Hysteroscopy pp 253-258 | Cite as

Refractory Endometrium and Hysteroscopy



It is widely known that an adequate growth of the endometrium is indispensable for implantation and successful pregnancy. However, there is no clear agreement on what proper growth is. When reviewing the literature, it is accepted that an endometrial thickness of less than 7 mm would be considered as a refractory endometrium (or thin endometrium) and that would entail to altered pregnancy and live birth rates [1, 2]. It has been long tried to define the optimal characteristics of that “ideal” endometrium in which to transfer the best possible embryo. Investigators have sought to determine it using ultrasonography regarding its thickness and its pattern, but no explicit agreement has been established to date. Moreover, pregnancies and live births have been documented both with thinner and normal endometrium [3]. Therefore, because of the difficulties in defining diagnostic criteria, it is challenging to calculate its true prevalence, although some researchers estimate it around 2.42% (260/10724 women) [4].


  1. 1.
    Dix E, Check J. Successful pregnancies following embryo transfer despite very thin late proliferative endometrium. Clin Exp Obstet Gynecol. 2009;37(1):15–6.Google Scholar
  2. 2.
    Garcia-Velasco JA, Acevedo B, Alvarez C, Alvarez M, Bellver J, Fontes J, et al. Strategies to manage refractory endometrium: state of the art in 2016. Reprod Biomed Online. 2016;32(5):474–89.CrossRefPubMedGoogle Scholar
  3. 3.
    Cruz F, Bellver J. Live birth after embryo transfer in an unresponsive thin endometrium. Gynecol Endocrinol. 2014;30(7):481–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(4):530–41.CrossRefPubMedGoogle Scholar
  5. 5.
    Takasaki A, Tamura H, Miwa I, Taketani T, Shimamura K, Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil Steril. 2010;93:1851.CrossRefPubMedGoogle Scholar
  6. 6.
    Check J, Lurie D, Dietterich C, Callan C, Baker A. Pregnancy: adverse effect of a homogeneous hyperechogenic endometrial sonographic pattern, despite adequate endometrial thickness on pregnancy rates following in-vitro fertilization. Hum Reprod. 1993;8(8):1293–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Amui J, Check J, Cohen R. Successful twin pregnancy in a donor oocyte recipient despite a maximum endometrial thickness in the late proliferative phase of 4 mm. Clin Exp Obstet Gynecol. 2010;38(4):328–9.Google Scholar
  8. 8.
    Luke B, Brown MB, Wantman E, Lederman A, Gibbons W, Schattman GL, et al. Cumulative birth rates with linked assisted reproductive technology cycles. N Engl J Med. 2012;366(26):2483–91.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Dalton VK, Saunders NA, Harris LH, Williams JA, Lebovic DI. Intrauterine adhesions after manual vacuum aspiration for early pregnancy failure. Fertil Steril. 2006;85(6):1823.e1–3.CrossRefGoogle Scholar
  10. 10.
    Bozdag G, Aksan G, Esinler I, Yarali H. What is the role of office hysteroscopy in women with failed IVF cycles? Reprod Biomed Online. 2008;17(3):410–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Urman B, Yakin K, Balaban B. Recurrent implantation failure in assisted reproduction: how to counsel and manage. A. General considerations and treatment options that may benefit the couple. Reprod Biomed Online. 2005;11(3):371–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Shamma FN, Lee G, Gutmann JN, Lavy G. The role of office hysteroscopy in in vitro fertilization. Fertil Steril. 1992;58(6):1237–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Bettocchi S, Nappi L, Ceci O, Silvaggi L. Office hysteroscopy. Obstet Gynecol Clin N Am. 2004;31(3):641–54.CrossRefGoogle Scholar
  14. 14.
    Asherman JG. Traumatic intra-uterine adhesions. J Obstet Gynaecol Br Emp. 1950;57(6):892–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Salma U, Xue M, Md Sayed AS, Xu D. Efficacy of intrauterine device in the treatment of intrauterine adhesions. Biomed Res Int. 2014;2014:589296.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Taskin O, Sadik S, Onoglu A, Gokdeniz R, Erturan E, Burak K, et al. Role of endometrial suppression on the frequency of intrauterine adhesions after resectoscopic surgery. J Am Assoc Gynecol Laparosc. 2000;7:351.CrossRefPubMedGoogle Scholar
  17. 17.
