The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.

BACKGROUND Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. METHODS Background presentations about current practice were given. RESULTS The expert panel developed a set of consensus points to define the minimum criteria for oocyte and embryo morphology assessment. CONCLUSIONS It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development.

[1]  Andres Salumets,et al.  Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures. , 2003, Human reproduction.

[2]  Luca Gianaroli,et al.  Chromosomal status of human embryos , 2007 .

[3]  J. Tesarik,et al.  The probability of abnormal preimplantation development can be predicted by a single static observation on pronuclear stage morphology. , 1999, Human reproduction.

[4]  A. Nuhoğlu,et al.  The effect of pronuclear morphology on embryo quality parameters and blastocyst transfer outcome. , 2001, Human reproduction.

[5]  D. De Neubourg,et al.  Calculating the implantation potential of day 3 embryos in women younger than 38 years of age: a new model. , 2001, Human reproduction.

[6]  Thorir Hardarson,et al.  There Is a Cutoff Limit in Diameter Between a Blastomere and a Small Anucleate Fragment , 2003, Journal of Assisted Reproduction and Genetics.

[7]  Elpida Fragouli,et al.  Comprehensive chromosome screening of polar bodies and blastocysts from couples experiencing repeated implantation failure. , 2010, Fertility and sterility.

[8]  M. Antczak,et al.  Temporal and spatial aspects of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory proteins from polarized domains. , 1999, Human reproduction.

[9]  B Rosenbusch,et al.  Cytogenetic analysis of giant oocytes and zygotes to assess their relevance for the development of digynic triploidy. , 2002, Human reproduction.

[10]  R. Henshaw,et al.  Day 4 embryo selection is equal to Day 5 using a new embryo scoring system validated in single embryo transfers. , 2008, Human reproduction.

[11]  Donald Maier,et al.  Predictive value of embryo grading for embryos with known outcomes. , 2004, Fertility and sterility.

[12]  Seang Lin Tan,et al.  Diploid-aneuploid mosaicism in human embryos cultured to the blastocyst stage. , 2005, Fertility and sterility.

[13]  J. Lemmen,et al.  Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI-fertilized oocytes. , 2008, Reproductive biomedicine online.

[14]  J Cohen,et al.  Chromosome abnormalities in human embryos. , 1998, Human reproduction update.

[15]  V. Bolton,et al.  The relationship between chromosomal abnormality in the human preimplantation embryo and development in vitro. , 1996, Reproduction, fertility, and development.

[16]  D. Gardner,et al.  Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. , 2000, Fertility and sterility.

[17]  Elpida Fragouli,et al.  Clinical application of comprehensive chromosomal screening at the blastocyst stage. , 2010, Fertility and sterility.

[18]  J Tesarík,et al.  Early morphological signs of embryonic genome expression in human preimplantation development as revealed by quantitative electron microscopy. , 1988, Developmental biology.

[19]  D. Payne,et al.  Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. , 1997, Human reproduction.

[20]  K Petersen,et al.  Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. , 1997, Human reproduction.

[21]  W R Edirisinghe,et al.  Association of pronuclear Z score with rates of aneuploidy in in vitro-fertilised embryos. , 2005, Reproduction, fertility, and development.

[22]  K Lundin,et al.  Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation. , 2001, Human reproduction.

[23]  J. van Blerkom,et al.  Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation. , 1992, Human reproduction.

[24]  P Barlow,et al.  Embryo scoring as a prognostic tool in IVF treatment. , 1987, Human reproduction.

[25]  J. Tesarik,et al.  Embryos with high implantation potential after intracytoplasmic sperm injection can be recognized by a simple, non-invasive examination of pronuclear morphology. , 2000, Human reproduction.

[26]  B Giraudeau,et al.  Limited value of morphological assessment at days 1 and 2 to predict blastocyst development potential: a prospective study based on 4042 embryos. , 2007, Human reproduction.

[27]  W. H. Freeman,et al.  An atlas of embryology , 1978 .

[28]  P. Sutter,et al.  Embryos cultured in vitro with multinucleated blastomeres have poor implantation potential in human in-vitro fertilization and intracytoplasmic sperm injection. , 1998, Human reproduction.

[29]  A. Revelli,et al.  Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval. , 2007, Human reproduction.

[30]  L. Veeck,et al.  An Atlas of Human Gametes and Conceptuses : An Illustrated Reference for Assisted Reproductive Technology , 1999 .

[31]  Basak Balaban,et al.  Choosing Between Day 3 and Day 5 Embryo Transfers , 2006, Clinical obstetrics and gynecology.

[32]  Clifford L. Librach,et al.  Morphological and cytogenetic analysis of human giant oocytes and giant embryos , 2002 .

[33]  Bagyalakshmi Mathiyalagan,et al.  Prediction of embryo developmental potential and pregnancy based on early stage morphological characteristics. , 2006, Fertility and sterility.

