Alexander’s Library

The search for the elixir of youth — what the record says, and how strongly. Double-click any word for an instant dictionary or scientific synopsis.

Library / Natural & Life Sciences / Medicine, Health & Longevity / Reproductive Medicine & Human Fertility / Assisted Reproductive Technology & Gamete Donation

Cleavage-Stage Embryo Morphology

Evaluation of cell number, blastomere symmetry, fragmentation percentage, multinucleation, and compaction speed on Day 2 and Day 3.

84 sources ↓Last researched 2026-10-20

Morphological Grading of Cleavage-Stage Embryos

Balancing Standardization and Predictive Reality in the IVF Laboratory

Synopsis · Executive Overview

Cleavage-stage embryo grading remains a cornerstone of IVF laboratory practice, relying on a synthesis of morphological snapshots. While clear associations exist between features like fragmentation and viability, the transition from static assessment to dynamic, time-lapse-informed selection continues to spark debate regarding clinical utility versus cost-effectiveness.

Section I · Foundations of Assessment

Standardizing the Morphology Framework

Current clinical practice relies heavily on morphological parameters defined by international consensus, including the ESHRE and Alpha Scientists criteria. The primary benchmarks for grading include the number of blastomeres, the presence of cytoplasmic fragmentation, blastomere symmetry, and the absence of multinucleation. These features are generally evaluated on Day 2 and Day 3, with 7-9 blastomeres often considered the gold standard for transfer potential.

Evidence consistently shows that heavy fragmentation (>25%) is an adverse indicator, correlating with higher apoptosis rates and poorer clinical outcomes. However, the interpretation of these features is subject to significant inter-observer variability, necessitating rigorous internal training and standardization protocols to maintain quality control.

Section II · Mechanisms and Innovations

Morphokinetics vs. Static Snapshot

With the advent of time-lapse imaging, the field has gained the ability to monitor developmental milestones such as the 'first cleavage-associated compensatory timing' (FACT). While these dynamic markers provide detailed biological insights, high-quality RCT evidence has not yet definitively shown that time-lapse systems significantly outperform conventional static assessment regarding live birth rates.

Furthermore, extrinsic factors like the composition of culture media are known to alter embryonic kinetics, which complicates the universal application of specific timing algorithms.

Evidence Hierarchy (Graded Claims)

  • T1Synthesis of trials
    4 (22%)
  • T2Randomised trial
    0 (0%)
  • T3Observational, large
    13 (72%)
  • T4Observational, small or case-based
    0 (0%)
  • T5Preclinical or mechanistic
    0 (0%)
  • T6Opinion, news or unverified
    1 (6%)
12 settled5 debated1 contested / frontier

Study Designs in Indexed Literature

  • Meta-analyses, Systematic Reviews & Guidelines7 (8%)
  • Randomised Controlled Trials (RCTs)9 (11%)
  • Prospective Cohorts & Clinical Registries28 (33%)
  • Observational & Clinical Case Series1 (1%)
  • Preclinical, Cellular & Computational Models7 (8%)
  • Primary Literature & Archive Records32 (38%)

Publication Timeline Velocity

Fig. 1 — Field Evidence Architecture & Publication Trajectory. Distribution of methodological study designs (84 indexed publications) and 18 extracted claims graded from T1 (meta-analyses and guidelines) to T6.

Epistemic Verdict Distribution Across Evaluated Levers & Mechanisms (2)

Guideline1 lever (50%)
Weak1 lever (50%)
Fig. 2 — Intervention & Mechanism Epistemic Calibration. Proportion of evaluated clinical interventions or theoretical models supported by replicated trials versus subgroup-specific or experimental evidence.
Primary Citations & Landmark Studies

Key Studies Anchoring This Monograph

Synthesis & Conclusions

State of the Field Conclusions

Static morphological grading is essential but imperfect. While abnormal features like trichotomic mitosis and severe fragmentation remain strong negative predictors, the field is cautious about over-relying on fine-grained time-lapse markers until clear evidence of improved clinical outcomes matures. The future likely involves an integration of morphological data with AI-assisted analysis and non-invasive metabolic monitoring.

Key Quantitative Takeaways

  • Standard static morphology (cell count, fragmentation, symmetry) remains the clinical guideline for grading.
  • Fragmentation exceeding 25% is strongly correlated with reduced viability (Established).
  • Time-lapse morphokinetics offer detailed predictive info but have not yet demonstrated superior clinical pregnancy rates (Contested).
  • Inter-observer variability is a major constraint that requires standardized training to minimize.
>25%

Extensive fragmentation threshold associated with reduced blastocyst formation and increased apoptosis

Alikani 2003

25-27 hours post-insemination

Timing for early cleavage to 2-cell stage as a predictor of higher blastocyst development

Fenwick 2002

Where each lever applies

A graded decision ledger of interventions across clinical subgroups. Each row names its best landmark evidence, measured effect, clinical reading, and epistemic verdict.

