Time-Lapse Systems: A Comprehensive Analysis on Effectiveness

Abstract

Time-lapse systems have quickly become a common feature of in vitro fertilization laboratories all over the world. Since being introduced over a decade ago, the alleged benefits of time-lapse technology have continued to grow, from undisturbed culture conditions and round the clock, noninvasive observations to more recent computer-assisted selection of embryos through the development of algorithms. Despite the global uptake of time-lapse technology, its real impact on clinical outcomes is still controversial. This review aims to explore the different features offered by time-lapse technology, discussing incubation, algorithms, artificial intelligence and the regulation of nonessential treatment interventions, while assessing evidence on whether any benefit is offered over conventional technology.

Keywords

Time lapse - embryo selection - algorithms - incubation - in vitro fertilization

Publikationsverlauf

Artikel online veröffentlicht:
10. Januar 2022

• References

• 1 Diedrich K, Fauser BCJM, Devroey P, Griesinger G. Evian Annual Reproduction (EVAR) Workshop Group. The role of the endometrium and embryo in human implantation. Hum Reprod Update 2007; 13 (04) 365-377
• 2 Zhang S, Lin H, Kong S. et al. Physiological and molecular determinants of embryo implantation. Mol Aspects Med 2013; 34 (05) 939-980
• 3 Gardner DK, Meseguer M, Rubio C, Treff NR. Diagnosis of human preimplantation embryo viability. Hum Reprod Update 2015; 21 (06) 727-747
• 4 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 (06) 1270-1283
• 5 Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 1999; 11 (03) 307-311
• 6 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 (10) 1115-1121
• 7 Desai N, Ploskonka S, Goodman LR, Austin C, Goldberg J, Falcone T. Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles. Reprod Biol Endocrinol 2014; 12: 54
• 8 Alhelou Y, Mat Adenan NA, Ali J. Embryo culture conditions are significantly improved during uninterrupted incubation: a randomized controlled trial. Reprod Biol 2018; 18 (01) 40-45
• 9 Leung AS, Son WY, Dahan MH. Time-lapse imaging of embryos: current evidence supporting its use. Expert Rev Med Devices 2016; 13 (10) 881-883
• 10 Harper J, Jackson E, Sermon K. et al. Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?. Hum Reprod 2017; 32 (03) 485-491
• 11 Ottosen LD, Hindkjaer J, Ingerslev J. Light exposure of the ovum and preimplantation embryo during ART procedures. J Assist Reprod Genet 2007; 24 (2-3): 99-103
• 12 Umaoka Y, Noda Y, Nakayama T, Narimoto K, Mori T, Iritani A. Effect of visual light on in vitro embryonic development in the hamster. Theriogenology 1992; 38 (06) 1043-1054
• 13 Mortimer D, Cohen J, Mortimer ST. et al. Cairo consensus on the IVF laboratory environment and air quality: report of an expert meeting. Reprod Biomed Online 2018; 36 (06) 658-674
• 14 Cairo Consensus Group. ‘There is only one thing that is truly important in an IVF laboratory: everything’ Cairo Consensus Guidelines on IVF Culture Conditions. Reprod Biomed Online 2020; 40 (01) 33-60
• 15 Zhang JQ, Li XL, Peng Y, Guo X, Heng BC, Tong GQ. Reduction in exposure of human embryos outside the incubator enhances embryo quality and blastulation rate. Reprod Biomed Online 2010; 20 (04) 510-515
• 16 Fujiwara M, Takahashi K, Izuno M. et al. Effect of micro-environment maintenance on embryo culture after in-vitro fertilization: comparison of top-load mini incubator and conventional front-load incubator. J Assist Reprod Genet 2007; 24 (01) 5-9
• 17 Li J, Huang J, Han W, Shen X, Gao Y, Huang G. Comparing transcriptome profiles of human embryo cultured in closed and standard incubators. PeerJ 2020; 8: e9738
• 18 Armstrong S, Bhide P, Jordan V, Pacey A, Marjoribanks J, Farquhar C. Time-lapse systems for embryo incubation and assessment in assisted reproduction. Cochrane Database Syst Rev 2019; 5 (05) CD011320
• 19 Kovacs P, Matyas S, Forgacs V, Sajgo A, Rarosi F, Pribenszky C. Time-lapse embryo selection for single blastocyst transfer – results of a multicenter, prospective, randomized clinical trial. Fertil Steril 2013; 100 (03) S90
