Advertisement

The Freeze-All Cycle: A New Paradigm Shift in ART

  • Bruce S. Shapiro
  • Forest C. Garner
  • Martha Aguirre
Chapter

Abstract

Advantages of the freeze-all strategy were discussed by Edwards and Steptoe before the first live birth from ART. Today, there are multiple established indications for freezing all embryos in order to improve success rates or reduce maternal risks. To date, there is no indication for fresh transfer. Further reported advantages of the freeze-all strategy include generally reduced perinatal risks and reduced cost per pregnancy. The US national average success rates have increased more rapidly with thawed embryo transfers than with fresh, and national average implantation rates are now greater with thawed embryos than with fresh embryos in each autologous age group. To date, every clinical trial comparing fresh and freeze-all strategies has employed ovarian stimulation protocols that were optimized for fresh transfers. Stimulation protocols for freeze-all remain to be optimized to reduce costs and improve outcomes without concern for endometrial impact. The freeze-all strategy should further advance as new opportunities are fully explored.

Keywords

In vitro fertilization Embryo cryopreservation Frozen embryo transfer Freeze-all Thawed embryos Ovarian stimulation 

References

  1. 1.
    Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet. 1978;2:366.PubMedCrossRefGoogle Scholar
  2. 2.
    Steptoe PC, Edwards RG. Reimplantation of a human embryo with subsequent tubal pregnancy. Lancet. 1976;1:880–2.PubMedCrossRefGoogle Scholar
  3. 3.
    Edwards RG, Steptoe PC. The relevance of the frozen storage of human embryos. Ciba Found Symp. 1977;52:235–50.Google Scholar
  4. 4.
    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;102:3–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Engmann L, Benadiva C, Humaidan P. GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis. Reprod Biomed Online. 2016;32:274–85.PubMedCrossRefGoogle Scholar
  6. 6.
    Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. Assisted reproductive technology fertility clinic success rates report. Atlanta, GA: US Department of Health and Human Services; 2014. p. 2016.Google Scholar
  7. 7.
    Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature. 1983;305:707–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC. Two pregnancies following transfer of intact frozen-thawed embryos. Fertil Steril. 1984;42:293–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Testart J. Evidence of uterine inadequacy to egg implantation in stimulated in vitro fertilization cycles. Fertil Steril. 1987;47:855–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Veeck LL, Bodine R, Clarke RN, Berrios R, Libraro J, Moschini RM, Zaninovic N, Rosenwaks Z. High pregnancy rates can be achieved after freezing and thawing human blastocysts. Fertil Steril. 2004;82:1418–27.PubMedCrossRefGoogle Scholar
  11. 11.
    Nikas G, Develioglu OH, Toner JP, Jones HW Jr. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod. 1999;14:787–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, Devroey P. 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;78:1025–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Chetkowski RJ, Kiltz RJ, Salyer WR. In premature luteinization, progesterone induces secretory transformation of the endometrium without impairment of embryo viability. Fertil Steril. 1997;68:292–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Develioglu OH, Hsiu JG, Nikas G, Toner JP, Oehninger S, Jones HW Jr. Endometrial estrogen and progesterone receptor and pinopode expression in stimulated cycles of oocyte donors. Fertil Steril. 1999;71:1040–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Fanchin R, Righini C, Olivennes F, Taieb J, de Ziegler D, Frydman R. Computerized assessment of endometrial echogenicity: clues to the endometrial effects of premature progesterone elevation. Fertil Steril. 1999;71:174–81.PubMedCrossRefGoogle Scholar
  16. 16.
    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;19:433–57.PubMedCrossRefGoogle Scholar
  17. 17.
    Venetis CA, Kolibianakis EM, Bosdou JK, Lainas GT, Sfontouris IA, Tarlatzis BC, Lainas TG. 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;30:684–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril. 2010;93:636–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Murata Y, Oku H, Morimoto Y, Tokuda M, Murata T, Sugihara K, Nagata F, Nakaoka Y, Fukuda A. Freeze-thaw programmes rescue the implantation of day 6 blastocysts. Reprod Biomed Online. 2005;11:428–33.PubMedCrossRefGoogle Scholar
