TIME-LAPSE technology in modern embryological practice

Abstract

This article describes the basic principles of TIME-LAPSE technology. We report the use of this technology in modern embryological practice and compare it with the conventional cultivation system. Herein, we overview modern incubators equipped with the TIME-LAPSE system, including domestic ones, with their advantages and disadvantages listed. The main events of early human embryo development are described and rare events noted, such as abnormal pronucleus formation and disappearance, multinucleation of blastomeres, reverse cleavage, or “direct cleavage” into three blastomeres, which can only be visualized using TIME-LAPSE technology, but not with traditional visual assessment of embryo morphology. The use of artificial intelligence in conjunction with TIME-LAPSE technology for objective assessment and ranking of embryos based on their morphokinetic characteristics is given a thorough consideration. In conclusion, the article presents data on the impact of using technology on the effectiveness of IVF programs. Moreover, we herein describe such unobvious advantages of the TIME-LAPSE system as the ability to train and transfer video data between participants in the IVF protocol.

Keywords

embryo culture / TIME-LAPSE technology / embryo selection / artificial intelligence

References

[1] Dayan N, Joseph KS, Fell DB, et al. Infertility treatment and risk of severe maternal morbidity: a propensity score-matched cohort study. Can Med Assoc J. 2019;191(5):118–127. DOI: 10.1503/cmaj.181124

[2] Dayan N., Joseph K.S., Fell D.B., et al. Infertility treatment and risk of severe maternal morbidity: A propensity score-matched cohort study // Can. Med. Assoc J. 2019. Vol. 191. No. 5. P. 118–127. DOI: 10.1503/cmaj.181124.

[3] Kulkarni AD, Jamieson DJ, Jones HW, et al. Fertility treatments and multiple births in the United States. N Engl J Med. 2013;369(23):2218–2225. DOI: 10.1056/NEJMoa1301467

[4] Kulkarni A.D., Jamieson D.J., Jones H.W., et al. Fertility treatments and multiple births in the United States // N. Engl. J. Med. 2013. Vol. 369. No. 23. P. 2218–2225. DOI: 10.1056/NEJMoa1301467

[5] Machtinger R, Racowsky C. Morphological systems of human embryo assessment and clinical evidence. Reprod Biomed Online. 2013;26(3):210–221. DOI: 10.1016/j.rbmo.2012.10.021

[6] Machtinger R., Racowsky C. Morphological systems of human embryo assessment and clinical evidence // Reprod. Biomed. Online. 2013. Vol. 26. No. 3. P. 210–221. DOI: 10.1016/j.rbmo.2012.10.021

[7] Gardner DK., Schoolcraft WB. In vitro culture of human blastocyst. In: Towards reproductive certainty: infertility and genetics beyond. Ed. by R. Jansen, D. Mortimer. Carnforth: Parthenon Press; 1999. P. 377–388.

[8] Gardner D.K., Schoolcraft W.B. In vitro culture of human blastocyst // Towards Reproductive Certainty: Infertility and Genetics Beyond / ed. by R. Jansen, D. Mortimer. Carnforth: Parthenon Press, 1999. P. 377–388.

[9] Gardner DK, Lane M, Stevens J, et al. Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155–1158. DOI: 10.1016/s0015-0282(00)00518-5

[10] Gardner D.K., Lane M., Stevens J., et al. Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer // Fertil. Steril. 2000. Vol. 73. No. 6. P. 1155–1158. DOI: 10.1016/s0015-0282(00)00518-5

[11] Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307–311. DOI: 10.1097/00001703-199906000-00013

[12] Gardner D.K., Schoolcraft W.B. Culture and transfer of human blastocysts // Curr. Opin. Obstet. Gynecol. 1999. Vol. 11. No. 3. P. 307–311. DOI: 10.1097/00001703-199906000-00013

[13] Payne D, Flaherty SP, Barry MF, et al. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod. 1997;12(3):532–541. DOI: 10.1093/humrep/12.3.532

[14] Payne D., Flaherty S.P., Barry M.F., et al. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography // Hum. Reprod. 1997. Vol. 12. No. 3. P. 532–541. DOI: 10.1093/humrep/12.3.532

[15] Mio Y, Maeda K. Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos. Am J Obstet Gynecol. 2008;199(6):660.e1–660.e5. DOI: 10.1016/j.ajog.2008.07.023

[16] Mio Y., Maeda K. Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos // Am. J. Obstet. Gynecol. 2008. Vol. 199. No. 6. P. 660.e1–660.e5. DOI: 10.1016/j.ajog.2008.07.023.

