During the natural conception, an intimate dialogue is established between the embryo and the endometrium from the earliest stages of embryo development to the implantation. While the embryo develops in the uterine cavity: the embryo can modulate the maternal microenvironment; the endometrium can adapt to the presence of the embryo, and vice versa, elicit developmental responses on the embryo.

This dialogue is mediated, through paracrine interactions, by a large panel of soluble molecules and receptors expressed by both the endometrium and the embryo. This complex molecular environment contains growth factors, hormones, interleukins, chemokines, matrix metalloproteinases, immunosuppressive factors, specific glycoproteins, lipids, miRNAs and many other molecules that are not present in the synthetic culture media used in traditional ART. Moreover, with the ART procedure, the embryos are not in the maternal environment during their culture in the incubator: during this time the crosstalk is not possible.

The embryo-endometrium crosstalk has been described to play important roles during the fertilization, the very early embryonic development stages and during the implantation process. This crosstalk is thought to mediate simultaneously the pre-implantation embryo development and the opening of the window of implantation (WOI) thus preparing the receptivity of the endometrium to the embryo implantation. (1-10).

Recent studies suggest that soluble embryonic molecular signals are used by the endometrium as a selection mechanism to promote or inhibit implantation. This mechanism depends on the activation of specific patterns of maternal genes that can be induced by embryos at different developmental potential (9,10).

A growing number of studies also highlight the role of microRNAs in embryo development and implantation. MicroRNnas regulate gene transcription and/or post transcriptional processing and as much as 135 miRNAs have been found to be expressed at the human blastocyst stage, including 39 unique miRNAs that are specific of the embryonic development. To date, the clear biological roles of these miRNAs are however less well defined (1,11-14).

The AneVivo device allows the embryo’s presence inside the women’s reproductive tract during the Natural Fertilization and Development procedure which enables this crucial crosstalk.


paracrine interaction: Paracrine interaction is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior or differentiation of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to endocrine factors (hormones which travel considerably longer distances via the circulatory system)

miRNA: A miRNA or micro RNA is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals, and some viruses, which functions in RNA silencing and post-transcriptional regulation of gene expression.


Thouas, Gardner, 2015, Endocr Rev
Boomsma, Macklon, 2009, Reprod Biomed Online
Díaz-Cueto, Gerton, 2001, Arch Med Res,
Duc-Goiran, Ferre, 1999, Eur J Obstet Gynecol Reprod Biol
Robertson, 2007, Cytokines & Growth Factor Reviews
Cavagna, Mantese, 2003, Placenta
Dimitriadis, Salamonsen, 2005, Human Reprod
Richter, 2008, Curr Opin Obstet Gynecol
Teklenburg, Macklon, 2010, PLoS One,
Brosens, Macklon, 2014, Sci Rep
Vilella, Simon, 2015, Development
McCallie, Katz-Jaffe, 2010, Fertil Steril
Rosenbluth, Van Voorhis, 2013, Fertil Steril
Rosenbluth, Van Voorhis, 2012, Human Reprod