The added value of embryo cryopreservation to cumulative ongoing pregnancy rates per IVF treatment: is cryopreservation worth the effort?

Purpose: To calculate the added benefit of a cryopreservation program to the cumulative ongoing pregnancy rate over a maximum of three cycles of IVF.

A total of 1251 couples beginning their first IVF treatment between January 1995 and December 1999 were evaluated. Ongoing pregnancies from fresh and subsequent cryopreserved embryo transfer cycles were analyzed. Pregnancies arising from the cryopreservation cycle were considered to augment the cumulative pregnancy rate when no ongoing pregnancy arose from the fresh embryo transfer cycle.

The ongoing pregnancy rate per cryopreserved embryo transfer was 11.7%. The cumulative ongoing pregnancy rate following three successive started fresh IVF cycles was 42.5%. When pregnancies arising from the transfer of thawed cryopreserved embryos were included, the cumulative ongoing pregnancy rate increased to 43.8%, rising to 44.8% when extrapolated data from as yet unthawed embryos was included.

When analyzed in these terms, the supplementary benefit of cryopreserving supranumerical embryos appears limited.

Blastocyst, cryopreservation, embryo, ethics, health economics, IVF, minimal ovarian stimulation, pregnancy Full Text The Full Text of this article is available as a PDF (128.2 KB).

