Effect of endometrial injury on in vitro fertilization pregnancy rates: a randomized, multicentre study

  • Jennifer Hilton
  • Kimberly E. LiuEmail author
  • Carl A. Laskin
  • Jon Havelock
Gynecologic Endocrinology and Reproductive Medicine



To determine if endometrial injury prior to the first or second in vitro fertilization (IVF) cycle affects clinical pregnancy rates.


This study was a randomized, multicentre, controlled study performed at three Canadian outpatient fertility clinics. Patients undergoing their first or second IVF cycle were randomized to a single endometrial injury 5–10 days prior to the start of gonadotropins in an IVF cycle compared to no injury. The primary outcome was clinical pregnancy rate. Secondary outcomes were live birth rates, implantation rate, endometrial thickness, number of oocytes retrieved and the rate of embryo cryopreservation.


Fifty-one women were randomized (25 in the en dometrial injury group and 26 in the control group); however, the study was terminated prematurely due to slow recruitment (target 332 patients). Groups were similar at baseline for: age, duration of infertility, BMI, day 3 FSH, and the number having first IVF cycle. The groups were similar for gonadotropin dose, endometrial thickness, number of oocytes retrieved, and embryo cryopreservation rate. The clinical pregnancy rate in the endometrial injury group was 52% (13/25) and 46% (12/26) in the control group (p = 0.45). Live birth rate in the endometrial injury group was 52% (13/25) and 35% (9/26) in the control group (p = 0.17). The implantation rate was also similar (58% vs. 45%, p = 0.17).


This study did not detect a difference in implantation, clinical pregnancy or live birth rates; however, the lack of difference in this study may be because it was underpowered.

Clinical trials registrations

gov: NCT01983423


Endometrium Local injury IVF outcomes Implantation 



This study was supported by an unrestricted Educational Grant from Ferring Inc. (Canada).

Author contributions

JH data collection, data analysis, manuscript writing. KEL protocol development, data collection, manuscript writing/editing. CAL protocol development, data collection, manuscript writing/editing. JH protocol development, data collection, data analysis, manuscript writing/editing.


This study was funded by an unrestricted Research Grant from Ferring Inc. (Canada). (No Grant number was provided).

Compliance with ethical standards

Conflict of interest

J Hilton: No conflicts to declare except for the study funding. KE Liu: No conflicts to declare except for the study funding. CA Laskin: No conflicts to declare except for the study funding. J Havelock: No conflicts to declare except for the study funding.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by The University of British Columbia Clinical Research Ethics Board, Vancouver BC, Canada (#H12-01484) and the Mount Sinai Hospital Research Ethics Board, Toronto ON, Canada (#12-0068-A).