    Johary J, Xue M, Zhu X, Xu D, Velu PP. Efficacy of estrogen therapy in patients with intrauterine adhesions: systematic review. J Minim Invasive Gynecol. 2014;21(1):44–54.CrossRefPubMedGoogle Scholar
  18. 18.
    Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome—one century later. Fertil Steril. 2008;89:759.CrossRefPubMedGoogle Scholar
  19. 19.
    Lin XN, Zhou F, Wei ML, Yang Y, Li Y, Li TC, et al. Randomized, controlled trial comparing the efficacy of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis. Fertil Steril. 2015;104(1):235–40.CrossRefPubMedGoogle Scholar
  20. 20.
    Deans R, Abbott J. Review of intrauterine adhesions. J Minim Invasive Gynecol. 2010;17:555.CrossRefPubMedGoogle Scholar
  21. 21.
    Bosteels J, Weyers S, Mol BW, D'Hooghe T. Anti-adhesion barrier gels following operative hysteroscopy for treating female infertility: a systematic review and meta-analysis. Gynecol Surg. 2014;11:113–27.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Aarts JW, Nieboer TE, Johnson N, Tavender E, Garry R, Mol BW, et al. Surgical approach to hysterectomy for benign gynaecological disease. Cochrane Database Syst Rev. 2015;8:CD003677.Google Scholar
  23. 23.
    Kodaman P, Arici A. Intra-uterine adhesions and fertility outcome: how to optimize success? Curr Opin Obstet Gynecol. 2007;19:207.CrossRefPubMedGoogle Scholar
  24. 24.
    Conforti A, Alviggi C, Mollo A, De Placido G, Magos A. The management of Asherman syndrome: a review of literature. Reprod Biol Endocrinol. 2013;11(1):1–11.CrossRefGoogle Scholar
  25. 25.
    Galliano D, Bellver J, Díaz-García C, Simón C, Pellicer A. ART and uterine pathology: how relevant is the maternal side for implantation? Human Reprod Update. 2015;21(1):13–38.CrossRefGoogle Scholar
  26. 26.
    Ferro J, Montoya P. Innovative alternatives in the postoperative management of Asherman syndrome. In: Deshmukh S, Shawki O, editors. Mastering the techniques in hysteroscopy. 1st ed. India: Jaypee; 2016. p. 431–7.Google Scholar
  27. 27.
    March CM. Management of Asherman syndrome. Reprod Biomed Online. 2011;23:63–76.CrossRefPubMedGoogle Scholar
  28. 28.
    Kupesic S. Clinical implications of sonographic detection of uterine anomalies for reproductive outcome. Ultrasound Obstet Gynecol. 2001;18(4):387–400.CrossRefPubMedGoogle Scholar
  29. 29.
    Serensen SS. Estimated prevalence of müllerian anomalies. Acta Obstet Gynecol Scand. 1988;67(5):441–5.CrossRefGoogle Scholar
  30. 30.
    Saravelos SH, Cocksedge KA, Li T-C. Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal. Hum Reprod Update. 2008;14(5):415–29.CrossRefPubMedGoogle Scholar
  31. 31.
    Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simón C, Pellicer A. Reproductive impact of congenital Müllerian anomalies. Hum Reprod. 1997;12(10):2277–81.CrossRefPubMedGoogle Scholar
  32. 32.
    Chan Y, Jayaprakasan K, Tan A, Thornton J, Coomarasamy A, Raine-Fenning N. Reproductive outcomes in women with congenital uterine anomalies: a systematic review. Ultrasound Obstet Gynecol. 2011;38(4):371–82.CrossRefPubMedGoogle Scholar
  33. 33.
    Fedele L, Arcaini L, Parazzini F, Vercellini P, Di Nola G. Reproductive prognosis after hysteroscopic metroplasty in 102 women: life-table analysis. Fertil Steril. 1993;59(4):768–72.CrossRefPubMedGoogle Scholar
  34. 34.
