Delayed versus immediate frozen embryo transfer after oocyte retrieval: a systematic review and meta-analysis

Abstract

Purpose

This systematic review and meta-analysis aimed to compare pregnancy outcomes between immediate frozen embryo transfer (FET) performed within the first menstrual cycle after oocyte retrieval and delayed FET following subsequent cycles.

Methods

PubMed, EMBASE, and Web of Science were searched for eligible studies through January 2020. The main outcome measures were clinical pregnancy rate (CPR), live birth rate (LBR), and pregnancy loss rate (PLR). The effect size was estimated as risk ratio (RR) with 95% confidence interval (CI) using a random effects model. Inter-study heterogeneity was assessed by the I2 statistic.

Results

Twelve retrospective cohort studies involving 18,230 cycles were included. The pooled results revealed no significant differences between delayed and immediate FET in CPR (RR 0.94, 95% CI 0.87–1.03; I2 = 67.9%), LBR (RR 0.94, 95% CI 0.85–1.03; I2 = 67.5%), and PLR (RR 1.05, 95% CI 0.87–1.26; I2 = 42.7%). Subgroup analyses of freeze-all cycles showed a marginal decrease of CPR in delayed FET (RR 0.93, 95% CI 0.86–1.00; I2 = 53.6%), but no significant changes were observed regarding LBR (RR 0.93, 95% CI 0.85–1.02; I2 = 65.2%) and PLR (RR 1.09, 95% CI 0.84–1.41; I2 = 59.1%). No statistical differences were found in effect estimates among other subgroup analyses by ovarian stimulation protocol, trigger agent, endometrial preparation regimen, and embryo stage.

Conclusion

Timing of the first FET after oocyte retrieval was not significantly associated with pregnancy outcomes. This finding refutes the current common practice to delay FET after oocyte retrieval and reassures patients who wish to proceed with FET at their earliest convenience. Due to the high heterogeneity and observational nature of included studies, further randomized controlled trials are needed to confirm the results.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. 1.

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

    Article  Google Scholar 

  2. 2.

    Polyzos NP, Drakopoulos P, Parra J, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including approximately 15,000 women. Fertil Steril. 2018;110(4):661–670.e661.

    Article  Google Scholar 

  3. 3.

    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  Google Scholar 

  4. 4.

    De Geyter C, Calhaz-Jorge C, Kupka MS, et al. ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(1):hoz038.

    Article  Google Scholar 

  5. 5.

    Blockeel C, Drakopoulos P, Santos-Ribeiro S, Polyzos NP, Tournaye H. A fresh look at the freeze-all protocol: a SWOT analysis. Hum Reprod. 2016;31(3):491–7.

    Article  Google Scholar 

  6. 6.

    Bosch E, De Vos M, Humaidan P. The Future of Cryopreservation in Assisted Reproductive Technologies. Front Endocrinol (Lausanne). 2020;11:67.

    Article  Google Scholar 

  7. 7.

    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  Google Scholar 

  8. 8.

    Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523–33.

    Article  Google Scholar 

  9. 9.

    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  Google Scholar 

  10. 10.

    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  Google Scholar 

  11. 11.

    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 transfers in high responders. Fertil Steril. 2011;96(2):516–8.

    Article  Google Scholar 

  12. 12.

    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  Google Scholar 

  13. 13.

    Bourdon M, Santulli P, Maignien C, Pocate-Cheriet K, Alwohaibi A, Marcellin L, et al. The interval between oocyte retrieval and frozen-thawed blastocyst transfer does not affect the live birth rate and obstetrical outcomes. PLoS One. 2018;13(10):e0206067.

    Article  Google Scholar 

  14. 14.

    He Y, Zheng H, Du H, et al. Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing. Reprod Biol Endocrinol. 2020;18(1):1.

    Article  Google Scholar 

  15. 15.

    Higgins C, Healey M, Jatkar S, Vollenhoven B. Interval between IVF stimulation cycle and frozen embryo transfer: is there a benefit to a delay between cycles? Aust N Z J Obstet Gynaecol. 2018;58(2):217–21.

    Article  Google Scholar 

  16. 16.

    Horowitz E, Mizrachi Y, Farhi J, Shalev A, Raziel A, Weissman A. Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle? Reprod BioMed Online. 2019;39:439–45.

    Article  Google Scholar 

  17. 17.

    Huang J, Lu X, Xie Q, Lin J, Cai R, Kuang Y. Timing of frozen-thawed embryo transfer after controlled ovarian stimulation in a non-elective freeze-all policy. Ann Transl Med. 2019;7(23):752.

    Article  Google Scholar 

  18. 18.

    Kaye L, Marsidi A, Rai P, Thorne J, Nulsen J, Engmann L, et al. Frozen blastocyst transfer outcomes in immediate versus delayed subsequent cycles following GnRH agonist or hCG triggers. J Assist Reprod Genet. 2018;35(4):669–75.

    Article  Google Scholar 

  19. 19.

    Lattes K, Checa MA, Vassena R, Brassesco M, Vernaeve V. There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Hum Reprod. 2017;32(2):368–74.

    CAS  Article  Google Scholar 

  20. 20.

