Variability in timing of human embryos cleavage monitored by time-lapse system in relation to patient age

Authors: R. Hampl 1;  M. Štěpán 2
Authors‘ workplace: První privátní chirurgické centrum s. r. o. Sanus Hradec Králové, primář MUDr. J. Štěpán, CSc. ;  Centrum asistované reprodukce Sanus, Pardubice 1;  Porodnická a gynekologická klinika LF UK a FN, Hradec Králové, přednosta doc. MUDr. J. Špaček, Ph. D., IFEPAG 2
Published in: Ceska Gynekol 2013; 78(6): 531-536
Category: Original Article


To monitor time variability of early embryo cleavage by continual monitoring system (time-lapse). To evaluate the impact of patient age for the embryonic growth. To compare pregnancy rate of the time-lapse selected embryos with embryos after ordinary/standard cultivation.

Case-control study.

Centre of assisted reproduction Sanus, Pardubice; PPCHC s.r.o. Hradec Kralove.

Development of 213 embryos from 44 females was monitored by PrimoVision (time-lapse) system with time frequency of recording 1 image in 12 minutes. The data were evaluated in two groups: infertile patients ≥ 35 years (group ≥ 35) and control ≤ 32 years (group ≤ 32). From the collected recordings, time of the first (t2) and of the second (t3) cell cleavage and the time interval between t2 and t3 (cc2) were determined. Symmetrical cellular division to even number of daughter cells, early cleavage and the attainment of blastocyst stage have become the major selection criteria for the embryotransfer.

The following average values of studied parameters were found:

Group ≥ 35: t2 = 27.0 hours, t3 = 38.7 hours, cc2 = 11.7 hours

Group ≤ 32: t2 = 27.1 hours, t3 = 39.0 hours, cc2 = 11.9 hours, with no significant differences between both groups.

Likewise, no significant difference was observed in mean variability of embryo cleavage timing in an individual patient and control:

Group ≥ 35: t2 = 4.5 hours, t3 = 5.7 hours,

Group ≤ 32: t2 = 4.5 hours, t3 = 5.1 hours.

No relation was observed between the patient age and t2, t3 and cc2 times when evaluated by regression curve (p = 0.60, p = 0.81, p = 0.57). However, embryos of early cleavage have remained in cc2 period significantly shorter period of time compared to embryos of slower cleavage(p = 0.0001). Pregnancy rate at time-lapse selected embryos reached 55.0% while embryos from standard cultivation only 47%.

The impact of patient age to the cleavage dynamic has not been proved. Relation between the first cell cleavage time and embryo persistence in this stage (cc2) was observed. We may hence recommend cc2 time as convenient parameter at embryo selection for embryotransfer in the centres of assisted reproduction. Our study has shown that embryo selection with time-lapse system (PrimoVision) enhances the success rate of treatment of aging patients.

human embryo – cell cleavage timing – time-lapse – age factor of infertility – assisted reproduction


1. Ajduk, A., Zernicka-Goetz, M. Advances in embryo selection methods. F1000 Biol Reprod, 2012, 4, p. 11.

2. Bischoff, M., Parfitt, DE., Zernicka-Goetz, M. Formation of the embryonic-abembryonic axis of the mouse blastocyst: relationships between orientation of early cleavage divisions and pattern of symmetric/asymmetric divisions. Development, 2008, 135, p. 953–962.

3. Brison, DR., Houghton, FD., Falconer, D., et al. Identification of viable embryos in IVF by non-invasive measurement of amoni acid turnover. Hum Reprod, 2004, 19, p. 2319–2324.

4. Cetin, MT., Kumtepe, Y., Kiran, H., Seydaoglu, G. Factors affecting pregnancy in IVF: age and duration of embryo transfer. Reprod Biomed Online, 2010, 20, p. 380–386.

5. Escrich, L., Grau, N., Meseguer, M., et al. Morphologic indicators predict the stage of chromatin condensation of human germinal vesicle oocytes recovered from stimulated cycles. Fertil Steril, 2010, 93, p. 2557–2564.

