Abstract
Research question
What is the intra- and inter-centre reliability in embryo grading performed according
to the Istanbul Consensus across several IVF clinics?
Design
Forty Day 3 embryos and 40 blastocysts were photographed on three focal planes. Senior
and junior embryologists from 65 clinics were invited to grade them according to the
Istanbul Consensus (Study Phase I). All participants then attended interactive training
where a panel of experts graded the same embryos (Study Phase II). Finally, a second
set of pictures was sent to both embryologists and experts for a blinded evaluation
(Study Phase III). Intra-centre reliability was reported for Study Phase I as Cohen's
kappa between senior and junior embryologists; inter-centre reliability was instead
calculated between senior/junior embryologists and experts in Study Phase I versus
III to outline improvements after training (i.e. upgrade of Cohen's kappa category
according to Landis and Koch).
Results
Thirty-six embryologists from 18 centres participated (28% participation rate). The
intra-centre reliability was (i) substantial (0.63) for blastomere symmetry (range
–0.02 to 1.0), (ii) substantial (0.72) for fragmentation (range 0.29–1.0), (iii) substantial
(0.66) for blastocyst expansion (range 0.19–1.0), (iv) moderate (0.59) for inner cell
mass quality (range 0.07–0.92), (v) moderate (0.56) for trophectoderm quality (range
0.01–0.97). The inter-centre reliability showed an overall improvement from Study
Phase I to III, from fair (0.21–0.4) to moderate (0.41–0.6) for all parameters under
analysis, except for blastomere fragmentation among senior embryologists, which was
already moderate before training.
Conclusions
Intra-centre reliability was generally moderate/substantial, while inter-centre reliability
was just fair. The interactive training improved it to moderate, hence this workflow
was deemed helpful. The establishment of external quality assessment services (e.g.
UK NEQAS) and the avant-garde of artificial intelligence might further improve the
reliability of this key practice for embryo selection.
Keywords
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References
- Morphology vs morphokinetics: a retrospective comparison of inter-observer and intra-observer agreement between embryologists on blastocysts with known implantation outcome.JBRA Assist. Reprod. 2018; 22: 228-237
- Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.Reprod. Biomed. Online. 2011; 22: 632-646
- The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.Hum. Reprod. 2011; 26: 1270-1283
- Eshre Working group on Time-lapse technology: Good practice recommendations for the use of time-lapse technology.Hum. Reprod. Open. 2020; (2020, hoaa008)
- Interobserver agreement and intraobserver reproducibility of embryo quality assessments.Hum. Reprod. 2006; 21: 2141-2148
- Time-lapse systems for embryo incubation and assessment in assisted reproduction.Cochrane Database Syst. Rev. 2018; 5CD011320
- Randomized comparison of two different blastocyst grading systems.Fertil. Steril. 2006; 85: 559-563
- Interobserver and intraobserver variation in day 3 embryo grading.Fertil. Steril. 2006; 86: 1608-1615
- Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts.Hum. Reprod. 2014; 29: 1173-1181
- Consistent and reproducible outcomes of blastocyst biopsy and aneuploidy screening across different biopsy practitioners: a multicentre study involving 2586 embryo biopsies.Hum. Reprod. 2016; 31: 199-208
- External quality control for embryology laboratories.Reprod. Biomed. Online. 2010; 20: 68-74
- Associations of blastocyst features, trophectoderm biopsy and other laboratory practice with post-warming behavior and implantation.Hum. Reprod. 2018; 33 (1992–2001)
- Definition, diagnostic and therapeutic options in recurrent implantation failure: an international survey of clinicians and embryologists.Hum. Reprod. 2021; 36: 305-317
- Inconclusive chromosomal assessment after blastocyst biopsy: prevalence, causative factors and outcomes after re-biopsy and re-vitrification. A multicenter experience.Hum. Reprod. 2018; 33: 1839-1846
- Looking past the appearance: a comprehensive description of the clinical contribution of poor-quality blastocysts to increase live birth rates during cycles with aneuploidy testing.Hum. Reprod. 2019; 34: 1206-1214
- Perturbations of morphogenesis at the compaction stage affect blastocyst implantation and live birth rates.Hum. Reprod. 2021; 36: 918-928
