To investigate the impact of late follicular phase serum estradiol (E2) levels on implantation and pregnancy outcomes of cleavage stage cryopreserved/thawed embryos transferred in programmed cycles with exogenous hormonal replacement.
Retrospective cohort analysis of IVF patients with transfer of cryopreserved-thawed day-3 embryos in E2 and progesterone (P4) supplemented cycles (n = 208 cycles). Main outcome measures: implantation and pregnancy rates according to late follicular phase serum E2 levels and early secretory phase E2/P4 ratios.
Logistic regression performed for embryo implantation and for pregnancy outcome in relation to E2 (day 15), P4 (day 15 and 16), before (crude analysis) and after adjustment (adjusted analysis) for baseline characteristics (including age, BMI, serum basal cycle day 3 FSH levels, embryo quality, endometrial lining thickness) showed no significant association. Similarly, ROC analysis showed no impact of cycle day 16 E2/P4 ratio.
Neither late follicular phase serum E2 nor the early E2/P4 ratio were able to predict implantation or pregnancy outcome of day-3 cryopreserved-thawed embryos transferred in artificially programmed cycles.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Toner JP, Brzyski RG, Oehninger S, Veeck LL, Simonetti S, Muasher SJ. Combined impact of the number of pre-ovulatory oocytes and cryopreservation on IVF outcome. Hum Reprod. 1991;6:284–9.
Oehninger S, Mayer J, Muasher S. Impact of different clinical variables on pregnancy outcome following embryo cryopreservation. Mol Cell Endocrinol. 2000;169:73–7.
Arslan M, Bocca S, Mirkin S, Barroso G, Stadtmauer L, Oehninger S. Controlled ovarian hyperstimulation protocols for in vitro fertilization: two decades of experience after the birth of Elizabeth Carr. Fertil Steril. 2005;84:555–69.
DeZiegler D. Hormonal control of endometrial receptivity. Hum Reprod. 1995;10:4–7.
Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013;19:458–70.
Muasher SJ, Kruithoff C, Simonetti S, Oehninger S, Acosta AA, Jones GS. Controlled preparation of the endometrium with exogenous steroids for the transfer of frozen-thawed pre-embryos in patients with anovulatory or irregular cycles. Hum Reprod. 1991;6:443–5.
Oehninger S, Toner JP, Veeck LL, Brzyski RG, Acosta AA, Muasher SJ. Performance of cryopreserved pre-embryos obtained in in vitro fertilization cycles with or without a gonadotropin-releasing hormone agonist. Fertil Steril. 1992;57:620–5.
Queenan Jr JT, Veeck LL, Seltman HJ, Muasher SJ. Transfer of cryopreserved-thawed pre-embryos in a natural cycle or a programmed cycle with exogenous hormonal replacement yields similar pregnancy results. Fertil Steril. 1994;62:545–50.
Paulson RJ, Sauer MV, Lobo RA. Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. Fertil Steril. 1990;53:870–4.
Simón C, Cano F, Valbuena D, Remohí J, Pellicer A. Clinical evidence for a detrimental effect on uterine receptivity of high serum estradiol levels in high and normal responder patients. Hum Reprod. 1995;10:2432–4.
Mirkin S, Nikas G, Hsiu JG, Díaz J, Oehninger S. Gene expression profiles and structural/functional features of the peri-implantation endometrium in natural and gonadotropin-stimulated cycles. J Clin Endocrinol Metab. 2004;89:5742–52.
Toner JP, Hassiakos DK, Muasher SJ, Hsiu JG, Jones Jr HW. Endometrial receptivities after leuprolide suppression and gonadotropin stimulation: histology, steroid receptor concentrations, and implantation rates. Ann N Y Acad Sci. 1991;622:220–9.
Arslan M, Bocca S, Arslan EO, Duran HE, Stadtmauer L, Oehninger S. Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation. J Assist Reprod Genet. 2007;24:111–7.
Riggs R, Mayer J, Dowling-Lacey D, Chi TF, Jones E, Oehninger S. Does storage time influence postthaw survival and pregnancy outcome? An analysis of 11,768 cryopreserved human embryos. Fertil Steril. 2010;93:109–15.
Ueno J, Oehninger S, Brzyski RG, Acosta AA, Philput CB, Muasher SJ. Ultrasonographic appearance of the endometrium in natural and stimulated in-vitro fertilization cycles and its correlation with outcome. Hum Reprod. 1991;6:901–4.
