title: OvAge: a new methodology to quantify ovarian reserve combining clinical, biochemical and 3D-ultrasonographic parameters.
abstract: BACKGROUND
  In the last decade, both endocrine and ultrasound data have been tested to verify their usefulness for assessing ovarian reserve, but the ideal marker does not yet exist. The purpose of this study was to find, if any, a statistical advanced model able to identify a simple, easy to understand and intuitive modality for defining ovarian age by combining clinical, biochemical and 3D-ultrasonographic data.
  
  
  METHODS
  This is a population-based observational study. From January 2012 to March 2014, we enrolled 652 healthy fertile women, 29 patients with clinical suspect of premature ovarian insufficiency (POI) and 29 patients with Polycystic Ovary syndrome (PCOS) at the Unit of Obstetrics & Gynecology of Magna Graecia University of Catanzaro (Italy). In all women we measured Anti Müllerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Estradiol (E2), 3D Antral Follicle Count (AFC), ovarian volume, Vascular Index (VI) and Flow Index (FI) between days 1 and 4 of menstrual cycle. We applied the Generalized Linear Models (GzLM) for producing an equation combining these data to provide a ready to use information about women ovarian reserve, here called OvAge. To introduce this new variable, expression of ovarian reserve, we assumed that in healthy fertile women ovarian age is identical to chronological age.
  
  
  RESULTS
  GzLM applied on the healthy fertile controls dataset produced the following equation OvAge = 48.05 - 3.14*AHM + 0.07*FSH - 0.77*AFC - 0.11*FI + 0.25*VI + 0.1*AMH*AFC + 0.02*FSH*AFC. This model showed a high statistical significance for each marker included in the equation. We applied the final equation on POI and PCOS datasets to test its ability of discovering significant deviation from normality and we obtained a mean of predicted ovarian age significantly different from the mean of chronological age in both groups.
  
  
  CONCLUSIONS
  OvAge is one of the first reliable attempt to create a new method able to identify a simple, easy to understand and intuitive modality for defining ovarian reserve by combining clinical, biochemical and 3D-ultrasonographic data. Although design data prove a statistical high accuracy of the model, we are going to plan a clinical validation of model reliability in predicting reproductive prognosis and distance to menopause.
authors.affiliation: Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. rovefa@libero.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Venturella
authors.affiliation: Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. dani.li@hotmail.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lico
authors.affiliation: School of Informatics and Biomedical Engineering-Bioinformatics Laboratory, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. alessia.sarica@gmail.com.
authors.forename: Alessia
authors.initials: A
authors.lastname: Sarica
authors.affiliation: Chair of Clinical Pathology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. falbopia@libero.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Falbo
authors.affiliation: Chair of Clinical Pathology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. gulletta@unicz.it.
authors.forename: Elio
authors.initials: E
authors.lastname: Gulletta
authors.affiliation: Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. morelli@unicz.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. ezupi@libero.it.
authors.forename: Errico
authors.initials: E
authors.lastname: Zupi
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy. gabriele.cevenini@dbm.unisi.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cevenini
authors.affiliation: School of Informatics and Biomedical Engineering-Bioinformatics Laboratory, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. cannataro@unicz.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Cannataro
authors.affiliation: Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, 88100, Catanzaro, Italy. zullo@unicz.it.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Zullo
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D021621:Imaging, Three-Dimensional; D016014:Linear Models; D008875:Middle Aged; D065851:Ovarian Reserve / Q000502:physiology*; D010053:Ovary / Q000000981:diagnostic imaging* / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology; D016649:Primary Ovarian Insufficiency / Q000503:physiopathology; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D004958:Estradiol; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone