TY - JOUR
T1 - Clinical outcomes of uninterrupted embryo culture with or without time-lapse-based embryo selection versus interrupted standard culture (SelecTIMO)
T2 - a three-armed, multicentre, double-blind, randomised controlled trial
AU - Kieslinger, D. C.
AU - Vergouw, C. G.
AU - Ramos, L.
AU - Arends, B.
AU - Curfs, M. H. J. M.
AU - Slappendel, E.
AU - Kostelijk, E. H.
AU - Pieters, M. H. E. C.
AU - Consten, D.
AU - Verhoeven, M. O.
AU - Besselink, D. E.
AU - Broekmans, F.
AU - Cohlen, B. J.
AU - Smeenk, J. M. J.
AU - Mastenbroek, S.
AU - de Koning, C. H.
AU - van Kasteren, Y. M.
AU - Moll, E.
AU - van Disseldorp, J.
AU - Brinkhuis, E. A.
AU - Kuijper, E. A. M.
AU - van Baal, W. M.
AU - van Weering, H. G. I.
AU - van der Linden, P. J. Q.
AU - Gerards, M. H.
AU - Bossuyt, P. M.
AU - van Wely, M.
AU - Lambalk, C. B.
N1 - Funding Information: The authors received a grant from the Netherlands Organisation for Health Research and Development (ZonMw) for the execution of the SelecTIMO study (Health Care Efficiency Research programme grant 843001602). Merck (Germany and Netherlands) supplied the six Geri+ time-lapse incubators, funded the laboratory adjustments, and provided technical support and training to laboratory personnel before and during the study. Merck (Germany) reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors. The authors are grateful to all couples willing to participate in this study. We would like to thank the Netherlands Society of Obstetrics and Gynaecology consortium and all staff for their contribution in the execution of this trial. We appreciate the efforts of all participating IVF clinics and their laboratory, research, clinical, and administrative personnel. Funding Information: The authors received a grant from the Netherlands Organisation for Health Research and Development (ZonMw) for the execution of the SelecTIMO study (Health Care Efficiency Research programme grant 843001602). Merck (Germany and Netherlands) supplied the six Geri+ time-lapse incubators, funded the laboratory adjustments, and provided technical support and training to laboratory personnel before and during the study. Merck (Germany) reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors. The authors are grateful to all couples willing to participate in this study. We would like to thank the Netherlands Society of Obstetrics and Gynaecology consortium and all staff for their contribution in the execution of this trial. We appreciate the efforts of all participating IVF clinics and their laboratory, research, clinical, and administrative personnel. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/4/29
Y1 - 2023/4/29
N2 - Background: Time-lapse monitoring is increasingly used in fertility laboratories to culture and select embryos for transfer. This method is offered to couples with the promise of improving pregnancy chances, even though there is currently insufficient evidence for superior clinical results. We aimed to evaluate whether a potential improvement by time-lapse monitoring is caused by the time-lapse-based embryo selection method itself or the uninterrupted culture environment that is part of the system. Methods: In this three-armed, multicentre, double-blind, randomised controlled trial, couples undergoing in-vitro fertilisation or intracytoplasmic sperm injection were recruited from 15 fertility clinics in the Netherlands and randomly assigned using a web-based, computerised randomisation service to one of three groups. Couples and physicians were masked to treatment group, but embryologists and laboratory technicians could not be. The time-lapse early embryo viability assessment (EEVA; TLE) group received embryo selection based on the EEVA time-lapse selection method and uninterrupted culture. The time-lapse routine (TLR) group received routine embryo selection and uninterrupted culture. The control group received routine embryo selection and interrupted culture. The co-primary endpoints were the cumulative ongoing pregnancy rate within 12 months in all women and the ongoing pregnancy rate after fresh single embryo transfer in a good prognosis population. Analysis was by intention to treat. This trial is registered on the ICTRP Search Portal, NTR5423, and is closed to new participants. Findings: 1731 couples were randomly assigned between June 15, 2017, and March 31, 2020 (577 to the TLE group, 579 to the TLR group, and 575 to the control group). The 12-month cumulative ongoing pregnancy rate did not differ significantly between the three groups: 50·8% (293 of 577) in the TLE group, 50·9% (295 of 579) in the TLR group, and 49·4% (284 of 575) in the control group (p=0·85). The ongoing pregnancy rates after fresh single embryo transfer in a good prognosis population were 38·2% (125 of 327) in the TLE group, 36·8% (119 of 323) in the TLR group, and 37·8% (123 of 325) in the control group (p=0·90). Ten serious adverse events were reported (five TLE, four TLR, and one in the control group), which were not related to study procedures. Interpretation: Neither time-lapse-based embryo selection using the EEVA test nor uninterrupted culture conditions in a time-lapse incubator improved clinical outcomes compared with routine methods. Widespread application of time-lapse monitoring for fertility treatments with the promise of improved results should be questioned. Funding: Health Care Efficiency Research programme from Netherlands Organisation for Health Research and Development and Merck.
