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 sufferingfrom
polycystic ovary syndrome remain controversial. The presentprospective
longitudinal follow-up study was designed to identifywhether certain
criteria assessed during standardized initialscreening could predict
the response to ovulation inductionwith clomiphene citrate (CC) in 201
patients presenting witholigomenorrhea or amenorrhea and infertility.
Serum FSH levelswere within the normal range (1–10 IU/L), and all
patientsunderwent spontaneous or progestin-induced withdrawal
bleeding.Initial CC doses were 50 mg daily for 5 days starting on
cycleday 3. In the case of an absent response, doses were increasedto
100 and 150 mg daily in subsequent cycles. First ovulationwith CC was
used as the end point. After a complete follow-up(in the case of a
nonresponse, at least 3 treatment cycles withdaily CC doses up to 150
mg), 156 patients (78%) ovulated. Thefree androgen index (FAI =
testosterone/sex hormone-bindingglobulin ratio), body mass index
(BMI), cycle history (oligomenorrheavs. amenorrhea),
serum androgen (testosterone and/or androstenedione)levels, and mean
ovarian volume assessed by transvaginal sonographywere all
significantly different (P < 0.01) in responders
fromthose in nonresponders. FAI was chosen to be the best predictorin
univariate analysis. The area under the receiver operating
characteristicscurve 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 stimulationby FSH
due to CC treatment can be predicted on the basis ofinitial screening
characteristics, such as FAI, BMI, cycle history(oligomenorrhea or
amenorrhea), and mean ovarian volume. Theseobservations may add to
ongoing discussion regarding etiologicalfactors involved in ovarian
dysfunction in these patients andclassification of normogonadotropic
anovulatory infertile women.
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