title: Soluble CD146, an innovative and non-invasive biomarker of embryo selection for in vitro fertilization.
abstract: Although progress was made in in vitro fertilization (IVF) techniques, the majority of embryos transferred fail to implant. Morphology embryo scoring is the standard procedure for most of IVF centres for choosing the best embryo, but remains limited since even the embryos classified as "top quality" may not implant. As it has been shown that i) CD146 is involved in embryo implantation and ii) membrane form is shed to generate soluble CD146 (sCD146), we propose that sCD146 in embryo supernatants may constitute a new biomarker of embryo selection. Immunocytochemical staining showed expression of CD146 in early embryo stages and sCD146 was detected by ELISA and Western-blot in embryo supernatants from D2. We retrospectively studied 126 couples who underwent IVF attempt. The embryo culture medium from each transferred embryo (n = 222) was collected for measurement of sCD146 by ELISA. Significantly higher sCD146 concentrations were present in embryo supernatants that did not implant (n = 185) as compared to those that successfully implanted (n = 37) (1310 +/- 1152 pg.mL-1 vs. 845+/- 1173 pg.mL-1, p = 0.024). Sensitivity analysis performed on single embryo transfers (n = 71) confirmed this association (p = 0.0054). The computed ROC curve established that the optimal sCD146 concentration for embryo implantation is under 1164 pg.mL-1 (sensitivity: 76%, specificity: 48%, PPV: 25% and NPV: 92%). Over this sCD146 threshold, the implantation rate was significantly lower (9% with sCD146 levels >1164 pg.ml-1 vs. 22% with sCD146 levels ≤ 1164 pg.mL-1, p = 0.01). Among the embryos preselected by morphologic scoring, sCD146 determination could allow a better selection of the embryo(s), thus improving the success of elective single embryo transfer. This study establishes the proof of concept for the use of sCD146 as a biomarker for IVF by excluding the embryo with the highest sCD146 level. A multicentre prospective study will now be necessary to further establish its use in clinical practice.
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bouvier
authors.affiliation: Assisted Reproductive Center, Laboratory of Reproduction, CHU La Conception, AP-HM, Marseille and Laboratory of Histology-Embryology/Biology of Reproduction, Aix-Marseille University, Marseille, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Paulmyer-Lacroix
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molinari
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Bertaud
authors.affiliation: Assisted Reproductive Center, Laboratory of Reproduction, CHU La Conception, AP-HM, Marseille and Laboratory of Histology-Embryology/Biology of Reproduction, Aix-Marseille University, Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Paci
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Leroyer
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Robert
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat George
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.
authors.forename: Marcel
authors.initials: M
authors.lastname: Blot-Chabaud
authors.affiliation: Aix Marseille Univ, Inserm U1076, Marseille, France.|Immunology Laboratory, Pole de Biologie, CHU Conception Marseille, AP-HM, Marseille, France.
authors.forename: Nathalie
authors.identifier: http://orcid.org/0000-0002-9870-9098
authors.initials: N
authors.lastname: Bardin
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D051929:CD146 Antigen / Q000276:immunology; D010064:Embryo Implantation; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans
chemical_list: D015415:Biomarkers; D051929:CD146 Antigen; C497902:MCAM protein, human