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

Journal of Ovarian Research

Fulvio Zullo³  Mario Cannataro⁵  Gabriele Cevenini²  Errico Zupi¹  Michele Morelli³  Elio Gulletta⁴  Maria Pia Falbo⁴  Alessia Sarica⁵  Daniela Lico³  Roberta Venturella³ 

[1] Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy;Department of Medical Biotechnologies, University of Siena, Siena, Italy;Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, Catanzaro, 88100, Italy;Chair of Clinical Pathology, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, Catanzaro, 88100, Italy;School of Informatics and Biomedical Engineering-Bioinformatics Laboratory, Magna Graecia University of Catanzaro, Viale Europa - Localitá Germaneto, Catanzaro, 88100, Italy

关键词: Generalized linear model;    Family planning;    Reproduction;    Distance to menopause;    3D Antral Follicle Count;    Anti Müllerian Hormone;    Follicle Stimulating Hormone;    Ovarian reserve;   

Others  :  1171515
DOI  :  10.1186/s13048-015-0149-z

 received in 2015-01-10, accepted in 2015-03-19,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Venturella et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Ferrell RJ, O’Connor KA, Holman DJ, Brindle E, Miller RC, Rodriguez G et al.. Monitoring reproductive aging in a 5-year prospective study: aggregate and individual changes in luteinizing hormone and follicle-stimulating hormone with age. Menopause. 2007; 14:29-37.
• [2]Navot D, Rosenwaks Z, Margalioth EJ. Prognostic assessment of female fecundity. Lancet. 1987; 2:645-7.
• [3]Ovarian reserve testing. Committee Opinion No. 618. Obstet Gynecol. 2015; 125:268-73.
• [4]Sun W, Stegmann BJ, Henne M, Catherino WH, Segars JH. A new approach to ovarian reserve testing. Fertil Steril. 2008; 90:2196-202.
• [5]Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis. 2006; 6:1-9.
• [6]Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81:19-25.
• [7]Mulders AG, Laven JS, Eijkemans MJ, de Jong FH, Themmen AP, Fauser BC. Changes in anti-Müllerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility. Hum Reprod. 2004; 19:2036-42.
• [8]Deb S, Campbell BK, Clewes JS, Raine-Fenning NJ. Quantitative analysis of antral follicle number and size: a comparison of two-dimensional and automated three-dimensional ultrasound techniques. Ultrasound Obstet Gynecol. 2010; 35:354-60.
• [9]Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Statist Med. 1992; 11:1305-19.
• [10]Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr. 1974; 19:716e723.
• [11]Tehrani FR, Solaymani-Dodaran M, Tohidi M, Gohari MR, Azizi F. Modeling age at menopause using serum concentration of anti-mullerian hormone. J Clin Endocrinol Metab. 2013; 98:729-35.
• [12]Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006; 12:685-718.
• [13]Bancsi LF, Broekmans FJ, Mol BW, Habbema JD, Te Velde ER. Performance of basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: a meta-analysis. Fertil Steril. 2003; 79:1091-100.
• [14]van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, de Jong FH et al.. Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. Hum Reprod. 2002; 17:3065-71.
• [15]Seifer DB, Baker VL, Leader B. Age-specific serum anti-Müllerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril. 2011; 95:747-50.
• [16]Hussain M, Cahill D, Akande V, Gordon U. Discrepancies between Antimullerian Hormone and Follicle Stimulating Hormone in Assisted Reproduction. Obstet Gynecol Int. 2013; 2013:383278.
• [17]Iliodromiti S, Kelsey TW, Wu O, Anderson RA, Nelson SM. The predictive accuracy of anti-Mullerian hormone for live birth after assisted conception: a systematic review and meta-analysis of the literature. Hum Reprod Update. 2014; 20:560-70.
• [18]Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R et al.. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update. 2014; 20:370-85.
• [19]Hendriks DJ, Mol BW, Bancsi LF, Te Velde ER, Broekmans FJ. Antral follicle count in the prediction of poor ovarian response and pregnancy after in vitro fertilization: a meta-analysis and comparison with basal follicle-stimulating hormone level. Fertil Steril. 2005; 83:291-301.
• [20]Gibreel A, Maheshwari A, Bhattacharya S, Johnson NP. Ultrasound tests of ovarian reserve; a systematic review of accuracy in predicting fertility outcomes. Hum Fertil (Camb). 2009; 12:95-106.
• [21]Kim SH, Lee JM, Kim YJ, Lee JY, Han JK, Choi BI. High-definition flow Doppler ultrasonographic technique to assess hepatic vasculature compared with color or power Doppler ultrasonography: preliminary experience. J Ultrasound Med. 2008; 27:1491-501.
• [22]Van Blerkom J, Antczak M, Schrader R. The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics. Hum Reprod. 1997; 12:1047-55.