[34]  Seang Lin Tan,et al.  Chromosomal mosaicism throughout human preimplantation development in vitro: incidence, type, and relevance to embryo outcome. , 2002, Human reproduction.

[35]  D. De Neubourg,et al.  Characterization of a top quality embryo, a step towards single-embryo transfer. , 1999, Human reproduction.

[36]  Peter Braude,et al.  Diagnosing and preventing inherited disease: An analysis of multinucleated blastomere formation in human embryos , 1995 .

[37]  Kay Elder,et al.  Human preimplantation embryo selection , 2007 .

[38]  J. Otsuki,et al.  The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes. , 2004, Human reproduction.

[39]  H Balakier,et al.  The frequency and developmental capability of human embryos containing multinucleated blastomeres. , 1997, Human reproduction.

[40]  Santiago Munné,et al.  Chromosomal abnormalities in embryos derived from testicular sperm extraction. , 2003, Fertility and sterility.

[41]  R. Alvero,et al.  The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. , 2000, Human reproduction.

[42]  Luca Gianaroli,et al.  Embryo morphology and development are dependent on the chromosomal complement. , 2007, Fertility and sterility.

[43]  H. Baker,et al.  Relationships between timing of syngamy, female age and implantation potential in human in vitro-fertilised oocytes. , 2007, Reproduction, fertility, and development.

[44]  Nikica Zaninovic,et al.  An atlas of human blastocysts , 2003 .

[45]  J Cohen,et al.  Unsuitability of multinucleated human blastomeres for preimplantation genetic diagnosis. , 1993, Human reproduction.

[46]  R. Edwards,et al.  ESTABLISHING FULL‐TERM HUMAN PREGNANCIES USING CLEAVING EMBRYOS GROWN IN VITRO * , 1980, British journal of obstetrics and gynaecology.

[47]  Judy E. Stern,et al.  Utility of the national embryo morphology data collected by SART: correlation between morphologic grade and live birth rate , 2009 .

[48]  Thomas Ebner,et al.  Is oocyte morphology prognostic of embryo developmental potential after ICSI? , 2006, Reproductive biomedicine online.

[49]  Santiago Munné,et al.  Chromosome abnormalities and their relationship to morphology and development of human embryos. , 2006, Reproductive biomedicine online.

[50]  Veljko Vlaisavljevic,et al.  Developmental capacity of different morphological types of day 5 human morulae and blastocysts. , 2004, Reproductive biomedicine online.

[51]  J Cohen,et al.  Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage. , 2001, Human reproduction.

[52]  L A Scott,et al.  The successful use of pronuclear embryo transfers the day following oocyte retrieval. , 1998, Human reproduction.

[53]  J Cohen,et al.  Monospermic polyploidy and atypical embryo morphology. , 1994, Human reproduction.

[54]  Dk Gardner,et al.  In-vitro culture of human blastocysts , 1999 .

[55]  S J Pickering,et al.  An analysis of multinucleated blastomere formation in human embryos. , 1995, Human reproduction.

[56]  J Cohen,et al.  Impaired development of zygotes with uneven pronuclear size , 1998, Zygote.

[57]  John D. Biggers,et al.  National collection of embryo morphology data in SARTCORS: associations among cell number, fragmentation and blastomere asymmetry on day 3 (d3) with live birth rate , 2009 .

[58]  Thomas Ebner,et al.  Prognosis of oocytes showing aggregation of smooth endoplasmic reticulum. , 2008, Reproductive biomedicine online.

[59]  Jan Gerris,et al.  Multinucleation in cleavage stage embryos. , 2003, Human reproduction.

[60]  C. Giorgetti,et al.  Implantation: Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers , 1995 .

[61]  L. Gianaroli,et al.  Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. , 2000, Human reproduction.

[62]  R Janssens,et al.  Timing of oocyte activation, pronucleus formation and cleavage in humans after intracytoplasmic sperm injection (ICSI) with testicular spermatozoa and after ICSI or in-vitro fertilization on sibling oocytes with ejaculated spermatozoa. , 1998, Human reproduction.

[63]  Lynette Scott,et al.  Pronuclear scoring as a predictor of embryo development. , 2003, Reproductive biomedicine online.

[64]  J Cohen,et al.  Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. , 2007, Reproductive biomedicine online.

[65]  B. Carr,et al.  Late stages of embryo progression are a much better predictor of clinical pregnancy than early cleavage in intracytoplasmic sperm injection and in vitro fertilization cycles with blastocyst-stage transfer. , 2007, Fertility and sterility.

[66]  K. Biberoğlu,et al.  Smooth endoplasmic reticulum aggregations in all retrieved oocytes causing recurrent multiple anomalies: case report. , 2009, Fertility and sterility.

[67]  J. Grifo,et al.  The use of first polar bodies for preimplantation diagnosis of aneuploidy. , 1995, Human reproduction.

[68]  M. Alikani,et al.  The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities. , 1996, Human reproduction.

