Archives of Gynecology and Obstetrics

, Volume 300, Issue 3, pp 751–761 | Cite as

Clinical outcomes after transfer of blastocysts derived from frozen–thawed cleavage embryos: a retrospective propensity-matched cohort study

  • Feng Xiong
  • Guangui Li
  • Qing Sun
  • Sisi Wang
  • Caiyun Wan
  • Peilin Chen
  • Zhihong Yao
  • Huixian Zhong
  • Yong ZengEmail author
Gynecologic Endocrinology and Reproductive Medicine



To evaluate the clinical outcomes after fresh transfer of blastocysts cultured from vitrified–thawed cleavage embryos (VTCE) compared with conventional frozen–thawed blastocysts transfer (FBT), or with the usual fresh blastocysts transfer (FRBT).


A total of 155 cycles undergoing fresh transfer of VTCE blastocysts, 4904 cycles undergoing FBT, and 1014 cycles undergoing FRBT were retrospectively analyzed from August 2014 to July 2017. Pregnancy, delivery, and neonatal outcomes were compared after propensity score matching.


VTCE blastocysts’ transfer resulted in a lower risk of early miscarriage (8.82% versus 19.70%, P < 0.05) and a decreased fetal birth weight (2611.90 ± 618.65 g versus 2931.86 ± 546.52 g, P < 0.01) compared to FBT. No significant difference was found regarding live birth rate, gestational age, and cesarean section. Correspondingly, VTCE blastocysts’ transfer led to significantly compromised pregnancy outcomes regarding clinical pregnancy rate and implantation, and even a slightly compromised live birth rate when compared with FRBT. Moreover, a higher occurrence of cesarean Section (88.89% versus 71.29%, P < 0.05) and a shorter gestational age (262.04 ± 14.99 days versus 268.06 ± 14.07, P < 0.05) were also found. Nevertheless, the risk of small for gestational age and large for gestational age, and the neonatal birth weight were comparable.


VTCE blastocysts’ transfer results in a comprehensively moderate outcome, which is an acceptable option for patients. Our results can provide efficient value for patients’ counseling. Furthermore, these findings indicate directions for exploring the mechanisms of low birth weight and short gestational age.


Vitrified–thawed Extended culture Blastocyst transfer Obstetric outcome Neonatal outcome 


Author contributions

FX: project development, data collection, manuscript writing. GGL and QS: data analysis, statistical support. SSW: methodology. CYW, PLC, ZHY and HXZ: manuscript editing. YZ: supervision and funding acquisition.


Funding has been received form Basic Research Program of Shenzhen with Grant no. (JCYJ20160427113153295), Sanming Project of Medicine in Shenzhen with Grant no. (SZSM201502035), National Natural Science Foundation of China with Grant no. (21807072) and clinical research special fund of Chinese Medical Association with Grant no. (18010120741).

Compliance with ethical standards

Conflict of interest

We declared that we have no conflict of interest.

Supplementary material

404_2019_5236_MOESM1_ESM.docx (14 kb)
Supplementary file1 (DOCX 14 kb)
404_2019_5236_MOESM2_ESM.tif (5.6 mb)
Supplementary file2 (TIFF 5766 kb)
404_2019_5236_MOESM3_ESM.docx (24 kb)
Supplementary file3 (DOCX 24 kb)
404_2019_5236_MOESM4_ESM.docx (23 kb)
Supplementary file4 (DOCX 24 kb)