Supported: RCT live-birth gainTargeted: specific subgroupGuideline: clinical consensusWeak: inconsistent/unproven gainNot supported: RCTs show no gainTrial: human trial in progressLab: preclinical / cell dish

Preparation & Transfer

Lever & MechanismBest Landmark EvidenceMeasured Effect & Clinical ReadingVerdict
Static Morphology Assessment

Scoring based on blastomere count, symmetry, fragmentation, and multinucleation.

ESHRE/Alpha Scientists Consensus

Effect: Standardized criteria across clinics

Clinical reading: Fundamental for ranking, but prone to inter-observer variability.

Guideline
Time-Lapse Morphokinetics

Dynamic tracking of cleavage milestones (e.g., t5, s2, cc2) and FACT relationships.

RCT evidence, e.g., Armstrong 2018

Effect: Insufficient improvement in LBR/pregnancy rates over static methods

Clinical reading: Adds predictive data but lacks proven clinical superiority for standard cohorts.

Weak

Questions for specialist consultations

High-yield clinical and laboratory inquiries directly derived from the evidence record.

  1. What is the standard operating procedure for mitigating inter-observer variability in embryo grading at this clinic?
  2. To what extent are specific cleavage milestones (e.g., t5 timing) utilized for decision-making compared to traditional day 3 blastomere morphology?
  3. How does the laboratory distinguish between embryos with transient versus permanent abnormal cleavage features (e.g., multinucleation)?

Queued for next research sweep

Frontier clinical trials, emerging biology, and targeted subgroup outcomes tracked by the autonomous research worker.

  • AI-driven morphological assessment versus conventional expert scoring for reproducibility.
  • Investigation into mitochondrial DNA content in culture media as a non-invasive adjunct to morphology.
  • Multi-center validation of specific cleavage-stage timing milestones for predicting euploidy.
Historical timeline (8 milestones, 1997–2025)
  1. 1997

    Cleavage Stage Superiority

    Demonstration that 4-cell embryos on day 2 significantly outperform other cell-number stages in IVF.

  2. 1998

    Early Cleavage Indicator

    Identification of early cleavage to the 2-cell stage as a marker for improved embryo viability in ICSI cycles.

  3. 2003

    Graduated Embryo Score (GES)

    Introduction of a weighted scoring system integrating cleavage rate, fragmentation, and morphology to improve prediction of blastocyst formation.

  4. 2011

    ESHRE and Alpha Scientists in Reproductive Medicine Consensus

    Standardization of pronuclear (PN) classification into three categories (1: symmetrical, 2: non-symmetrical, 3: abnormal) to improve embryo evaluation consistency.

  5. 2011

    Istanbul Consensus on Embryo Assessment

    First international consensus meeting organized by ESHRE and Alpha Scientists in Reproductive Medicine to establish standardized terminology and criteria for static morphological assessment of oocytes, zygotes, cleavage embryos, and blastocysts.

  6. 2012

    Time-Lapse Cleavage Rating

    Introduction of time-lapse morphokinetics as a predictive tool for embryo viability, identifying unviable embryos that appear normal under static observation.

  7. 2024

    Istanbul Consensus Revision

    Publication of updated 2024 criteria for morphological assessment of oocytes and embryos by ESHRE/Alpha working group.

  8. 2025

    Updated ESHRE/Alpha Consensus on Embryo Assessment

    Comprehensive revision of the Istanbul Consensus integrating static and dynamic time-lapse morphological criteria, developmental timelines, and ranking recommendations for embryo evaluation.

Evidence by study design (18 findings across T1–T6)

Strongest support first. The bar beside each finding shows its grade.

Synthesis of trials

  1. #1 The primary morphological indicators for assessing human cleavage-stage embryos include the number of blastomeres, degree of fragmentation, blastomere symmetry, multinucleation, and compaction status.

    The Istanbul consensus update: a revised ESHRE/ALPHA consensus on oo… (2025); Expert consensus on the morphological evaluation of human cleavage-s… (2023); The cleavage stage embryo (2012); The Istanbul consensus workshop on embryo assessment: proceedings of… (2011)

    These indicators form the core of current consensus-based grading systems in IVF laboratories.

  2. #2 There is insufficient evidence that time-lapse embryo incubation and dynamic assessment systems improve live birth, clinical pregnancy, or miscarriage rates compared with conventional static morphological assessment.

    ContestedTime-lapse systems for embryo incubation and assessment in assisted … (2018)

    Commercial adoption of time-lapse monitoring systems has outpaced high-quality randomized trial evidence demonstrating superior clinical efficacy over standard morphological grading.

