Time lapse monitoring: hype, hope & everyday use

Giles Palmer, Mitera, Athens

There are no commercial relationships or other activities that might be perceived as a potential

conflict of interest

Less disturbance/More observations

Innovation trigger

Peak of inflated

expectations

Trough ofDisillusionment Slope of Enlightenment Plateau of

productivity

Gartner’s hype cycleVisibility

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

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

Karyokinetics and cytokinetics

Karyokinetics and cytokinetics

Second cell cycle

Third cell cycle

3-4 cell

5-8 cell

Karyokinetics and cytokinetics

Second cell cycle

Third cell cycle

3-4 cell

5-8 cell

*

*

TLM in practice

Too quick!

Too slow!

Just right!

Perfect timing?

Embryo

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

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.

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 (Redlines).

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 (Redlines).

Adapted 5C-8C: from <6hrs to < 3hrs

Time line profile

e

Time line profile

e

eCGH profile

3-4 Cells

Abnormal cell division & aneuploidy

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 CGHThe timing of first and second divisions were delayed in aneuploidy and more marked in those with multiple aneuploidy2-4 cell transition: Euploidy<single aneuploidy<multiple aneuploidy

Basile (2013) Increasing the probability of selecting chromosomally normal embryos by studying their kineticsClassification 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

PGS & TLM

PGS & TLM

PGS & TLM

PGS & TLM

BC

BC BC

BC BC

BC

BC

EUPLOID

EUPLOID CHAOTIC

PGS & TLM

CHAOTIC

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

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

Innovation trigger

Peak of inflated

expectations

Trough ofDisillusionment 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

Any questions?