Association between blastocyst morphology and pregnancy and perinatal outcomes following fresh and cryopreserved embryo transfer

  • Jennifer B. BakkensenEmail author
  • Paula Brady
  • Daniela Carusi
  • Phillip Romanski
  • Ann M. Thomas
  • Catherine Racowsky
Assisted Reproduction Technologies



To assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes.


This single-center retrospective cohort study included blastocyst single embryo transfers (SET) performed between 1/2012–2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality. Among cycles resulting in live birth, associations with preterm birth, small for gestational age (SGA) and large for gestational age (LGA), were evaluated using logistic regression.


A total of 1023 fresh and 1222 CET cycles were included, of which 465 (45.1%) fresh and 600 (48.5%) CET cycles resulted in singleton live birth. Clinical pregnancy rates increased with increasing expansion among fresh transfers (p for trend = 0.001) but not CET (p = 0.221), and with TE quality for both fresh and CET cycles (p = 0.005 and < 0.0001, respectively). Live birth rates increased with increasing expansion (fresh p = 0.005, CET p = 0.018) and TE quality (fresh p = 0.028, CET p = 0.023). ICM grade was not associated with pregnancy outcomes; however, higher ICM quality among CET cycles was associated with increased chance of preterm birth (p = 0.005).


In blastocyst SET, blastocyst expansion and TE quality were each associated with clinical pregnancy and live birth. While higher ICM quality was associated with increased chance of preterm birth among CET, no other associations with perinatal outcomes were identified. Clinicians can be reassured that pregnancies from blastocysts with lower expansion, ICM, or TE qualities are not more likely to result in adverse perinatal outcomes.


Blastocyst morphology Perinatal outcomes Birthweight Preterm birth In vitro fertilization 


Compliance with ethical standards

This study was approved by the Partners Human Research Committee at the Brigham and Women’s Hospital (Protocol #2018P000317). All data was retrieved from standard records collected during clinical care, thus informed consent was not required.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10815_2019_1580_MOESM1_ESM.docx (28 kb)
ESM 1 (DOCX 27 kb)