  3. #3 Cytoplasmic fragmentation is inversely associated with embryo quality and implantation potential, and increased fragmentation correlates with higher levels of cell-free mitochondrial DNA in culture media.

    Effect of cytoplasmic fragmentation on embryo development, quality, … (2024); Nuclear and mitochondrial DNA in blastocoele fluid and embryo cultur… (2016); Mitochondrial DNA content in embryo culture medium is significantly … (2013)

    Fragmentation reflects underlying cellular health and is linked to the release of apoptotic markers.

  4. #4 Pronuclear (PN) morphology scoring is a non-invasive tool, but evidence for its efficacy in improving clinical pregnancy outcomes remains inconsistent.

    DebatedPronuclear score improves prediction of embryo implantation success … (2021); Pronuclear morphology evaluation for fresh in vitro fertilization (I… (2013); Clinical use of a pronuclear stage score following intracytoplasmic … (2000)

    Different classification methods (like ESHRE-Alpha) have been introduced to standardize assessment, but clinical utility is still contested.

Observational, large

  1. #5 Extensive fragmentation (>25%) in cleavage-stage embryos is associated with reduced blastocyst formation, lower cell numbers in resulting blastocysts, and higher rates of apoptosis.

    Maintenance of the Inner Cell Mass in Human Blastocysts from Fragmen… (2003)

    Fragmentation is consistently cited as a negative prognostic indicator for later development.

  2. #6 Time-lapse imaging provides predictive information on embryo viability, including the 'first cleavage-associated compensatory timing' (FACT) relationship, that complements static morphological assessment.

    First cleavage signatures define a temporal trade-off and predict em… (2026); Embryo morphokinetics derived from fresh and vitrified bovine oocyte… (2023); Time-lapse imaging derived morphokinetic variables reveal associatio… (2020); Effect of morphokinetics and morphological dynamics of cleavage stag… (2018)

    Dynamic morphokinetic observations can identify developmental arrest or errors that are missed by static grading.

  3. #7 Blastomere multinucleation in cleavage-stage embryos is associated with decreased implantation rates and higher abortion rates.

    DebatedMultinucleation in the early human cleavage-stage embryo in vitro is… (2020); Factors contributing to frozen embryo transfer outcomes : assessment… (2019)

    While associated with lower potential, some studies note that transfer can still result in live births.

  4. #8 Transfer of 4-cell cleavage-stage embryos on day 2 is associated with higher implantation and pregnancy rates compared to 2-cell, 3-cell, or >4-cell stage embryos.

    Embryo morphology or cleavage stage: how to select the best embryos … (1997)

    Cleavage stage and cell number are fundamental metrics for early embryo selection in IVF.

  5. #9 Early cleavage (to the 2-cell stage by 25-27 hours post-insemination/injection) is a positive predictor of blastocyst development and clinical pregnancy.

    Time from insemination to first cleavage predicts developmental comp… (2002); Early cleavage of human embryos to the two-cell stage after intracyt… (1998)

    Temporal markers of division provide additional prognostic value for viability.

  6. #10 Abnormal cleavage-stage features, including multinucleation at the 4-cell stage, uneven blastomere size at the 2-cell stage, and abrupt direct cleavage to three or more cells, severely impair or largely preclude embryo implantation.

    The use of morphokinetics as a predictor of embryo implantation. (2011)

    Blastomere symmetry and the presence of multinucleation are standard morphological deselection markers in cleavage-stage assessment.

  7. #11 The use of culture media can significantly alter the morphokinetics of cleavage-stage embryos, potentially affecting selection algorithms.

    The Impact of Culture Medium on Morphokinetics of Cleavage Stage Emb… (2022)

    Standardized selection tools (e.g., KIDScore) must account for the specific culture environment to maintain accuracy.

  8. #12 Specific morphokinetic cleavage milestones, such as division to 5 cells between 48.8 and 56.6 hours post-ICSI (t5), second-cleavage synchrony of 0.76 hours or less (s2), and cell cycle two duration of 11.9 hours or less (cc2), are predictive of successful embryo implantation.

    DebatedThe use of morphokinetics as a predictor of embryo implantation. (2011)

    Automated time-lapse tracking allows dynamic kinetic parameters to augment traditional static morphological grading of Day 2 and Day 3 cleavage embryos.

  9. #13 Cleavage-stage embryo morphology, including cell number and fragmentation, is a predictive factor for live birth rates in day 3 transfers.

    Effect of Age and Morphology on Live Birth Rate After Cleavage Stage… (2020)

    Morphological grading (e.g., 8-cell embryos with low fragmentation) is a standard clinical tool for embryo selection.

  10. #14 Direct uneven cleavage, irregular chaotic division, and multinucleation are associated with reduced developmental potential, although some embryos exhibiting these traits can still reach the blastocyst stage.

