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Hum. Reprod. Advance Access published online on May 7, 2007
Human Reproduction, doi:10.1093/humrep/dem089
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Predictors of low response to mild ovarian stimulation initiated on cycle day 5 for IVF

M.F.G. Verberg1,3, M.J.C. Eijkemans1,2, N.S. Macklon1, E.M.E.W. Heijnen1, B.C.J.M. Fauser1 and F.J. Broekmans1

1 Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CS Utrecht, The Netherlands 2 Department of Public Health, Erasmus MC, University Medical Center, Dr. Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, The Netherlands

3 Correspondence address. Tel: + 31(0)302508373; Fax: + 31(0)302505433; E-mail: m.f.g.verberg{at}umcutrecht.nl

BACKGROUND: Milder stimulation protocols are being developed to minimize adverse effects of ovarian stimulation in in vitro fertilization (IVF) programs. A drawback is the possibility of an increased rate of insufficient ovarian response. This study aimed to develop a prognostic model for the prediction of cycle cancellation due to insufficient response to mild stimulation.

METHODS: A total of 174 IVF patients aged <38 years and with a body mass index (BMI) <28 Kg/m2 were treated with mild ovarian stimulation using a fixed daily dose (150 IU) of recombinant follicle-stimulating hormone (rFSH) from cycle day 5 and GnRH antagonist from the late follicular phase. In women with mono- or bifollicular growth (17%), the cycle was cancelled and the treatment was adjusted in a second treatment cycle by starting rFSH on cycle day 2.

RESULTS: In a multivariable logistic regression analysis, duration of infertility, menstrual cycle length, secondary infertility and BMI were included in the prediction model. The area under the receiver-operating characteristics curve of the model was 0.69. A probability cut-off for cancellation of 0.3 yielded an expected sensitivity of 33% and specificity of 92%. Analysis of ovarian response in the subsequent treatment cycle showed an improved ovarian response and a significant reduction in the cancellation rate.

CONCLUSIONS: With the presented model, it is possible to identify patients at risk for cycle cancellation, during mild ovarian stimulation, due to insufficient response. The contributing factors of the model suggest that ovarian aging and BMI are related to insufficient response to mild stimulation.

Key words: mild ovarian stimulation/ovarian response/prediction models/IVF cycle cancellation

Submitted on November 30, 2006; resubmitted on February 26, 2007; accepted on March 5, 2007.


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