Optimization of endometrial preparation results in a normal endometrial function test® (EFT®) and good reproductive outcome in donor ovum recipients

  • H. J. Kliman
  • S. Honig
  • D. Walls
  • M. Luna
  • J. C. McSweet
  • Alan B. CoppermanEmail author
Original Paper


Purpose: Numerous studies have investigated potential markers of endometrial receptivity as predictors of successful implantation. Cyclin E and p27 have recently been studied using the endometrial function test (EFT). Our objective is to determine the correlation between the expression of cyclin E and p27 and the adequacy of uterine preparation of recipients using donor oocytes. Methods: Twenty recipients undergoing preparatory cycles with leuprolide acetate, estrogen, and progesterone. Endometrial biopsies were obtained 10–12 days after progesterone supplementation following the course of estrogen. The tissue was prepared for histological analysis and immunohistochemical staining for cyclin E assessment. The outcome of their subsequent ovum donation cycle was blinded to the reviewer of the EFT. Results: All recipients showed normal luteal transformation. Nineteen (95%) of the recipients had a normal EFT. This is significantly higher than what we demonstrated, previously, in unexplained infertility patients, where only 40% of such patients had a normal EFT. Thirteen recipients with a normal EFT had a clinical pregnancy, while 6 did not become pregnant in their subsequent transfer cycles. The sole patient with an abnormal EFT did not conceive on 2 subsequent cycles. Conclusions: While a normal EFT does not guarantee a successful pregnancy, an abnormal EFT appears to be associated with pregnancy failure. This may be useful in identifying women who need adjustments to their stimulation protocols prior to progressing to a physically, emotionally, and financially costly cycle.


Cyclin E Donor ovum recipients Endometrial function test Implantation Markers of receptivity P27 


  1. 1.
    Navot D, Bergh P. Preparation of the human endometrium for implantation. Ann NY Acad Sci 1991;622:212–9PubMedGoogle Scholar
  2. 2.
    Navot D, Scott R, Droesch K, Veek L, Liu H, Rosenwaks C. The window of embryo transfer and the efficiency of human conception in vitro. Fertil Steril 1991;55(1):114–8PubMedGoogle Scholar
  3. 3.
    Noyes R, Hertig A, Rock J. Dating the endometrial biopsy. Fertil Steril 1950;1:3–25Google Scholar
  4. 4.
    Li T, Dockery P, Rogers A, Cooke I. How precise is histological dating of endometrium using the standard dating criteria? Fertil Steril 1989;51:576–82Google Scholar
  5. 5.
    Gibson M, Badger G, Byrn F, Lee K, Korson R. Error in histologic dating of secretory endometrium: variance component analysis. Fertil Steril 1991;56:242–47PubMedGoogle Scholar
  6. 6.
    Murray M, Meyer W, Zaino R, Lessey B, Novotny D, Ireland K et al. A critical analysis of the accuracy, reproductibility and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 2004;81:1333–43PubMedCrossRefGoogle Scholar
  7. 7.
    Coutifaris C, Myers E, Guzick D, Diamond M, Carson S, Legro R et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 2004;82:1264–72PubMedCrossRefGoogle Scholar
  8. 8.
    Lessey B, Castelbaum A, Wolf L, Greene W, Paulson M, Meyer W et al. Use of integrins to date the endometrium. Fertil Steril 2000;73:779–87PubMedCrossRefGoogle Scholar
  9. 9.
    Nardo L, Sabatini L, Nardo R, Nardo F. Pinopode expression during human implantation. Eur J Obstet Gynecol Reprod Biol 2002;101:104–8PubMedCrossRefGoogle Scholar
  10. 10.
    Dunglison G, Barlow D, Sergeant I. Leukaemia inhibitory factor significantly enhances the blastocyst formation rates of human embryos cultured in serum free medium. Hum Reprod 1996;11:191–6PubMedGoogle Scholar
  11. 11.
    Lai T, Shih I, Vlahos N, Ho C, Wallach E, Zhao Y. Differential expression of L-selectin ligand in the endometrium during the menstrual cycle. Fertil Steril 2005;83(1):1297–302PubMedCrossRefGoogle Scholar
  12. 12.
    Eun Kwon H, Taylor H. The role of HOX genes in human implantation. Ann NY Acad Sci 2004;1034:1–18PubMedCrossRefGoogle Scholar
  13. 13.
    Lindhard A, Bentin U, Ravn V, Islin H, Hviid T, Rex S et al. Biochemical evaluation of endometrial function at the time of implantation. Fertil Steril 2002;78:221–33PubMedCrossRefGoogle Scholar
  14. 14.
    Hey N, Graham R, Seif M, Aplin J. Polymorphic epithelial mucin MUC-1 in human endometrium is regulated with maximal expression in the implantation phase. J Clin Endo Metabol 1994;78: 337–42CrossRefGoogle Scholar
  15. 15.
    Cullinan E, Abbondanzo S, Anderson P, Pollard J, Lessey B, Stewart C. Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. Proc Natl Acad Sci USA 1996;93:3115–20PubMedCrossRefGoogle Scholar
  16. 16.
    Simon C, Pellicer A, Polan M. Interleukin-1 system crosstalk between embryo and endometrium in implantation. Hum Reprod 1995;10:43–54PubMedGoogle Scholar
  17. 17.
    Martin J, Dominguez F, Avila S, Castrillo J, Remohi J, Pellicer A et al. Human endometrial receptivity: gene regulation. J Reprod Immunol 2002;55:131–39PubMedCrossRefGoogle Scholar
  18. 18.
    Kliman HJ, Feinberg RF, Schwartz LB, Feinman MA, Lavi E, Meaddough EL. A human endometrial mucin identified by MAG (mouse ascites Golgi) antibodies: menstrual cycle-dependent localization suggests a link to early implantation events. Am J Pathology 1995;146:166–181Google Scholar
  19. 19.
    Brown S, Mandeline E, Oehninger S, Toner J, Seppala M, Jones H. Endometrial glycodelin-A expression in the luteal phase of stimulated ovarian cycles. Fertil Steril 2000;74: 130–33PubMedCrossRefGoogle Scholar
  20. 20.
    Brooks P, Stromblad S, Sanders L, Von Schalscha T, Aimes R, Stetler-Stevenson W, Quigley J, Cheresh D. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 1996;85: 683–93PubMedCrossRefGoogle Scholar
  21. 21.
    Moyer D, Felix J. The effects of progesterone and progestins on endometrial proliferation. Contraception 1998;57:399– 403PubMedCrossRefGoogle Scholar
  22. 22.
    Dubowy R, Feinberg R, Keefe D, Doncel G, Williams S, McSweet J, Kliman HJ. Improved endometrial assessment using cyclin E and p27. Fertil Steril 2003;80(1):146–56PubMedCrossRefGoogle Scholar
  23. 23.
    Grunfeld L, Walker B, Bergh PA, Sandler B, Hofmann G, Navot D. High-resolution endovaginal ultrasonography of the endometrium: a noninvasive test for endometrial adequacy. Obstet Gynecol 1991;78(2):200–4PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • H. J. Kliman
    • 1
  • S. Honig
    • 2
  • D. Walls
    • 3
  • M. Luna
    • 2
    • 3
  • J. C. McSweet
    • 1
  • Alan B. Copperman
    • 2
    • 3
    Email author
  1. 1.Yale UniversityNew HavenUSA
  2. 2.Department of Reproductive Endocrinology and InfertilityMount Sinai School of MedicineNew YorkUSA
  3. 3.Mount Sinai Medical CenterReproductive Medicine Associates of New YorkNew YorkUSA

Personalised recommendations