Time-lapse algorithms and morphological selection of day-5 embryos for transfer: a preclinical validation study

Abstract Study question Does blastocyst quality scoring by central assessment deviate from local assessment and potentially lead to the selection of a different single blastocyst for transfer? Summary answer Central and local assessment provided the same quality classification (poor / good / top) in 69% of all blastocysts and 63% of all transferred blastocysts. What is known already Blastocyst quality is scored most frequently by three morphological parameters, namely expansion and hatching (EH) status, inner cell mass (ICM) grading and trophectoderm (TE) grading. The score is used to define the quality classification (poor / good / top) which determines which embryo is to be transferred or cryopreserved. Blastocyst scoring and grading can be highly subjective, which does influence the choice for transfer and cryopreservation. Time-lapse imaging technology captures additional input about embryo development as well as enables centralized data storage and sharing for independent central assessments. Study design, size, duration Pooled embryo analysis from a prospective, randomized, multicenter trial (RAINBOW) of 619 women undergoing ovarian stimulation with an individualized dose of follitropin delta in a long GnRH agonist protocol between May 2018 and January 2020. Blastocysts were centrally assessed using time-lapse images by two independent assessors and one adjudicator . Selection of the blastocyst for transfer by local assessment was based on morphological scoring and not on morphokinetic time-lapse parameters. Participants/materials, setting, methods Oocytes were fertilized by ICSI and cultured in the Embryoscopeâ (Vitrolife) up to day 5 for transfer or day 5/6 for cryopreservation. Embryos were assessed as either non-blastocyst or blastocyst. Blastocysts were graded centrally and locally at 116 hrs of development, based on EH status (1–6), ICM (A-D) and TE grading (A-D). Central assessors were blinded to local assessment and embryo transfer selection. Main results and the role of chance In total 4282 embryos were assessed centrally, of which 2046 day 5 embryos (48%) were adjudicated due to a scoring difference of at least one parameter between the two central assessors. In total 38% of day 5 embryos were judged as non-blastocysts and 62% as blastocysts of which 61% (i.e. 38% of all embryos) were determined to be of good or top quality. Identical results in terms of quality classification (poor / good / top) were obtained for 69% of blastocysts between local and central assessment and in 78%, between the two central assessors. Moreover, central and local scoring were identical in 62% for EH status, 53% for ICM grading and 57% for TE grading. For all transferred blastocysts (n = 508), central and local quality assessment was aligned for 63%. The ongoing pregnancy rate following single blastocyst transfer (SBT) was 41% (202/489), and similar to when considering only the transfers for which the central assessment had the same or a higher classification than the local assessment (166/411=40%). In 16% of all SBT, central quality assessment gave a lower score for the transferred blastocyst than the central assessment. This discrepancy could potentially have led to transfer of a different blastocyst. Limitations, reasons for caution This trial included assessments made by embryologists from 20 IVF centres. Some centres has limited experience with time-lapse technology for morphological blastocyst scoring. Scoring could therefore have been affected by differences in focal planes, magnification and contrast compared to inverted microscopy, with potential influence on blastocyst scores and quality classification. Wider implications of the findings: Local and central blastocyst quality classification based on morphology aligns well but remains subjective. Embryo assessment may benefit from using tools like artificial intelligence-based algorithms for a more objective analysis. Trial registration number NCT03564509

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Selection of preimplantation embryos using time-lapse microscopy in in vitro fertilization: State of the technology and future directions

Birth Defects Research ◽

10.1002/bdr2.1226 ◽

2018 ◽

Vol 110 (8) ◽

pp. 648-653 ◽

Cited By ~ 5

Author(s):

Belén Aparicio-Ruiz ◽

Laura Romany ◽

Marcos Meseguer

Keyword(s):

In Vitro Fertilization ◽

Time Lapse ◽

Preimplantation Embryos ◽

Future Directions ◽

Vitro Fertilization ◽

Time Lapse Microscopy ◽

Selection Of

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Good practice recommendations for the use of time-lapse technology†

Human Reproduction Open ◽

10.1093/hropen/hoaa008 ◽

2020 ◽

Vol 2020 (2) ◽

Cited By ~ 10

Author(s):

Susanna Apter ◽

Thomas Ebner ◽

Thomas Freour ◽

Yves Guns ◽

Borut Kovacic ◽

...

