Understanding Time-Lapse Systems
Time-lapse systems (e.g., Embryoscope™ time-lapse system for IVF) take digital images at set time intervals, e.g., every 5 to 15 minutes. In IVF laboratory, time-lapse systems can be installed into an existing embryo incubator or can be used as a separate stand-alone system that combines incubation with time-lapse. Specialist software compiles the images to create a timed sequence of embryo development that can be digitally displayed on a monitor. Specific events such as timing of cleavage divisions, irregular cleavage, fragmentation, fragment resorption, blastocoele formation, and blastocyst expansion can be visualized without disturbing the culture system.
Objective and accurate information is recorded, which can be analyzed in detail. Early studies using time-lapse systems assessed the sequence and timing of morphological events up to formation of pronuclei in ICSI-generated human zygotes. After further refinements in technology, optics, software, etc., their use in IVF laboratories on a larger scale was introduced from around 2010 onwards. Embryo development is a highly dynamic process, driven by fundamental molecular and cellular mechanisms that regulate the kinetics of the cell cycle. Static periodic observations necessary in routine IVF culture cannot truly reflect the details of such a dynamic process, and important events that are crucial to normal development may be missed or overlooked.
Continuous monitoring by time-lapse systems provides a more complete picture, including pro-nuclear patterns, timing of cell divisions, intervals between cell cycles, presence of multi-nucleation and blastomere symmetry, allowing potential dynamic markers of embryo development to be identified. Embryos that have shown aberrant cleavage patterns or have a high potential of developmental arrest can be excluded from transfer.
The systems can provide a stable tightly controlled closed culture environment, avoiding fluctuations in light, pH and temperature that are inevitably associated with removing culture dishes from the incubator for routine intermittent microscopic assessment.
Sample handling is minimized, and this may also reduce the risk of human error. However, embryos may sometimes move out of the microscope’s field of view, or air bubbles may form that prevent adequate image capture. Embryos are exposed to light during each image acquisition, and a potential for harm due to UV radiation cannot so far be excluded. Modern systems incorporate a reduced oxygen atmosphere, and this had been shown to have an effect on rates of embryo development.
Some systems offer computer-assisted assessment of morpho-kinetic parameters and developmental milestones, incorporating algorithms to improve selection of embryos with the highest implantation potential. Numerous studies and trials have so far documented a great deal of information about embryo development, identifying several phenomena whose detailed analysis could ultimately improve the outcome of treatment cycles.
Parameters that have been investigated in detail include:
- Duration of time for visible pronuclei, syngamy, timing of each cell division, initiation of compaction, initiation of blastulation, completion of blastulation,
- Analysis of abnormal cleavage patterns: abnormal syngamy, direct cleavage, reverse cleavage, absent cleavage in the presence of karyokinesis, chaotic cleavage, and cell lysis,
- Early prediction of blastocyst development,
- Negative parameters: multi-nucleation, micronuclei, fragmentation, blastomere asymmetry, direct cleavage from 1 to 3 cells,
- Association between morpho-kinetic parameters and aneuploidy.
However, the parameters observed and correlations identified have varied widely between different investigators, with contradictory results published. Embryo development is highly subject to biological and technical variations, and the algorithms for embryo selection differ: timings that are prognostic for one laboratory may not be directly applicable in another laboratory setting. It is clear that prediction models based on morpho-kinetics are more complicated than first anticipated, and it may not be feasible to establish a universal algorithm for embryo selection.
Each IVF unit should instead work toward building a specific model based on its own patients and practice.
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