Intrauterine CRH-treated PBMC in repeated implantation failure

Eur J Clin Invest. 2019 May;49(5):e13084. doi: 10.1111/eci.13084. Epub 2019 Feb 27.


Background: The intrauterine administration of activated autologous peripheral blood monocytes (PBMC) prior to embryo transfer seems to improve reproductive outcomes in women with repeated implantation failure (RIF). We have previously shown that the intrauterine administration of PBMC treated with corticotropin-releasing hormone (CRH) prior to blastocyst transfer (day 5) improves significantly the clinical pregnancy rate of women with RIF. In the present crossover pilot study, we have investigated whether CRH-PBMC treatment could be of benefit in case of fresh early cleavage stage embryo transfer (day 3) in women with RIF.

Methods: Twenty-six (n = 26) women with at least three previous failed IVF attempts and no history of clinical pregnancy in the past were recruited in this study. Ovarian stimulation was performed following either the long or the short protocol. PBMC were collected during the oocyte retrieval, were treated with CRH, and transferred in the uterine cavity 2 days later. Good quality cleavage stage embryos were transferred at day 3, following oocyte retrieval.

Results: Following the intrauterine administration of CRH-treated autologous PBMC, 15/26 clinical pregnancies occurred (57.69%). Compared to the null result of the same women prior to recruitment, this observation was considered significant (P < 10-2 ).

Conclusion: Our findings further support the role of the intrauterine administration of CRH-treated PBMC as an effective approach when transferring cleavage stage embryos in women with RIF. Prospective randomized studies are needed to clarify whether such intervention could be of benefit in clinical practice.

Keywords: corticotrophin-releasing hormone; implantation; in vitro fertilization; peripheral blood mononuclear cells; repeated implantation failure.

MeSH terms

  • Adolescent
  • Adult
  • Corticotropin-Releasing Hormone / administration & dosage*
  • Cross-Over Studies
  • Embryo Implantation / physiology
  • Embryo Transfer / methods*
  • Female
  • Fertilization in Vitro / methods
  • Hormones / administration & dosage*
  • Humans
  • Infertility, Female / therapy
  • Leukocytes, Mononuclear
  • Pilot Projects
  • Uterus
  • Young Adult


  • Hormones
  • Corticotropin-Releasing Hormone