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I (2003) Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril. 79(6):1317–1322CrossRefGoogle Scholar
  2. 2.
    Baum M, Yerushalmi GM, Maman E et al (2012) Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo controlled trial. Gynecol Endocrinol 28(12):933–936CrossRefGoogle Scholar
  3. 3.
    Gnainsky Y, Granot I, Aldo P et al (2015) Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action. Reproduction 149(1):75–85CrossRefGoogle Scholar
  4. 4.
    Hayashi T, Kitaya K, Tada Y, Taguchi S, Funabiki M, Nakamura Y (2013) Single curettage endometrial biopsy injury in the proliferative phase improves reproductive outcome of subsequent in vitro fertilization-embryo transfer cycle in infertile patients with repeated embryo implantation failure. Clin Exp Obstet Gynecol 40(3):323–326Google Scholar
  5. 5.
    Huang SY, Wang CJ, Soong YK, et al. Site-specific endometrial injury improves implantation and pregnancy in patients with repeated implantation failures. Reprod Biol Endocrinol. 2011;9:140-7827-9-140Google Scholar
  6. 6.
    Kara M, Aydin T, Turktekin N, S K. Efficacy of the local endometrial injury in patients who had previous failed IVF-ICSI outcome. Iran J Reprod Med. 2012;10(6):567-570Google Scholar
  7. 7.
    Karimzadeh MA, Ayazi Rozbahani M, Tabibnejad N (2009) Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Aust N Z J Obstet Gynaecol 49(6):677–680CrossRefGoogle Scholar
  8. 8.
    Narvekar SA, Gupta N, Shetty N, Kottur A, Srinivas M, Rao KA (2010) 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 3(1):15–19CrossRefGoogle Scholar
  9. 9.
    Reljic M, Knez J, Kovac V, Kovacic B (2017) Endometrial injury, the quality of embryos, and blastocyst transfer are the most important prognostic factors for in vitro fertilization success after previous repeated unsuccessful attempts. J Assist Reprod Genet 34(6):775–779CrossRefGoogle Scholar
  10. 10.
    Salehpour S, Zamaniyan M, Saharkhiz N et al (2016) Does intrauterine saline infusion by intrauterine insemination (IUI) catheter as endometrial injury during IVF cycles improve pregnancy outcomes among patients with recurrent implantation failure? An RCT. Int J Reprod Biomed (Yazd) 14(9):583–588CrossRefGoogle Scholar
  11. 11.
    Shahrokh-Tehraninejad E, Dashti M, Hossein-Rashidi B, Azimi-Nekoo E, Haghollahi F, Kalantari V (2016) A randomized trial to evaluate the effect of local endometrial injury on the clinical pregnancy rate of frozen embryo transfer cycles in patients with repeated implantation failure. J Family Reprod Health. 10(3):108–114Google Scholar
  12. 12.
    Singh N, Toshyan V, Kumar S, Vanamail P, Madhu M (2015) Does endometrial injury enhances implantation in recurrent in-vitro fertilization failures? A prospective randomized control study from tertiary care center. J Hum Reprod Sci. 8(4):218–223CrossRefGoogle Scholar
  13. 13.
    Siristatidis C, Kreatsa M, Koutlaki N, Galazios G, Pergialiotis V, Papantoniou N (2017) Endometrial injury for RIF patients undergoing IVF/ICSI: a prospective nonrandomized controlled trial. Gynecol Endocrinol. 33(4):297–300CrossRefGoogle Scholar
  14. 14.
    Tk A, Singhal H, S Premkumar P, Acharya M, S Kamath M, George K. Local endometrial injury in women with failed IVF undergoing a repeat cycle: a randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2017;214:109-114Google Scholar
  15. 15.
    van Hoogenhuijze NE, Torrance HL, Mol F, et al. Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? the SCRaTCH study: a randomized controlled trial (NTR 5342). BMC Womens Health. 2017;17(1):47-017-0378-yGoogle Scholar
  16. 16.
    S Lensen D Osavyluk S Armstrong et al 2018 Endometrial scratching by pipelle biopsy in IVF (the PIP study): a pragmatic randomised controlled trial Human Reprod Oxford, England 33 Suppl 1 O139Google Scholar
  17. 17.
    El-Toukhy T, Sunkara S, Khalaf Y (2012) Local endometrial injury and IVF outcome: a systematic review and meta-analysis. Reprod Biomed Online. 25(4):345–354CrossRefGoogle Scholar
  18. 18.
    Potdar N, Gelbaya T, Nardo LG (2012) Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. Reprod Biomed Online. 25(6):561–571CrossRefGoogle Scholar
  19. 19.
    Gnainsky Y, Granot I, Aldo PB et al (2010) Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril. 94(6):2030–2036CrossRefGoogle Scholar
  20. 20.
    Liang Y, Han J, Jia C et al (2015) Effect of endometrial injury on secretion of endometrial cytokines and IVF outcomes in women with unexplained subfertility. Mediators Inflamm. 2015:757184CrossRefGoogle Scholar
  21. 21.
    Liu W, Tal R, Chao H, Liu M, Liu Y. Effect of local endometrial injury in proliferative vs. luteal phase on IVF outcomes in unselected subfertile women undergoing in vitro fertilization. Reprod Biol Endocrinol. 2017;15(1):75-017-0296-8Google Scholar
  22. 22.
    Mahran A, Ibrahim M, Bahaa H (2016) The effect of endometrial injury on first cycle IVF/ICSI outcome: A randomized controlled trial. Int J Reprod Biomed (Yazd). 14(3):193–198CrossRefGoogle Scholar
  23. 23.
    Safdarian L, Movahedi S, Aleyasine A, Aghahosaini M, Fallah P, Rezaiian Z (2011) Local injury to the endometrium does not improve the implantation rate in good responder patients undergoing in-vitro fertilization. Iran J Reprod Med. 9(4):285–288Google Scholar
  24. 24.
    Yeung TW, Chai J, Li RH, Lee VC, Ho PC, Ng EH (2014) The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: A randomized controlled trial. Hum Reprod. 29(11):2474–2481CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pacific Centre for Reproductive MedicineEdmontonCanada
  2. 2.Mount Sinai FertilityTorontoCanada
  3. 3.Department of Obstetrics and GynecologyUniversity of TorontoTorontoCanada
  4. 4.Department of MedicineUniversity of TorontoTorontoCanada
  5. 5.TRIO FertilityTorontoCanada
  6. 6.Pacific Centre for Reproductive MedicineBurnabyCanada

Personalised recommendations