[17] Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–1283. DOI: 10.1093/humrep/der037

[18] Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting // Hum. Reprod. 2011. Vol. 26. No. 6. P. 1270–1283. DOI: 10.1093/humrep/der037

[19] ESHRE Guideline Group on Good Practice in IVF Labs, De los Santos MJ, Apter S, Coticchio G, et al. Revised guidelines for good practice in IVF laboratories (2015). Hum Reprod. 2016;31(4):685–686. DOI: 10.1093/humrep/dew016

[20] ESHRE Guideline Group on Good Practice in IVF Labs, De los Santos M., Apter S., Coticchio G., et al. Revised guidelines for good practice in IVF laboratories (2015) // Hum. Reprod. 2016. Vol. 31. No. 4. P. 685–686. DOI: 10.1093/humrep/dew016

[21] Lim AS, Goh VH, Su CL, et al. Microscopic assessment of pronuclear embryos is not definitive. Hum Genet. 2000;107(1):62–68. DOI: 10.1007/s004390000335

[22] Lim A.S., Goh V.H., Su C.L., et al. Microscopic assessment of pronuclear embryos is not definitive // Hum. Genet. 2000. Vol. 107. No. 1. P. 62–68. DOI: 10.1007/s004390000335.

[23] Manor D, Kol S, Lewit N, et al. Undocumented embryos: do not trash them, FISH them. Hum Reprod. 1996;11(11):2502–2506. DOI: 10.1093/oxfordjournals.humrep.a019148

[24] Manor D., Kol S., Lewit N., et al. Undocumented embryos: do not trash them, FISH them // Hum. Reprod. 1996. Vol. 11. No. 11. P. 2502–2506. DOI: 10.1093/oxfordjournals.humrep.a019148

[25] Li M, Lin S, Chen Y, et al. Value of transferring embryos that show no evidence of fertilization at the time of fertilization assessment. Fertil Steril. 2015;104(3):607–611. DOI: 10.1016/j.fertnstert.2015.05.016

[26] Li M., Lin S., Chen Y., et al. Value of transferring embryos that show no evidence of fertilization at the time of fertilization assessment // Fertil. Steril. 2015. Vol. 104. No. 3. P. 607–611. DOI: 10.1016/j.fertnstert.2015.05.016

[27] Yao G, Xu J, Xin Z, et al. Developmental potential of clinically discarded human embryos and associated chromosomal analysis. Sci Rep. 2016;5(6). DOI: 10.1038/srep23995

[28] Yao G., Xu J., Xin Z., et al. Developmental potential of clinically discarded human embryos and associated chromosomal analysis // Sci. Rep. 2016. Vol. 5. No. 6. DOI: 10.1038/srep23995.

[29] Yin BL, Hao HY, Zhang YN, et al. Good quality blastocyst from non-/mono-pronuclear zygote may be used for transfer during IVF. Syst Biol Reprod Med. 2016;62(2):139–145. DOI: 10.3109/19396368.2015.1137993

[30] Yin B.L., Hao H.Y., Zhang Y.N., et al. Good quality blastocyst from non-/mono-pronuclear zygote may be used for transfer during IVF // Syst. Biol. Reprod. Med. 2016. Vol. 62. No. 2. P. 139–145. DOI: 10.3109/19396368.2015.1137993

[31] Rosenbusch B. The chromosomal constitution of embryos arising from monopronuclear oocytes in programmes of assisted reproduction. Int J Reprod Med. 2014;2014. DOI: 10.1155/2014/418198

[32] Rosenbusch B. The chromosomal constitution of embryos arising from monopronuclear oocytes in programmes of assisted reproduction // Int. J. Reprod. Med. 2014. Vol. 2014. DOI: 10.1155/2014/418198

[33] Destouni A, Dimitriadou E, Masset H, et al. Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M. Hum Reprod. 2018;33(12):2302–2311. DOI: 10.1093/humrep/dey325

