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TEMPORAL ODDESSEY:
EXPLORING THE HORIZONS OF
TIME-LAPSE EMRBYO MONITORING
DR. RAHUL SEN
Ph.D. MSc.
CHIEF CONSULTANT EMBRYOLOGIST
NEELKANTH IVF
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
LEARNING OBJECTIVES
ABOUT TIME LAPSE TECHNOLOGY ?
EMBRYO CULTURE SYSTEM TECHNIQUES IN TLT
DOES IT REALLY WORTH TO ADD TIME LAPSE TECHNOLOGY IN A LAB ?
INCORPORATING TIME-LAPSE UNIT IN A ROUTINE LAB?
COMPARING OUTCOMES WITH STANDARD INCUBATORS ¨C CURRENT EVIDENCES
ADDED ADVANTAGES ¨C CURRENT EVIDENCES
INTRODUCTION
The introduction of TLT has led to the emergence of "morphokinetics" assessment, which
integrates morphology with kinetics to provide a comprehensive framework for
understanding and evaluating embryo viability
The incubator component consists of ¨C High Quality Contrast Optics, Microscope, Camera,
Culture Dish Compartment, Gas chamber & Function Panel. The imaging software
component consists of ¨C Morphokinetic Annotation & Predictive Algorithm to assess
embryo viability.
TLT allows continuous non-invasive observation of embryo development with minimal
manipulation, significantly contributing to understand developmental events and
enhancing morphology assessments of embryo
INTRODUCTION
Although time-lapse technology (TLT) was introduced in ART many years ago (Payne
et al., 1997), it was not until 2010 that TLT shifted from a mere observation of human
embryos while in culture, to a selection and prediction tool.
The year of 2011 marked the official introduction of TLT in the embryology
laboratory, when embryo implantation was shown to be associated with specific cell
division timing parameters, introducing the term ¡®morphokinetics¡¯
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
IMPACT ON EMBRYO CULTURE CONDITIONS -
CULTURE MEDIUM & DISHES -
NO LIMITATION WITH UTILIZATION OF CULTURE MEDIUM STRATEGY;
CULTURE DISHES ARE LIMITED AS PRODUCT MANUFACTURER¡®S
CO2/ O2 GAS TENSION ¨C CAN HOLD ANY GAS CONCENTRATION
(LOW, ULTRALOW, TRIGAS)
EMBRYO DENSITY ¨C INDIVIDUAL EMBRYO CULTURE APPROACH
SAFETY ISSUES ¨C TYPE OF MICROSCOPY; EXPOSURE TO LIGHT; INBUILT HEATH DISSIPATION
SAFETY ISSUES WITH TLT
no safety issues have been reported following embryo culture in TLT incubators, and
obstetric and perinatal outcomes, such as duration of gestation, congenital malformations
and birth weight, are comparable (Costa-Borges et al., 2016; Insua et al., 2017; Kovacs et
al., 2019) or better (Mascarenhas et al., 2019) compared to standard incubation.
Conclusions: The strategy of
culturing embryo in time-lapse
incubation systems would not
increase adverse risks of neonatal
outcomes comparing to SI.
SETTING UP OF A TIME-LAPSE INCUBATOR IN LAB
WHY, WHAT, WHICH, WHERE, HOW?
Clearly identify the reasons to introduce a TLT system
? Assess pros and cons of acquiring a TLT system, both
financially and operatively
? Identify whether morphokinetic parameters will be
used in selection/de-selection /ranking of embryos
? Selection of suitable time lapse equipment
? Evaluate technical/customer support available
? Once introduced in the lab, find the appropriate
system settings
? Training of embryologists with current evidences in TLT
COMPARING TIME LAPSE WITH STANDARD INCUBATORS
CONNECTS WITH A LOGGER THAT MONITOR LEVEL/PRESSURE OF GASES
INSIDE THE INCUBATOR
EMBRYO ASSESSMENT TO BE DONE MANUALLY AT A SPECIFIC TIME INTERVAL
NO SCOPE FOR AUTOMATION IN NEAR FUTURE
CONNECTS THE INCUBATOR WITH A COMPUTER USING SPECIALLY
DESIGNED SOFTWARE THAT MONITOR ALL STAGES OF EMBRYO
DEVELOPMENT
EMBRYO ASSESSMENT TO BE DONE USING DESIGNED ALGORITHMS, AI
SCOPE FOR AUTOMATION/ UPGRADATION IN FUTURE
LONG TERM STORAGE FOR PICTURES/ VIDEOS ¨C QC, RECORD KEEPING,
DOCUMENTATION PURPOSE (ART ACT 2021)
UNDERSTANDING EMBRYO DEVELOPMENT EVENTS
68 hrs
44 hrs
27 hrs
17 hrs 96 hrs 108 hrs
the static ¡®snap-shot¡¯ assessment being performed outside of the incubator
Whole embryo development is recorded that can include more information how an embryo
divided in between those fixed time frames
`
Fan YL, et. Al., 2016 JARG
BLASTOCYST STRINGS
SPONTANEOUS BLASTOCYST COLLAPSE
EBNAR, 2008
? The aim was to study whether a limited exposure of embryos outside the incubator has an effect on
embryo development, blastocyst quality and euploid outcomes.
