally conceived children. However, these results are still contradictory.ObjectiveTo determine whether children born from a cohort of ART-clinical gestations have a higher risk of suffering neurodevelopmental disorders in comparison to a control group. The potential associated ART-factors associated were also determined.Material and methodsThe study included the assessment of children up to 3 years old conceived by ART, and born from a cohort of women treated by the reproduction unit of a public hospital from May 2012 to May 2014. A simultaneous assessment was made of matched controls, by following the newborn naturally conceived after the ART-case, of the same group of maternal age, gestational age, and type of gestation.ResultsThere were 243 clinical gestations and 267 ART-newborns, of which 231 were assessed (87%). A simultaneous assessment was carried out in 208/230 controls (90%). There were no differences in neurodevelopmental disorders (global developmental delay, autism spectrum or language delay). Multivariate analysis of potential ART factors only showed an association between transfer of frozen embryos with language delay that has not been previously described.ConclusionsThere were no differences between groups after adjusting the results according to maternal age, multiple pregnancy, and other possible confounding factors, supporting that the role of these factors may be more relevant than the ART itself. The association between frozen embryo transfer and language delay has not been previously described. Thus, more studies are needed to confirm or refute this relationship.     

Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.