  20. 20.
    Richter KS, Shipley SK, McVearry I, Tucker MJ, Widra EA. Cryopreserved embryo transfers suggest that endometrial receptivity may contribute to reduced success rates of later developing embryos. Fertil Steril. 2006;86:862–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Ross R. Contrasting patterns in in vitro fertilization pregnancy rates among fresh autologous, fresh oocyte donor, and cryopreserved cycles with the use of day 5 or day 6 blastocysts may reflect differences in embryo-endometrium synchrony. Fertil Steril. 2008;89:20–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Thomas S. Large blastocyst diameter, early blastulation, and low preovulatory serum progesterone are dominant predictors of clinical pregnancy in fresh autologous cycles. Fertil Steril. 2008;90:302–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Sunkara SK, Siozos A, Bolton VN, Khalaf Y, Braude PR, El-Toukhy T. The influence of delayed blastocyst formation on the outcome of frozen-thawed blastocyst transfer: a systematic review and meta-analysis. Hum Reprod. 2010;25:1906–15.PubMedCrossRefGoogle Scholar
  24. 24.
    Shapiro BS, Daneshmand ST, Restrepo H, Garner FC, Aguirre M, Hudson C. Matched-cohort comparison of single-embryo transfers in fresh and frozen-thawed embryo transfer cycles. Fertil Steril. 2013;99:389–92.PubMedCrossRefGoogle Scholar
  25. 25.
    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;96:344–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, Yang J, Liu J, Wei D, Weng N, Tian L, Hao C, Yang D, Zhou F, Shi J, Xu Y, Li J, Yan J, Qin Y, Zhao H, Zhang H, Legro RS. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375:523–33.PubMedCrossRefGoogle Scholar
  27. 27.
    Coates A, Kung A, Mounts E, Hesla J, Bankowski B, Barbieri E, Ata B, Cohen J, Munné S. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial. Fertil Steril. 2017;107:723–30.PubMedCrossRefGoogle Scholar
  28. 28.
    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;96:516–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Healy MW, Yamasaki M, Patounakis G, Richter KS, Devine K, DeCherney AH, Hill MJ. The slow growing embryo and premature progesterone elevation: compounding factors for embryo-endometrial asynchrony. Hum Reprod. 2017;32:362–7.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Freeze-all can be a superior therapy to another fresh cycle in patients with prior fresh blastocyst implantation failure. Reprod Biomed Online. 2014;29:286–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Shapiro BS, Daneshmand ST, Desai J, Garner FC, Aguirre M, Hudson C. The risk of embryo-endometrium asynchrony increases with maternal age after ovarian stimulation and IVF. Reprod Biomed Online. 2016;33:50–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Youssef MA, Van der Veen F, Al-Inany HG, Griesinger G, Mochtar MH, Aboulfoutouh I, Khattab SM, van Wely M. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles. Cochrane Database Syst Rev. 2011;1:CD008046.Google Scholar
  33. 33.
    Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod. 2011;26:2593–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Dosouto C, Haahr T, Humaidan P. Gonadotropin-releasing hormone agonist (GnRHa) trigger – state of the art. Reprod Biol. 2017;17:1–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Forman EJ, Tao X, Ferry KM, Taylor D, Treff NR, Scott RT Jr. Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates. Hum Reprod. 2012;27(4):1217–22.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Rodriguez-Purata J, Lee J, Whitehouse M, Duke M, Grunfeld L, Sandler B, Copperman A, Mukherjee T. Reproductive outcome is optimized by genomic embryo screening, vitrification, and subsequent transfer into a prepared synchronous endometrium. J Assist Reprod Genet. 2016;33:401–12.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Grifo J, Kofinas J, Schoolcraft WB. The practice of in vitro fertilization according to the published literature. Fertil Steril. 2014;102:658–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Shapiro BS, Daneshmand ST, De Leon L, Garner FC, Aguirre M, Hudson C. Frozen-thawed embryo transfer is associated with a significantly reduced incidence of ectopic pregnancy. Fertil Steril. 2012;98:1490–4.PubMedCrossRefGoogle Scholar
  39. 39.
