A predictive formula for selecting individual FSH starting dose based on ovarian reserve markers in IVF/ICSI cycles
Although exogenous follicle-stimulating hormone (FSH) has been used for decades and millions of cycles have been performed worldwide until now, criteria for selecting the proper FSH starting dose have not been clearly identified. The aim of this study was to elaborate a formula based on markers of ovarian reserve for the calculation of the appropriate starting dose of FSH.
A total of 931 patients underwent in vitro fertilization (IVF) treatment using long GnRH agonist protocol was retrospectively identified and reviewed. 673 cases of them with a normal ovarian response (4–14 retrieved oocytes) were used to analysis the predictive formula. All follicles 4–7 mm in diameter were counted in the same day of blood sample in both ovaries using transvaginal ultrasound scan. The modified protocol of each patient was recorded and analyzed in the same center. In another center were the numbers of retrieved oocytes of 750 validated patients recorded and analyzed.
A formula model based on age, AMH, and antral follicle count (AFC) was able to accurately predict the ovarian sensitivity and accounted for 57.2% of the variability of ovarian response to FSH. When tested in the same total population used to elaborate the model it predicts a high 46.88% rate of step-down protocol in higher-starting FSH dose group and about 57.92% of patients had their dose step-up modified in lower-starting FSH dose group during their treatment, respectively. And when tested in different population from another center used to elaborate the model it predicts a high 64.40% rate of ≥ 15 retrieved oocytes in higher-starting FSH dose group and about 22.50% of patients had ≤ 7 retrieved oocytes in lower-starting FSH dose group during their treatment, respectively.
In the present study we demonstrated that the individualized FSH starting dose may be calculated on the basis of a woman’s age, AMH and AFC. The formula model might be a useful, immediate, and easily applicable tool for clinicians to predict the tailored starting dose of FSH during their daily clinical practice.
KeywordsAge AMH AFC Ovarian reserve Starting FSH dose
HS protocol/project development. JZ protocol/project development, manuscript correction and revision. MZ protocol/project development, data collection and management, manuscript writing and editing, data analysis. SW data collection and management, manuscript editing, data analysis. SY data collection and management. XH data collection and management. JNM: data collection and management. LC validated data collection and management.
This study was supported by Chinese National Natural Science Foundation (81771537, 81571504, 81200450), Nanjing Medical Science and technique Development Foundation (QRX11166), Maternal and fetus medicine Key Lab of Jiangsu Province (XK 201102, BL2014003).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.Howles CM, Saunders H, Alam V et al (2006) 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 1378 patients. Curr Med Res Opin 22(5):907–918. https://doi.org/10.1185/030079906X104678 CrossRefGoogle Scholar
- 21.Todorovic BP, Loft A, Bredkjæer HE et al (2003) 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 18(11):2275–2282CrossRefGoogle Scholar
- 23.Popovic Todorovic B, Loft A, Ziebe S et al (2004) 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 83(9):842–849. https://doi.org/10.1111/j.0001-6349.2004.00573.x CrossRefGoogle Scholar
- 26.Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK et al (2010) Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT). Hum Reprod 25(3):683–689. https://doi.org/10.1093/humrep/dep436 CrossRefGoogle Scholar
- 27.Marca AL, Papaleo E, Grisendi V et al (2012) Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles. BJOG 119(10):1171–1179. https://doi.org/10.1111/j.1471-0528.2012.03412.x CrossRefGoogle Scholar
- 31.Arce JC, Andersen AN, Fernández-Sánchez M, Visnova H, Bosch E, García-Velasco JA et al (2014) Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril 102(6):1633–1640.e5. https://doi.org/10.1016/j.fertnstert.2014.08.013 CrossRefGoogle Scholar