Dr. Antonio Capalbo - G.E.N.E.R.A. Reproductive Medicine Centre, Milan

Dr. Capalbo received his Bachelor of Science degree in Biotechnology from University of Rome ‘La Sapienza’ and his Ph.D. magna cum laude in Human Genetics at the Catholic University of Sacred Heart of Rome in 2011. In 2011 he obtained II level Master Degree in Epidemiology and statistical data analysis at the Catholic University of Sacred Heart of Rome.

Since 2008 he has been working as clinical embryologist at GENERA, Reproductive Medicine in Rome. Since then, his research has focused on preimplantation genetic diagnosis and screening and on the development of novel molecular biology techniques to improve pregnancy and take-home baby rates in ART.

In 2011 he worked as research fellow at Reproductive Biology Associates, Atlanta, GA, USA and from 2012 he is collaborating as consultant embryologist at the Embryonic Stem Cell Laboratories, Assisted Conception Unit of Guy’s Hospital, KCL, London working on molecular figures of human blastocyst differentiation. From 2012 he is genetic consultant and PGD/PGS program coordinator at GENERA, Reproductive medicine centres, Italy.

From 2014 he is Scientific and Laboratory Director of GENETYX, molecular genetics laboratory.

Project: Clinical translation of a new procedure for embryo evaluation based on miRNAs profiling from spent blastocyst culture media: prospective multicenter study

MiRNAs are evolutionarily conserved, single-stranded, non-coding RNA molecules of ~22 nucleotides in length and they are major transcriptional/post-transcriptional regulators of gene expression. It has been extensively shown that miRNAs are secreted from donor cells and can be internalized into recipient cells, where they can exert their genetic regulatory function and mediate a cell-to-cell communication. We hypothesized that human embryos could also secrete specific miRNAs in the extracellular environment as part of the blastocyst-endometrium interaction, which is necessary for implantation success and that miRNAs profiling from blastocyst spent culture media samples (SBM) can be used to non invasively assess embryo quality and its reproductive competence. Accordingly, miRNAs may be an ideal embryonic biomarker candidates because they are specific to the embryo, stable over time, resistant to degradation, easily detected and have already been shown to correlate with a variety of pathologic conditions. Furthermore, miRNAs quantification trough qPCR can be completed in-house in a matter of hours, rendering fresh blastocyst transfers a feasible solution during IVF treatments with same-day media analysis. Recently, we comprehensively characterized the profile of miRNAs secreted by human preimplantation embryos in spent culture media and provided preliminary evidences that secreted miRNAs can be used as predictive markers of clinical outcomes in IVF cycles.

In this new project we aim at translating these preliminary findings into a robust and consolidated clinical application, analyzing prospectively 1.000 media samples obtained from six different private and academic IVF clinics worldwide performing single blastocyst transfers. This prospective multicenter trial will provide a further validation of our customized platform for miRNAs analysis of SBM samples using a prospective design with a high samples size and in different IVF settings.

Spent blastocyst culture media droplets (20 uL each) will be collected from embryos reaching the blastocyst stage immediately before embryo transfer or cryopreservation. The analysis of miRNAs secretion profile of implanted versus not implanted embryos during fresh or frozen single embryo transfer cycles will be carried out using our customized plate, that includes 46 different key miRNAs already shown to be secreted from blastocysts in the SBM and related to embryonic reproductive competence. This prospective multicenter trial will provide a further robust validation of the customized platform for miRNAs analysis of SBM samples in multiple IVF settings using different embryo culture systems, thus making possible to assess the reproducibility and translational capacity of the newly proposed approach for embryo selection.

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