[34] Destouni A., Dimitriadou E., Masset H., et al. Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M // Hum. Reprod. 2018. Vol. 33. No. 12. P. 2302–2311. DOI: 10.1093/humrep/dey325

[35] Liu Y, Chapple V, Roberts P, et al. Prevalence, consequence, and significance of reverse cleavage by human embryos viewed with the use of the Embryoscope time-lapse video system. Fertil Steril. 2014;102(5.):1295–1300. DOI: 10.1016/j.fertnstert.2014.07.1235

[36] Liu Y., Chapple V., Roberts P., et al. Prevalence, consequence, and significance of reverse cleavage by human embryos viewed with the use of the Embryoscope time-lapse video system // Fertil. Steril. 2014. Vol. 102. No. 5. P. 1295–1300. DOI: 10.1016/j.fertnstert.2014.07.1235

[37] Desch L, Bruno C, Luu M, et al. Embryo multinucleation at the two-cell stage is an independent predictor of intracytoplasmic sperm injection outcomes. Fertil Steril. 2017;107(1):97–103. DOI: 10.1016/j.fertnstert.2016.09.022

[38] Desch L., Bruno C., Luu M., et al. Embryo multinucleation at the two-cell stage is an independent predictor of intracytoplasmic sperm injection outcomes // Fertil. Steril. 2017. Vol. 107. No. 1. P. 97–103. DOI: 10.1016/j.fertnstert.2016.09.022

[39] Zhan Q, Ye Z, Clarke R, et al. Direct unequal cleavages: embryo developmental competence, genetic constitution and clinical outcome. PloS One. 2016;11(12). DOI: 10.1371/journal.pone.0166398

[40] Zhan Q., Ye Z., Clarke R., et al. Direct unequal cleavages: embryo developmental competence, genetic constitution and clinical outcome // PloS One. 2016. Vol. 11. No. 12. DOI: 10.1371/journal.pone.0166398

[41] Ozbek IY, Mumusoglu S, Polat M, et al. Comparison of single euploid blastocyst transfer cycle outcome derived from embryos with normal or abnormal cleavage patterns. Reprod Biomed Online. 2021;42(5):892–900. DOI: 10.1016/j.rbmo.2021.02.005

[42] Ozbek I.Y., Mumusoglu S., Polat M., et al. Comparison of single euploid blastocyst transfer cycle outcome derived from embryos with normal or abnormal cleavage patterns // Reprod. Biomed. Online. 2021. Vol. 42. No. 5. P. 892–900. DOI: 10.1016/j.rbmo.2021.02.005

[43] Márquez-Hinojosa S, Noriega-Hoces L, Guzmán L. Time-lapse embryo culture: a better understanding of embryo development and clinical application. JBRA Assist Reprod. 2022;26(3):432–443. DOI: 10.5935/1518-0557.20210107

[44] Márquez-Hinojosa S., Noriega-Hoces L., Guzmán L. Time-lapse embryo culture: a better understanding of embryo development and clinical application // JBRA Assist. Reprod. 2022. Vol. 26. No. 3. P. 432–443. DOI: 10.5935/1518-0557.20210107

[45] Amir H, Barbash-Hazan S, Kalma Y, et al. Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations. J Assist Reprod Genet. 2019;36(2):315–324. DOI: 10.1007/s10815-018-1361-8

[46] Amir H., Barbash-Hazan S., Kalma Y., et al. Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations // J. Assist. Reprod. Genet. 2019. Vol. 36. No. 2. P. 315–324. DOI: 10.1007/s10815-018-1361-8

[47] Huang B, Tan W, Li Z, et al. An artificial intelligence model (euploid prediction algorithm) can predict embryo ploidy status based on time-lapse data. Reprod Biol Endocrinol. 2021;19(1):185. DOI: 10.1186/s12958-021-00864-4

[48] Huang B., Tan W., Li Z., et al. An artificial intelligence model ( euploid prediction algorithm) can predict embryo ploidy status based on time-lapse data // Reprod. Biol. Endocrinol. 2021. Vol. 19. No. 1. P. 185. DOI: 10.1186/s12958-021-00864-4