    Perkins KM, Boulet SL, Kissin DM, Jamieson DJ, National ART Surveillance (NASS) Group. Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001–2011. Obstet Gynecol. 2015;125:70–8.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Muller V, Makhmadalieva M, Kogan I, Fedorova I, Lesik E, Komarova E, Dzhemlikhanova L, Niauri D, Gzgzyan A, Ailamazyan E. Ectopic pregnancy following in vitro fertilization: meta-analysis and single-center experience during 6 years. Gynecol Endocrinol. 2016;32(sup2):69–74.PubMedCrossRefGoogle Scholar
  41. 41.
    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;98:368–77.PubMedCrossRefGoogle Scholar
  42. 42.
    Pinborg A, Henningsen AA, Loft A, Malchau SS, Forman J, Andersen AN. Large baby syndrome in singletons born after frozen embryo transfer (FET): is it due to maternal factors or the cryotechnique? Hum Reprod. 2014;29:618–27.PubMedCrossRefGoogle Scholar
  43. 43.
    Shapiro BS, Daneshmand ST, Bedient CE, Garner FC. Comparison of birth weights in patients randomly assigned to fresh or frozen-thawed embryo transfer. Fertil Steril. 2016;106:317–21.PubMedCrossRefGoogle Scholar
  44. 44.
    Shih W, Rushford DD, Bourne H, Garrett C, McBain JC, Healy DL, Baker HW. 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;23:1644–53.PubMedCrossRefGoogle Scholar
  45. 45.
    Kalra SK, Ratcliffe SJ, Coutifaris C, Molinaro T, Barnhart KT. Ovarian stimulation and low birth weight in newborns conceived through in vitro fertilization. Obstet Gynecol. 2011;118:863–71.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Galliano D, Garrido N, Serra-Serra V, Pellicer A. Difference in birth weight of consecutive sibling singletons is not found in oocyte donation when comparing fresh versus frozen embryo replacements. Fertil Steril. 2015;104:1411–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Mainigi MA, Olalere D, Burd I, Sapienza C, Bartolomei M, Coutifaris C. Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. Biol Reprod. 2014;90:26.PubMedCrossRefGoogle Scholar
  48. 48.
    Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med. 2002;346:731–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Wilcox AJ. On the importance--and the unimportance--of birthweight. Int J Epidemiol. 2001;30:1233–41.PubMedCrossRefGoogle Scholar
  50. 50.
    Shah PS, Balkhair T, Ohlsson A, Beyene J, Scott F, Frick C. Intention to become pregnant and low birth weight and preterm birth: a systematic review. Matern Child Health J. 2011;15:205–16.PubMedCrossRefGoogle Scholar
  51. 51.
    Finer LB, Zolna MR. Shifts in intended and unintended pregnancies in the United States, 2001–2008. Am J Public Health. 2014;104(Suppl 1):S43–8.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Mosher WD, Jones J, Abma JC. Intended and unintended births in the United States: 1982–2010. Natl Health Stat Report. 2012;55:1–28.Google Scholar
  53. 53.
    Ghosh J, Coutifaris C, Sapienza C, Mainigi M. Global DNA methylation levels are altered by modifiable clinical manipulations in assisted reproductive technologies. Clin Epigenetics. 2017;9:14.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Rosen MP, Shen S, Dobson AT, Rinaudo PF, McCulloch CE, Cedars MI. A quantitative assessment of follicle size on oocyte developmental competence. Fertil Steril. 2008;90:684–90.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kolibianakis EM, Albano C, Camus M, Tournaye H, van Steirteghem AC, Devroey P. Prolongation of the follicular phase in in vitro fertilization results in a lower ongoing pregnancy rate in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists. Fertil Steril. 2004;82:102–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015;104:62–70.PubMedCrossRefGoogle Scholar
  57. 57.
    Allen BD, Adashi EY, Jones HW. On the cost and prevention of iatrogenic multiple pregnancies. Reprod Biomed Online. 2014;29:281–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Cost-effectiveness of the freeze-all policy. JBRA Assist Reprod. 2015;19:125–30.PubMedCrossRefGoogle Scholar
  59. 59.
    Papaleo E, Pagliardini L, Vanni VS, Delprato D, Rubino R, Caniani M, Vigiano P. A direct healthcare cost analysis of the cryopreserved versus fresh transfer policy at the blastocyst stage. Reprod Biomed Online. 2017;34(1):19–26.PubMedCrossRefGoogle Scholar
  60. 60.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Freeze-all at the blastocyst or bipronuclear stage: a randomized clinical trial. Fertil Steril. 2015;104:1138–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bruce S. Shapiro
    • 1
  • Forest C. Garner
    • 1
  • Martha Aguirre
    • 1
  1. 1.Fertility Center of Las VegasLas VegasUSA

Personalised recommendations