• 20 Rubio I, Galán A, Larreategui Z. et al. Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. Fertil Steril 2014; 102 (05) 1287-1294.e5
• 21 Yang L, Cai S, Zhang S. et al. Single embryo transfer by Day 3 time-lapse selection versus Day 5 conventional morphological selection: a randomized, open-label, non-inferiority trial. Hum Reprod 2018; 33 (05) 869-876
• 22 Park H, Bergh C, Selleskog U, Thurin-Kjellberg A, Lundin K. No benefit of culturing embryos in a closed system compared with a conventional incubator in terms of number of good quality embryos: results from an RCT. Hum Reprod 2015; 30 (02) 268-275
• 23 Kahraman S, Çetinkaya M, Pirkevi C, Yelke H, Kumtepe Y. Comparison of blastocyst development and cycle outcome in patients with eSET using either conventional or time lapse incubators. a prospective study of good prognosis patients. J Reprod Stem Cell Biotechnol 2012; 3 (02) 55-61
• 24 Wu Y-G, Lazzaroni-Tealdi E, Wang Q. et al. Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScope(TM)) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study. Reprod Biol Endocrinol 2016; 14 (01) 49
• 25 Barberet J, Chammas J, Bruno C. et al. Randomized controlled trial comparing embryo culture in two incubator systems: G185 K-System versus EmbryoScope. Fertil Steril 2018; 109 (02) 302-309.e1
• 26 Kalleas D, McEvoy K, Horne G, Roberts SA, Brison DR. Live birth rate following undisturbed embryo culture at low oxygen in a time-lapse incubator compared to a high-quality bench top incubator. Hum Fertil (Camb) 2020; 1-7
• 27 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 (03) 385-391
• 28 Payne D, Flaherty SP, Barry MF, Matthews CD. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod 1997; 12 (03) 532-541
• 29 Hardarson T, Löfman C, Coull G, Sjögren A, Hamberger L, Edwards RG. Internalization of cellular fragments in a human embryo: time-lapse recordings. Reprod Biomed Online 2002; 5 (01) 36-38
• 30 Rubio I, Kuhlmann R, Agerholm I. et al. Limited implantation success of direct-cleaved human zygotes: a time-lapse study. Fertil Steril 2012; 98 (06) 1458-1463
• 31 Athayde Wirka K, Chen AA, Conaghan J. et al. Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development. Fertil Steril 2014; 101 (06) 1637-1648.e1631 –1635
• 32 Liu Y, Chapple V, Roberts P, Matson P. 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 (05) 1295-1300.e2
• 33 Session 69: Embryology – cause and effect of bad timing. Hum Reprod 2012; 27 (Suppl. 02) ii103-ii105
• 34 Derrick R, Hickman C, Oliana O. et al. Perivitelline threads associated with fragments in human cleavage stage embryos observed through time-lapse microscopy. Reprod Biomed Online 2017; 35 (06) 640-645
• 35 Kellam L, Pastorelli LM, Bastida AM. et al. Perivitelline threads in cleavage-stage human embryos: observations using time-lapse imaging. Reprod Biomed Online 2017; 35 (06) 646-656
• 36 Marcos J, Pérez-Albalá S, Mifsud A, Molla M, Landeras J, Meseguer M. Collapse of blastocysts is strongly related to lower implantation success: a time-lapse study. Hum Reprod 2015; 30 (11) 2501-2508
• 37 Viñals Gonzalez X, Odia R, Cawood S. et al. Contraction behaviour reduces embryo competence in high-quality euploid blastocysts. J Assist Reprod Genet 2018; 35 (08) 1509-1517
• 38 Desai N, Goldberg JM, Austin C, Falcone T. Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy?. Fertil Steril 2018; 109 (04) 665-674
• 39 Conaghan J, Chen AA, Willman SP. et al. Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial. Fertil Steril 2013; 100 (02) 412-9.e5
• 40 VerMilyea MD, Tan L, Anthony JT. et al. Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study. Reprod Biomed Online 2014; 29 (06) 729-736
• 41 Yalçınkaya E, Ergin EG, Calışkan E, Oztel Z, Ozay A, Ozörnek H. Reproducibility of a time-lapse embryo selection model based on morphokinetic data in a sequential culture media setting. J Turk Ger Gynecol Assoc 2014; 15 (03) 156-160
• 42 Fréour T, Le Fleuter N, Lammers J, Splingart C, Reignier A, Barrière P. External validation of a time-lapse prediction model. Fertil Steril 2015; 103 (04) 917-922
• 43 Liu Y, Copeland C, Stevens A. et al. Assessment of human embryos by time-lapse videography: a comparison of quantitative and qualitative measures between two independent laboratories. Reprod Biol 2015; 15 (04) 210-216
