Implantation failure: molecular mechanisms and clinical treatment

BACKGROUND: Implantation is a complex initial step in the establishment of a successful pregnancy. Although embryo quality is an important determinant of implantation, temporally coordinated differentiation of endometrial cells to attain uterine receptivity and a synchronized dialog between maternal and embryonic tissues are crucial. The exact mechanism of implantation failure is still poorly understood. METHODS: This review summarizes the current knowledge about the proposed mechanisms of implantation failure in gynecological diseases, the evaluation of endometrial receptivity and the treatment methods to improve implantation. RESULTS: The absence or suppression of molecules essential for endometrial receptivity results in decreased implantation rates in animal models and gynecological diseases, including endometriosis, hydrosalpinx, leiomyoma and polycystic ovarian syndrome. The mechanisms are diverse and include abnormal cytokine and hormonal signaling as well as epigenetic alterations. CONCLUSIONS: Optimizing endometrial receptivity in fertility treatment will improve success rates. Evaluation of implantation markers may help to predict pregnancy outcome and detect occult implantation deficiency. Treating the underlying gynecological disease with medical or surgical interventions is the optimal current therapy. Manipulating the expression of key endometrial genes with gene or stem cell-based therapies may some day be used to further improve implantation rates.