Skip to main content

A freeze-all strategy does not increase live birth rates in women of advanced reproductive age


Research question

Does a freeze-all strategy improve live birth rates in women of different age groups?


Retrospective cohort study of 1882 first embryo transfer cycles, performed between January 2013 and December 2015. Reproductive outcomes between fresh (FRESH) or frozen (FROZEN) embryo transfers were compared in patients stratified by age: < 35, between 35 and 38, or > 38 years. Student’s t test for independent samples and χ2 analyses were used as needed. A multivariable logistic regression analysis was performed adjusting for age, triggering drug, number of retrieved oocytes, number of transferred embryos, and percentage of top-quality embryos.

Main results and the role of chance

Live birth rates (LBR) were significantly higher for FROZEN in the < 35 years group (43.7% vs 24%; p < 0.001). In both the 35–38 and > 38 years groups, LBR for FROZEN vs FRESH were not statistically different (30.9% in the FROZEN group vs 29.3% in the FRESH group, p = 0.70, and 19.8% in the FROZEN group vs 12.7% in the FRESH group, p = 0.07, respectively). The multivariate analysis found a significantly positive effect of performing FROZEN on LBR in the younger group (OR 2.46, 95% CI 1.31–4.62; p = 0.005) but had no impact in women between 35 and 38 years (OR 1.01, 95% CI 0.55–1.83; p = 0.98) or older (OR 0.96, 95% CI 0.43–2.13; p = 0.92).


Performing a freeze-all strategy seems to result in better reproductive outcomes when compared with a fresh ET in women under 35 years, with no significant impact on older women.

This is a preview of subscription content, access via your institution.


  1. 1.

    Edwards RG, Steptoe PC, Purdy JM. Establishing full-term human pregnancies using cleaving embryos grown in vitro. Br J Obstet Gynaecol. 1980;87(9):737–56.

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Barnhart KT. Introduction: are we ready to eliminate the transfer of fresh embryos in in vitro fertilization? Fertil Steril. 2014;102(1):1–2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Ubaldi F, Bourgain C, Tournaye H, Smitz J, Van Steirteghem A, Devroey P. Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase. Fertil Steril. 1997;67(3):521–6.

    Article  PubMed  CAS  Google Scholar 

  4. 4.

    Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002;78(5):1025–9.

    Article  PubMed  Google Scholar 

  5. 5.

    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril. 2011;96(2):344–8.

    Article  PubMed  Google Scholar 

  6. 6.

    Check JH, Choe JK, Katsoff D, Summers-Chase D, Wilson C. Controlled ovarian hyperstimulation adversely affects implantation following in vitro fertilization-embryo transfer. J Assist Reprod Genet. 1999;16(8):416–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 7.

    Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S, et al. Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod. 2005;11(3):195–205.

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    Horcajadas JA, Minguez P, Dopazo J, Esteban FJ, Dominguez F, Giudice LC, et al. Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications. J Clin Endocrinol Metab. 2008;93(11):4500–10.

    Article  PubMed  CAS  Google Scholar 

  9. 9.

    Simon C, Oberye J, Bellver J, Vidal C, Bosch E, Horcajadas JA, et al. Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles. Hum Reprod. 2005;20(12):3318–27.

    Article  PubMed  CAS  Google Scholar 

  10. 10.

    Haouzi D, Assou S, Mahmoud K, Tondeur S, Reme T, Hedon B, et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod. 2009;24(6):1436–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. 11.

    Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update. 2013;19(5):433–57.

    Article  PubMed  CAS  Google Scholar 

  12. 12.

    Venetis CA, Kolibianakis EM, Bosdou JK, Lainas GT, Sfontouris IA, Tarlatzis BC, et al. Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles. Hum Reprod. 2015;30(3):684–91.

    Article  PubMed  CAS  Google Scholar 

  13. 13.

    Roque M. Freeze-all policy: is it time for that? J Assist Reprod Genet. 2015;32(2):171–6.