• 44 Dal Canto M, Coticchio G, Mignini Renzini M. et al. Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reprod Biomed Online 2012; 25 (05) 474-480
• 45 Cruz M, Garrido N, Herrero J, Pérez-Cano I, Muñoz M, Meseguer M. Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality. Reprod Biomed Online 2012; 25 (04) 371-381
• 46 Azzarello A, Hoest T, Mikkelsen AL. The impact of pronuclei morphology and dynamicity on live birth outcome after time-lapse culture. Hum Reprod 2012; 27 (09) 2649-2657
• 47 Chamayou S, Patrizio P, Storaci G. et al. The use of morphokinetic parameters to select all embryos with full capacity to implant. J Assist Reprod Genet 2013; 30 (05) 703-710
• 48 Basile N, Vime P, Florensa M. et al. The use of morphokinetics as a predictor of implantation: a multicentric study to define and validate an algorithm for embryo selection. Hum Reprod 2015; 30 (02) 276-283
• 49 Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Hickman CF. Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. Reprod Biomed Online 2013; 26 (05) 477-485
• 50 Barrie A, Homburg R, McDowell G, Brown J, Kingsland C, Troup S. Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms. Fertil Steril 2017; 107 (03) 613-621
• 51 Meseguer M, Herrero J, Tejera A, Hilligsøe KM, Ramsing NB, Remohí J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod 2011; 26 (10) 2658-2671
• 52 Goodman LR, Goldberg J, Falcone T, Austin C, Desai N. Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial. Fertil Steril 2016; 105 (02) 275-85.e10
• 53 Petersen BM, Boel M, Montag M, Gardner DK. Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on Day 3. Hum Reprod 2016; 31 (10) 2231-2244
• 54 Liu Y, Chapple V, Feenan K, Roberts P, Matson P. Time-lapse deselection model for human day 3 in vitro fertilization embryos: the combination of qualitative and quantitative measures of embryo growth. Fertil Steril 2016; 105 (03) 656-662.e1
• 55 Storr A, Venetis C, Cooke S, Kilani S, Ledger W. Time-lapse algorithms and morphological selection of day-5 embryos for transfer: a preclinical validation study. Fertil Steril 2018; 109 (02) 276-283.e3
• 56 Barrie A, McDowell G, Troup S. An investigation into the effect of potential confounding patient and treatment parameters on human embryo morphokinetics. Fertil Steril 2021; 115 (04) 1014-1022
• 57 Cruz M, Garrido N, Gadea B, Muñoz M, Pérez-Cano I, Meseguer M. Oocyte insemination techniques are related to alterations of embryo developmental timing in an oocyte donation model. Reprod Biomed Online 2013; 27 (04) 367-375
• 58 Bodri D, Sugimoto T, Serna JY. et al. Influence of different oocyte insemination techniques on early and late morphokinetic parameters: retrospective analysis of 500 time-lapse monitored blastocysts. Fertil Steril 2015; 104 (05) 1175-1181.e1171 –1172
• 59 Ciray HN, Aksoy T, Goktas C, Ozturk B, Bahceci M. Time-lapse evaluation of human embryo development in single versus sequential culture media–a sibling oocyte study. J Assist Reprod Genet 2012; 29 (09) 891-900
• 60 Simopoulou M, Sfakianoudis K, Maziotis E. et al. Are computational applications the “crystal ball” in the IVF laboratory? The evolution from mathematics to artificial intelligence. J Assist Reprod Genet 2018; 35 (09) 1545-1557
• 61 Apter S, Ebner T, Freour T. et al. Good practice recommendations for the use of time-lapse technology. Hum Reprod Open 2020; 2020 (02) hoaa008
• 62 Khosravi P, Kazemi E, Zhan Q. et al. Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization. NPJ Digit Med 2019; 2: 21
• 63 Tran D, Cooke S, Illingworth PJ, Gardner DK. Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer. Hum Reprod 2019; 34 (06) 1011-1018
• 64 Bormann CL, Thirumalaraju P, Kanakasabapathy MK. et al. Consistency and objectivity of automated embryo assessments using deep neural networks. Fertil Steril 2020; 113 (04) 781-787.e1
• 65 VerMilyea M, Hall JMM, Diakiw SM. et al. Development of an artificial intelligence-based assessment model for prediction of embryo viability using static images captured by optical light microscopy during IVF. Hum Reprod 2020; 35 (04) 770-784
• 66 Zaninovic N, Rosenwaks Z. Artificial intelligence in human in vitro fertilization and embryology. Fertil Steril 2020; 114 (05) 914-920
