OvAge: a new methodology to quantify ovarian reserve combining clinical, biochemical and 3D-ultrasonographic parameters

Roberta Venturella, Daniela Lico, Alessia Sarica, Maria Pia Falbo, Elio Gulletta, Michele Morelli, Errico Zupi, Gabriele Cevenini, Mario Cannataro, Fulvio Zullo, Roberta Venturella, Daniela Lico, Alessia Sarica, Maria Pia Falbo, Elio Gulletta, Michele Morelli, Errico Zupi, Gabriele Cevenini, Mario Cannataro, Fulvio Zullo

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.

Figures

Figure 1
Figure 1
Plots of growth curve centile (3th, 10th, 25th, 50th, 75th, 90th, 97th) for each feature where Age is the covariate. The LMS method and penalized likelihood is used for fitting distributions.
Figure 2
Figure 2
Diagnostic plots for (a) model GzLM#2* and (b) model GzLM#2**. On the left Pearson residuals plotted against predicted values and on the right the Normal Q-Q plot. The red line in the plot of residuals of GzLM#2** presents a slight improvement in the linear trend compared to the plot of model GzLM#2*.

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Source: PubMed

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