Emerging role of embryo secretome in the paracrine communication at the implantation site: a proof of concept

Molecules/factors secreted by implanting embryos are able to regulate the endometrial glycodelin A and to improve the pregnancy rate when the embryo secretome is added at the embryo transfer.

VOLUME 115, ISSUE 4, P1054-1062


Alice Luddi, Ph.D., Valentina Pavone, Ph.D., Laura Governini, Ph.D., Angela Capaldo, Ph.D., Claudia Landi, Ph.D., Francesca Ietta, Ph.D., Eugenio Paccagnini, Ph.D., Giuseppe Morgante, M.D., Vincenzo De Leo, M.D., Paola Piomboni, Ph.D. 



To assess the role of embryo secretome in modifying the molecular profile of glycodelin A (GdA) in endometrial organoids (ORG) mimicking the implantation window. To verify whether the use of embryo-conditioned culture medium at the time of the embryo transfer may increase in vitro fertilization outcome.


Molecular study with human endometrial ORG and embryo-conditioned culture medium. Retrospective study using prospectively recorded data.


University hospital.


For isolation and culture of endometrial glandular ORG, endometrial biopsy specimens from five white women of proven fertility undergoing laparoscopy for tubal sterilization. A total of 75 women undergoing intracytoplasmic sperm injection for tubal and/or male infertility factor.


In vitro fertilization.

Main Outcome Measure(s)

Pinopodes presence in human endometrial ORG. Glycodelin A expression profile by means of two-dimensional electrophoresis. In vitro fertilization outcome.


This in vitro study demonstrated that the treatment of endometrial ORG with the secretome of medium conditioned by the growing embryo increased the GdA relative abundance and induced a different glycoform pattern. Biochemical and clinical pregnancy rate significantly increased when the spent medium was loaded during the transfer (17.5% vs. 36.6% and 16.5% vs. 35.1%, respectively).


This study demonstrated that the secretome of implanting embryos is able to induce the expression as well as to determine the relative abundance and the glycosilation profile of endometrial GdA, a protein having a key role in the embryo-endometrial cross talk. Moreover, a significant increase in pregnancy rate was observed when the embryo transfer was performed by using the culture medium conditioned by the growing embryo.