Does artificial intelligence have a role in the IVF clinic?

Funding: K R D is supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). K D is supported by the UK Engineering and Physical Sciences Research Council (grants EP/P030017/1 and EP/R004854/1).Lay summary The success of IVF has remained stagnant for a decade. The focus of a great deal of research is to improve on the current ~30% success rate of IVF. Artificial intelligence (AI), or machines that mimic human intelligence, has been gaining traction for its potential to improve outcomes in medicine, such as cancer diagnosis from medical images. In this commentary, we discuss whether AI has the potential to improve fertility outcomes in the IVF clinic. Based on existing research, we examine the potential of adopting AI within multiple facets of an IVF cycle, including egg/sperm and embryo selection, as well as formulation of an IVF treatment regimen. We discuss both the potential benefits and concerns of the patient and clinician in adopting AI in the clinic. We outline hurdles that need to be overcome prior to implementation. We conclude that AI has an important future in improving IVF success.Publisher PDFPeer reviewe

Feature coding dataset for trained and untrained working memory tasks in randomized controlled trials of working memory training.

The data presented in this article are produced as part of the original research article entitled "Working memory training involves learning new skills" (Gathercole, Dunning, Holmes & Norris, in press). This article presents a dataset of coded features for pairs of trained and untrained working memory (WM) tasks from randomized controlled trials of WM training with active control groups. Feature coding is provided for 113 untrained WM tasks each paired with the most similar task in the training program, taken from 23 training studies. A spreadsheet provides summary information for each task pair, its transfer effect size, and coding of the following features for each task: stimulus category, stimulus domain, stimulus modality, response modality, and recall paradigm

Investigation of refractive index dynamics during in vitro embryo development using off-axis digital holographic microscopy

Funding: Engineering and Physical Sciences Research Council - EP/P030017/1, EP/R004854/1; Australian Research Council - FL210100099; National Health and Medical Research Council - APP2003786; Future Making Fellowship (University of Adelaide); Hospital Research Foundation (Mid-career fellowship C-MCF58-2019).Embryo quality is a crucial factor affecting live birth outcomes. However, an accurate diagnostic for embryo quality remains elusive in the in vitro fertilization clinic. Determining physical parameters of the embryo may offer key information for this purpose. Here, we demonstrate that digital holographic microscopy (DHM) can rapidly and non-invasively assess the refractive index of mouse embryos. Murine embryos were cultured in either low- or high-lipid containing media and digital holograms recorded at various stages of development. The phase of the recorded hologram was numerically retrieved, from which the refractive index of the embryo was calculated. We showed that DHM can detect spatio-temporal changes in refractive index during embryo development that are reflective of its lipid content. As accumulation of intracellular lipid is known to compromise embryo health, DHM may prove beneficial in developing an accurate, non-invasive, multimodal diagnostic.Publisher PDFPeer reviewe

Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams

This project was funded by the UK Engineering and Physical Sciences Research Council (grants EP/P030017/1 and EP/R004854/1), and has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement (EC-GA 871212) and H2020 FETOPEN project "Dynamic” (EC-GA 863203). P.W. was supported by the 1851 Research Fellowship from the Royal Commission. KRD was supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). K.D. acknowledges support from the Australian Research Council through a Laureate Fellowship. S.S. was funded by BBSRC (BB/M00905X/1).Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000–10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.Publisher PDFPeer reviewe

Research Review: The effects of mindfulness-based interventions on cognition and mental health in children and adolescents - a meta-analysis of randomized controlled trials.