• 67 Zaninovic N, Irani M, Meseguer M. Assessment of embryo morphology and developmental dynamics by time-lapse microscopy: is there a relation to implantation and ploidy?. Fertil Steril 2017; 108 (05) 722-729
• 68 Rienzi L, Capalbo A, Stoppa M. et al. No evidence of association between blastocyst aneuploidy and morphokinetic assessment in a selected population of poor-prognosis patients: a longitudinal cohort study. Reprod Biomed Online 2015; 30 (01) 57-66
• 69 Kramer YG, Kofinas JD, Melzer K. et al. Assessing morphokinetic parameters via time lapse microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal?. J Assist Reprod Genet 2014; 31 (09) 1231-1242
• 70 Chawla M, Fakih M, Shunnar A. et al. Morphokinetic analysis of cleavage stage embryos and its relationship to aneuploidy in a retrospective time-lapse imaging study. J Assist Reprod Genet 2015; 32 (01) 69-75
• 71 Rienzi L, Cimadomo D, Delgado A. et al. Time of morulation and trophectoderm quality are predictors of a live birth after euploid blastocyst transfer: a multicenter study. Fertil Steril 2019; 112 (06) 1080-1093.e1
• 72 Lee CI, Chen CH, Huang CC. et al. Embryo morphokinetics is potentially associated with clinical outcomes of single-embryo transfers in preimplantation genetic testing for aneuploidy cycles. Reprod Biomed Online 2019; 39 (04) 569-579
• 73 Bori L, Valera MÁ, Gilboa D. et al. O-084 Computer vision can distinguish between euploid and aneuploid embryos. A novel artificial intelligence (AI) approach to measure cell division activity associated with chromosomal status. Human Reproduction 2021;36(Supplement_1)
• 74 Campbell M, Fitzpatrick R, Haines A. et al. Framework for design and evaluation of complex interventions to improve health. BMJ 2000; 321 (7262): 694-696
• 75 Harper J, Magli MC, Lundin K, Barratt CL, Brison D. When and how should new technology be introduced into the IVF laboratory?. Hum Reprod 2012; 27 (02) 303-313
• 76 Perrotta M, Geampana A. The trouble with IVF and randomised control trials: professional legitimation narratives on time-lapse imaging and evidence-informed care. Soc Sci Med 2020; 258: 113115
• 77 Human cells, tissues, and cellular and tissue-based products; establishment registration and listing. Food and Drug Administration, HHS. Final rule. Fed Regist 2001; 66 (13) 5447-5469
• 78 Human Fertilization and Embryology Authority. Treatment add-ons. 2021 . Accessed September 10, 2021 at: https://www.hfea.gov.uk/treatments/treatment-add-ons/
• 79 Victorian Assisted Reproductive Treatment Authority. Treatment Add-ons. Accessed December 20, 2021 at: https://www.varta.org.au/resources/news-and-blogs/what-you-need-know-about-ivf-add-ons
• 80 European Society of Human Reproduction and Embryology. Press Room 2021
• 81 Kirkegaard K, Kesmodel US, Hindkjær JJ, Ingerslev HJ. Time-lapse parameters as predictors of blastocyst development and pregnancy outcome in embryos from good prognosis patients: a prospective cohort study. Hum Reprod 2013; 28 (10) 2643-2651
• 82 Aguilar J, Motato Y, Escribá MJ, Ojeda M, Muñoz E, Meseguer M. The human first cell cycle: impact on implantation. Reprod Biomed Online 2014; 28 (04) 475-484
• 83 Milewski R, Kuć P, Kuczyńska A, Stankiewicz B, Łukaszuk K, Kuczyński W. A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development. J Assist Reprod Genet 2015; 32 (04) 571-579
• 84 Storr A, Venetis CA, Cooke S, Susetio D, Kilani S, Ledger W. Morphokinetic parameters using time-lapse technology and day 5 embryo quality: a prospective cohort study. J Assist Reprod Genet 2015; 32 (07) 1151-1160
• 85 Motato Y, de los Santos MJ, Escriba MJ, Ruiz BA, Remohí J, Meseguer M. Morphokinetic analysis and embryonic prediction for blastocyst formation through an integrated time-lapse system. Fertil Steril 2016; 105 (02) 376-84.e9
• 86 Mizobe Y, Oya N, Iwakiri R. et al. Effects of early cleavage patterns of human embryos on subsequent in vitro development and implantation. Fertil Steril 2016; 106 (02) 348-353.e2
• 87 Mizobe Y, Tokunaga M, Oya N. et al. Synchrony of the first division as an index of the blastocyst formation rate during embryonic development. Reprod Med Biol 2017; 17 (01) 64-70