- 1.Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature. 1983;305:707–709. doi: 10.1038/305707a0. [DOI] [PubMed] [Google Scholar] - 2.Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC. Two pregnancies following transfer of intact frozen–thawed embryos. Fertil Steril. 1984;42:293–296. doi: 10.1016/s0015-0282(16)48029-5. [DOI] [PubMed] [Google Scholar] - 3.The American Fertility Society: Revised minimum standards for in vitro fertilization, gamete intrafallopian transfer, and related procedures. Fertil Steril 1990;53:225–226 [DOI] [PubMed] - 4.Fugger EF. Clinical status of human embryo cryopreservation in the United States of America. Fertil Steril. 1989;52:986–990. doi: 10.1016/s0015-0282(16)53163-x. [DOI] [PubMed] [Google Scholar] - 5.Quigley MM, Wolf DP, Maklad NF, Dandekar PV, Sokoloski JE. Follicular size and number in human in vitro fertilization. Fertil Steril. 1982;38:678–681. [PubMed] [Google Scholar] - 6.MacDougall MJ, Tan SL, Hall V, Balen A, Mason BA, Jacobs HS. Comparison of natural with clomiphene citrate-stimulated cycles in in vitro fertilization: A prospective, randomized trial. Fertil Steril. 1994;61:1052–1057. doi: 10.1016/s0015-0282(16)56755-7. [DOI] [PubMed] [Google Scholar] - 7.Tan SL, Kingsland C, Campbell S, Mills C, Bradfield J, Alexander N, Yovich J, Jacobs HS. The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization. Fertil Steril. 1992;57:810–814. doi: 10.1016/s0015-0282(16)54963-2. [DOI] [PubMed] [Google Scholar] - 8.Hughes EG, Fedorkow DM, Daya S, Sagle MA, Van deKoppel P, Collins JA. The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: A meta-analysis of randomized controlled trials. Fertil Steril. 1992;58:888–896. doi: 10.1016/s0015-0282(16)55430-2. [DOI] [PubMed] [Google Scholar] - 9.Schieve LA, Peterson HB, Meikle SF, Jeng G, Danel I, Burnett NM, Wilcox LS. Live-birth rates and multiple-birth risk using in vitro fertilization. JAMA. 1999;282:832–1838. doi: 10.1001/jama.282.19.1832. [DOI] [PubMed] [Google Scholar] - 10.Mandelbaum J, Belaisch-Allart J, Junca AM, Antoine JM, Plachot M, Alvarez S, Alnot MO, Salat-Baroux J. Cryopreservation in human assisted reproduction is now routine for embryos but remains a research procedure for oocytes. Hum Reprod. 1998;13(Suppl3):161–174. doi: 10.1093/humrep/13.suppl_3.161. [DOI] [PubMed] [Google Scholar] - 11.Edwards RG, Lobo R, Bouchard P. Time to revolutionize ovarian stimulation. Hum Reprod. 1996;11:917–919. doi: 10.1093/oxfordjournals.humrep.a019317. [DOI] [PubMed] [Google Scholar] - 12.Olivennes F, Frydman R. Friendly IVF: The way of the future? Hum Reprod. 1998;13:1121–1124. doi: 10.1093/humrep/13.5.1121. [DOI] [PubMed] [Google Scholar] - 13.Fauser BC, Devroey P, Yen SS, Gosden R, Crowley WF, Jr, Baird DT, Bouchard P. Minimal ovarian stimulation for IVF: Appraisal of potential benefits and drawbacks. Hum Reprod. 1999;14:2681–2686. doi: 10.1093/humrep/14.11.2681. [DOI] [PubMed] [Google Scholar] - 14.De Vries MJ, De Sutter P, Dhont M. Prognostic factors in patients continuing in vitro fertilization or intracytoplasmic sperm injection treatment and dropouts. Fertil Steril. 1999;72:674–678. doi: 10.1016/s0015-0282(99)00334-9. [DOI] [PubMed] [Google Scholar] - 15.Osmanagaoglu K, Tournaye H, Camus M, Vandervorst M. V. S., Devroey P. Cumulative delivery rates after intracytoplasmic sperm injection: 5 year follow-up of 498 patients. Hum Reprod. 1999;14:2651–2655. doi: 10.1093/humrep/14.10.2651. [DOI] [PubMed] [Google Scholar] - 16.Schenker JG. Assisted reproduction practice in Europe: Legal and ethical aspects. Hum Reprod Update. 1997;3:173–184. doi: 10.1093/humupd/3.2.173. [DOI] [PubMed] [Google Scholar] - 17.Fasouliotis SJ, Schenker JG. Cryopreservation of embryos: Medical, ethical, and legal issues. J Assist Reprod Genet. 1996;13:756–761. doi: 10.1007/BF02066493. [DOI] [PubMed] [Google Scholar] - 18.Jones HWJ, Veeck LL, Muasher SJ. Cryopreservation: The problem of evaluation. Hum Reprod. 1995;10:2136–2138. doi: 10.1093/oxfordjournals.humrep.a136248. [DOI] [PubMed] [Google Scholar] - 19.Van der Elst J, Camus M, Van den Abbeel E, Maes R, Devroey P, Van Steirteghem AC. Prospective randomized study on the cryopreservation of human embryos with dimethylsulfoxide or 1,2-propanediol protocols. Fertil Steril. 1995;63:92–100. [PubMed] [Google Scholar] - 20.Van Steirteghem AC, Van der Elst J, Van den Abbeel E, Joris H, Camus M, Devroey P. Cryopreservation of supernumerary multicellular human embryos obtained after intracytoplasmic sperm injection. Fertil Steril. 1994;62:775–780. [PubMed] [Google Scholar] - 21.Macklon NS, Pieters MH, Fauser BCJM. Indications for IVF treatment: from diagnosis to prognosis. In: Gardner DK, Weissman A, Howles CM, Shoham Z, editors. In Textbook of Assisted Reproductive Techniques. London: Martin Dunitz; 2001. pp. 393–400. [Google Scholar] - 22.Huisman GJ, Fauser BC, Eijkemans MJ, Pieters MH. Implantation rates after in vitro fertilization and transfer of a maximum of two embryos that have undergone three to five days of culture. Fertil Steril. 