    DebatedAre cleavage anomalies, multinucleation, or specific cell cycle kine… (2018); Delayed blastulation, multinucleation, and expansion grade are indep… (2016); Direct Unequal Cleavages: Embryo Developmental Competence, Genetic C… (2016); Analysis of embryo morphokinetics, multinucleation and cleavage anom… (2014)

    Morphological dysmorphisms are visible under time-lapse but are not always exclusionary for later development.

  11. #15 A higher number of blastomeres at the cleavage stage (Day 3) is associated with increased live birth rates in human clinical transfers, with some evidence suggesting superior outcomes for embryos reaching 10-11+ cells.

    DebatedIncreased blastomere number is associated with higher live birth rat… (2022)

    This finding challenges the traditional consensus that very fast-cleaving embryos have reduced developmental potential.

  12. #16 Embryos with synchronous cleavage show higher survival rates post-thaw than those with asynchronous cleavage, though clinical pregnancy rates may not differ.

    Synchronous and Asynchronous Blastomere Cleavage at Cryopreservation… (2014)

    This suggests that both patterns can be safely cryopreserved despite morphological differences.

  13. #17 Trichotomic mitosis is an indicator of low viability in cleavage-stage embryos.

    Time-Lapse Cleavage Rating Predicts Human Embryo Viability (2012)

    Time-lapse imaging can reveal catastrophic mitotic errors invisible to standard static microscopy.

Opinion, news or unverified

  1. #18 Morphological scoring remains subject to significant inter-observer variability, though standardized training sessions can improve reliability among embryologists.

    Expert consensus on the morphological evaluation of human cleavage-s… (2023); Intra- and inter-observer analysis in the morphological assessment o… (2009)

    The inherent subjectivity of visual embryo grading necessitates strict quality management and standardized criteria.

Where the record disagrees (2 controversies)
  • While commercial systems market time-lapse as superior, multiple systematic reviews and trials suggest no significant improvement in clinical outcomes over standard methods.

    Findings #2

  • Specific kinetic milestones and very high blastomere counts on Day 3 lack broad consensus and may be specific to certain lab conditions or media.

    Findings #12, #15

Node lineage & crossover disciplines

Parent lineage, active node, direct child sub-branches, and associated crossover disciplines across the Tree of Knowledge.

+ Associated nodes:

Branches

AI Tree OrganiserExpand Cleavage-Stage Embryo Morphology

Branches are never named or placed manually. Ask any scientific question — AI decomposes multi-part inquiries into one, two, three, or more canonical sub-branches and places each under its proper discipline.

Public archive: please keep questions to general scientific concepts (no names, dates of birth, or personal health identifiers). Privacy & copyright.

Auto-classifies taxonomy & cross-links
Primary indexed sources (84)

Primary scientific literature, systematic reviews, and clinical trial registrations indexed for this branch.

