Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

A Comparison of the Effects of Transdermal Estradiol and Estradiol Valerate on Endometrial Receptivity in Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial

Authors
Robab Davar 1
Sima Janati 2
Fereshteh Mohseni 1
Mehdi Khabazkhoob 3
Soheila Asgari 4
1 Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Research and Clinical Center for Infertility, Dezful University of Medical Sciences, Dezful, Iran
3 Department of Epidemiology, Faculty of Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: The purpose of this study was to determine the optimal endometrial preparation protocol by comparing the clinical outcome of two methods of endometrial preparation in frozen-thawed embryo transfer (FET) cycles, including that is, oral estradiol and 17ß-estradiol transdermal patch. Methods: In this randomized controlled trial, women underwent either conventional IVF or intracytoplasmic sperm injection (ICSI) who had at least two top-quality embryos appropriate for cryopreservation and frozen embryos from previous cycles. In the study group (n=45), 17-B estradiol transdermal patches 100 µg were applied from the second day of the cycle and continued every other day. Then, each patch was removed after four days. In the control group (n=45), oral estradiol valerate 6 mg was started at the same time and continued daily. Results: There was a significant difference in estradiol level on the day of progesterone administration and the day of embryo transfer between the two groups (p=0.001 in both), but no significant difference was observed between them in biochemical and clinical pregnancy rates (32.6% vs. 33.3%, p=1.000 and 30.2% vs. 33.3%, p=0.810, respectively). Conclusion: It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles. Due to the reduced costs, drug dose, and emotional stress as well as the simplicity of the protocol for patients.
Keywords
Endometrial preparation
frozen
thawed embryo transfer
Pregnancy rate
Transdermal estradiol patchs
  1. Aflatoonian A, Mansoori Moghaddam F, Mashayekhy M, Mohamadian F. Comparison of early pregnancy and neonatal outcomes after frozen and fresh embryo transfer in ART cycles. J Assist Reprod Genet. 2010;27(12):695-700.
  2. 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(11):2316-9.
  3. Hancke K, More S, Kreienberg R, Weiss JM. Patients undergoing frozen-thawed embryo transfer have similar live birth rates in spontaneous and artificial cycles. J Assist Reprod Genet. 2012;29(5):403-7.
  4. Kyrou D, Fatemi HM, Popovic-Todorovic B, Van den Abbeel E, Camus M, Devroey P. Vaginal progesterone supplementation has no effect on ongoing pregnancy rate in hCG-induced natural frozen-thawed embryo transfer cycles. Eur J Obstet Gynecol Reprod Biol. 2010;150(2):175-9.
  5. Salumets A, Suikkari AM, Makinen S, Karro H, Roos A, Tuuri T. Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome. Hum Reprod. 2006;21(9):2368-74.
  6. Gelbaya TA, Nardo LG, Hunter HR, Fitzgerald CT, Horne G, Pease EE, et al. Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study. Fertil Steril. 2006;85(3):603-9.
  7. Ma WG, Song H, Das SK, Paria BC, Dey SK. Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proc Natl Acad Sci USA. 2003;100(5):2963-8.
  8. Yu Ng EH, Yeung WS, Yee Lan Lau E, So WW, Ho PC. High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles. Hum Reprod. 2000;15(2):250-5.
  9. Lieberman BA, Troup SA, Matson PL. Cryopreservation of embryos and pregnancy rates after IVF. Lancet. 1992;340(8811):116.
  10. Konc J, Kanyo K, Varga E, Kriston R, Cseh S. The effect of cycle regimen used for endometrium preparation on the outcome of day 3 frozen embryo transfer cycle. Fertil Steril. 2010;94(2):767-8.
  11. Morozov V, Ruman J, Kenigsberg D, Moodie G, Brenner S. Natural cycle cryo-thaw transfer may improve pregnancy outcome. J Assist Reprod Genet. 2007;24(4):119-23.
  12. 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(4):775-80.
  13. Salumets A, Tuuri T, Makinen S, Vilska S, Husu L, Tainio R, et al. Effect of developmental stage of embryo at freezing on pregnancy outcome of frozen-thawed embryo transfer. Hum Reprod. 2003;18(9):1890-5.
  14. Schalkoff ME, Oskowitz SP, Powers RD. A multifactorial analysis of the pregnancy outcome in a successful embryo cryopreservation program. Fertil Steril. 1993;59(5):1070-4.
  15. Edgar DH, Bourne H, Speirs AL, McBain JC. A quantitative analysis of the impact of cryopreservation on the implantation potential of human early cleavage stage embryos. Hum Reprod. 2000;15(1):175-9.
  16. Van der Elst J, Van den Abbeel E, Vitrier S, Camus M, Devroey P, Van Steirteghem AC. Selective transfer of cryopreserved human embryos with further cleavage after thawing increases delivery and implantation rates. Hum Reprod. 1997;12(7):1513-21.
  17. Moini A, Zadeh Modarress S, Amirchaghmaghi E, Mirghavam N, Khafri S, Reza Akhoond M, et al. The effect of adding oral oestradiol to progesterone as luteal phase support in ART cycles - a randomized controlled study. Arch Med Sci. 2011;7(1):112-6.
  18. Roque M, Lattes K, Serra S, Sola I, Geber S, Carreras R, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013;99(1):156-62.
  19. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731-46.
  20. Kuhl H. Pharmacokinetics of oestrogens and progestogens. Maturitas. 1990;12(3):171-97.
  21. Krasnow JS, Lessey BA, Naus G, Hall LL, Guzick DS, Berga SL. Comparison of transdermal versus oral estradiol on endometrial receptivity. Fertil Steril. 1996;65(2):332-6.
  22. Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril. 2011;96(3):530-5.
  23. Banz C, Katalinic A, Al-Hasani S, Seelig AS, Weiss JM, Diedrich K, et al. Preparation of cycles for cryopreservation transfers using estradiol patches and Crinone 8% vaginal gel is effective and does not need any monitoring. Eur J Obstet Gynecol Reprod Biol. 2002;103(1):43-7.
  24. von Holst T, Salbach B. Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints. Maturitas. 2000;34(2):143-53.
  25. Davar R, Eftekhar M, Tayebi N. Transfer of Cryopreserved-Thawed Embryos in a Cycle Using Exogenous Steroids with or Without Prior Gonadotropihin-Releasing Hormone Agonist. J Med Sci. 2007;7:880-3.
  26. Dal Prato L, Borini A, Cattoli M, Bonu MA, Sciajno R, Flamigni C. Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Fertil Steril. 2002;77(5):956-60.
  27. 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.
  28. Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008;89(3):554-61.
  29. Jabbour HN, Kelly RW, Fraser HM, Critchley HO. Endocrine regulation of menstruation. Endocr Rev. 2006;27(1):17-46.
  30. Navot D, Anderson TL, Droesch K, Scott RT, Kreiner D, Rosenwaks Z. Hormonal manipulation of endometrial maturation. J Clin Endocrinol Metab.1989;68(4):801-7.
Journal of Reproduction & Infertility
Volume 17, Issue 2
Spring 2016
Pages 97-103