Dowling-Lacey D, Jones E, Mayer J, Bocca S, Stadtmauer L, Oehninger S. Elective transfer of two embryos: reduction of multiple gestations while maintaining high pregnancy rates. J Assist Reprod Genet. 2007;24:11–5.
Oehninger S. Ovulation induction in IVF. Minerva Ginecol. 2011;63:137–56.
Veeck LL. Freezing of preembryos: early vs late stages. J Assist Reprod Genet. 1993;10:181–5.
Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Fertil Steril. 1998;69:96–101.
Veeck LL. Cryopreservation. In: Veeck LL, editor. Atlas of human oocyte and early conceptus, 2. Baltimore: Williams & Wilkins; 1991. p. 257–303.
Mirkin S, Jones EL, Mayer JF, Stadtmauer L, Gibbons WE, Oehninger S. Impact of transabdominal ultrasound guidance on performance and outcome of transcervical uterine embryo transfer. J Assist Reprod Genet. 2003;20:318–22.
Remohí J, Ardiles G, García-Velasco JA, Gaitán P, Simón C, Pellicer A. Endometrial thickness and serum oestradiol concentrations as predictors of outcome in oocyte donation. Hum Reprod. 1997;12:2271–6.
Cicinelli E, de Ziegler D. Transvaginal progesterone: evidence for a new functional ‘portal system’ flowing from the vagina to the uterus. Hum Reprod Update. 1999;5:365–72.
Psychoyos A. The implantation window; basic and clinical aspects. In Mori et al. (eds) Perspectives on Assisted Reproduction. Ares-Serono Symposium 4, Roma; 1994. pp 57–63
Navot D, Scott RT, Droesch K, Veeck LL, Liu HC, Rosenwaks Z. The window of embryo transfer and the efficiency of human conception in vitro. Fertil Steril. 1991;55:114–8.
Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and loss of pregnancy. New Engl J Med. 1999;340:1796–9.
Sunderam S, Kissin DM, Crawford S, Anderson JE, Folger SG, Jamieson DJ, et al. Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. Assisted reproductive technology surveillance - United States, 2010. MMWR Surveill Summ. 2013;62:1–24.
van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2011;(10):CD 009154.
Young SL. Oestrogen and progesterone action on endometrium: a translational approach to understanding endometrial receptivity. Reprod BioMed Online. 2013;27:497–505.
Giudice LC. Elucidating endometrial function in the post-genomic era. Hum Reprod Update. 2003;9:223–35.
Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S, et al. Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod. 2005;11:195–205.
Oehninger S. Revealing the enigmas of implantation: what is the true impact of ovarian hyperstimulation? Fertil Steril. 2008;89:27–30.
Van Voorhis BJ, Thomas M, Surrey ES, Sparks A. What do consistently high-performing in vitro fertilization programs in the U.S. do? Fertil Steril. 2010;94:1346–9.
Díaz-Gimeno P, Ruiz-Alonso M, Blesa D, Bosch N, Martínez-Conejero JA, Alamá P, et al. The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity. Fertil Steril. 2013;99:508–17.
Maheshwari A, Bhattacharya S. Elective frozen replacement cycles for all: ready for prime time? Hum Reprod. 2013;28:6–9.
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.
Stehlik E, Stehlik J, Katayama KP, Kuwayama M, Jambor V, Brohammer R, et al. Vitrification demonstrates significant improvement versus slow freezing of human blastocysts. Reprod BioMed Online. 2005;11:53–7.
Kato O, Kawasaki N, Bodri D, Kuroda T, Kawachiya S, Kato K, et al. Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer. Eur J Obstet Gynecol Reprod Biol. 2012;161:46–50.
Cohen J, Alikani M. The time has come to radically rethink assisted reproduction. Reprod BioMed Online. 2013;27:323–4.
Capsule This retrospective cohort study showed that neither late follicular phase serum E2 nor the early E2/P4 ratio were able to predict implantation or pregnancy outcome of day-3 cryopreserved-thawed embryos transferred in artificially programmed cycles.
Rights and permissions
About this article
Cite this article
Bocca, S., Real, E.B., Lynch, S. et al. Impact of serum estradiol levels on the implantation rate of cleavage stage cryopreserved-thawed embryos transferred in programmed cycles with exogenous hormonal replacement. J Assist Reprod Genet 32, 395–400 (2015). https://doi.org/10.1007/s10815-014-0402-1