Optimization of a single-embryo transfer by using time-lapse microscopy in IVF and ICSI programs

Introduction. Due to refinements of assisted reproductive technology, the number of multiple pregnancies has increased substantially. Therefore, transfer of a single embryo, as opposed to multiple embryos, is a top-priority task in ART-based infertility treatment. Time-lapse microscopy (TLM) is a tool for selecting quality embryos for transfer.

The aim of the study was to assess the outcomes of single-embryo transfer following embryo incubation in a TLM-equipped incubator in patients undergoing IVF and ICSI.

Methods. The study was carried out in 743 infertile women. Single-embryo transfer following incubation in a TLM-equipped incubator was performed in 282 patients, who formed the main group; the control group consisted of 461 patients undergoing singleembryo transfer following a traditional culture and embryo selection procedure. We assessed the quality of transferred embryos, the rates of clinical pregnancy and live birth rates.

Results. The groups did not differ in the proportion of IVF and ICSI cycles, terms of age and infertility factors. In the study group, there was a higher proportion of excellent quality embryos for transfer (p = 0.001), a higher proportion of cycles with elective embryo transfer (p = 0.001) and a higher proportion of cycles with cryopreservation of embryos (p <0.001). In the subgroup of non-elective embryo transfer with using of TLM, the clinical pregnancy rate was 10% higher than in the control group (p = 0.03). The live birth rates did not differ between the TLM group and the conventional culture group depending on the type of embryo transfer.

Conclusion. Our studies show that the use of time-lapse microscopy can increase the effectiveness of IVF and ICSI programs. Continuous monitoring with short intervals provides more information about the development of embryos than the standard daily assessment.

1. Min J.K., Breheny S.A., MacLachLan V., HeaLy D.L. What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, Live birth rate per cycLe initiated: the BESST endpoint for assisted reproduction. Hum Reprod. 2004;19(1):3-7. doi: 10.1093/humrep/deh028.

2. WennerhoLm U.B., Bergh C. What is the most reLevant standard of success in assisted reproduction? SingLeton Live births shouLd aLso incLude preterm births. Hum Reprod. 2004;19(9):1943-1945. doi: 10.1093/humrep/deh392.

3. Krasnoshchoka O.E., SmoL'nikova V.Iu., KaLinina E.A. RationaL approach to the strategy of eLective singLe embryo transfer in IVF programs. Problemy reproduktsii = Russian Journal of Human Reproduction. 2014;(6):17-22. (In Russ.) AvaiLabLe at: https://www.mediasphera.ru/issues/probLemy-reproduktsii/2014/6/031025-7217201464.

4. Kissin D.M., KuLkarni A.D., Mneimneh A., Warner L., BouLet S.L., Crawford S. et aL. Embryo transfer practices and muLtipLe births resuLting from assisted reproductive technoLogy: an opportunity for prevention. Fertil Steril. 2015;103(4):954-961. doi: 10.1016/j.fertnstert.2014.12.127.

5. ELective singLe-embryo transfer. Practice Committee of Society for Assisted Reproductive TechnoLogy and Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2012;97(4):835-842. doi: 10.1016/j.fertnstert.2011.11.050.

6. Gardner D.K., Meseguer M., Rubio С., Treff N.R. Diagnosis of human preimpLantation embryo viabiLity. Hum Reprod Update. 2015;21(6):727-747. doi: 10.1093/humupd/dmu064.

7. Bavister B.D. CuLture of preimpLantation embryos: facts and artifacts. Hum Reprod Update. 1995;1(2):91-148. doi: 10.1093/humupd/1.2.91.

8. Meseguer M. Time-Lapse: the remaining questions to be answered. Fertil Steril. 2016;105(2):295-296. doi: 10.1016/j.fertnstert.2015.12.126.

9. Pribenszky C., Mаtyаs S., Kovаcs P, Losonczi E., Zadori J., Vajta G. Pregnancy achieved by transfer of a singLe bLastocyst seLected by time-Lapse monitoring. Reprod Biomed Online. 2010;21(4):533-536. doi: 10.1016/j.rbmo.2010.04.015.

10. Wang S.X.Y. The past, present, and future of embryo seLection in in vitro fertiLization: Frontiers in Reproduction Conference. Yale J Biol Med. 2011;84(4):487-490. AvaiLabLe at: https://www.ncbi.nLm.nih.gov/pmc/arti-cLes/PMC3238312.