  1. Epigenetic, environmental, and sex-specific programming of long-term health in Assisted Reproductive Technologies–conceived offspring — Eric A. Rhon‐Calderón, Cassidy N. Hemphill, Marisa S. Bartolomei Biology of Reproduction, 2026, unknown · DOI: 10.1093/biolre/ioag137
  2. Evaluation of an Undisturbed Embryo Culture System for Embryo Development in IVF/ICSI Cycles Sun Yat-sen University, 2026, rct
  3. Ncbp1 deficiency affects morula-to-blastocyst transition through lipid metabolic dysregulation. — Liu Y, He Y, Wang X et al. Reproduction (Cambridge, England), 2026, animal · DOI: 10.1093/reprod/xaaf020
  4. Embryo signals for successful implantation — Scarlett Salter Warwick Research Archive Portal (University of Warwick), 2026, unknown · DOI: 10.82444/warw.33723679
  5. IRE1/FAM134B-mediated ER-phagy alleviates zearalenone-induced ER stress and developmental defects in porcine embryos. — Kim DW, Koo DB, Park HJ Ecotoxicology and environmental safety, 2026, animal · DOI: 10.1016/j.ecoenv.2026.120022
  6. Postfertilization telomere marker testing in human embryos: a pilot study of a novel embryo evaluation assay — Wei-Che Lo, En‐Hui Cheng, Hui-Hsin Shih et al. Fertility and Sterility, 2026, cohort · DOI: 10.1016/j.fertnstert.2026.04.003
  7. First cleavage signatures define a temporal trade-off and predict embryo fitness. — Crasta DN, Lee SW, Fredrickson J et al. Scientific reports, 2026, unknown · DOI: 10.1038/s41598-026-68288-x
  8. The Istanbul consensus update: a revised ESHRE/ALPHA consensus on oocyte and embryo static and dynamic morphological assessment, — The Working Group on the update of the ESHRE/ALPHA Istanbul Consensus, Giovanni Coticchio, Aisling Ahlström et al. Human Reproduction, 2025, unknown, 74 citations · DOI: 10.1093/humrep/deaf021
  9. Artificial intelligence in in-vitro fertilization (IVF): A new era of precision and personalization in fertility treatments. — Olawade DB, Teke J, Adeleye KK et al. Journal of gynecology obstetrics and human reproduction, 2025, expert opinion, 42 citations · DOI: 10.1016/j.jogoh.2024.102903
  10. Time-Lapse Imaging in IVF: Bridging the Gap Between Promises and Clinical Realities — Grzegorz Mrugacz, Igor Bołkun, Tomasz Magoń et al. International Journal of Molecular Sciences, 2025, unknown, 9 citations · DOI: 10.3390/ijms26199609
  11. Evaluation of the Effectiveness and Accuracy of Non-Invasive Preimplantation Genetic Testing (niPGT) Compared to Invasive Embryo Biopsy — Charalampos Voros, Menelaos Darlas, Diamantis Athanasiou et al. Biomedicines, 2025, systematic review, 8 citations · DOI: 10.3390/biomedicines13082010
  12. The prospect of artificial intelligence to personalize assisted reproductive technology — Simon Hanassab, Ali Abbara, Arthur C. Yeung et al. npj Digital Medicine, 2024, expert opinion, 96 citations · DOI: 10.1038/s41746-024-01006-x
  13. Shape of the first mitotic spindles impacts multinucleation in human embryos — Yuki Ono, Hiromitsu Shirasawa, Kazumasa Takahashi et al. Nature Communications, 2024, animal, 27 citations · DOI: 10.1038/s41467-024-49815-8
  14. Effect of cytoplasmic fragmentation on embryo development, quality, and pregnancy outcome: a systematic review of the literature — Ariella Yazdani, Iman Halvaei, Catherine Boniface et al. Reproductive Biology and Endocrinology, 2024, systematic review, 24 citations · DOI: 10.1186/s12958-024-01217-7
  15. O-240 Embryo assessment: the Istanbul consensus revised — G Coticchio, Aisling Ahlström, Gemma Arroyo et al. Human Reproduction, 2024, expert opinion, 1 citations · DOI: 10.1093/humrep/deae108.283
  16. Poster Presentations - Abstracts of the 28th Annual Congress of the SBRA. Florianópolis/SC - Brazil, 2024 — SBRA JBRA, 2024, cohort, 1 citations · DOI: 10.5935/1518-0557.20240063
  17. Embryo morphokinetics derived from fresh and vitrified bovine oocytes predict blastocyst development and nuclear abnormalities — Daniel Angel‐Velez, Tine De Coster, Nima Azari‐Dolatabad et al. Scientific Reports, 2023, unknown, 29 citations · DOI: 10.1038/s41598-023-31268-6
  18. Expert consensus on the morphological evaluation of human cleavage-stage embryos and blastocysts — Da Li, Lodovico Parmegiani, Dalei Yang et al. Chinese Medical Journal, 2023, expert opinion, 26 citations · DOI: 10.1097/cm9.0000000000002609
  19. Novel Time-Lapse Parameters Correlate with Embryo Ploidy and Suggest an Improvement in Non-Invasive Embryo Selection — Clara Serrano‐Novillo, Laia Uroz, Carmen Márquez Journal of Clinical Medicine, 2023, cohort, 15 citations · DOI: 10.3390/jcm12082983