    Article  PubMed  Google Scholar 

  14. 14.

    Wong KM, Mastenbroek S, Repping S. Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014;102(1):19–26.

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Balaban B, Urman B, Ata B, Isiklar A, Larman MG, Hamilton R, et al. A randomized controlled study of human day 3 embryo cryopreservation by slow freezing or vitrification: vitrification is associated with higher survival, metabolism and blastocyst formation. Hum Reprod. 2008;23(9):1976–82.

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Fasano G, Fontenelle N, Vannin AS, Biramane J, Devreker F, Englert Y, et al. A randomized controlled trial comparing two vitrification methods versus slow-freezing for cryopreservation of human cleavage stage embryos. J Assist Reprod Genet. 2014;31(2):241–7.

    Article  PubMed  Google Scholar 

  17. 17.

    Li Z, Wang YA, Ledger W, Edgar DH, Sullivan EA. Clinical outcomes following cryopreservation of blastocysts by vitrification or slow freezing: a population-based cohort study. Hum Reprod. 2014;29(12):2794–801.

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Feng G, Zhang B, Zhou H, Shu J, Gan X, Wu F, et al. Comparable clinical outcomes and live births after single vitrified-warmed and fresh blastocyst transfer. Reprod BioMed Online. 2012;25(5):466–73.

    Article  PubMed  Google Scholar 

  19. 19.

    Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod. 2011;26(10):2593–7.

    Article  PubMed  Google Scholar 

  20. 20.

    Shih W, Rushford DD, Bourne H, Garrett C, McBain JC, Healy DL, et al. 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. 2008;23(7):1644–53.

    Article  PubMed  CAS  Google Scholar 

  21. 21.

    Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, et al. Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia. Hum Reprod. 2010;25(1):265–74.

    Article  PubMed  CAS  Google Scholar 

  22. 22.

    Londra L, Moreau C, Strobino D, Garcia J, Zacur H, Zhao Y. Ectopic pregnancy after in vitro fertilization: differences between fresh and frozen-thawed cycles. Fertil Steril. 2015;104(1):110–8.

    Article  PubMed  Google Scholar 

  23. 23.

    Maheshwari A, Pandey S, Amalraj Raja E, Shetty A, Hamilton M, Bhattacharya S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update. 2018;24(1):35–58.

    Article  PubMed  Google Scholar 

  24. 24.

    Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. 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. 2012;98(2):368–77 e1–9.

    Article  PubMed  Google Scholar 

  25. 25.

    Pelkonen S, Gissler M, Koivurova S, Lehtinen S, Martikainen H, Hartikainen AL, et al. Physical health of singleton children born after frozen embryo transfer using slow freezing: a 3-year follow-up study. Hum Reprod. 2015;30(10):2411–8.

    Article  PubMed  CAS  Google Scholar 

  26. 26.

    Pelkonen S, Hartikainen AL, Ritvanen A, Koivunen R, Martikainen H, Gissler M, et al. Major congenital anomalies in children born after frozen embryo transfer: a cohort study 1995-2006. Hum Reprod. 2014;29(7):1552–7.

    Article  PubMed  CAS  Google Scholar 

  27. 27.

    Doody KJ. Cryopreservation and delayed embryo transfer-assisted reproductive technology registry and reporting implications. Fertil Steril. 2014;102(1):27–31.

    Article  PubMed  Google Scholar 

  28. 28.

    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer. Fertil Steril. 2014;102(1):3–9.

    Article  PubMed  Google Scholar 

  29. 29.

    Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2017;3:CD011184.

    Article  PubMed  Google Scholar 

  30. 30.

    Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med. 2018;378(2):126–36.

    Article  PubMed  Google Scholar 

  31. 31.

    Vuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, et al. IVF transfer of fresh or frozen embryos in women without polycystic ovaries. N Engl J Med. 2018;378(2):137–47.

    Article  PubMed  Google Scholar 

  32. 32.

    Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019;393(10178):1310–8.

    Article  PubMed  Google Scholar 

  33. 33.

