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Eur J Clin Invest. 2015 Apr;45(4):380-4. doi: 10.1111/eci.12417.

Repeated implantation failure: a new potential treatment option.

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Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion, Greece.



Previous studies have shown that the intrauterine administration of peripheral blood mononuclear cells (PBMC) may improve pregnancy outcome of women with repeated implantation failure (RIF). We have demonstrated that, during implantation, corticotropin-releasing hormone (CRH) plays a key role in facilitating endometrial decidualization and maternal-foetal immunotolerance. In the present preliminary study, we investigated whether the intrauterine administration of autologous CRH-treated PBMC can improve clinical pregnancy rates of women with RIF.


Forty-five (n = 45) women with at least three failed in vitro fertilization (IVF) attempts and no previously reported clinical pregnancy were included in this crossover study. All women underwent controlled ovarian stimulation using the long GnRH agonist protocol. PBMC were isolated at day of oocyte retrieval, treated with CRH and administered in the uterine cavity at day 2, following oocyte retrieval. Blastocyst transfer was performed on day 5.


Following the CRH-PBMC intrauterine administration, a significant increase was observed in the clinical pregnancy rate of this cohort of women with RIF (20/45 women had a clinical pregnancy; 44.44%, P < 10(-3)) compared to the previous null clinical pregnancy rate prior to the intervention.


The current findings support a possible role for the intrauterine administration of autologous CRH-treated PBMC in treating women with RIF. Further randomized controlled trials are needed to investigate the efficacy of this intervention.


Corticotropin-releasing hormone; implantation; in vitro fertilization; peripheral blood mononuclear cells; repeated implantation failure

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