Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count

Journal of Ovarian Research

Annibale Volpe²  Enrico Papaleo¹  Giulia Dondi²  Alessandra Tirelli²  Cindy Argento²  Simone Giulini²  Valentina Grisendi²  Antonio La Marca² 

[1] Centro Natalità, Gynecological-Obstetrics Department, San Raffaele Hospital, Vita-Salute San Raffaele, Milano, Italy;Mother-Infant Department, Institute of Obstetrics and Gynecology, University of Modena and Reggio Emilia, 41100, Modena, Italy

关键词: Ovarian reserve;    FSH;    AFC;    ART;    Starting FSH dose;   

Others  :  811067
DOI  :  10.1186/1757-2215-6-11

 received in 2012-12-09, accepted in 2013-01-29,  发布年份 2013

【 摘 要 】

Background

The FSH starting dose is usually chosen according to women’s age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles.

Methods

This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model.

Results

A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively.

Conclusions

The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

【 授权许可】

   
2013 La Marca et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Fauser BC, Diedrich K, Devroey P, Evian Annual Reproduction Workshop Group 2007: Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update 2008, 14:1-14.
• [2]Alviggi C, Humaidan P, Ezcurra D: Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols. Reprod Biol Endocrinol 2012, 10:9. BioMed Central Full Text
• [3]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.
• [4]La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A: Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update 2010, 16:113-130.
• [5]Nelson SM, Yates RW, Fleming R: Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles–implications for individualization of therapy. Hum Reprod 2007, 22:2414-2421.
• [6]Broekmans FJ, de Ziegler D, Howles CM, Gougeon A, Trew G, Olivennes F: The antral follicle count: practical recommendations for better standardization. Fertil Steril 2010, 94:1044-1051.
• [7]La Marca A, Spada E, Sighinolfi G, Argento C, Tirelli A, Giulini S, Milani S, Volpe A: Age-specific nomogram for the decline in antral follicle count throughout the reproductive period. Fertil Steril 2011, 95:684-688.
• [8]Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ: AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update 2011, 17:46-54.
• [9]Hendriks DJ, Kwee J, Mol BW, te Velde ER, Broekmans FJ: Ultrasonography as a tool for the prediction of outcome in IVF patients: a comparative meta-analysis of ovarian volume and antral follicle count. Fertil Steril 2007, 87:764-775.
• [10]Broekmans FJ, Faddy MJ, Scheffer G, te Velde ER: Antral follicle counts are related to age at natural fertility loss and age at menopause. Menopause 2004, 11:607-614.
• [11]Nelson SM, Yates RW, Lyall H, Jamieson M, Traynor I, Gaudoin M, Mitchell P, Ambrose P, Fleming R: Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception. Hum Reprod 2009, 24:867-875.
• [12]Yates AP, Rustamov O, Roberts SA, Lim HY, Pemberton PW, Smith A, Nardo LG: Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF. Hum Reprod 2011, 26:2353-2362.
• [13]La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A: Development of a nomogram based on markers of ovarian reserve for the individualization of the FSH starting dose in IVF cycles. BJOG 2012, 119:1171-1179.
• [14]Fauser BC, Van Heusden AM: Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev 1997, 18:71-106.
• [15]Fleming R, Deshpande N, Traynor I, Yates RW: Dynamics of FSH-induced follicular growth in subfertile women: relationship with age, insulin resistance, oocyte yield and anti-Mullerian hormone. Hum Reprod 2006, 21:1436-1441.
• [16]Harrison RF, Jacob S, Spillane H, Mallon E, Hennelly B: A prospective randomized clinical trial of differing starter doses of recombinant follicle-stimulating hormone (follitropin-beta) for first time in vitro fertilization and intracytoplasmic sperm injection treatment cycles. Fertil Steril 2001, 75:23-31.
• [17]Karlsson MO, Wade JR, Loumaye E, Munafo A: A population model for the follicular growth in women treated with follicle stimulating hormone. Clin Pharmacol Ther 1997, 62:665-674.
• [18]Howles CM, Saunders H, Alam V, Engrand P: FSH Treatment Guidelines Clinical Panel Predictive factors and a corresponding treatment algorithm for controlled ovarian stimulation in patients treated with recombinant human follicle stimulating hormone (follitropin alfa) during assisted reproduction technology (ART) procedures. An analysis of 1378 patients. Curr Med Res Opin 2006, 22:907-918.
• [19]Popovic-Todorovic B, Loft A, Lindhard A, Bangsbøll S, Andersson AM, Andersen AN: A prospective study of predictive factors of ovarian response in 'standard' IVF/ICSI patients treated with recombinant FSH. A suggestion for a recombinant FSH dosage normogram. Hum Reprod 2003, 18:781-787.
• [20]Olivennes F, Howles CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V, CONSORT study group: Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online 2009, 18:195-204.
• [21]Popovic-Todorovic B, Loft A, Ziebe S, Andersen AN: Impact of recombinant FSH dose adjustments on ovarian response in the second treatment cycle with IVF or ICSI in "standard" patients treated with 150 IU/day during the first cycle. Acta Obstet Gynecol Scand 2004, 83:842-849.
• [22]Popovic-Todorovic B, Loft A, Bredkjaeer HE, Bangsbøll S, Nielsen IK, Andersen AN: A prospective randomized clinical trial comparing an individual dose of recombinant FSH based on predictive factors versus a 'standard' dose of 150 IU/day in 'standard' patients undergoing IVF/ICSI treatment. Hum Reprod 2003, 18:2275-2282.
• [23]Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, ESHRE working group on Poor Ovarian Response Definition: ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011, 26:1616-1624.
• [24]Eldar-Geva T, Ben-Chetrit A, Spitz IM, Rabinowitz R, Markowitz E, Mimoni T, Gal M, Zylber-Haran E, Margalioth EJ: Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome. Hum Reprod 2005, 20:3178-3183.
• [25]La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, Volpe A: Anti-Müllerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod 2007, 22:766-771.
• [26]van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, de Jong FH, Themmen AP: Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. Hum Reprod 2002, 17:3065-3071.
• [27]La Marca A, Argento C, Sighinolfi G, Grisendi V, Carbone M, D'Ippolito G, Artenisio AC, Stabile G, Volpe A: Possibilities and Limits of Ovarian Reserve Testing in ART. Curr Pharm Biotechnol 2012, 13:398-408.