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*CLOMIPHENE
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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 7 2361-2365
Copyright © 1998 by The Endocrine Society

Original Studies

Predictors of Patients Remaining Anovulatory during Clomiphene Citrate Induction of Ovulation in Normogonadotropic Oligoamenorrheic Infertility1

Babek Imani, Marinus J. C. Eijkemans, Egbert R. te Velde, J. Dik F. Habbema and Bart C. J. M. Fauser

Division of Reproductive Medicine, Department of Obstetrics and Gynecology (B.I., B.C.J.M.F.), and Department of Public Health (M.J.C.E., J.D.F.H.), Center for Clinical Decision Sciences, University Hospital and Erasmus University, Rotterdam; and the Department of Obstetrics and Gynecology, University Hospital Utrecht (E.R.t.V.), Utrecht, The Netherlands

Address all correspondence and requests for reprints to: Prof. B. C. J. M. Fauser, M.D., Ph.D., Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Dijkzigt Academic Hospital, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail: fauser{at}gyna.azr.nl

The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial. The present prospective longitudinal follow-up study was designed to identify whether certain criteria assessed during standardized initial screening could predict the response to ovulation induction with clomiphene citrate (CC) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility. Serum FSH levels were within the normal range (1–10 IU/L), and all patients underwent spontaneous or progestin-induced withdrawal bleeding. Initial CC doses were 50 mg daily for 5 days starting on cycle day 3. In the case of an absent response, doses were increased to 100 and 150 mg daily in subsequent cycles. First ovulation with CC was used as the end point. After a complete follow-up (in the case of a nonresponse, at least 3 treatment cycles with daily CC doses up to 150 mg), 156 patients (78%) ovulated. The free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), body mass index (BMI), cycle history (oligomenorrhea vs. amenorrhea), serum androgen (testosterone and/or androstenedione) levels, and mean ovarian volume assessed by transvaginal sonography were all significantly different (P < 0.01) in responders from those in nonresponders. FAI was chosen to be the best predictor in univariate analysis. The area under the receiver operating characteristics curve in a multivariate prediction model including FAI, BMI, cycle history, and mean ovarian volume was 0.82.

Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics, such as FAI, BMI, cycle history (oligomenorrhea or amenorrhea), and mean ovarian volume. These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women.




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