Time lapse monitoring of IVF embryos is not only about morphokinetic predictions but a more detailed evaluation of morphology

1. Time lapse monitoring: hype, hope & everyday use
Giles Palmer, Mitera, Athens

2. There are no commercial relationships or other
activities that might be perceived as a
potential conflict of interest

3. Less disturbance/More observations

4. Innovation trigger
Peak of
inflated
expectations
Trough of
Disillusionment Slope of Enlightenment Plateau of
productivity
Gartner’s hype cycle
Visibility
Time
Payne
1997
Plethora of
TLM papers
Suggestions of
algorithm for
embryo
competence
Aneuploidy risk model
To have
or not to
have
TLM??
First RCT’s

5. In vitro culture of embryos
Conventional observation’s
• Maturity
• Fertilization
• Fragmentation
• Cleavage rate/Blastocyst rate
• Multinucleation/Aneuploidy
TLM
• Ability to check and score in a
dynamic manner
• Follow up on normality of
cleavages
• Exclude “out of range” timelines
• Objective scoring
• Communication

6. Karyokinetics and cytokinetics

7. Karyokinetics and cytokinetics
Second cell cycle
Third cell cycle
3-4 cell
5-8 cell

8. Karyokinetics and cytokinetics
Second cell cycle
Third cell cycle
3-4 cell
5-8 cell
*
*

9. TLM in practice
Too quick!
Too slow!
Just right!

10. Perfect timing?

11. Intervals:
• DPN to 2C: 2-3 hrs
• 2C -3C: 8-12hrs
• 3C-4C: <45min
• 4c-5C: 13-16hrs
• 5C-8C: <6hrs
• 8C-BC: <72hrs
Milestones:
• DPN: 22-26hrs
• t2: 24-28hrs
• t3: 30-38hrs
• t4: 35-41hrs
• t5: 48-57hrs
• t8: 50-59hrs

13. J. Assist Reprod Genet (2015) 32:563-570
In conjunction with similar studies, our results indicate the importance of the timing of cleavage events on embryo
competence and the positive effect that embryo selection via TLM has on ICSI outcomes.
We found higher clinical, ongoing and live birth rates in participants whose embryos were monitored through TLM, as
compared to those whose embryos were monitored by morphological assessment. This difference was maintained in
women over 40 years.

14. Figure 2. Percentage of transferred embryos of Group 1 (TLM) that exhibited “in range”
cellular events in patients with positive outcomes (Blue lines) and negative outcomes (Red
lines).

15. Figure 2. Percentage of transferred embryos of Group 1 (TLM) that exhibited “in range”
cellular events in patients with positive outcomes (Blue lines) and negative outcomes (Red
lines).
Adapted 5C-8C: from <6hrs to < 3hrs

16. Time line profile
e
Time line profile
e
eCGH profile
3-4 Cells
Abnormal cell division & aneuploidy

17. Time line profile
e
Time line profile
e
e
3-4 Cells
Davies (ESHRE 2012) Delayed cleavage divisions and prolonged transition between 2-4-cell stages
identified as aneuploid at 8-cell by array CGH
The timing of first and second divisions were delayed in aneuploidy and more marked in those with
multiple aneuploidy
2-4 cell transition: Euploidy<single aneuploidy<multiple aneuploidy
Basile (2013) Increasing the probability of selecting chromosomally normal embryos by studying their
kinetics
Classification system based on time parameters relates to selection of euploid embryos
Normal embryos A+: 36,3%, A: 33,9%;B+: 32,0%, B:19,5%;C+:14,3%, C:11,5%;D+: 10,0%, D: 9,0%
Campbell (2013) Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived
from time-lapse imaging without PGS Aneuploidy risk model
Abnormal cell division & aneuploidy

18. PGS & TLM

19. PGS & TLM

20. PGS & TLM

21. PGS & TLM
BC
BC BC
BC BC
BC
BC
EUPLOID
EUPLOID CHAOTIC

22. PGS & TLM
CHAOTIC

23. Indications for TLM
• Older patients with high # oocytes
• Previous unsuccessful IVF patients
• Previous successful patients (sET)
• Good prognosis patients (D2/3 not BC
ET)
Confidence of transferring fewer embryos
Satisfied patients with greater information
given

24. Appeals to patients & clinicians/
commercial world
Combined conventional and TLM can
increase embryo selection and
pregnancy rate:
Help selection by exclusion
More sophisticated way of culturing
embryos
RCT have confirmed earlier studies-
now in your hands!
Less disturbance/More observations

25. Innovation trigger
Peak of
inflated
expectations
Trough of
Disillusionment Slope of Enlightenment Plateau of
productivity
Visibility
Time
METABOLIC STUDY &
TIME LAPSE,
Gardner
OOCYTE MATURATION,
Yi, Li
QC & KPI’S,
Morbeck
MICROFLUIDS,
Swain, Smith
Gartner’s hype cycle

26. Any questions?