[49] Muñoz M, Cruz M, Humaidan P, et al. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study. Eur J Obstet Gynecol Reprod Biol. 2013;168(2):167–172. DOI: 10.1016/j.ejogrb.2012.12.038

[50] Muñoz M., Cruz M., Humaidan P., et al. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study // Eur. J. Obstet. Gynecol. Reprod. Biol. 2013. Vol. 168. No. 2. P. 167–172. DOI: 10.1016/j.ejogrb.2012.12.038

[51] Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Hatching of in vitro fertilized human embryos is influenced by fertilization method. Fertil Steril. 2013;100(5):1277–1282. DOI: 10.1016/j.fertnstert.2013.07.005

[52] Kirkegaard K., Hindkjaer J.J., Ingerslev H.J. Hatching of in vitro fertilized human embryos is influenced by fertilization method // Fertil. Steril. 2013. Vol. 100. No. 5. P. 1277–1282. DOI: 10.1016/j.fertnstert.2013.07.005

[53] Cruz M, Garrido N, Gadea B, et al. Oocyte insemination techniques are related to alterations of embryo developmental timing in an oocyte donation model. Reprod Biomed Online. 2013;27(4):367–375. DOI: 10.1016/j.rbmo.2013.06.017

[54] Cruz M., Garrido N., Gadea B., et al. Oocyte insemination techniques are related to alterations of embryo developmental timing in an oocyte donation model // Reprod. Biomed. Online. 2013. Vol. 27. No. 4. P. 367–375. DOI: 10.1016/j.rbmo.2013.06.017

[55] Ciray HN, Aksoy T, Goktas C, et al. Time-lapse evaluation of human embryo development in single versus sequential culture media – a sibling oocyte study. J Assist Reprod Genet. 2012;29(9):891–900. DOI: 10.1007/s10815-012-9818-7

[56] Ciray H.N., Aksoy T., Goktas C., et al. Time-lapse evaluation of human embryo development in single versus sequential culture media – a sibling oocyte study // J. Assist. Reprod. Genet. 2012. Vol. 29. No. 9. P. 891–900. DOI: 10.1007/s10815-012-9818-7.

[57] Hardarson T, Bungum M, Conaghan J, et al. Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup. Fertil Steril. 2015;104(6):1452–1459. DOI: 10.1016/j.fertnstert.2015.08.037

[58] Hardarson T., Bungum M., Conaghan J., et al. Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup // Fertil. Steril. 2015. Vol. 104. No. 6. P. 1452–1459. DOI: 10.1016/j.fertnstert.2015.08.037.

[59] Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring. Fertil Steril. 2013;99(3):738–744. DOI: 10.1016/j.fertnstert.2012.11.028

[60] Kirkegaard K., Hindkjaer J. J., Ingerslev H. J. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring // Fertil. Steril. 2013. Vol. 99. No. 3. P. 738–744. DOI: 10.1016/j.fertnstert.2012.11.028

[61] Reignier A, Lefebvre T, Loubersac S, et al. Time-lapse technology improves total cumulative live birth rate and shortens time to live birth as compared to conventional incubation system in couples undergoing ICSI. J Assist Reprod Genet. 2021;38(4):917–923. DOI: 10.1007/s10815-021-02099-z

[62] Reignier A., Lefebvre T., Loubersac S., et al. Time-lapse technology improves total cumulative live birth rate and shortens time to live birth as compared to conventional incubation system in couples undergoing ICSI // J. Assist. Reprod. Genet. 2021. Vol. 38. No. 4. P. 917–923. DOI: 10.1007/s10815-021-02099-z

[63] Zhang XD, Zhang Q, Han W, et al. Comparison of embryo implantation potential between time-lapse incubators and standard incubators: a randomized controlled study. Reprod Biomed Online. 2022;45(5):858–866. DOI: 10.1016/j.rbmo.2022.06.017

[64] Zhang X.D., Zhang Q., Han W., et al. Comparison of embryo implantation potential between time-lapse incubators and standard incubators: a randomized controlled study // Reprod. Biomed. Online. 2022. Vol. 45. No. 5. P. 858–866. DOI: 10.1016/j.rbmo.2022.06.017

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