  1. 1.
    Choudhary M, Soni R, Swarankar M, Garg S (2017) Comparison of vitrification and slow freezing for cryopreservation of cleavage stage embryos (day 3) and its impact on clinical outcome. Int J Res Med Sci 10(3):2751–2756Google Scholar
  2. 2.
    Dyer S, Chambers GM, de Mouzon J, Nygren KG, Zegers-Hochschild F, Mansour R, Ishihara O, Banker M, Adamson GD (2016) International committee for monitoring assisted reproductive technologies world report: assisted reproductive technology 2008, 2009 and 2010. Hum Reprod 31(7):1588–1609. CrossRefGoogle Scholar
  3. 3.
    Pereira N, Rosenwaks Z (2016) A fresh(er) perspective on frozen embryo transfers. Fertil Steril 106(2):257–258. CrossRefGoogle Scholar
  4. 4.
    Meldrum DR (1999) Blastocyst transfer—a natural evolution. Fertil Steril 72(2):216–217CrossRefGoogle Scholar
  5. 5.
    Sundhararaj UM, Madne MV, Biliangady R, Gurunath S, Swamy AG, Gopal IST (2017) Single blastocyst transfer: the key to reduce multiple pregnancy rates without compromising the live birth rate. J Hum Reprod Sci 10(3):201–207. CrossRefGoogle Scholar
  6. 6.
    Practice Committees of the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology (2013) Blastocyst culture and transfer in clinical-assisted reproduction: a committee opinion. Fertil Steril 99(3):667–672. CrossRefGoogle Scholar
  7. 7.
    Glujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D (2016) Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 6:CD002118. doi:10.1002/14651858.CD002118.pub5.Google Scholar
  8. 8.
    Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB (2000) Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril 73(6):1155–1158CrossRefGoogle Scholar
  9. 9.
    Wan CY, Song C, Diao LH, Li GG, Bao ZJ, Hu XD, Zhang HZ, Zeng Y (2014) Laser-assisted hatching improves clinical outcomes of vitrified-warmed blastocysts developed from low-grade cleavage-stage embryos: a prospective randomized study. Reprod Biomed Online 28(5):582–589. CrossRefGoogle Scholar
  10. 10.
    Cobo A, Serra V, Garrido N, Olmo I, Pellicer A, Remohi J (2014) Obstetric and perinatal outcome of babies born from vitrified oocytes. Fertil Steril 102(4):1006–1015 e1004. CrossRefGoogle Scholar
  11. 11.
    Bartmann C, Segerer SE, Rieger L, Kapp M, Sutterlin M, Kammerer U (2014) Quantification of the predominant immune cell populations in decidua throughout human pregnancy. Am J Reprod Immunol 71(2):109–119. CrossRefGoogle Scholar
  12. 12.
    Thoemmes F (2012) Propensity score matching in SPSS. arXiv:1201.6385
  13. 13.
    Thoemmes F, Liao W (2013) Propensity score matching (with multi level data) using SPSS and R. In: Modern modeling methods conference, Storrs, Connecticut, USAGoogle Scholar
  14. 14.
    Fasano G, Fontenelle N, Vannin AS, Biramane J, Devreker F, Englert Y, Delbaere A (2014) A randomized controlled trial comparing two vitrification methods versus slow-freezing for cryopreservation of human cleavage stage embryos. J Assist Reprod Genet 31(2):241–247. CrossRefGoogle Scholar
  15. 15.
    Gordts S, Roziers P, Campo R, Noto V (1990) Survival and pregnancy outcome after ultrarapid freezing of human embryos. Fertil Steril 53(3):469–472CrossRefGoogle Scholar
  16. 16.
    Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC (2008) Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril 90(1):186–193. CrossRefGoogle Scholar
  17. 17.
    Maheshwari A, Raja EA, Bhattacharya S (2016) Obstetric and perinatal outcomes after either fresh or thawed frozen embryo transfer: an analysis of 112,432 singleton pregnancies recorded in the Human Fertilisation and Embryology Authority anonymized dataset. Fertil Steril 106(7):1703–1708. CrossRefGoogle Scholar