  20. Poster Presentations - Abstracts of the 27th Annual Congress of the SBRA. Aracaju/SE - Brazil, 2023 — SBRA - Brazilian Society of Assisted Reproduction JBRA, 2023, cross sectional · DOI: 10.5935/1518-0557.20230071
  21. Increased blastomere number is associated with higher live birth rate in day 3 embryo transfer — Lifeng Tian, Leizhen Xia, Hongbo Liu et al. BMC Pregnancy and Childbirth, 2022, cohort, 23 citations · DOI: 10.1186/s12884-022-04521-5
  22. Melatonin accelerates the developmental competence and telomere elongation in ovine SCNT embryos — Parisa Nadri, Saeid Ansari Mahyari, Farnoosh Jafarpour et al. PLoS ONE, 2022, animal, 19 citations · DOI: 10.1371/journal.pone.0267598
  23. The Impact of Culture Medium on Morphokinetics of Cleavage Stage Embryos: An Observational Study — Linette van Duijn, Melek Rousian, Charlotte S. Kramer et al. Reproductive Sciences, 2022, cohort, 16 citations · DOI: 10.1007/s43032-022-00962-7
  24. Preimplantation Genetic Testing for Aneuploidy Improves Live Birth Rates with In Vitro Produced Bovine Embryos: A Blind Retrospective Study — Giuseppe Silvestri, Carla Canedo‐Ribeiro, María Serrano Albal et al. Cells, 2021, unknown, 39 citations · DOI: 10.3390/cells10092284
  25. Biological and Clinical Significance of Mosaicism in Human Preimplantation Embryos — Ioanna Bouba, Elissavet G. Hatzi, Paris Ladias et al. Journal of Developmental Biology, 2021, unknown, 16 citations · DOI: 10.3390/jdb9020018
  26. Pronuclear score improves prediction of embryo implantation success in ICSI cycles. — Stigliani S, Massarotti C, Bovis F et al. BMC pregnancy and childbirth, 2021, cohort, 13 citations · DOI: 10.1186/s12884-021-03820-7
  27. Analysis of Morphokinetic Parameters of Feline Embryos Using a Time-Lapse System — Joanna Kochan, Agnieszka Nowak, Barbara Kij-Mitka et al. Animals, 2021, unknown, 10 citations · DOI: 10.3390/ani11030748
  28. Towards the selection of embryos with the greatest implantation potential. — Khalife D, Abu-Musa A, Khalil A et al. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology, 2021, unknown, 5 citations · DOI: 10.1080/01443615.2020.1835842
  29. P–187 Multinucleation and reverse cleavage, sings of early embryo self-repair mechanisms — Ana Puigvert, V. Montalv Pallès, J Mass. Hernáez et al. Human Reproduction, 2021 · DOI: 10.1093/humrep/deab130.186
  30. Clinical Outcomes of Single Mosaic Embryo Transfer: High-Level or Low-Level Mosaic Embryo, Does It Matter? — Pin‐Yao Lin, Chun‐I Lee, En‐Hui Cheng et al. Journal of Clinical Medicine, 2020, cohort, 71 citations · DOI: 10.3390/jcm9061695
  31. The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A — for the International Do No Harm Group in IVF (IDNHG-IVF), Norbert Gleicher, David Fred Albertini et al. Reproductive Biology and Endocrinology, 2020, expert opinion, 58 citations · DOI: 10.1186/s12958-020-00616-w
  32. Time-lapse imaging derived morphokinetic variables reveal association with implantation and live birth following in vitro fertilization: A retrospective study using data from transferred human embryos — Shabana Sayed, Marte Myhre Reigstad, Bjørn Molt Petersen et al. PLoS ONE, 2020, cohort, 40 citations · DOI: 10.1371/journal.pone.0242377
  33. Analysis of bovine blastocysts indicates ovarian stimulation does not induce chromosome errors, nor discordance between inner-cell mass and trophectoderm lineages — Desmond A. R. Tutt, Giuseppe Silvestri, María Serrano Albal et al. Theriogenology, 2020, animal, 33 citations · DOI: 10.1016/j.theriogenology.2020.11.021
  34. Effect of Age and Morphology on Live Birth Rate After Cleavage Stage Embryo Transfer — Michael S. Awadalla, Nicole L. Vestal, Lynda K. McGinnis et al. Reproductive Sciences, 2020, cohort, 13 citations · DOI: 10.1007/s43032-020-00249-9
  35. Multinucleation in the early human cleavage-stage embryo in vitro is associated with reduced pregnancy rate and an increased number of abortions — D. Hladik, L Sela, Nina Rogenhofer et al. Geburtshilfe und Frauenheilkunde, 2020, cohort · DOI: 10.1055/s-0040-1717677
  36. Effect of GnRH Agonist vs GnRH Antagonist on Oocyte Morphology in Polycystic Ovary Syndrome Patients During IVF/ICSI Damascus University, 2020, rct
  37. Pronuclear score improves prediction of implantation rate in ICSI cycles — Stigliani S, Massarotti C, Casciano I et al. Research Square, 2020, unknown · DOI: 10.21203/rs.3.rs-88564/v1
  38. [Chromosomal polymorphisms are associated with blastomere multinucleation in IVF/ICSI cycles]. — Chen Z, Yang L, Yi C et al. Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2020 · DOI: 10.12122/j.issn.1673-4254.2020.01.12
  39. Effect of GnRH Agonist vs GnRH Antagonist on Oocyte Morphology During IVF/ICSI Damascus University, 2020, rct