    Basile N, Garcia-Velasco JA. The state of “freeze-for-all” in human ARTs. J Assist Reprod Genet. 2016;33(12):1543–50.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Lopez S, Lattes K, Vassena R, Brassesco M, Vernaeve V. Freeze-all in older women: benefit or loss? Hum Reprod. 2016;31:i5.

    Google Scholar 

  35. 35.

    Santistevan AHCK, Arredondo F, Miller B, Ory S, Leondires M. Multi-center study demonstrates freeze-all IVF protocols are correlated with higher ongoing pregnancy rates in women of advanced maternal age. Hum Reprod. 2016;3:1i102–3.

    Google Scholar 

  36. 36.

    Grunfeld L, Walker B, Bergh PA, Sandler B, Hofmann G, Navot D. High-resolution endovaginal ultrasonography of the endometrium: a noninvasive test for endometrial adequacy. Obstet Gynecol. 1991;78(2):200–4.

    PubMed  CAS  Google Scholar 

  37. 37.

    Alpha Scientists In Reproductive M. The Alpha consensus meeting on cryopreservation key performance indicators and benchmarks: proceedings of an expert meeting. Reprod BioMed Online. 2012;25(2):146–67.

    Article  Google Scholar 

  38. 38.

    Giorlandino C, Cignini P, Padula F, Giannarelli D, d’Emidio L, Aloisi A, et al. Effects of exogenous progesterone on fetal nuchal translucency: an observational prospective study. Am J Obstet Gynecol. 2015;212(3):335 e1–7.

    Article  CAS  Google Scholar 

  39. 39.

    Bosdou JK, Venetis CA, Tarlatzis BC, Grimbizis GF, Kolibianakis EM. Higher probability of live-birth in high, but not normal, responders after first frozen-embryo transfer in a freeze-only cycle strategy compared to fresh-embryo transfer: a meta-analysis. Hum Reprod. 2019;34(3):491–505.

    Article  PubMed  CAS  Google Scholar 

  40. 40.

    Wang A, Santistevan A, Hunter Cohn K, Copperman A, Nulsen J, Miller BT, et al. Freeze-only versus fresh embryo transfer in a multicenter matched cohort study: contribution of progesterone and maternal age to success rates. Fertil Steril. 2017;108(2):254–61 e4.

    Article  PubMed  CAS  Google Scholar 

  41. 41.

    Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group? Hum Reprod. 2015;30(9):2005–8.

    Article  PubMed  CAS  Google Scholar 

  42. 42.

    Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31(2):370–6.

    Article  PubMed  Google Scholar 

  43. 43.

    Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2019;25(1):2–14.

    Article  PubMed  Google Scholar 

  44. 44.

    Zhang W, Xiao X, Zhang J, Wang W, Wu J, Peng L, et al. Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2018;298(2):259–72.

    Article  PubMed  Google Scholar 

Download references


We would like to thank Rosa Borràs, Maite Castro, Enrique Fabián, Manuel Gómez, Sara López, and Alicia Maqueda for their collaboration in recruiting, providing, and caring for study patients. We would also like to thank Francesc Figueras for statistical advice.

Author information




KL initiated and designed the study, interpreted the data, and wrote the manuscript. SL participated in data collection and interpretation and manuscript revision. MAC participated in data interpretation, provided expert knowledge, and was involved in manuscript revision. MB provided expert knowledge. DG performed the statistical analysis. RV was involved in study supervision, provided expert knowledge, and participated in data analysis and manuscript preparation.

Corresponding author

Correspondence to R. Vassena.

Ethics declarations

This study was approved by the local Research Ethics Committee.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lattes, K., López, S., Checa, M.A. et al. A freeze-all strategy does not increase live birth rates in women of advanced reproductive age. J Assist Reprod Genet 37, 2443–2451 (2020).

Download citation


  • Freeze-all
  • IVF
  • Frozen embryo transfer
  • Embryo transfer
  • Endometrial receptivity