    Pabuçcu R, Gomel V. Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril. 2004;81(6):1675–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Zlopaša G, Škrablin S, Kalafatić D, Banović V, Lešin J. Uterine anomalies and pregnancy outcome following resectoscope metroplasty. Int J Gynecol Obstet. 2007;98(2):129–33.CrossRefGoogle Scholar
  36. 36.
    Bakas P, Gregoriou O, Hassiakos D, Liapis A, Creatsas M, Konidaris S. Hysteroscopic resection of uterine septum and reproductive outcome in women with unexplained infertility. Gynecol Obstet Investig. 2012;73(4):321–5.CrossRefGoogle Scholar
  37. 37.
    Fatemi H, Kasius J, Timmermans A, Van Disseldorp J, Fauser B, Devroey P, et al. Prevalence of unsuspected uterine cavity abnormalities diagnosed by office hysteroscopy prior to in vitro fertilization. Hum Reprod. 2010;25(8):1959–65.CrossRefPubMedGoogle Scholar
  38. 38.
    Pundir J, Pundir V, Omanwa K, Khalaf Y, El-Toukhy T. Hysteroscopy prior to the first IVF cycle: a systematic review and meta-analysis. Reprod Biomed Online. 2014;28(2):151–61.CrossRefPubMedGoogle Scholar
  39. 39.
    Bosteels J, Weyers S, Puttemans P, Panayotidis C, Van Herendael B, Gomel V, et al. The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review. Hum Reprod Update. 2010;16(1):1–11.CrossRefPubMedGoogle Scholar
  40. 40.
    Nastri CO, Lensen SF, Gibreel A, Raine-Fenning N, Ferriani RA, Bhattacharya S, et al. Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015.Google Scholar
  41. 41.
    Siristatidis C, Vrachnis N, Vogiatzi P, Chrelias C, Retamar AQ, Bettocchi S, et al. Potential pathophysiological mechanisms of the beneficial role of endometrial injury in in vitro fertilization outcome. Reprod Sci. 2014;21(8):955–65.CrossRefPubMedGoogle Scholar
  42. 42.
    Gnainsky Y, Granot I, Aldo PB, Barash A, Or Y, Schechtman E, et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril. 2010;94(6):2030–6.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Li R, Hao G. Local injury to the endometrium: its effect on implantation. Curr Opin Obstet Gynecol. 2009;21(3):236–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Shohayeb A, El-Khayat W. Does a single endometrial biopsy regimen (S-EBR) improve ICSI outcome in patients with repeated implantation failure? A randomised controlled trial. Eur J Obstet Gynecol Reprod Biol. 2012;164(2):176–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Narvekar SA, Gupta N, Shetty N, Kottur A, Srinivas M, Rao KA. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study. J Hum Reprod Sci. 2010;3(1):15.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Santamaria X, Cabanillas S, Cervelló I, Arbona C, Raga F, Ferro J, et al. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study. Hum Reprod. 2016;31(5):1087–96.CrossRefPubMedGoogle Scholar
  47. 47.
    Gargett CE, Nguyen HP, Ye L. Endometrial regeneration and endometrial stem/progenitor cells. Rev Endocr Metab Disord. 2012;13:235–51.CrossRefPubMedGoogle Scholar
  48. 48.
    Casper RF. It’s time to pay attention to the endometrium. Fertil Steril. 2011;96(3):519–21.CrossRefPubMedGoogle Scholar
  49. 49.
    Jensen JR, Witz CA, Schenken RS, Tekmal RR. A potential role for colony-stimulating factor 1 in the genesis of the early endometriotic lesion. Fertil Steril. 2010;93(1):251–6.CrossRefPubMedGoogle Scholar
  50. 50.
    Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, et al. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015;8(1):1286.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Dentali F, Ageno W, Rezoagli E, Rancan E, Squizzato A, Middeldorp S, et al. Low-dose aspirin for in vitro fertilization or intracytoplasmic sperm injection: a systematic review and a meta-analysis of the literature. J Thromb Haemost. 2012;10(10):2075–85.CrossRefPubMedGoogle Scholar
  52. 52.
    Chiao TB, Lee AJ. Role of pentoxifylline and vitamin E in attenuation of radiation-induced fibrosis. Ann Pharmacother. 2005;39(3):516–22.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Instituto Universitario Instituto Valenciano de Infertilidad, IVIValenciaSpain

Personalised recommendations