BACKGROUND: Mindfulness based interventions (MBIs) are an increasingly popular way of attempting to improve the behavioural, cognitive and mental health outcomes of children and adolescents, though there is a suggestion that enthusiasm has moved ahead of the evidence base. Most evaluations of MBIs are either uncontrolled or nonrandomized trials. This meta-analysis aims to establish the efficacy of MBIs for children and adolescents in studies that have adopted a randomized, controlled trial (RCT) design. METHODS: A systematic literature search of RCTs of MBIs was conducted up to October 2017. Thirty-three independent studies including 3,666 children and adolescents were included in random effects meta-analyses with outcome measures categorized into cognitive, behavioural and emotional factors. Separate random effects meta-analyses were completed for the seventeen studies (n = 1,762) that used an RCT design with an active control condition. RESULTS: Across all RCTs we found significant positive effects of MBIs, relative to controls, for the outcome categories of Mindfulness, Executive Functioning, Attention, Depression, Anxiety/Stress and Negative Behaviours, with small effect sizes (Cohen's d), ranging from .16 to .30. However, when considering only those RCTs with active control groups, significant benefits of an MBI were restricted to the outcomes of Mindfulness (d = .42), Depression (d = .47) and Anxiety/Stress (d = .18) only. CONCLUSIONS: This meta-analysis reinforces the efficacy of using MBIs for improving the mental health and wellbeing of youth as assessed using the gold standard RCT methodology. Future RCT evaluations should incorporate scaled-up definitive trial designs to further evaluate the robustness of MBIs in youth, with an embedded focus on mechanisms of action

Working memory training involves learning new skills

We present a new framework characterizing training-induced changes in WM as the acquisition of novel cognitive routines akin to learning a new skill. Predictions were tested in three studies analyzing the transfer between WM tasks following WM training. Study 1 reports a meta-analysis establishing substantial transfer when trained and untrained tasks shared either a serial recall, complex span or backward span paradigm. Transfer was weaker for serial recall of verbal than visuo-spatial material, suggesting that this paradigm is served by an existing verbal STM system and does not require a new routine. Re-analysis of published WM training data in Study 2 showed that transfer was restricted to tasks sharing properties proposed to require new routines. In a re-analysis of data from four studies, Study 3 demonstrated that transfer was greatest for children with higher fluid cognitive abilities. These findings suggest that development of new routines depends on general cognitive resources and that they can only be applied to other similarly-structured tasks

UVA hyperspectral light-sheet microscopy for volumetric metabolic imaging : application to preimplantation embryo development

Funding: This work was supported by funding from the UK Engineering and Physical Sciences Research Council (EP/P030017/1, EP/R004854/1), the Australian Research Council (FL210100099), the National Health and Medical Research Council (APP2003786), and the European Union’s Horizon 2020 research and innovation program under the H2020 FETOPEN project “Dynamic” (EC-GA 863203) and “Proscope” (871212). K.R.D is supported by a Hospital Research Foundation Fellowship (Midcareer fellowship C-MCF-58-2019) and a Future Making Fellowship (University of Adelaide).Cellular metabolism is a key regulator of energetics, cell growth, regeneration, and homeostasis. Spatially mapping the heterogeneity of cellular metabolic activity is of great importance for unraveling the overall cell and tissue health. In this regard, imaging the endogenous metabolic cofactors, nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), with subcellular resolution and in a noninvasive manner would be useful to determine tissue and cell viability in a clinical environment, but practical use is limited by current imaging techniques. In this paper, we demonstrate the use of phasor-based hyperspectral light-sheet (HS-LS) microscopy using a single UVA excitation wavelength as a route to mapping metabolism in three dimensions. We show that excitation solely at a UVA wavelength of 375 nm can simultaneously excite NAD(P)H and FAD autofluorescence, while their relative contributions can be readily quantified using a hardware-based spectral phasor analysis. We demonstrate the potential of our HS-LS system by capturing dynamic changes in metabolic activity during preimplantation embryo development. To validate our approach, we delineate metabolic changes during preimplantation embryo development from volumetric maps of metabolic activity. Importantly, our approach overcomes the need for multiple excitation wavelengths, two-photon imaging, or significant postprocessing of data, paving the way toward clinical translation, such as in situ, noninvasive assessment of embryo viability.Publisher PDFPeer reviewe

Vitrification within a nanoliter volume : oocyte and embryo cryopreservation within a 3D photopolymerized device

