Embryo and Endometrial Synchrony in Implantation Failure

Chapter

Abstract

Normal implantation requires synchronous timing between the endometrium and the embryo. A loss of this synchrony—termed dyssynchrony—occurs when the endometrium is not optimally receptive at the time the embryo is ready to implant. This issue related to timing may lead to implantation failure even when the endometrial is capable of being receptive and the embryo was capable of implantation and progressing through pregnancy to delivery. While the traditional view has represented dyssynchrony as pathology attributed singularly to the embryo or the endometrium, it is clear that both entities can have robust reproductive potential in isolation, and the issue lies in the combination of both of these entities at the appropriate time. The timing of the stimulus for secretory transformation may vary from cycle to cycle, and embryonic development can also vary with age. Thus, their respective contribution to dyssynchrony is not always reproducible from cycle to cycle—thus it may not be screened for in advance. All patients undergoing superovulation during IVF are at risk for embryonic-endometrial dyssynchrony based on timing when a critical level of progesterone is attained and the timing of embryonic blastulation.

Keywords

Blastocyst Endometrium Implantation Synchrony Timing 

References

  1. 1.
    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(1):20–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Barrenetxea G, López de Larruzea A, Ganzabal T, Jiménez R, Carbonero K, Mandiola M. Blastocyst culture after repeated failure of cleavage-stage embryo transfers: a comparison of day 5 and day 6 transfers. Fertil Steril. 2005;83(1):49–53.CrossRefPubMedGoogle Scholar
  3. 3.
    Silverberg KM, Burns WN, Olive DL, Riehl RM, Schenken RS. Serum progesterone levels predict success of in vitro fertilization/embryo transfer in patients stimulated with leuprolide acetate and human menopausal gonadotropins. J Clin Endocrinol Metab. 1991;73(4):797–803.CrossRefPubMedGoogle Scholar
  4. 4.
    Bosch E, Labarta E, Crespo J, Simon C, Remohi J, Jenkins J, et al. Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod. 2010;25:2092–100.CrossRefPubMedGoogle Scholar
  5. 5.
    Franasiak JM, Ruiz-Alonso M, Scott RT, Simón C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril. 2016;105(4):861–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, Gómez E, Fernández-Sánchez M, Carranza F, et al. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013;100(3):818–24.CrossRefPubMedGoogle Scholar
  7. 7.
    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(1):114–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Prapas Y, Prapas N, Jones EE, Duleba AJ, Olive DL, Chatziparasidou A, et al. The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy. Hum Reprod Oxf Engl. 1998;13(3):720–3.CrossRefGoogle Scholar
  9. 9.
    Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and loss of pregnancy. N Engl J Med. 1999;340(23):1796–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Usadi RS, Groll JM, Lessey BA, Lininger RA, Zaino RJ, Fritz MA, et al. Endometrial development and function in experimentally induced luteal phase deficiency. J Clin Endocrinol Metab. 2008;93(10):4058–64.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mesen TB, Young SL. Progesterone and the luteal phase: a requisite to reproduction. Obstet Gynecol Clin N Am. 2015;42(1):135–51.CrossRefGoogle Scholar
  12. 12.
    Healy MW, Patounakis G, Connell MT, Devine K, DeCherney AH, Levy MJ, et al. Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles? Fertil Steril. 2016;105(1):93–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Factors related to embryo-endometrium asynchrony in fresh IVF cycles increase in prevalence with maternal age. Fertil Steril. 2013;100(3):S287.CrossRefGoogle Scholar
  14. 14.
    Forman EJ, Franasiak JM, Hong KH, Scott RT. Late expanding euploid embryos that are cryopreserved (CRYO) with subsequent synchronous transfer have high sustained implantation rates (SIR) similar to fresh normally blastulating euploid embryos. Fertil Steril. 2013;100(3):S99.CrossRefGoogle Scholar
  15. 15.
    Franasiak J, Forman EJ, Hong KH, Werner MD, Upham KM, Scott RT Jr. Investigating the impact of the timing of blastulation on implantation: active management of embryo-endometrial synchrony increases implantation rates. Fertil Steril. 2013;100(3):S97.CrossRefGoogle Scholar
  16. 16.
    Werner MD, Forman EJ, Hong KH, Franasiak JM, Molinaro TA, Scott RT. Defining the “sweet spot” for administered luteinizing hormone-to-follicle-stimulating hormone gonadotropin ratios during ovarian stimulation to protect against a clinically significant late follicular increase in progesterone: an analysis of 10,280 first in vitro fertilization cycles. Fertil Steril. 2014;102(5):1312–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Franasiak JM, Thomas S, Ng S, Fano M, Ruiz A, Scott RT, et al. Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF. J Assist Reprod Genet. 2016;33(3):387–91.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Sidney Kimmel Medical CollegeThomas Jefferson University PhiladelphiaPhiladelphiaUSA
  2. 2.IVI-RMA of New JerseyBasking RidgeUSA

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