Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.
R. Homburg1,*, M.L. Hendriks1, T.E. König1, R.A. Anderson2, A.H. Balen3, M. Brincat4, T. Child5, M. Davies6, T. D’Hooghe7, A. Martinez8, M. Rajkhowa9, R. Rueda-Saenz10, P. Hompes1, and C.B. Lambalk1
1Reproductive Medicine, VU University Medical Center, Amsterdam, The Netherlands 2Centre for Reproductive Biology, University of Edinburgh, Edinburgh, UK 3Department of Reproductive Medicine, Leeds Teaching Hospitals, Leeds, UK 4Department of Obstetrics and Gynaecology, St Luke’s Hospital, G’mangia, Malta 5Oxford Fertility Unit, John Radcliffe Hospital, Oxford, UK 6Department of Obstetrics and Gynaecology, UCH, London, UK 7Fertility Centre, UZ Leuven, Leuven, Belgium 8Fertility Centre, Instituto Medicina Reproductiva, Mendoza, Argentina 9Assisted Conception Unit, Ninewells Hospital, Dundee, UK 10Reprotec Fertility Center, Bogota, Colombia
*Correspondence address. E-mail: r.homburg@vumc.nl
Submitted on February 17, 2011; resubmitted on September 13, 2011; accepted on September 27, 2011
background: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syn- drome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment.
methods: Infertile women (,40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50–150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR.
results: Patients (n 1⁄4 302) were randomized to OI with FSH (n 1⁄4 132 women; 288 cycles) or CC (n 1⁄4 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3 – 25.8, P 1⁄4 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5 – 25.8, P 1⁄4 0.03), LBR per woman (52 versus 39%, 95% CI 0.4 – 24.6, P 1⁄4 0.04), cumulative PR (52.1 versus 41.2%, P 1⁄4 0.021) and cumulative LBR (47.4 versus 36.9%, P 1⁄4 0.031), within three cycles of OI.
conclusions: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.
clinical trials registration: ISRCTN41865643.
Key words: clomifene citrate / low-dose FSH / polycystic ovary syndrome / ovulation induction
Key words: clomifene citrate / low-dose FSH / polycystic ovary syndrome / ovulation induction
Ver mas...
