TABLE 1.
Human embryo time-lapse observations and markers, and the status of their practical application in the clinical IVF laboratory.
| Study | Time-lapse observation or marker | Outcomes | Biological study in humans | Technology to quantify time-lapse marker | Validation through prospective clinical trial |
|---|---|---|---|---|---|
| Payne et al. 1997 (2) | Time from ICSI to extrusion of PB2 | Day-3 embryo quality (n = 50) | No | Manual review | No |
| Synchrony of formation of gametic PN | |||||
| Time from ICSI to PN abuttal | |||||
| Periodicity of the cytoplasmic wave | |||||
| Lemmen et al. 2008 (3) | Time from fertilization to PN disappearancea | No | Manual review | No | |
| Time from fertilization to first cleavage (2-cell)b | Day-2 cell number (n = 102)a,b Ongoing pregnancy (n = 29)b |
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| Time and synchrony of nuclei appearance after first cleavageb | |||||
| Pribenszky et al. 2010 (4) | Time of cell cleavages and lack of fragmentation | Live birth (n = 5) | No | Manual review | No |
| Wong et al. 2010 (5) | Duration of first cytokinesis | Blastocyst formation (n = 100) | Gene expression of whole embryos and single blastomeres (n = 142) | Automated cell tracking measurements and outcome prediction | Nod |
| Time between first and second mitosis (2- to 3-cell stage) | |||||
| Synchrony of second and third mitosis (3- to 4-cell stage) | |||||
| Meseguer et al. 2011 (6) | Time between first and second mitosis (2- to 3-cell stage) | Implantation for Day-3 transfer (n = 247) | No | Manual review | Nod |
| Synchrony of second and third mitosis (3- to 4-cell stage) | |||||
| Time from ICSI to 5-cell stage | |||||
| Hashimoto et al. 2012 (7) | Synchrony of second and third mitosis (3- to 4-cell stage) | Blastocyst formation and quality (n = 80) | No | Manual review | No |
| Time of third cell division (5- to 8-cell stage) | |||||
| Swann et al. 2012 (8) | Cytoplasmic waves | Ca2+ oscillations (n = 10) | No | Automated velocity measurements | No |
| Cruz et al. 2012 (9) | Time between first and second mitosis (2- to 3-cell stage)a | No | Manual review | No | |
| Synchrony of second and third mitosis (3- to 4-cell stage)a,b | Blastocyst formation (n = 834)a | ||||
| Time from ICSI to 5-cell stageb | Blastocyst quality (n = 293)b | ||||
| Time to morula formationb | |||||
| Hlinka et al. 2012 (10) | Time between first and second mitosis (2- to 3-cell stage) | No | Manual review | No | |
| Synchrony of second and third mitosis (3- to 4-cell stage) | |||||
| Time between third and forth mitosis (4- to 5-cell stage) | Blastocyst formation (n = 180) | ||||
| Synchrony of fourth to seventh mitosis (5- to 8-cell stage) | Implantation for Day-5 transfer (n = 114) | ||||
| Time between seventh and eighth mitosis (8- to 9-cell stage) | |||||
| Synchrony of 8th to 15th mitosis (9- to 16-cell stage) | |||||
| Dal Canto et al. 2012 (11) | Time from insemination to 7-cell stagea,b | No | Manual review | No | |
| Time from insemination to 8-cell stagea,b,c | |||||
| Time from 4- to 8-cell stagea,b | |||||
| Time from 5- to 8-cell stagea,b | Blastocyst formation (n = 459)a | ||||
| Time from insemination to 3-cell stageb | Blastocyst expansion (n = 151)b | ||||
| Time from insemination to 4-cell stageb | Implantation for Day-3 or Day-5 transfer (n = 134)c | ||||
| Time from insemination to 5-cell stageb | |||||
| Time from insemination to 6-cell stageb | |||||
| Time from 2- to 3-cell stage | |||||
| Time from 3- to 4-cell stage | |||||
| Time from 2- to 4-cell stage | |||||
| Rubio et al. 2012 (12) | Time between first and second mitosis (2- to 3-cell stage) | Implantation for Day-3 transfer (n = 1,659) | No | Manual review | No |
| Azzarello et al. 2012 (13) | Time from ICSI to PN breakdown | Live birth for 4-cell transfer (n = 159) | No | Manual review | Yes |
| Chavez et al. 2012 (14) | Duration of first cytokinesis | Chromosomes were found in fragments | Manual review and automation method developed | No | |
| Time between first and second mitosis (2- to 3-cell stage) | Ploidy of blastomeres at 4-cell stage (n = 45) | ||||
| Synchrony of second and third mitosis (3- to 4-cell stage) | |||||
| Dynamic assessment of fragmentation |
Note: Matching superscript letters “a,b,c” indicate correlation between a time-lapse observation or marker and an outcome. Implantation was confirmed by ultrasound scan at 6 to 7 weeks for presence of gestational sac [Dal Canto et al. 2012 (11) and Rubio et al. 2012 (12)] or fetal heartbeat [Meseguer et al. 2011 (6) and Hlinka et al. 2012 (10)]. ICSI = intracytoplasmic sperm injection; PB = polar body; PN = pronuclei.
a,b,c
Matching superscript letters indicate correlation between a time-lapse observation or marker and an outcome.