? 796 mature sibling oocytes that were split randomly between two incubators: benchtop vs. timelapse
? The fertilization, cleavage, embryo/blastocyst qualities, useable blastocyst and euploid rates were
assessed to evaluate the incubator performance.
? No differences observed in fertilization rates, cleavage rate and day3 embryo quality rate.
? Embryos cultured in time-lapse had a significantly higher blastocyst biopsy rate, increased euploid
rate, improved blastocyst quality
? We found that exposure of embryos outside the incubator may negatively affect the in vitro blastocyst
development and euploid rate on Day 5.
? This large multicentre, single-blinded, randomized controlled study included 1224 participants
randomly assigned (1:1) to the time-lapse or standard incubator group.
? embryo transfer cycle was still significantly higher in the time-lapse group
? The embryo assessment method offered by time-lapse systems rather than an undisturbed
environment may play an important role in improving the implantation rate
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
? This consensus paper provides updated recommendations on criteria and terminology for assessing oocyte, zygote, cleavage-
stage embryo, morulae, and blastocyst development thorough review of evidence accumulated over the past decade.
? Critical information gained from application of TLT has revised timings of developmental milestones
? The document recommends incorporating morphokinetic features since the introduction of TLT into the assessment criteria,
can inform and complement the static observation approach.
? The document suggests that future research should focus on addressing the knowledge gaps in understanding the impact of
various factors on embryo developmental timing
RESEARCH PROSPECTS
RESEARCH PROSPECTS
TRAINING, VALIDATION & EMBRYO GRADING QC
COMPARING CLINIC PERFORMANCES ¨C KPI
PREDICTING EMBRYO OUTCOMES
Embryo culture has already been fully automated with use of time-lapse incubators which allow continuous monitoring of
embryo development.
Data generated from time-lapse incubators can be analyzed with machine learning to aid in the selection of embryos with the
highest pregnancy potential.
Additional information about embryo viability may be gleaned from other omics technologies which can either sample the
embryo directly or indirectly via its culture media. The technologies in question include genomic, transcriptomic, proteomic, and
metabolomic analyses
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
CONCLUSION
Time-lapse systems have quickly become a common feature of in vitro fertilization laboratories all over
the world.
the alleged benefits of time-lapse technology have continued to grow, from undisturbed culture
conditions and round the clock, noninvasive observations to more recent computer-assisted selection of
embryos through the development of algorithms.
Applications of time lapse with Metabolomic profiling, non-invasive PGT are still unexplored
Despite the global uptake of time-lapse technology, its real impact on clinical outcomes is still
controversial.
Can it be a path way to hit for Universal Single Embryo Transfer Policy.
THANK YOU

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NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf

  • 1. TEMPORAL ODDESSEY: EXPLORING THE HORIZONS OF TIME-LAPSE EMRBYO MONITORING DR. RAHUL SEN Ph.D. MSc. CHIEF CONSULTANT EMBRYOLOGIST NEELKANTH IVF
  • 3. LEARNING OBJECTIVES ABOUT TIME LAPSE TECHNOLOGY ? EMBRYO CULTURE SYSTEM TECHNIQUES IN TLT DOES IT REALLY WORTH TO ADD TIME LAPSE TECHNOLOGY IN A LAB ? INCORPORATING TIME-LAPSE UNIT IN A ROUTINE LAB? COMPARING OUTCOMES WITH STANDARD INCUBATORS ¨C CURRENT EVIDENCES ADDED ADVANTAGES ¨C CURRENT EVIDENCES
  • 4. INTRODUCTION The introduction of TLT has led to the emergence of "morphokinetics" assessment, which integrates morphology with kinetics to provide a comprehensive framework for understanding and evaluating embryo viability The incubator component consists of ¨C High Quality Contrast Optics, Microscope, Camera, Culture Dish Compartment, Gas chamber & Function Panel. The imaging software component consists of ¨C Morphokinetic Annotation & Predictive Algorithm to assess embryo viability. TLT allows continuous non-invasive observation of embryo development with minimal manipulation, significantly contributing to understand developmental events and enhancing morphology assessments of embryo
  • 5. INTRODUCTION Although time-lapse technology (TLT) was introduced in ART many years ago (Payne et al., 1997), it was not until 2010 that TLT shifted from a mere observation of human embryos while in culture, to a selection and prediction tool. The year of 2011 marked the official introduction of TLT in the embryology laboratory, when embryo implantation was shown to be associated with specific cell division timing parameters, introducing the term ¡®morphokinetics¡¯
  • 8. IMPACT ON EMBRYO CULTURE CONDITIONS - CULTURE MEDIUM & DISHES - NO LIMITATION WITH UTILIZATION OF CULTURE MEDIUM STRATEGY; CULTURE DISHES ARE LIMITED AS PRODUCT MANUFACTURER¡®S CO2/ O2 GAS TENSION ¨C CAN HOLD ANY GAS CONCENTRATION (LOW, ULTRALOW, TRIGAS) EMBRYO DENSITY ¨C INDIVIDUAL EMBRYO CULTURE APPROACH SAFETY ISSUES ¨C TYPE OF MICROSCOPY; EXPOSURE TO LIGHT; INBUILT HEATH DISSIPATION
  • 9. SAFETY ISSUES WITH TLT no safety issues have been reported following embryo culture in TLT incubators, and obstetric and perinatal outcomes, such as duration of gestation, congenital malformations and birth weight, are comparable (Costa-Borges et al., 2016; Insua et al., 2017; Kovacs et al., 2019) or better (Mascarenhas et al., 2019) compared to standard incubation. Conclusions: The strategy of culturing embryo in time-lapse incubation systems would not increase adverse risks of neonatal outcomes comparing to SI.
