Effect of time post warming to embryo transfer on human blastocyst metabolism and pregnancy outcome.

Purpose: This study is aiming to test whether variation in post warming culture time impacts blastocyst metabolism or pregnancy outcome.

Methods: In this single center retrospective cohort study, outcomes of 11,520 single frozen embryo transfer (FET) cycles were analyzed from January 2015 to December 2020. Patient treatments included both natural and programmed cycles.

Metabolic imaging of human embryos is predictive of ploidy status but is not associated with clinical pregnancy outcomes: a pilot trial.

Study Question: Does fluorescence lifetime imaging microscopy (FLIM)-based metabolic imaging assessment of human blastocysts prior to frozen transfer correlate with pregnancy outcomes?

Summary Answer: FLIM failed to distinguish consistent patterns in mitochondrial metabolism between blastocysts leading to pregnancy compared to those that did not.

What Is Known Already: FLIM measurements provide quantitative information on NAD(P)H and flavin adenine dinucleotide (FAD+) concentrations. The metabolism of embryos has long been linked to their viability, suggesting the potential utility of metabolic measurements to aid in selection.

Fluorescence lifetime imaging microscopy (FLIM) detects differences in metabolic signatures between euploid and aneuploid human blastocysts.

Study Question: Can non-invasive imaging with fluorescence lifetime imaging microscopy (FLIM) detect metabolic differences in euploid versus aneuploid human blastocysts?

Summary Answer: FLIM has identified significant metabolic differences between euploid and aneuploid blastocysts.

What Is Known Already: Prior studies have demonstrated that FLIM can detect metabolic differences in mouse oocytes and embryos and in discarded human blastocysts.

Study Design, Size, Duration: This was a prospective observational study from August 2019 to February 2020.

Metabolic state of human blastocysts measured by fluorescence lifetime imaging microscopy.

Study Question: Can non-invasive metabolic imaging via fluorescence lifetime imaging microscopy (FLIM) detect variations in metabolic profiles between discarded human blastocysts?

Summary Answer: FLIM revealed extensive variations in the metabolic state of discarded human blastocysts associated with blastocyst development over 36 h, the day after fertilization and blastocyst developmental stage, as well as metabolic heterogeneity within individual blastocysts.

What Is Known Already: Mammalian embryos undergo large changes in metabolism over the course of preimplantation development. Embryo metabolism has long been linked to embryo viability, suggesting its potential utility in ART to aid in selecting high quality embryos.

Combined noninvasive metabolic and spindle imaging as potential tools for embryo and oocyte assessment.

Study Question: Is the combined use of fluorescence lifetime imaging microscopy (FLIM)-based metabolic imaging and second harmonic generation (SHG) spindle imaging a feasible and safe approach for noninvasive embryo assessment?

Summary Answer: Metabolic imaging can sensitively detect meaningful metabolic changes in embryos, SHG produces high-quality images of spindles and the methods do not significantly impair embryo viability.

What Is Known Already: Proper metabolism is essential for embryo viability. Metabolic imaging is a well-tested method for measuring metabolism of cells and tissues, but it is unclear if it is sensitive enough and safe enough for use in embryo assessment.

Metabolic imaging via fluorescence lifetime imaging microscopy for egg and embryo assessment.

Current strategies for embryo assessment in the assisted reproductive technology laboratories rely primarily on morphologic parameters that have limited accuracy for determining embryo viability. Even with the addition of invasive diagnostic interventions such as preimplantation genetic testing for aneuploidy alone or in combination with mitochondrial DNA copy number assessment, at least one third of embryos fail to implant. Therefore, at a time when the clinical benefits of single ET are widely accepted, improving viability assessment of embryos is ever more important.

Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes.

Objective: To determine whether metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) identifies metabolic differences between normal oocytes and those with metabolic dysfunction.

Design: Experimental study.

Setting: Academic research laboratories.

Will noninvasive methods surpass invasive for assessing gametes and embryos?

The need to identify the most viable embryo following in vitro fertilization (IVF) was established early in the history of human IVF. The stalwart of identifying the best embryos has been morphology. Other techniques have however seen wide acceptance, including the use of preimplantation genetic screening, even though concerns exist over the invasive nature of the technique.

Tunable dynamics of microtubule-based active isotropic gels.

We investigate the dynamics of an active gel of bundled microtubules (MTs) that is driven by clusters of kinesin molecular motors. Upon the addition of ATP, the coordinated action of thousands of molecular motors drives the gel to a highly dynamical turbulent-like state that persists for hours and is only limited by the stability of constituent proteins and the availability of the chemical fuel. We characterize how enhanced transport and emergent macroscopic flows of active gels depend on relevant molecular parameters, including ATP, kinesin motor and depletant concentrations, MT volume fraction, as well as the stoichiometry of the constituent motor clusters.

Topology and dynamics of active nematic vesicles.

Engineering synthetic materials that mimic the remarkable complexity of living organisms is a fundamental challenge in science and technology. We studied the spatiotemporal patterns that emerge when an active nematic film of microtubules and molecular motors is encapsulated within a shape-changing lipid vesicle. Unlike in equilibrium systems, where defects are largely static structures, in active nematics defects move spontaneously and can be described as self-propelled particles.

Spontaneous motion in hierarchically assembled active matter.

With remarkable precision and reproducibility, cells orchestrate the cooperative action of thousands of nanometre-sized molecular motors to carry out mechanical tasks at much larger length scales, such as cell motility, division and replication. Besides their biological importance, such inherently non-equilibrium processes suggest approaches for developing biomimetic active materials from microscopic components that consume energy to generate continuous motion. Being actively driven, these materials are not constrained by the laws of equilibrium statistical mechanics and can thus exhibit sought-after properties such as autonomous motility, internally generated flows and self-organized beating.