Journal of Assisted Reproduction and Genetics

, Volume 27, Issue 12, pp 683–689

Transfer of cryopreserved - thawed embryos in hCG induced natural or clomiphene citrate cycles yields similar live birth rates in normo-ovulatory women

  • Dimitra Kyrou
  • Human M. Fatemi
  • Christophe Blockeel
  • Dominic Stoop
  • H. Albuarki
  • Greta Verheyen
  • Paul Devroey
Assisted Reproduction Technologies



The purpose of this retrospective analysis is to compare the efficiency of hCG-induced natural and Clomiphene citrate (CC) cycles in normovulatory patients undergoing frozen embryo transfer (FET).

Materials and methods

It was retrospectively conducted in the Dutchspeaking Free University of Brussels and covered the period from April 2003 to August 2006. In particular, 428 day-three FET cycles belonging to the two comparative groups were recruited. Of these FET cycles, 261 were hCG-induced natural and 167 clomiphene citrate-induced cycles.


No statistically significant difference was observed in live birth rate between CC and natural group (22.2% versus 22.6%), respectively (P = 0.708). Except for the number of embryos transferred (1.72 ± 0.46 for CC group versus 1.63 ± 0.48 for natural group, P = 0.045), no other parameters seem to influence the outcome.


To our knowledge, this is the first attempt to investigate which of the above mentioned regimens is optimal for normo-ovulatory women in FET cycles. A similar delivery outcome was observed for hCG–induced natural and CC-induced cycles used for endometrial preparation in FET.