6. Gardner, DK., Phil, D., Lane, M., Stevens, J., et al. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril, 2000, 37, p. 1155–1158.

7. Giorgetti, C., Hans, E., Terriou, P., et al. Early cleavage: an additional predictor of high implantation rate following elective single embryo transfer. Reprod Biomed Online, 2007, 14, p. 85–91.

8. Gomes, LM., Canha Ados, S., Dzik, A., et al. The age as a predictive factor in vitro fertilization cycles. Rev Bras Ginecol Obstet, 2009, 31, p. 230–234.

9. Haggarty, A., Wood, M., Ferguson, E., et al. Fatty acid metabolism in human preimplantation embryos. Hum Reprod, 2006, 21, p. 766–773.

10. Hlinka, D., Lazarovská, S., Rutarová, J., et al. Neinvazívne meranie dĺžky bunkového cyklu v prvých dňoch embryonálneho vývoja – objektívne merateĺný ukazovateĺ životaschopnosti ĺudských embryí. Čes. Gynek, 2012, 77, 1, s. 52–57.

11. Houghton, FD., Hawkhead, JA., Humpherson, PG., et al. Non-invasive amino acid turnover predicts human embryo developmental capacity. Hum Reprod, 2002, 17, p. 999–1005.

12. Lechniak, D., Pers-Kamczyc, E., Pawlak, P. Timing of the first zygotic cleavage as a marker of developmental potential of mammalian embryos. Reprod Biol, 2008, 8, p. 23–42.

13. Lemmen, JG., Agerholm, I., Ziebe, S. Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI fertilized oocytes. Reprod Biomed Online, 2008, 17, p. 385–391.

14. Lundin, K., Bergh, C., Hardarson, T. Early embryo cleavage is a strong indicator of embryo quality in human IVF. Hum Reprod, 2001, 16, p. 2652–2657.

15. Meseguer, M., Herrero, J., Tejera, A., et al. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod, 2011, 26, p. 2658–2671.

16. Munné, S., Chen, S., Fischer, J., et al. Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of reccurent miscarriages. Fertil Steril, 2005, 84, p. 331–335.

17. Nakahara, T., Iwase, A., Goto, M., et al. Evaluation of the safety of time-lapse observations for human embryo. J Assist Reprod Genet, 2010, 27, p. 93–96.

18. Ogilvie, CM., Braude, PR., Scriven, PN. Preimplantation genetic diagnosis – an overview. J Histochem Cytochem, 2005, 53, p. 255–260.

19. Petanovski, Z., Dimitrov, G., Ajdin, B., et al. Impact of body mass index (BMI) and age on the outcome of the IVF process. Prilozi, 2011, 32, p. 155–171.

20. Ragione, T., Verheyen, G., Papanikolaou, EG., et al. Developmental top-stage on day-5 and fragmentation rate on day-3 can influence the implantation potential of quality blastocysts in IVF cycles with single embryo transfer. Reprod Biol Endocrinol, 2007, 26, p. 2.

21. Romao, GS., Araújo, MCPM., Demelo, AS., et al. Oocyte diameter as a predictor of fertilization and embryo quality in assisted reproduction cycles. Fertil Steril, 2010, 93, p. 621–625.

22. Scott, L., Finn, A., Leary, TO., et al. Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates. Hum Reprod, 2007, 22, p. 230–240.

23. Schwärzler, P., Zech, H., Auer, M., et al. Pregnancy outcome after blastocyst transfer as compared to early cleavage stage embryo transfer. Hum Reprod, 2004, 19, p. 2097–2102.

24. Terriou, P., Giorgetti, C., Hans, E., et al. Relationship between even early cleavage and day 2 embryo score and assessment of their predictive value for pregnancy. Reprod Biomed Online, 2007, 14, p. 294–299.

25. Wong, CC., Loewke, KE., Bossert, NL., et al. Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat Biotechnol, 2010, 28, p. 1115–1121.

Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine

Article was published in

Czech Gynaecology

Issue 6

2013 Issue 6

Most read in this issue
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account