11. Shurygina O.V., Saraeva N.V., Tugushev M.T., Pekarev V.A., Bayzarova A.A., Krasnova O.V. et aL. Long-term resuLts of ART programs using time-Lapse embryo monitoring. In: Anshina M.B., Smirnova A.A. (eds) Reproductive technologies Today and Tomorrow: proceedings of the 17h International Conference of the Russian Association for Human Reproduction, September 6-9, 2017. (In Russ.) AvaiLabLe at: http://www.rahr.ru/d_pech_mat_konf/Abstracts_RAHR%20IFFS%202017.pdf.

12. Adamson G.D., Abusief M.E., PaLao L., Witmer J., PaLao L.M., Gvakharia M. Improved impLantation rates of day 3 embryo transfers with the use of an auto mated time-Lapse - enabLed test to aid in embryo seLection. Fertil Steril. 2016;105(2):369-375. doi: 10.1016/j.fertns-tert.2015.10.030.

13. Diamond M.P., Suraj V., Behnke EJ.,Yang X., Angle MJ., Lambe-Steinmiller J.C. et al. Using the Eeva Test™ adjunctively to traditional day 3 morphology is informative for consistent embryo assessment within a panel of embryologists with diverse experience. J Assist Reprod Genet. 2015;32(1):61-68. doi: 10.1007/s10815-014-0366-1.

14. VerMilyea M.D., Tan L., Antony J.T., Conaghan J., Ivani K., Gvakharia M. 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(6):729-736. doi: 10.1016/j.rbmo.2014.09.005.

15. Kirkegaard K., Hindkjaer JJ., Grondahl M.L., Kesmodel U.S., Ingerslev HJ. A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator. J Assist Reprod Genet. 2012;29(6):565-572. doi: 10.1007/s10815-012-9750-x.

16. Minasi M.G., Colasante A., Riccio T., Ruberti A., Casciani V., Scarselli F. et al. Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016;31(10):2245-2254. doi: 10.1093/hum-rep/dew183.

17. Gardner D.K., Schoolcraft W.B. Culture and transfer of human blastocysts. Curr Opin Obstet Gynacol. 1999;11(3):307-311. Available at: https://jour-nals.lww.com/co-obgyn/Abstract/1999/06000/Culture_and_transfer_of_human_blastocysts.13.aspx.

18. Lee A.M., Connell M.T., Csokmay J.M., Styer A.K. Elective single embryo transfer - the power of one. Contracept Reprod Med. 2016;1:11. doi: 10.1186/s40834-016-0023-4.

19. Goodman L.R., 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(2):275-285. doi: 10.1016/j.fertnstert.2015.10.013.

20. Apter S., Ebner T., Freour T., Guns Y., Kovacic B., Le Clef N. et al. Good practice recommendations for the use of time-lapse technology. Hum Reprod Open. 2020;(2):hoaa008. doi: 10.1093/hropen/hoaa008.

21. Thompson S.M., Onwubalili N., Brown K., Jindal S.K., McGovern P.G. Blastocyst expansion score and trophectoderm morphology strongly predict successful clinical pregnancy and live birth following elective single embryo blastocyst transfer (eSET): a national study. J Assist Reprod Genet. 2013;30(12):1577-1581. doi: 10.1007/s10815-013-0100-4.

22. Mascarenhas M., Fox SJ., Thompson K., Balen A.H. Cumulative live birth rates and perinatal outcomes with the use of time-lapse imaging incubators for embryo culture: a retrospective cohort study of 1882 ART cycles. BJOG. 2019;126(2):280-286. doi: 10.1111/1471-0528.15161.

23. Khosravi P., Kazemi E., Zhan Q., Malmsten J.E., Toschi M., Zisimopoulos P. et al. Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization. NPJ Digital Med. 2019;2:21. doi: 10.1038/s41746-019-0096-y.

24. Tran D., Cooke S., Illingworth PJ., Gardner D.K. Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer. Hum Reprod. 2019;34(6):1011-1018. doi: 10.1093/humrep/dez064.

25. Pennetta F., Lagalla C., Borini A. Embryo morphokinetic characteristics and euploidy. Curr Opin Obstet Gynecol. 2018;30(3):185-196. doi: 10.1097/GCO.0000000000000453.

26. Taborin M., Kovacic B. Morphometric protocol for the objective assessment of blastocyst behavior during vitrification and warming steps. J Vis Exp. 2019;(144):e58540. doi: 10.3791/58540.