Keyword(s):

Clinical Judgment ◽

Working Group ◽

Scientific Evidence ◽

Good Practice ◽

Time Lapse ◽

Steering Committee ◽

Success Rates ◽

Practice Recommendations ◽

Use Of Time ◽

Selection Of

Abstract STUDY QUESTION What recommendations can be provided on the approach to and use of time-lapse technology (TLT) in an IVF laboratory? SUMMARY ANSWER The present ESHRE document provides 11 recommendations on how to introduce TLT in the IVF laboratory. WHAT IS KNOWN ALREADY Studies have been published on the use of TLT in clinical embryology. However, a systematic assessment of how to approach and introduce this technology is currently missing. STUDY DESIGN, SIZE, DURATION A working group of members of the Steering Committee of the ESHRE Special Interest Group in Embryology and selected ESHRE members was formed in order to write recommendations on the practical aspects of TLT for the IVF laboratory. PARTICIPANTS/MATERIALS, SETTING, METHODS The working group included 11 members of different nationalities with internationally recognized experience in clinical embryology and basic science embryology, in addition to TLT. This document is developed according to the manual for development of ESHRE recommendations for good practice. Where possible, the statements are supported by studies retrieved from a PUBMED literature search on ‘time-lapse’ and ART. MAIN RESULTS AND THE ROLE OF CHANCE A clear clinical benefit of the use of TLT, i.e. an increase in IVF success rates, remains to be proven. Meanwhile, TLT systems are being introduced in IVF laboratories. The working group listed 11 recommendations on what to do before introducing TLT in the lab. These statements include an assessment of the pros and cons of acquiring a TLT system, selection of relevant morphokinetic parameters, selection of an appropriate TLT system with technical and customer support, development of an internal checklist and education of staff. All these aspects are explained further here, based on the current literature and expert opinion. LIMITATIONS, REASONS FOR CAUTION Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise. The paper provides technical advice, but leaves any decision on whether or not to use TLT to the individual centres. WIDER IMPLICATIONS OF THE FINDINGS This document is expected to have a significant impact on future developments of clinical embryology, considering the increasing role and impact of TLT. STUDY FUNDING/COMPETING INTEREST(S) The meetings of the working group were funded by ESHRE. S.A. declares participation in the Nordic Embryology Academic Team with meetings sponsored by Gedeon Richter. T.E. declares to have organized workshops for Esco and receiving consulting fees from Ferring and Gynemed and speakers’ fees from Esco and honorarium from Merck and MSD. T.F. received consulting fees from Vitrolife and Laboratoires Genévrier, speakers’ fees from Merck Serono, Gedeon Richter, MSD and Ferring and research grants from Gedeon Richter and MSD. M.M. received sponsorship from Merck. M.M.E. received speakers’ fees from Merck, Ferring and MSD. R.S. received a research grant from ESHRE. G.C. received speakers’ fees from IBSA and Excemed. The other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A. DISCLAIMER This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation. ESHRE’s GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring of any of the included technologies by ESHRE. †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

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Morphological selection of human spermatozoa in vivo and in vitro

Reproduction ◽

10.1530/jrf.0.0640391 ◽

1982 ◽

Vol 64 (2) ◽

pp. 391-399 ◽

Cited By ~ 60

Author(s):

D. Mortimer ◽

E. E. Leslie ◽

R. W. Kelly ◽

A. A. Templeton

Keyword(s):

Human Spermatozoa ◽

Morphological Selection ◽

Selection Of

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The validation of physical activity instruments for measuring energy expenditure: problems and pitfalls

Public Health Nutrition ◽

10.1079/phn19980043 ◽

1998 ◽

Vol 1 (4) ◽

pp. 265-271 ◽

Cited By ~ 68

Author(s):

Kirsten L Rennie ◽

Nicholas J Wareham

Keyword(s):

Physical Activity ◽

Energy Expenditure ◽

Validation Study ◽

Measurement Instrument ◽

Frame Of Reference ◽

Exposure Measurement ◽

Planning Stage ◽

Correlated Error ◽

Comparison Technique ◽

Selection Of

AbstractObjective:To review and categorize the problems associated with undertaking physical activity validation studies and to construct a checklist against which any study could be compared.Results:The studies reviewed demonstrated problems in defining the dimension of physical activity that is of interest and in the selection of an appropriate comparison technique. Ideally this should be closely related to the true exposure of interest and assess that exposure objectively and without correlated error from the study instrument in question. In many studies inappropriate comparison methods have been chosen which do not measure the true underlying exposure and which are likely to have correlated error. The choice of study populations, the frame of reference of the exposure measurement and the use of appropriate statistical methods are also problematic areas.Conclusions:There is no ideal measurement instrument or validation study design that is suitable for all situations. However, the checklist in this paper provides a means whereby the appropriateness of studies already undertaken or at the planning stage can be assessed.

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