  18. 18.
    Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, Zhu Y, Deng X, Qi X, Li H, Ma X, Ren H, Wang Y, Zhang D, Wang B, Liu F, Wu Q, Wang Z, Bai H, Li Y, Zhou Y, Sun M, Liu H, Li J, Zhang L, Chen X, Zhang S, Sun X, Legro RS, Chen ZJ (2018) Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med 378(2):126–136. CrossRefGoogle Scholar
  19. 19.
    Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S (2017) Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev 3:CD011184. Google Scholar
  20. 20.
    Fauque P, Jouannet P, Davy C, Guibert J, Viallon V, Epelboin S, Kunstmann JM, Patrat C (2010) Cumulative results including obstetrical and neonatal outcome of fresh and frozen-thawed cycles in elective single versus double fresh embryo transfers. Fertil Steril 94(3):927–935. CrossRefGoogle Scholar
  21. 21.
    Le Lannou D, Griveau JF, Laurent MC, Gueho A, Veron E, Morcel K (2006) Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI. Reprod Biomed Online 13(3):368–375CrossRefGoogle Scholar
  22. 22.
    Lundin K, Bergh C (2007) Cumulative impact of adding frozen-thawed cycles to single versus double fresh embryo transfers. Reprod Biomed Online 15(1):76–82CrossRefGoogle Scholar
  23. 23.
    Pantos K, Stefanidis K, Pappas K, Kokkinopoulos P, Petroutsou K, Kokkali G, Stavrou D, Tzigounis V (2001) Cryopreservation of embryos, blastocysts, and pregnancy rates of blastocysts derived from frozen-thawed embryos and frozen-thawed blastocysts. J Assist Reprod Genet 18(11):579–582CrossRefGoogle Scholar
  24. 24.
    Wang H-b, Li Y-h (2009) Extended culture of early stage embryos in frozen-thawed cycles. Journal of Reproduction and Contraception 20(1):11–18CrossRefGoogle Scholar
  25. 25.
    Butterworth S (2001) Blastocyst culture: myth or magic? Hum Fertil (Camb) 4(2):109–116CrossRefGoogle Scholar
  26. 26.
    Wang YA, Costello M, Chapman M, Black D, Sullivan EA (2011) Transfers of fresh blastocysts and blastocysts cultured from thawed cleavage embryos are associated with fewer miscarriages. Reprod Biomed Online 23(6):777–788. CrossRefGoogle Scholar
  27. 27.
    Haas J, Meriano J, Laskin C, Bentov Y, Barzilay E, Casper RF, Cadesky K (2016) Clinical pregnancy rate following frozen embryo transfer is higher with blastocysts vitrified on day 5 than on day 6. J Assist Reprod Genet 33(12):1553–1557. CrossRefGoogle Scholar
  28. 28.
    Wirleitner B, Schuff M, Stecher A, Murtinger M, Vanderzwalmen P (2016) Pregnancy and birth outcomes following fresh or vitrified embryo transfer according to blastocyst morphology and expansion stage, and culturing strategy for delayed development. Hum Reprod 31(8):1685–1695. CrossRefGoogle Scholar
  29. 29.
    Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, Nagy ZP, Ubaldi FM (2014) Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod 29(6):1173–1181. CrossRefGoogle Scholar
  30. 30.
    Klimczak AM, Pacheco LE, Lewis KE, Massahi N, Richards JP, Kearns WG, Saad AF, Crochet JR (2018) Embryonal mitochondrial DNA: relationship to embryo quality and transfer outcomes. J Assist Reprod Genet 35(5):871–877. CrossRefGoogle Scholar
  31. 31.
    Vidal M, Vellve K, Gonzalez-Comadran M, Robles A, Prat M, Torne M, Carreras R, Checa MA (2017) Perinatal outcomes in children born after fresh or frozen embryo transfer: a Catalan cohort study based on 14,262 newborns. Fertil Steril 107(4):940–947. CrossRefGoogle Scholar
  32. 32.
    Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S (2012) Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 98(2):368–377. CrossRefGoogle Scholar
  33. 33.
    Aflatoonian A, Karimzadeh Maybodi MA, Aflatoonian N, Tabibnejad N, Amir-Arjmand MH, Soleimani M, Aflatoonian B, Aflatoonian A (2016) Perinatal outcome in fresh versus frozen embryo transfer in ART cycles. Int J Reprod Biomed (Yazd) 14(3):167–172CrossRefGoogle Scholar
  34. 34.
    Shapiro BS, Daneshmand ST, Bedient CE, Garner FC (2016) Comparison of birth weights in patients randomly assigned to fresh or frozen-thawed embryo transfer. Fertil Steril 106(2):317–321. CrossRefGoogle Scholar
  35. 35.
    Zhang J, Du M, Li Z, Wang L, Hu J, Zhao B, Feng Y, Chen X, Sun L (2018) Fresh versus frozen embryo transfer for full-term singleton birth: a retrospective cohort study. J Ovarian Res 11(1):59. CrossRefGoogle Scholar
  36. 36.
    Shih W, Rushford DD, Bourne H, Garrett C, McBain JC, Healy DL, Baker HW (2008) Factors affecting low birthweight after assisted reproduction technology: difference between transfer of fresh and cryopreserved embryos suggests an adverse effect of oocyte collection. Hum Reprod 23(7):1644–1653. CrossRefGoogle Scholar
  37. 37.
    Galliano D, Garrido N, Serra-Serra V, Pellicer A (2015) Difference in birth weight of consecutive sibling singletons is not found in oocyte donation when comparing fresh versus frozen embryo replacements. Fertil Steril 104(6):1411–1418. CrossRefGoogle Scholar
  38. 38.
    Kalra SK, Ratcliffe SJ, Coutifaris C, Molinaro T, Barnhart KT (2011) Ovarian stimulation and low birth weight in newborns conceived through in vitro fertilization. Obstet Gynecol 118(4):863–871. CrossRefGoogle Scholar
  39. 39.
    De Geyter C, De Geyter M, Steimann S, Zhang H, Holzgreve W (2006) Comparative birth weights of singletons born after assisted reproduction and natural conception in previously infertile women. Hum Reprod 21(3):705–712. CrossRefGoogle Scholar
  40. 40.
    Eftekhar M, Aflatoonian A, Mohammadian F, Tabibnejad N (2012) Transfer of blastocysts derived from frozen-thawed cleavage stage embryos improved ongoing pregnancy. Arch Gynecol Obstet 286(2):511–516. CrossRefGoogle Scholar
  41. 41.
    Stoop D, Van Landuyt L, Van den Abbeel E, Camus M, Verheyen G, Devroey P (2011) Should a single blastocyst transfer policy be a clinical decision or should it depend on the embryological evaluation on day 3? Reprod Biol Endocrinol 9:60. CrossRefGoogle Scholar
  42. 42.
    Papanikolaou EG, D'Haeseleer E, Verheyen G, Van de Velde H, Camus M, Van Steirteghem A, Devroey P, Tournaye H (2005) 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. Hum Reprod 20(11):3198–3203. CrossRefGoogle Scholar
  43. 43.
    Papanikolaou EG, Kolibianakis EM, Tournaye H, Venetis CA, Fatemi H, Tarlatzis B, Devroey P (2008) Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis. Hum Reprod 23(1):91–99. CrossRefGoogle Scholar
  44. 44.
    Martins WP, Nastri CO, Rienzi L, van der Poel SZ, Gracia C, Racowsky C (2017) Blastocyst vs cleavage-stage embryo transfer: systematic review and meta-analysis of reproductive outcomes. Ultrasound Obstetr Gynecol 49(5):583–591. CrossRefGoogle Scholar
  45. 45.
    De Vos A, Van Landuyt L, Santos-Ribeiro S, Camus M, Van de Velde H, Tournaye H, Verheyen G (2016) Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle. Hum Reprod 31(11):2442–2449. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility CenterShenzhen Zhongshan Urology HospitalShenzhenPeople’s Republic of China

Personalised recommendations