2000;73:117–122. doi: 10.1016/s0015-0282(99)00458-6. [DOI] [PubMed] [Google Scholar] - 23.Hunault CC, Eijkemans MJ, Pieters MH, te Velde ER, Habbema JD, Fauser BC, Macklon NS. Aprediction model for selecting patients for elective single embryo transfer in IVF. Fertil Steril. 2002;77:725–732. doi: 10.1016/s0015-0282(01)03243-5. [DOI] [PubMed] [Google Scholar] - 24.Veeck LL. Preembryo grading and degree of cytoplasmic fragmentation. In: Veeck LL, editor. In An Atlas of Human Gametes and Conceptuses. New York: Parthenon Publishing; 1998. pp. 40–45. [Google Scholar] - 25.HWJ J., Kolm P J. D. Cryopreservation: A simplified method of evaluation. Hum Reprod. 1997;12:548–553. doi: 10.1093/humrep/12.3.548. [DOI] [PubMed] [Google Scholar] - 26.LR M., LV R. Markov models for covariate dependence of binary sequences. Biometrics. 1985;41:91–101. [PubMed] [Google Scholar] - 27.The ganirelix dose-finding study group: A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). Hum Reprod 1998;13:3023–3031 [PubMed] - 28.The European Orgalutran Study group, BormG, Mannaerts B: Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: Results of a controlled, randomized, multicentre trial. Hum Reprod 2000;15:1490–1498 [DOI] [PubMed] - 29.The European IVF-monitoring programme (EIM), Nygren K, Nyboe Andersen A for the European Society of Human Reproduction and Embryology (ESHRE): Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE. Hum Reprod 2001;16:384–391 [DOI] [PubMed] - 30.Ludwig M, Al-Hasani S, Felberbaum R, Diedrich K. No impact of cryopreservation on embryo development potential—one more example of the problems of retrospective, non-controlled data. Hum Reprod. 1998;13:786–787. doi: 10.1093/oxfordjournals.humrep.a019697. [DOI] [PubMed] [Google Scholar] - 31.Testart J. Episcientific aspects of the epigenetic factors in arti-ficial procreation. Hum Reprod. 1998;13:783–785. doi: 10.1093/humrep/13.4.783. [DOI] [PubMed] [Google Scholar] - 32.Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine: Assisted reproductive technology in the United States: 1997 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2000;74:641–654 [DOI] [PubMed] - 33.Van den Abbeel E, Van Steirteghem A. Zona pellucida damage to human embryos after cryopreservation and the consequences for their blastomere survival and in-vitro viability. Hum Reprod. 2000;15:373–378. doi: 10.1093/humrep/15.2.373. [DOI] [PubMed] [Google Scholar] - 34.Jones HWJ, Out HJ, Hoomans EH, Driessen SG, Coelingh Bennink HJ. Cryopreservation: The practicalities of evaluation. Hum Reprod. 1997;12:1522–1524. doi: 10.1093/humrep/12.7.1522. [DOI] [PubMed] [Google Scholar] - 35.Van der Elst J, Van den Abbeel E, Camus M, Smitz J, Devroey P, Van Steirteghem A. Long-term evaluation of implantation of fresh and cryopreserved human embryos following ovarian stimulation with buserelin acetate-human menopausal gonadotrophin (HMG) or clomiphene citrate-HMG. Hum Reprod. 1996;11:2097–2106. doi: 10.1093/oxfordjournals.humrep.a019056. [DOI] [PubMed] [Google Scholar] - 36.Edgar DH, Bourne H, Spiers AL, McBain JC. A quantative analysis of the impact of cryopreservation on the implantation potential of human early cleavage stage embryos. HumReprod. 2000;15:175–179. doi: 10.1093/humrep/15.1.175. [DOI] [PubMed] [Google Scholar] - 37.Fauser BC, Bouchard P, Coelingh Bennink HJ, Collins JA, Devroey P, Evers JL, Van Steirteghem A. Alternative approaches in IVF. Hum Reprod Update. 2002;8:1–9. doi: 10.1093/humupd/8.1.1. [DOI] [PubMed] [Google Scholar] - 38.Troup SA, Matson PL, Critchlow JD, Morroll DR, Lieberman BA, Burslem RW. Cryopreservation of human embryos at the pronucleate, early cleavage, or expanded blastocyst stages. Eur J Obstet Gynecol Reprod Biol. 1991;38:133–139. doi: 10.1016/0028-2243(91)90190-v. [DOI] [PubMed] [Google Scholar] - 39.Kaufman RA, Menezo Y, Hazout A, Nicollet B, DuMont M., Servy EJ. Cocultured blastocyst cryopreservation: Experience of more than 500 transfer cycles. Fertil Steril. 1995;64:1125–1129. [PubMed] [Google Scholar] - 40.Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine: Assisted reproductive technology in the United States: 1998 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2002;77:18–31 [DOI] [PubMed] - 41.Eugster A, Vingerhoets AJ. Psychological aspects of in vitro fertilization: A review. Soc Sci Med. 1999;48:575–589. doi: 10.1016/s0277-9536(98)00386-4. [DOI] [PubMed] [Google Scholar] - 42.Shannon TA. Ethical issues involved with in vitro fertilization. AORN J. 1990;52:627–631. doi: 10.1016/s0001-2092(07)69891-3. [DOI] [PubMed] [Google Scholar] - 43.de Jong D., Macklon NS, Fauser BC. A pilot study involving minimal ovarian stimulation for in vitro fertilization: Extending the “follicle-stimulating hormone window” combined with the gonadotropin-releasing hormone antagonist cetrorelix. Fertil Steril. 2000;73:1051–1054. doi: 10.1016/s0015-0282(00)00414-3. [DOI] [PubMed] [Google Scholar] - 44.Macklon NS, Fauser BCJM. Alternative approaches to ovarian stimulation for IVF. Reprod Med Rev. 2001;9:77–89. [Google Scholar] - 45.Hojgaard A, Ingerslev HJ, Dinesen Friendly IVF: Patient opinions. Hum Reprod. 2001;16:1391–1396. doi: 10.1093/humrep/16.7.1391. [DOI] [PubMed] [Google Scholar]