[69]  L. Gianaroli,et al.  Chromosomal abnormalities in embryos , 2001, Molecular and Cellular Endocrinology.

[70]  C. Márquez,et al.  Chromosome abnormalities in 1255 cleavage-stage human embryos. , 2000, Reproductive biomedicine online.

[71]  Stephen A. Roberts,et al.  Elective Single Embryo Transfer: Guidelines for Practice British Fertility Society and Association of Clinical Embryologists , 2008, Human fertility.

[72]  Gilles Lefebvre,et al.  How viable are zygotes in which the PN are still intact at 25 hours? Impact on the choice of embryo for transfer. , 2008, Fertility and sterility.

[73]  D. Gardner,et al.  Extended embryo culture in human assisted reproduction treatments. , 2001, Human reproduction.

[74]  A. Salumets,et al.  The predictive value of pronuclear morphology of zygotes in the assessment of human embryo quality. , 2001, Human reproduction.

[75]  Peter Braude,et al.  Human gene expression first occurs between the four- and eight-cell stages of preimplantation development , 1988, Nature.

[76]  Jacques Cohen,et al.  Diagnosing and preventing inherited disease: The use of first polar bodies for preimplantation diagnosis of aneuploidy , 1995 .

[77]  D H Barlow,et al.  Human blastocyst grading: an indicator of developmental potential? , 1993, Human reproduction.

[78]  Charles Hanson,et al.  A morphological and chromosomal study of blastocysts developing from morphologically suboptimal human pre-embryos compared with control blastocysts. , 2003, Human reproduction.

[79]  A. Campana,et al.  Early cleavage of in-vitro fertilized human embryos to the 2-cell stage: a novel indicator of embryo quality and viability. , 1997, Human reproduction.

[80]  S J Pickering,et al.  Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte. , 1990, Fertility and sterility.

[81]  K Lundin,et al.  Early embryo cleavage is a strong indicator of embryo quality in human IVF. , 2001, Human reproduction.

[82]  Klaus Wiemer,et al.  The limited importance of pronuclear scoring of human zygotes. , 2006, Human reproduction.

[83]  A. Campana,et al.  Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability. , 1998, Human reproduction.

[84]  D. Gardner,et al.  Culture and transfer of human blastocysts. , 1999, Current opinion in obstetrics & gynecology.

[85]  Y Verlinsky,et al.  Mosaicism in the inner cell mass of human blastocysts. , 1998, Human reproduction.

[86]  B. Williams,et al.  The neglected morula/compact stage embryo transfer. , 2002, Human reproduction.

[87]  J Tesarík,et al.  Ultrastructural and autoradiographic observations on multinucleated blastomeres of human cleaving embryos obtained by in-vitro fertilization. , 1987, Human reproduction.

[88]  Kazuhiro Kikuchi,et al.  Oocyte aging: cellular and molecular changes, developmental potential and reversal possibility. , 2009, Human reproduction update.

[89]  D. Turnbull,et al.  In-vitro genetic modification of mitochondrial function. , 2000, Human reproduction.

[90]  J. Jarow,et al.  Chromosomal abnormalities in embryos derived from testicular sperm extraction. , 2003, The Journal of urology.

[91]  Laura Rienzi,et al.  Pronuclear morphology evaluation with subsequent evaluation of embryo morphology significantly increases implantation rates. , 2003, Fertility and sterility.

[92]  S. Hacıoğlu,et al.  Endometriosis in two sisters with Glanzmann's thrombasthenia. , 2009, Fertility and sterility.

[93]  K Lundin,et al.  FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of IVF pre-embryos from 144 randomly selected donated human oocytes and impact on pre-embryo morphology. , 2003, Human reproduction.

[94]  E. Ginsburg,et al.  Multinucleation in normally fertilized embryos is associated with an accelerated ovulation induction response and lower implantation and pregnancy rates in in vitro fertilization-embryo transfer cycles. , 1998, Fertility and sterility.

[95]  A Finn,et al.  Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates. , 2007, Human reproduction.

[96]  A. V. Van Steirteghem,et al.  The genetic constitution of multinuclear blastomeres and their derivative daughter blastomeres. , 1998, Human reproduction.

[97]  S J Pickering,et al.  The incidence of abnormal morphology and nucleocytoplasmic ratios in 2-, 3- and 5-day human pre-embryos. , 1991, Human reproduction.

[98]  Basak Balaban,et al.  Randomized comparison of two different blastocyst grading systems. , 2006, Fertility and sterility.

[99]  Chris Mason,et al.  International community consensus standard for reporting derivation of human embryonic stem cell lines. , 2007, Regenerative medicine.

[100]  P. Maddox-Hyttel,et al.  Nucleolar re‐activation is delayed in mouse embryos cloned from two different cell lines , 2009, Molecular reproduction and development.

[101]  Luca Gianaroli,et al.  Pronuclear morphology and chromosomal abnormalities as scoring criteria for embryo selection. , 2003, Fertility and sterility.