Objective way to support embryo transfer: a probabilistic decision

Gianaroli, Luca and Magli, Cristina and Gambardella, Luca Maria and Giusti, Alessandro and Grugnetti, Carla and Corani, Giorgio (2013) Objective way to support embryo transfer: a probabilistic decision. Human Reproduction, 28 (5). pp. 1210-1220. ISSN 1460-2350

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Embryo implantation represents a critical step in the reproductive process during which the blastocyst penetrates the endometrium to establish an interface between the growing fetus and the maternal circulation (Guzeloglu-Kayisli et al., 2009). For a successful implantation to occur a viable embryo must establish a synchronized dialog with a receptive endometrium (Simon et al., 2000). Owing to the complexity of this process, several factors can determine implantation failure including chromosomal abnormalities, which are especially frequent in female gametes in a manner that is closely related to age (Gianaroli et al., 2005a; Kuliev et al., 2005; Munne et al. 2007; Gianaroli et al., 2010), a poor uterine receptivity, sometimes due to asynchrony between the embryonic development and the endometrium (Norwitz et al., 2001; Margalioth et al., 2006; Swain and Smith, 2011), and factors associated with ART interventions comprising the potential adverse effects of ovarian stimulation (Santos et al.,2010)andof in vitro culture systems (Jones et al., 2001; Horsthemke and Ludwig, 2005; Dumoulin et al., 2010) on embryo development. Looking at clinical data where single implantation frequently results from the transfer of two or more embryos of comparable morphology, it is clear that a large proportion of failed implantations must be ascribed to the embryo. Despite numerous advances in culture systems and the introduction of more refined tools for the classification of the embryo’s developmental capacity (Katz-Jaffe et al ., 2006; Brison et al ., 2007 ; Jones et al., 2008a, b; Wong et al., 2010; Meseguer et al ., 2011), the lack of a strong predictor of embryo viability imposes severe restrictions to the general implementation of elective single-embryo transfer. In comparative trials between elective single- and elective double-embryo transfers in selected patient groups, the resulting live birth rates are comparable only when the transfer of cryopreserved embryos in subsequent cycles is included (Pandian et al., 2009; Gelbaya et al., 2010). These considerations lead to the conclusion that the key requirement for achieving a single live birth within an IVF-ICSI cycle is the capacity to estimate the embryo’s potential for further development in relation to maternal receptivity, which is a general term including factors associated with the patient characteristics and the treatment cycle. Morphological criteria have been, and still are, routinely used to select embryos for transfer or cryopreservation, and comprise the evaluation of pronucleate oocytes, the occurrence of early cleavage at 25–27 h post-insemination, scoring systems for day 2–3 embryos (including number of cells and synchrony of cleavage as well as the degree and pattern of fragmentation) and grading systems for morulas(progression of compaction) and blastocysts (including the timing of blastocyst formation and the degree of expansion as well as the characteristics of the inner cell mass and trophectoderm cell lineages) (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011). These criteria brought the definition of top-quality embryos. They are currently the most predictive markers of embryo developmental competence and are widely used in most IVF laboratories (Kovacic et al., 2004; Volpes et al., 2004; Gianaroli et al., 2007; Magli et al.,2007; Racowsky et al., 2011). Other studies have shown that the predictive capacity can be further improved by combining the scores obtained by the morphology of the same embryo at different stages(De Placido et al., 2002; Lan et al., 2003; Sjoblom et al., 2006; Loi et al., 2008; Brezinova et al., 2009) as well as by using the information coming from morphokinetic observations (Wong et al., 2010; Mese-guer et al., 2011). Nevertheless, reliable prediction of which embryos will implant remains an open problem, as prognostic models generally achieve only limited accuracy (Saith et al., 1998; Beuchat et al., 2008).Based on the assumption that for a successful implantation to occur a viable embryo must meet a receptive uterus, this study proposes a predictor of pregnancy that was designed by analyzing a series of cycles with known clinical outcomes. This was done to identify the factors that, being specifically related to embryo viability and maternal receptivity, were shown to affect the clinical outcome. The resulting predictor is able to discriminate with reasonable reliability not only between pregnancy and no pregnancy, but also between the occurrence of a single pregnancy or multiple pregnancy. This could represent an effective support to decide for each couple how many embryos and which embryos to transfer.

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