Changing etiology of tubal pregnancy following IVF

BACKGROUND: Tubal pregnancy (TP) is twice as common following IVF when compared with natural conception. This is surprising, since embryo transfer is aimed for an accurate area in the uterine cavity. We thus hypothesized that either the embryo or the Fallopian tube actively participates in a pathological process leading to implantation outside the uterine cavity. Since we recently found that E-cadherin expression is a useful marker of endometrial receptivity, we considered that it may have a role in TP following IVF. Therefore, the aim of this study was to compare E-cadherin expression and localization in tubal implantation sites from spontaneous TP and TP post-IVF. METHODS: We compared E-cadherin immunohistochemistry levels on cross-sections of Fallopian tubes in 11 spontaneous (antegrade) versus 13 post-IVF (retrograde) TP. The intensity of immunoreactivity was scored in a semi-qualitative blinded manner. RESULTS: The semi-quantitative intensity score in IVF tubal samples was more than double that observed in spontaneous TP (16.9 versus 7.3, respectively, P< 0.0005). E-cadherin showed the most intense immunostaining in cytotrophoblast cells of chorionic villi in ectopic TP post-IVF compared with negative or weak staining in spontaneous ectopic TP. CONCLUSIONS: E-cadherin can serve as a marker of implantation. Differential expression of this adhesion molecule in TP post-IVF, when compared with natural conception, may reflect a different mechanism of embryo implantation. Moreover, the observation that E-cadherin is mostly expressed in trophoblasts, and not in the tubal wall, suggests that the preimplantation embryo may actively participate in locating a suitable implantation site.