  40. Factors contributing to frozen embryo transfer outcomes : assessment of blastomere multinucleation and luteal phase GnRH agonist support in relation to reproductive outcome — Jaana Seikkula UTUPub (University of Turku), 2019, unknown
  41. Factors affecting the survival and implantation of human blastocysts following vitrification — Hamish Barblett Australasian Journal of Paramedicine, 2019
  42. Impact of Maternal Age on Oocyte and Embryo Competence. — Cimadomo D, Fabozzi G, Vaiarelli A et al. Frontiers in endocrinology, 2018, expert opinion, 472 citations · DOI: 10.3389/fendo.2018.00327
  43. Time-lapse systems for embryo incubation and assessment in assisted reproduction — Sarah Armstrong, Priya Bhide, Vanessa Jordan et al. Cochrane Database of Systematic Reviews, 2018, systematic review, 145 citations · DOI: 10.1002/14651858.cd011320.pub3
  44. Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy? — Desai N, Goldberg JM, Austin C et al. Fertility and sterility, 2018, cohort, 143 citations · DOI: 10.1016/j.fertnstert.2017.12.025
  45. Effect of morphokinetics and morphological dynamics of cleavage stage on embryo developmental potential: A time-lapse study — Shiao-Hsuan Yang, Cheng-Hsuan Wu, Yu‐Ching Chen et al. Taiwanese Journal of Obstetrics and Gynecology, 2018, cohort, 44 citations · DOI: 10.1016/j.tjog.2017.12.013
  46. Enhancing the developmental competence of bovine oocytes and embryos — H. O. Alhilfi Nottingham ePrints (University of Nottingham), 2018
  47. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. — Rienzi L, Gracia C, Maggiulli R et al. Human reproduction update, 2017, meta analysis, 738 citations · DOI: 10.1093/humupd/dmw038
  48. Time-lapse imaging of cleavage divisions in embryo quality assessment — Robert Jay Milewski, Anna Ajduk Reproduction, 2017, expert opinion, 77 citations · DOI: 10.1530/rep-17-0004
  49. Delayed blastocyst formation or an extra day culture increases apoptosis in pig blastocysts. — Lin T, Lee JE, Oqani RK et al. Animal reproduction science, 2017, animal, 18 citations · DOI: 10.1016/j.anireprosci.2017.08.012
  50. Embryo Morphokinetics Based on Time-Lapse Observation — Nasim Tabibnejad InTech eBooks, 2017, unknown · DOI: 10.5772/intechopen.69226
  51. Delayed blastulation, multinucleation, and expansion grade are independently associated with live-birth rates in frozen blastocyst transfer cycles — Nina Desai, Stephanie Ploskonka, Linnea R. Goodman et al. Fertility and Sterility, 2016, cohort, 132 citations · DOI: 10.1016/j.fertnstert.2016.07.1095
  52. Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome. — Zhan Q, Ye Z, Clarke R et al. PloS one, 2016, cohort, 115 citations · DOI: 10.1371/journal.pone.0166398
  53. Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use — Elizabeth R. Andersen Hammond, Andrew Neil Shelling, Lynsey M. Cree Human Reproduction, 2016, unknown, 84 citations · DOI: 10.1093/humrep/dew132
  54. Time-Lapse Incubation for Embryo Culture - Morphokinetics and Environmental Stability Shaare Zedek Medical Center, 2016, rct
  55. A Study Select Top-grade Embryo by Time-lapse Imaging Shanghai First Maternity and Infant Hospital, 2016, rct
  56. A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development — Robert Jay Milewski, Paweł Kuć, Agnieszka Kuczyńska et al. Journal of Assisted Reproduction and Genetics, 2015, cohort, 113 citations · DOI: 10.1007/s10815-015-0440-3
  57. Embryo apoptosis identification: Oocyte grade or cleavage stage? — Noraina Mohd Bakri, Siti Fatimah Ibrahim, Nurul Atikah Osman et al. Saudi Journal of Biological Sciences, 2015, animal, 33 citations · DOI: 10.1016/j.sjbs.2015.10.023
  58. Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles. — Desai N, Ploskonka S, Goodman LR et al. Reproductive biology and endocrinology : RB&E, 2014, cohort, 192 citations · DOI: 10.1186/1477-7827-12-54
  59. Is preimplantation genetic diagnosis the ideal embryo selection method in aneuploidy screening? — Levent Şahi̇n, Murat Bozkurt, Hilal Sahin et al. The Kaohsiung Journal of Medical Sciences, 2014, unknown, 11 citations · DOI: 10.1016/j.kjms.2014.05.008
  60. Synchronous and Asynchronous Blastomere Cleavage at Cryopreservation: Effect on Subsequent Embryo Survival, Pregnancy and Live Birth Rates — Zofnat Wiener‐Megnazi, Maria Fridman, Mara Koifman et al. Journal of Biomedical Science and Engineering, 2014, cohort, 3 citations · DOI: 10.4236/jbise.2014.75027
  61. Randomized Controlled Trial Comparing Embryonic Quality in rFSH Versus hMG in IVF Protocol With GnRH Antagonist Hospital de Clinicas de Porto Alegre, 2014, rct
