الفهرس 
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Abstract
One of the most frustrating group of patients for IVF specialists are those with recurrent implantation failure, patients who had done multiple IVF cycles, but who still do not get pregnant. Implantation refers to the process of the embryo embedding into the endometrium to produce a pregnancy. In clinical practice implantation is considered to be successful when there is ultrasonographic evidence of intrauterine pregnancy, meaning intrauterine gestational sac. (Makrakis and Pantos 2010)
So, implantation failure means failure to reach a stage in which there is ultrasonographic evidence of intrauterine pregnancy. This may occur very early on, during the attachement or migration stages, the result being there is no objective evidence of a pregnancy (negative urine or blood pregnancy test); it may also occur later on, after the migration of the embryo through the luminal surface of the endometrium, when hCG produced by the embryo may be detected in the blood or urine, but the process was disrupted prior to the formation of an intrauterine gestational sac (biochemical pregnancy). (Coughlan et al., 2014).
The definition of recurrent implantation failure (RIF) derived from the practice of IVF, so it changed through the years for numerous times. Its criterias are varied: from the cumulative number of transferred embryos (Coulam etal., 1994) and (Ster et al., 2003), and their quality (Margalioth et al., 2006) and (Cutting et al., 2008), to the number of IVF cycles (Margalioth et al., 2006) and (Tan et al., 2005) , maternal age (Devroey et al., 1996) and (Spandorfer et al., 2000) and other factors.
There are two main groups of reasons for RIF: embryo factors and uterine factors. Although many papers discussed the embryo factors (such as oocyte quality, sperm quality, parental chromosomal anomalies, etc), RIF is, based on the definition proposed in 2014, most probably due to uterine factors. These can be divided into congenital uterine anomalies, like septate uterus or defects in the development or fusion of the Mullerian ducts during embryogenesis, and acquired intracavity conditions, like submucous fibroids, endometrial polyps, intrautherine adhesions and adenomyosis (Coughlan et al., 2014).
One of the most important investigations in women with RIF is hysteroscopy, because it allows reliable visual assessment of the cervical canal and uterine cavity. The hysteroscopy is considered to be the gold standard to diagnose intrauterine pathology and it is also a therapeutic tool for most of uterine pathology (fibroids, endometrial polyps, intrauterine adhesions, uterine septae) with minimal intraoperative and postoperative morbidity (Coughlan et al., 2014). Hysteroscopy significantly increased clinical pregnancy rates in women with RIF in 2 prospective randomized controlled studies (Demirol and Gurgan 2004) and (Rama et al., 2006).
Talking about non-cavity-distorting intramural fibroids, some studies suggest an adverse effect on implantation and pregnancy rates in women undergoing IVF (particularly large fibroids >4 cm), whereas other studies fail to demonstrate such an association. There are three recent meta-analyses published on this particular subject (Pritts et al., 2009), (Metwally et al., 2011) and (Sunkara et al., 2010).
All three analyses agree that women with intramural fibroids appear to have reduced implantation rates compared with women without intramural fibroids. However, myomectomy did not appear to significantly increase the clinical pregnancy and live birth rates (Pritts et al., 2009) and the most recent meta-analysis cautioned that the available evidence is weak because of significant heterogeneity and methodological issues (Metwally et al., 2011).
An endometrial polyp may also interfere with embryo implantation. A recent systematic review found that hysteroscopic removal of endometrial polyps resulted in doubling of the clinical pregnancy rate in women undergoing intrauterine insemination treatment (Bosteels et al., 2010). It seems likely that endometrial polyps contribute to RIF. Congenital uterine anomalies may affect endometrial receptivity manifesting as either infertility or recurrent pregnancy loss (Taylor and Gomel. 2008).