Open Access funding enabled and organized by CAUL and its Member Institutions. KRD is supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58–2019). KD acknowledges funding from the UK Engineering and Physical Sciences Research Council (grants EP/P030017/1). This study was funded by the Australian Research Council (ARC) Centre of Excellence for Nanoscale BioPhotonics (CE140100003).Purpose Vitrification permits long-term banking of oocytes and embryos. It is a technically challenging procedure requiring direct handling and movement of cells between potentially cytotoxic cryoprotectant solutions. Variation in adherence to timing, and ability to trace cells during the procedure, affects survival post-warming. We hypothesized that minimizing direct handling will simplify the procedure and improve traceability. To address this, we present a novel photopolymerized device that houses the sample during vitrification. Methods The fabricated device consisted of two components: the Pod and Garage. Single mouse oocytes or embryos were housed in a Pod, with multiple Pods docked into a Garage. The suitability of the device for cryogenic application was assessed by repeated vitrification and warming cycles. Oocytes or early blastocyst-stage embryos were vitrified either using standard practice or within Pods and a Garage and compared to non-vitrified control groups. Post-warming, we assessed survival rate, oocyte developmental potential (fertilization and subsequent development) and metabolism (autofluorescence). Results Vitrification within the device occurred within ~ 3 nL of cryoprotectant: this volume being ~ 1000-fold lower than standard vitrification. Compared to standard practice, vitrification and warming within our device showed no differences in viability, developmental competency, or metabolism for oocytes and embryos. The device housed the sample during processing, which improved traceability and minimized handling. Interestingly, vitrification-warming itself, altered oocyte and embryo metabolism. Conclusion The Pod and Garage system minimized the volume of cryoprotectant at vitrification—by ~ 1000-fold—improved traceability and reduced direct handling of the sample. This is a major step in simplifying the procedure.Publisher PDFPeer reviewe

The effect of discrete wavelengths of visible light on the developing murine embryo

Open Access funding enabled and organized by CAUL and its Member Institutions KRD is supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58–2019). KD is supported by funding from the UK Engineering and Physical Sciences Research Council (EP/P030017/1) and the Australian Research Council (FL210100099). CC acknowledges the support of a PhD scholarship jointly from the University of Adelaide and University of Nottingham. This study was funded by the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CE140100003). PR acknowledges funding through the RMIT Vice-Chancellor’s Research Fellowship and ARC DECRA Fellowship scheme (DE200100279).Purpose A current focus of the IVF field is non-invasive imaging of the embryo to quantify developmental potential. Such approaches use varying wavelengths to gain maximum biological information. The impact of irradiating the developing embryo with discrete wavelengths of light is not fully understood. Here, we assess the impact of a range of wavelengths on the developing embryo. Methods Murine preimplantation embryos were exposed daily to wavelengths within the blue, green, yellow, and red spectral bands and compared to an unexposed control group. Development to blastocyst, DNA damage, and cell number/allocation to blastocyst cell lineages were assessed. For the longer wavelengths (yellow and red), pregnancy/fetal outcomes and the abundance of intracellular lipid were investigated. Results Significantly fewer embryos developed to the blastocyst stage when exposed to the yellow wavelength. Elevated DNA damage was observed within embryos exposed to blue, green, or red wavelengths. There was no effect on blastocyst cell number/lineage allocation for all wavelengths except red, where there was a significant decrease in total cell number. Pregnancy rate was significantly reduced when embryos were irradiated with the red wavelength. Weight at weaning was significantly higher when embryos were exposed to yellow or red wavelengths. Lipid abundance was significantly elevated following exposure to the yellow wavelength. Conclusion Our results demonstrate that the impact of light is wavelength-specific, with longer wavelengths also impacting the embryo. We also show that effects are energy-dependent. This data shows that damage is multifaceted and developmental rate alone may not fully reflect the impact of light exposure.Publisher PDFPeer reviewe

Susceptibility to prosocial and antisocial influence in adolescence following mindfulness training

Mindfulness training programmes have shown to encourage prosocial behaviours and reduce antisocial tendencies in adolescents. However, less is known about whether training affects susceptibility to prosocial and antisocial influence. The current study investigated the effect of mindfulness training (compared with an active control) on self-reported prosocial and antisocial tendencies and susceptibility to prosocial and antisocial influence. 465 adolescents aged 11–16 years were randomly allocated to one of two training programmes. Pre- and post-training, participants completed a social influence task. Self-reported likelihood of engaging in prosocial and antisocial behaviours did not change post-training, and regardless of training group, participants showed a higher propensity for prosocial influence than for antisocial influence. Finally, participants were less influenced by antisocial ratings following both training programmes