FET Clomiphene citrate hCG Natural cycle Live birth 


  1. 1.
    Trounson A, Mohr L. Human Pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature. 1983;305:707–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Cohen J, Simons RF, Edwards RG, Fehilly CB, Fishel SB. Pregnancies following the frozen storage of expanding human blastocysts. J In Vitro Fert Embryo Transf. 1985;2:59–64.CrossRefPubMedGoogle Scholar
  3. 3.
    Tiitinen A, Halttunen M, Harkki P, Vuoristo P, Hyden-Granskog C. Elective single embryo transfer: the value of cryopreservation. Hum Reprod. 2001;16:1140–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Sutcliffe AG, D’Souza SW, Cadman J, Richards B, McKinlay IA, Lieberman B. Minor congenital anomalies, mayor congenital malformations and development in children conceived from cryopreserved embryos. Hum Reprod. 1995;10:3332–7.PubMedGoogle Scholar
  5. 5.
    Wada I, Macnamee MC, Wick K, Bradfield JM, Brinsden PR. Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos. Hum Reprod. 1994;9:543–6.PubMedGoogle Scholar
  6. 6.
    Mandelbaum J. Embryo and oocyte cryopreservation. Hum Reprod. 2000;15:43–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Lieberman BA, Trouo SA, Matson PL. Cryopreservation of embryos and pregnancy rates after IVF (Letter). Lancet. 1992;340:116.CrossRefPubMedGoogle Scholar
  8. 8.
    Horne G, Critchlow JD, Neuman MC, Edozien L, Matson PL, Lieberman BA. A prospective evaluation of cryopreservation strategies in a two-embryo transfer program. Hum Reprod. 1992;7:117–9.Google Scholar
  9. 9.
    Nardo LG, Nikas G, Makrigiannakis A. Molecules in blastocyst implantation. Role of matrix metalloproteinases, cytokines and growth factors. J Reprod Med. 2003;48:137–47.PubMedGoogle Scholar
  10. 10.
    Ghobara T, Vandekerckhove P. Cycle regimens for frozen-thawed embryo transfer (Review). The Cochrane Library. 2008;Issue 2.Google Scholar
  11. 11.
    Morozov V, Ruman J, Kenigsberg D, Moodie G, Brenner S. Natural cycle cryo-thaw transfer may improve pregnancy outcome. J Assist Reprod Gen. 2007;24:119–23.CrossRefGoogle Scholar
  12. 12.
    Gelbaya T, Nardo L, Hunter H, Fitzgerald CT, Horne G, Pease EE, et al. Cryopreserved-thawed embryo transfer in natural cycle or down-regulated hormonally controlled cycles: a retrospective study. Fertil Steril. 2006;85:603–9.CrossRefPubMedGoogle Scholar
  13. 13.
    al-Shawaf T, Yang D, al-Magud Y, Seaton A, Iketubosin F, Craft I. Ultrasonic monitoring during replacement of frozen/thawed embryos in natural and hormone replacement cycles. Hum Reprod. 1993;8:2068–74.PubMedGoogle Scholar
  14. 14.
    Thibault C, Levasseur MC. Ovulation. Hum Reprod. 1988;3:513–23.PubMedGoogle Scholar
  15. 15.
    Weissman A, Levin D, Ravhon A, Eran H, Golan A, Levran D. What is the preferred method for timing natural cycle frozen-thawed embryo transfer? Reprod Bio Med Online. 2009;19:66–7.CrossRefGoogle Scholar
  16. 16.
    Dickey RP, Olar TT, Curole DN, Taylor SN, Rye PH. Endometrial pattern and thickness associated with pregnancy outcome after assisted reproduction technologies. Hum Reprod. 1992;7:418–21.PubMedGoogle Scholar
  17. 17.
    Geier A, Lunenfeld B, Pariente C, Kotev-Emeth S, Shadmi A, Kokia E, et al. Estrogen receptor binding material in blood of patients after clomiphene citrate administration: detection by a radioreceptor assay. Fertil Steril. 1987;47:778–84.PubMedGoogle Scholar
  18. 18.
    Zayed F, Lenton EA, Cooke ID. Natural cycle in-vitro fertilization in couples with unexplained infertility: impact of various factors on outcome. Hum Reprod. 1997;12:2402–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Kosmas IP, Janssens R, De Munck L, Al Turki H, Van der Elst J, Tournaye H, et al. Ultrasound-guided embryo transfer does not offer any benefit in clinical outcome: a randomized controlled trial. Hum Reprod. 2007;22:1327–34.CrossRefPubMedGoogle Scholar
  20. 20.
    Van Landuyt L, De Vos A, Joris H, Verheyen G, Devroey P, Van Steirteghem A. Blastocyst formation in in vitro fertilization versus intracytoplasmic sperm injection cycles: influence of the fertilization procedure. Fertil Steril. 2005;83:1397–403.CrossRefPubMedGoogle Scholar
  21. 21.
    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;15:373–8.CrossRefGoogle Scholar
  22. 22.
    Gordts S, Campo R, Puttemans P, Brosens I, Valkenburg M, Norre J, et al. Belgian legislation and the effect of elective single embryo transfer on IVF outcome. Reprod Biomed Online. 2005;10:436–41.CrossRefPubMedGoogle Scholar
  23. 23.
    Saldeen P, Sundstrom P. Would legislation imposing single embryo transfer be a feasible way to reduce the rate of multiple pregnancies after IVF treatment? Hum Reprod. 2005;20:4–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Van Voorhis BJ, Syrop CH, Allen BD, Sparks AE, Stovall DW. The efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques. Fertil Steril. 1995;64:647–50.PubMedGoogle Scholar
  25. 25.
    Katsoff B, Check JH, Choe JK, Wilson C. A novel method to evaluate pregnancy rates following in vitro fertilization to enable to better understanding of the true efficacy of the procedure. Cl and Exp Obst and Gyn. 2005;32:213–6.Google Scholar
  26. 26.
    Mandelbaum J, Junca A, Placchot M, Alnot MO, Alvarez S, Debache C, et al. Human embryo cryopreservation, extrinisic and intrinisic parameters of success. Hum Reprod. 1987;2:709–14.PubMedGoogle Scholar
  27. 27.
    Loh SKE, Ganesan G, Leong N. Clomid versus hormone endometrial preparation in FET cycles. Abstract book of the 17th World Congress on Fertility Sterility (IFFS) 2001;3.Google Scholar
  28. 28.
    Van Der Auwera I, Meuleman C, Koninckx P. Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova. Hum Reprod. 1994;9:1556–60.PubMedGoogle Scholar
  29. 29.
    Gonen Y, Casper RF. Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod. 1990;5:670–4.PubMedGoogle Scholar
  30. 30.
    Rogers PAW, Polson D, Murphy CR, Hosie M, Susil B, Leoni M, et al. Correlation of endometrial histology, morphology, and ultrasound appearance after different stimulation protocols for in vitro fertilization. Fertil Steril. 1991;55:583–7.PubMedGoogle Scholar
  31. 31.
    Licht P, Fluhr H, Neuwinger J, Wallwiener D, Wildt L. Is human chorionic gonadotropin directly involved in the regulation of human implantation? Review. Mol Cel Endocrin. 2007;15:85–92.CrossRefGoogle Scholar
  32. 32.
    Queenan JT, Ramey JW, Seltman HJ, Eure L, Veeck LL, Muasher SJ. Transfer of cryopreserved-thawed embryos in a natural cycle or a programme cycle with exogenous hormonal replacement yields similar pregnancy results. Fertil Steril. 1994;62:545–50.PubMedGoogle Scholar
  33. 33.
    Karlstrom PO, Bergh T, Forsberg AS, Sandkvist U, Wikland M. Prognostic factors for the success rate of embryo freezing. Hum Reprod. 1997;12:1263–6.CrossRefPubMedGoogle Scholar
  34. 34.
    Wang JX, Yap YY, Matthews CD. Frozen-thawed embryo transfer: influence of clinical factors on implantation rate and risk of multiple conception. Hum Reprod. 2001;16:2316–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Dimitra Kyrou
    • 1
    • 2
  • Human M. Fatemi
    • 1
  • Christophe Blockeel
    • 1
  • Dominic Stoop
    • 1
  • H. Albuarki
    • 1
  • Greta Verheyen
    • 1
  • Paul Devroey
    • 1
  1. 1.Centre for Reproductive MedicineUniversitair Ziekenhuis Brussel, Vrije Universiteit BrusselBrusselBelgium
  2. 2.V.U.B/C.R.G.BrusselsBelgium

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