  • 10. SETTING UP OF A TIME-LAPSE INCUBATOR IN LAB WHY, WHAT, WHICH, WHERE, HOW? Clearly identify the reasons to introduce a TLT system ? Assess pros and cons of acquiring a TLT system, both financially and operatively ? Identify whether morphokinetic parameters will be used in selection/de-selection /ranking of embryos ? Selection of suitable time lapse equipment ? Evaluate technical/customer support available ? Once introduced in the lab, find the appropriate system settings ? Training of embryologists with current evidences in TLT
  • 11. COMPARING TIME LAPSE WITH STANDARD INCUBATORS CONNECTS WITH A LOGGER THAT MONITOR LEVEL/PRESSURE OF GASES INSIDE THE INCUBATOR EMBRYO ASSESSMENT TO BE DONE MANUALLY AT A SPECIFIC TIME INTERVAL NO SCOPE FOR AUTOMATION IN NEAR FUTURE CONNECTS THE INCUBATOR WITH A COMPUTER USING SPECIALLY DESIGNED SOFTWARE THAT MONITOR ALL STAGES OF EMBRYO DEVELOPMENT EMBRYO ASSESSMENT TO BE DONE USING DESIGNED ALGORITHMS, AI SCOPE FOR AUTOMATION/ UPGRADATION IN FUTURE LONG TERM STORAGE FOR PICTURES/ VIDEOS ¨C QC, RECORD KEEPING, DOCUMENTATION PURPOSE (ART ACT 2021)
  • 12. UNDERSTANDING EMBRYO DEVELOPMENT EVENTS 68 hrs 44 hrs 27 hrs 17 hrs 96 hrs 108 hrs the static ¡®snap-shot¡¯ assessment being performed outside of the incubator Whole embryo development is recorded that can include more information how an embryo divided in between those fixed time frames
  • 13. ` Fan YL, et. Al., 2016 JARG
  • 15. ? The aim was to study whether a limited exposure of embryos outside the incubator has an effect on embryo development, blastocyst quality and euploid outcomes. ? 796 mature sibling oocytes that were split randomly between two incubators: benchtop vs. timelapse ? The fertilization, cleavage, embryo/blastocyst qualities, useable blastocyst and euploid rates were assessed to evaluate the incubator performance. ? No differences observed in fertilization rates, cleavage rate and day3 embryo quality rate. ? Embryos cultured in time-lapse had a significantly higher blastocyst biopsy rate, increased euploid rate, improved blastocyst quality ? We found that exposure of embryos outside the incubator may negatively affect the in vitro blastocyst development and euploid rate on Day 5.
  • 16. ? This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. ? embryo transfer cycle was still significantly higher in the time-lapse group ? The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate
  • 19. ? This consensus paper provides updated recommendations on criteria and terminology for assessing oocyte, zygote, cleavage- stage embryo, morulae, and blastocyst development thorough review of evidence accumulated over the past decade. ? Critical information gained from application of TLT has revised timings of developmental milestones ? The document recommends incorporating morphokinetic features since the introduction of TLT into the assessment criteria, can inform and complement the static observation approach. ? The document suggests that future research should focus on addressing the knowledge gaps in understanding the impact of various factors on embryo developmental timing
  • 21. TRAINING, VALIDATION & EMBRYO GRADING QC
  • 24. Embryo culture has already been fully automated with use of time-lapse incubators which allow continuous monitoring of embryo development. Data generated from time-lapse incubators can be analyzed with machine learning to aid in the selection of embryos with the highest pregnancy potential. Additional information about embryo viability may be gleaned from other omics technologies which can either sample the embryo directly or indirectly via its culture media. The technologies in question include genomic, transcriptomic, proteomic, and metabolomic analyses
  • 26. CONCLUSION Time-lapse systems have quickly become a common feature of in vitro fertilization laboratories all over the world. the alleged benefits of time-lapse technology have continued to grow, from undisturbed culture conditions and round the clock, noninvasive observations to more recent computer-assisted selection of embryos through the development of algorithms. Applications of time lapse with Metabolomic profiling, non-invasive PGT are still unexplored Despite the global uptake of time-lapse technology, its real impact on clinical outcomes is still controversial. Can it be a path way to hit for Universal Single Embryo Transfer Policy.