- The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART.Hum. Reprod. Update. 2019; 25: 422-438
- High outcome predictability after IVF using a combined score for zygote and embryo morphology and growth rate.Hum. Reprod. 2002; 17: 2402-2409
- Revised guidelines for good practice in IVF laboratories (2015).Hum. Reprod. 2016; 31: 685-686
- ESHRE PGT Consortium and SIG Embryology good practice recommendations for polar body and embryo biopsy for PGT.Hum. Reprod. Open. 2020; (2020, hoaa020)
- Morphological assessment on day 4 and its prognostic power in selecting viable embryos for transfer.Zygote. 2016; 24: 477-484
- Which key performance indicators are most effective in evaluating and managing an in vitro fertilization laboratory?.Fertil. Steril. 2020; 114: 9-15
- Day 4 embryo selection is equal to Day 5 using a new embryo scoring system validated in single embryo transfers.Hum. Reprod. 2008; 23: 1505-1510
- Culture and transfer of human blastocysts.Curr. Opin. Obstet. Gynecol. 1999; 11: 307-311
- Should we freeze it? Agreement on fate of borderline blastocysts is poor and does not improve with a modified blastocyst grading system.Hum. Reprod. 2020; 35: 1045-1053
- Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction.Fertil. Steril. 2011; 96 (e2): 1473-1478
- Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization.NPJ Digital Medicine. 2019; 2: 21
- A novel transnational fresh oocyte donation (TOD) program based on transport of frozen sperm and embryos.Hum. Reprod. 2019; 34: 285-290
- Alternative patterns of partial embryo compaction: prevalence, morphokinetic history and possible implications.Reprod. Biomed. Online. 2020; 40: 347-354
- An application of hierarchical kappa-type statistics in the assessment of majority agreement among multiple observers.Biometrics. 1977; 33: 363-374
- The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174
- Morphological systems of human embryo assessment and clinical evidence.Reprod. Biomed. Online. 2013; 26: 210-221
- Human blastocyst biopsy and vitrification.J. Vis. Exp. 2019; (Jul 26): 149
- Reliability and agreement on embryo assessment: 5 years of an external quality control programme.Reprod. Biomed. Online. 2018; 36: 259-268
- Inter-laboratory agreement on embryo classification and clinical decision: conventional morphological assessment vs. time lapse.PLoS One. 2017; 12e0183328
- Blastocyst culture in the era of PGS and FreezeAlls: is a ‘C’ a failing grade?.Hum. Reprod. Open. 2017; (2017, hox017)
- Intra- and interobserver analysis in the morphological assessment of early stage embryos during an IVF procedure: a multicentre study.Reprod. Biol. Endocrinol. 2011; 9: 127
- Time-lapse culture with morphokinetic embryo selection improves pregnancy and live birth chances and reduces early pregnancy loss: a meta-analysis.Reprod. Biomed. Online. 2017; 35: 511-520
- Is there an advantage in scoring early embryos on more than one day?.Hum. Reprod. 2009; 24: 2104-2113
- Time of morulation and trophectoderm quality are predictors of a live birth after euploid blastocyst transfer: a multicenter study.Fertil. Steril. 2019; 112 (e1): 1080-1093
- Significance of morphological attributes of the early embryo.Reprod. Biomed. Online. 2005; 10: 669-681
- Blasts from the past: is morphology useful in PGT-A tested and untested frozen embryo transfers?.Reprod. Biomed. Online. 2020; 41: 981-989
- Inter-observer and intra-observer agreement between embryologists during selection of a single Day 5 embryo for transfer: a multicenter study.Hum. Reprod. 2017; 32: 307-314
- Inter- and intra-observer variability of time-lapse annotations.Hum. Reprod. 2013; 28: 3215-3221
- Pregnancies achieved after transferring frozen morula/compact stage embryos.Fertil. Steril. 2001; 75: 629-631
- Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer.Hum. Reprod. 2019; 34: 1011-1018
Biography

Danilo Cimadomo, MSc, PhD, is a molecular biologist, Science and Research Manager of GeneraLife IVF, member of the Executive Committee of SIERR, and Basic Science Officer of the ESHRE Special Interest Group Implantation and Early Pregnancy. He has authored over 80 peer-reviewed manuscripts concerning embryology, embryo selection and PGT.
Article info
Publication history
Published online: October 06, 2021
Accepted:
September 26,
2021
Received in revised form:
September 1,
2021
Received:
April 7,
2021
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.