AB - Background: Time-lapse monitoring is increasingly used in fertility laboratories to culture and select embryos for transfer. This method is offered to couples with the promise of improving pregnancy chances, even though there is currently insufficient evidence for superior clinical results. We aimed to evaluate whether a potential improvement by time-lapse monitoring is caused by the time-lapse-based embryo selection method itself or the uninterrupted culture environment that is part of the system. Methods: In this three-armed, multicentre, double-blind, randomised controlled trial, couples undergoing in-vitro fertilisation or intracytoplasmic sperm injection were recruited from 15 fertility clinics in the Netherlands and randomly assigned using a web-based, computerised randomisation service to one of three groups. Couples and physicians were masked to treatment group, but embryologists and laboratory technicians could not be. The time-lapse early embryo viability assessment (EEVA; TLE) group received embryo selection based on the EEVA time-lapse selection method and uninterrupted culture. The time-lapse routine (TLR) group received routine embryo selection and uninterrupted culture. The control group received routine embryo selection and interrupted culture. The co-primary endpoints were the cumulative ongoing pregnancy rate within 12 months in all women and the ongoing pregnancy rate after fresh single embryo transfer in a good prognosis population. Analysis was by intention to treat. This trial is registered on the ICTRP Search Portal, NTR5423, and is closed to new participants. Findings: 1731 couples were randomly assigned between June 15, 2017, and March 31, 2020 (577 to the TLE group, 579 to the TLR group, and 575 to the control group). The 12-month cumulative ongoing pregnancy rate did not differ significantly between the three groups: 50·8% (293 of 577) in the TLE group, 50·9% (295 of 579) in the TLR group, and 49·4% (284 of 575) in the control group (p=0·85). The ongoing pregnancy rates after fresh single embryo transfer in a good prognosis population were 38·2% (125 of 327) in the TLE group, 36·8% (119 of 323) in the TLR group, and 37·8% (123 of 325) in the control group (p=0·90). Ten serious adverse events were reported (five TLE, four TLR, and one in the control group), which were not related to study procedures. Interpretation: Neither time-lapse-based embryo selection using the EEVA test nor uninterrupted culture conditions in a time-lapse incubator improved clinical outcomes compared with routine methods. Widespread application of time-lapse monitoring for fertility treatments with the promise of improved results should be questioned. Funding: Health Care Efficiency Research programme from Netherlands Organisation for Health Research and Development and Merck.
UR - http://www.scopus.com/inward/record.url?scp=85153379202&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(23)00168-X
DO - https://doi.org/10.1016/S0140-6736(23)00168-X
M3 - Article
C2 - 37004670
SN - 0140-6736
VL - 401
SP - 1438
EP - 1446
JO - The Lancet
JF - The Lancet
IS - 10386
ER -