  62. Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation — Sara Stigliani, Paola Anserini, P. L. Venturini et al. Human Reproduction, 2013, cohort, 169 citations · DOI: 10.1093/humrep/det314
  63. Pronuclear morphology evaluation for fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles: a systematic review. — Nicoli A, Palomba S, Capodanno F et al. Journal of ovarian research, 2013, systematic review, 32 citations · DOI: 10.1186/1757-2215-6-64
  64. Time-lapse monitoring as a tool for clinical embryo assessment — Kirstine Kirkegaard, Inge Agerholm, Hans Jakob Ingerslev Human Reproduction, 2012, expert opinion, 240 citations · DOI: 10.1093/humrep/des079
  65. Time-Lapse Cleavage Rating Predicts Human Embryo Viability — Daniel Hlinka, Beata Kalatova, Ivana Uhrinová et al. Physiological Research, 2012, cohort, 111 citations · DOI: 10.33549/physiolres.932287
  66. The cleavage stage embryo — Fernando J. Prados, Sophie Debrock, Josephine Gabriela Lemmen et al. Human Reproduction, 2012, unknown, 90 citations · DOI: 10.1093/humrep/des224
  67. Eeva 12-well Dish Study Progyny, Inc., 2012, cohort
  68. Faculty Opinions recommendation of Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. — Magdalena Zernicka‐Goetz, Anna Ajduk Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2012 · DOI: 10.3410/f.715897916.791352825
  69. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting — Alpha Scientists in Reproductive Medicine, ESHRE Special Interest Group of Embryology Human Reproduction, 2011, guideline, 2018 citations · DOI: 10.1093/humrep/der037
  70. The use of morphokinetics as a predictor of embryo implantation. — Meseguer M, Herrero J, Tejera A et al. Human reproduction (Oxford, England), 2011, cohort, 918 citations · DOI: 10.1093/humrep/der256
  71. Eeva™ System Study: Noninvasive Recording and Visualization of Individual Embryos Cultured to Blastocyst Stage Progyny, Inc., 2011, cohort
  72. Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence — Jie Qiao, Huai L. Feng Human Reproduction Update, 2010, systematic review, 479 citations · DOI: 10.1093/humupd/dmq032
  73. Telomere lengths in human oocytes, cleavage stage embryos and blastocysts — S. Turner, H.-P. Wong, J. Rai et al. Molecular Human Reproduction, 2010, unknown, 83 citations · DOI: 10.1093/molehr/gaq048
  74. Intra- and inter-observer analysis in the morphological assessment of early-stage embryos — Goedele Paternot, Johanna Devroe, Sophie Debrock et al. Reproductive Biology and Endocrinology, 2009, unknown, 82 citations · DOI: 10.1186/1477-7827-7-105
  75. Influence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF. — Ziebe S, Lundin K, Janssens R et al. Human reproduction (Oxford, England), 2007, rct, 100 citations · DOI: 10.1093/humrep/dem221
  76. Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study — E.G. Papanikolaou Human Reproduction, 2005, rct, 224 citations · DOI: 10.1093/humrep/dei217
  77. Maintenance of the Inner Cell Mass in Human Blastocysts from Fragmented Embryos — Kate Hardy, Jaroslav Stark, Robert M L Winston Biology of Reproduction, 2003, cohort, 151 citations · DOI: 10.1095/biolreprod.102.010090
  78. Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro — Jeanette Fenwick Human Reproduction, 2002, cohort, 212 citations · DOI: 10.1093/humrep/17.2.407
  79. The Graduated Embryo Score (GES) predicts blastocyst formation and pregnancy rate from cleavage-stage embryos* — Jeffrey D Fisch, H.F. Rodriguez, Richard John M Ross et al. Human Reproduction, 2001, cohort, 159 citations · DOI: 10.1093/humrep/16.9.1970
  80. Clinical use of a pronuclear stage score following intracytoplasmic sperm injection: impact on pregnancy rates under the conditions of the German embryo protection law. — Ludwig M, Schöpper B, Al-Hasani S et al. Human reproduction (Oxford, England), 2000, cohort, 107 citations · DOI: 10.1093/humrep/15.2.325
  81. Apoptosis in the human embryo — Kate Hardy Reviews of Reproduction, 1999, unknown, 294 citations · DOI: 10.1530/revreprod/4.3.125
  82. Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability — Denny Sakkas, Youssef Shoukir, Didier Chardonnens et al. Human Reproduction, 1998, cohort, 253 citations · DOI: 10.1093/humrep/13.1.182
  83. Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization — Søren Ziebe, K. Petersen, Svend Lindenberg et al. Human Reproduction, 1997, cohort, 475 citations · DOI: 10.1093/humrep/12.7.1545
  84. Improved cleavage rate of human embryos cultured in antibiotic-free medium. — Magli MC, Gianaroli L, Fiorentino A et al. Human reproduction (Oxford, England), 1996, rct, 22 citations · DOI: 10.1093/oxfordjournals.humrep.a019430