  1. 1.
    Penzias A, Bendikson K, Butts S, Coutifaris C, Fossum G, Falcone T, et al. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril. 2017;107:901–3.CrossRefGoogle Scholar
  2. 2.
    Gardner DK, Schoolcraft WB. In Vitro culture of human blastocyst. In: Jansen R, Mortimer D, editors. Towar Reprod Certain Infertil Genet Beyond. 1999. p. 377–388.Google Scholar
  3. 3.
    Balaban B, Urman B, Sertac A, Alatas C, Aksoy S, Mercan R. Blastocyst quality affects the success of blastocyst-stage embryo transfer. Fertil Steril. 2000;74:282–7.CrossRefGoogle Scholar
  4. 4.
    Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155–8.CrossRefGoogle Scholar
  5. 5.
    Racowsky C, Combelles CM, Nureddin A, Pan Y, Finn A, Miles L, et al. Day 3 and day 5 morphological predictors of embryo viability. Reprod BioMed Online. 2003;6:323–31.CrossRefGoogle Scholar
  6. 6.
    Honnma H, Baba T, Sasaki M, Hashiba Y, Ohno H, Fukunaga T, et al. Trophectoderm morphology significantly affects the rates of ongoing pregnancy and miscarriage in frozen-thawed single-blastocyst transfer cycle in vitro fertilization. Fertil Steril. 2012;98:361–7.CrossRefGoogle Scholar
  7. 7.
    Chen X, Zhang J, Wu X, Cao S, Zhou L, Wang Y, et al. Trophectoderm morphology predicts outcomes of pregnancy in vitrified-warmed single-blastocyst transfer cycle in a Chinese population. J Assist Reprod Genet. 2014;31:1475–81.CrossRefGoogle Scholar
  8. 8.
    Thompson SM, Onwubalili N, Brown K, Jindal SK, McGovern PG. Blastocyst expansion score and trophectoderm morphology strongly predict successful clinical pregnancy and live birth following elective single embryo blastocyst transfer (eSET): a national study. J Assist Reprod Genet. 2013;30:1577–81.CrossRefGoogle Scholar
  9. 9.
    Ahlstrom A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod. 2011;26:3289–96.CrossRefGoogle Scholar
  10. 10.
    Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, Decherney AH, et al. Trophectoderm grade predicts outcomes of single-blastocyst transfers. Fertil Steril. 2013;99:1283–9.CrossRefGoogle Scholar
  11. 11.
    Van Den Abbeel E, Balaban B, Ziebe S, Lundin K, Cuesta MJG, Klein BM, et al. Association between blastocyst morphology and outcome of single-blastocyst transfer. Reprod BioMed Online. 2013;27:353–61.CrossRefGoogle Scholar
  12. 12.
    Subira J, Craig J, Turner K, Bevan A, Ohuma E, McVeigh E, Child T, Fatum M Grade of the inner cell mass, but not trophectoderm, predicts live birth in fresh blastocyst single transfers. Hum Fertil [Internet] Taylor & Francis; 2016;19:254–261. Available from:
  13. 13.
    Oron G, Son WY, Buckett W, Tulandi T, Holzer H. The association between embryo quality and perinatal outcome of singletons born after single embryo transfers: a pilot study. Hum Reprod. 2014;29:1444–51.CrossRefGoogle Scholar
  14. 14.
    Bouillon C, Celton N, Kassem S, Frapsauce C, Guérif F. Obstetric and perinatal outcomes of singletons after single blastocyst transfer: is there any difference according to blastocyst morphology? Reprod BioMed Online. 2019;35:197–207.CrossRefGoogle Scholar
  15. 15.
    Licciardi F, Mccaffrey C, Ph D, Oh C, Ph D, Schmidt-sarosi C. Birth weight is associated with inner cell mass grade of blastocysts. Fertil Steril. 2015;103:382–7.CrossRefGoogle Scholar
  16. 16.
    Ebner T, Tritscher K, Mayer RB, Oppelt P, Duba HC, Maurer M, et al. Quantitative and qualitative trophectoderm grading allows for prediction of live birth and gender. J Assist Reprod Genet. 2016;33:49–57.CrossRefGoogle Scholar
  17. 17.
    Miyazaki Y, Matsumoto H, Ida M, Fukuda A, Morimoto Y. Relation between newborn data and blastocyst quality of either ICM or TE grade in frozen-thawed single blastocyst transfer cycles [abstract]. Fertil Steril. 2017;108:e351.CrossRefGoogle Scholar
  18. 18.
    Cheung L, Lam P, Lok IH, Chiu TT, Yeung S, Tjer C, et al. GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF : a randomized controlled trial. 2005;20:616–621.Google Scholar
  19. 19.
    Dragisic K, Davis O, Fasouliotis S, Rosenwaks Z. Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders. Fertil Steril. 2005;84:1023–6.CrossRefGoogle Scholar
  20. 20.
    Tummon I, Daniel S, Kaplan B, Nisker J, Yuzpe A. Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization. Fertil Steril. 1992;58:563–8.CrossRefGoogle Scholar
  21. 21.
    Surrey ES, Bower J, Hill D, Ramsey J, Surrey MW. Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril. 1998;69:419–24.CrossRefGoogle Scholar
  22. 22.
    Oken E, Kleinman KP, Rich-edwards J, Gillman MW. A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr. 2003;3:6.CrossRefGoogle Scholar
  23. 23.
    Mickey R, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989;129:125–37.CrossRefGoogle Scholar
  24. 24.
    SAS Institute Inc. (Cary, NC) SAS Software Version 9.4. 2013.Google Scholar
  25. 25.
    Wennerholm U, Soderstrom-Anttila V, Bergh C, Aittomaki K, Hazekamp J, Nygren K, et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. 2009;24:2158–2172.Google Scholar
  26. 26.
    Pinborg A, Sci DM, Loft A, Henningsen AA. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995–2006. Fertil Steril Elsevier Ltd. 2010;94:1320–7.CrossRefGoogle Scholar
  27. 27.
    Pelkonen S, Koivunen R, Gissler M, Martikainen H, Tiitinen A, Suikkari A, et al. Perinatal outcome of children born after frozen and fresh embryo transfer : the Finnish cohort study 1995–2006. 2010;25:914–923.Google Scholar
  28. 28.
    Maheshwari A, Kalampokas T, Davidson J, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavage-stage embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril Elsevier. 2013;100:368–77.Google Scholar
  29. 29.
    Pinborg A. To transfer fresh or thawed embryos ? Semin Reprod Med. 2012;30:230–5.CrossRefGoogle Scholar
  30. 30.
    Zhao YY, Yu Y, Zhang XW. Overall blastocyst quality, trophectoderm grade, and inner cell mass grade predict pregnancy outcome in euploid blastocyst transfer cycles. Chin Med J. 2018;131:1261–7.CrossRefGoogle Scholar
  31. 31.
    Minasi MG, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F, et al. Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016;31:2245–54.CrossRefGoogle Scholar
  32. 32.
    Abbeel E Van Den, Balaban B, Ziebe S, Lundin K, Mirner B, Helmgaard L, et al. Association between blastocyst morphology and outcome of single-blastocyst transfer. 2013;353–361.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology, and Reproductive BiologyBrigham & Women’s Hospital and Harvard Medical SchoolBostonUSA

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