    Ozgur K, Bulut H, Berkkanoglu M, Humaidan P, Coetzee K. Frozen embryo transfer can be performed in the cycle immediately following the freeze-all cycle. J Assist Reprod Genet. 2018;35(1):135–42.

    Article  Google Scholar 

  21. 21.

    Santos-Ribeiro S, Siffain J, Polyzos NP, et al. To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt? Fertil Steril. 2016;105(5):1202–1207.e1201.

    Article  Google Scholar 

  22. 22.

    Santos-Ribeiro S, Polyzos NP, Lan VT, et al. The effect of an immediate frozen embryo transfer following a freeze-all protocol: a retrospective analysis from two centres. Hum Reprod. 2016;31(11):2541–8.

    Article  Google Scholar 

  23. 23.

    Song J, Xiang S, Sun Z. Frozen embryo transfer at the cleavage stage can be performed within the first menstrual cycle following the freeze-all strategy without adversely affecting the live birth rate: a STROBE-compliant retrospective study. Medicine (Baltimore). 2019;98(38):e17329.

    Article  Google Scholar 

  24. 24.

    Volodarsky-Perel A, Eldar-Geva T, Holzer HE, Schonberger O, Reichman O, Gal M. Cryopreserved embryo transfer: adjacent or non-adjacent to failed fresh long GnRH-agonist protocol IVF cycle. Reprod BioMed Online. 2017;34(3):267–73.

    CAS  Article  Google Scholar 

  25. 25.

    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.

    CAS  Article  Google Scholar 

  26. 26.

    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Article  Google Scholar 

  27. 27.

    Wells GA, Shea B, O’Connell D et al The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed 14 Jan 2020

  28. 28.

    Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. Chichester: Wiley; 2009.

    Google Scholar 

  29. 29.

    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.

    Article  Google Scholar 

  30. 30.

    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    CAS  Article  Google Scholar 

  31. 31.

    An Y, Sun Z, Li L, Zhang Y, Ji H. Relationship between psychological stress and reproductive outcome in women undergoing in vitro fertilization treatment: psychological and neurohormonal assessment. J Assist Reprod Genet. 2013;30(1):35–41.

    Article  Google Scholar 

  32. 32.

    Gameiro S, Boivin J, Domar A. Optimal in vitro fertilization in 2020 should reduce treatment burden and enhance care delivery for patients and staff. Fertil Steril. 2013;100(2):302–9.

    Article  Google Scholar 

  33. 33.

    Cesta CE, Viktorin A, Olsson H, et al. Depression, anxiety, and antidepressant treatment in women: association with in vitro fertilization outcome. Fertil Steril. 2016;105(6):1594–1602.e1593.

    CAS  Article  Google Scholar 

  34. 34.

    Humaidan P, Papanikolaou EG, Kyrou D, Alsbjerg B, Polyzos NP, Devroey P, et al. The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives. Reprod BioMed Online. 2012;24(2):134–41.

    CAS  Article  Google Scholar 

  35. 35.

    IVF-Worldwide. Survey results: frozen-thawed embryo transfer. Available at: http://ivf-worldwide.com/survey/frozen-thawed-embryo-transfer/results-frozen-thawed-embryotransfer.html. Assessed 23 June 2019

  36. 36.

    Aflatoonian A, Oskouian H, Ahmadi S, Oskouian L. Can fresh embryo transfers be replaced by cryopreserved-thawed embryo transfers in assisted reproductive cycles? A randomized controlled trial. J Assist Reprod Genet. 2010;27(7):357–63.

    Article  Google Scholar 

  37. 37.

    Li H, Sun X, Yang J, et al. Comparison of the ongoing pregnancy rate of immediate versus delayed frozen-thawed embryo transfer following a stimulated IVF cycle: a prospective randomized controlled trial. Hum Reprod. 2019;34(Supplement_1):i29–31.

    Google Scholar 

  38. 38.

    Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary on ART terminology, 2009. Hum Reprod. 2009;24(11):2683–7.

    CAS  Article  Google Scholar 

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Acknowledgments

The authors would like to express sincere gratitude to Dr. Hengye Huang, Department of Epidemiology, Shanghai Jiao Tong University School of Public Health, for her assistance in statistical analysis.

Funding

This study was funded by the National Key Research and Development Program of China (2018YFC1003000), National Natural Science Foundation of China (81771533) and Elite Group Project of Shanghai Ninth People’s Hospital (JY201801).

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Authors

Contributions

J.H. and Y.K. contributed to the conception of the study. J.H. and J.L. performed the literature search, data extraction, and study quality assessment. J.H., J.L. and X.L. were involved in statistical analysis. J.H., N.S., and R.C. contributed to the interpretation of the results. J.H. was responsible for the manuscript drafting. All authors approved the final manuscript after critical revision for intellectual content.

Corresponding author

Correspondence to Yanping Kuang.

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Huang, J., Lin, J., Lu, X. et al. Delayed versus immediate frozen embryo transfer after oocyte retrieval: a systematic review and meta-analysis. J Assist Reprod Genet (2020). https://doi.org/10.1007/s10815-020-01857-9

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Keywords

  • Frozen embryo transfer
  • Oocyte retrieval
  • Pregnancy outcome
  • Meta-analysis