Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

doi:10.1136/bmj.38867.631551.55

BMJ 2006;332:1485 (24 June), doi:10.1136/bmj.38867.631551.55 (published 12 June 2006)

Research

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

Etelka Moll, registrar obstetrics and gynaecology¹, Patrick M M Bossuyt, professor in clinical epidemiology², Johanna C Korevaar, clinical epidemiologist², Cornelis B Lambalk, gynaecologist³, Fulco van der Veen, professor in reproductive medicine¹

¹ Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, PO Box 22700, 1100 DE, Amsterdam, Netherlands, ² Clinical Epidemiology and Biostatistics, Academic Medical Centre, Amsterdam, Netherlands, ³ Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB, Amsterdam, Netherlands

Correspondence to: E Moll e.moll{at}amc.uva.nl

Abstract

Objective To compare the effectiveness of clomifene citrateplus metformin and clomifene citrate plus placebo in women withnewly diagnosed polycystic ovary syndrome.

Design Randomised clinical trial.

Setting Multicentre trial in 20 Dutch hospitals.

Participants 228 women with polycystic ovary syndrome.

Interventions Clomifene citrate plus metformin or clomifenecitrate plus placebo.

Main outcome measure The primary outcome measure was ovulation.Secondary outcome measures were ongoing pregnancy, spontaneousabortion, and clomifene resistance.

Results 111 women were allocated to clomifene citrate plus metformin(metformin group) and 114 women were allocated to clomifenecitrate plus placebo (placebo group). The ovulation rate inthe metformin group was 64% compared with 72% in the placebogroup, a non-significant difference (risk difference - 8%, 95%confidence interval - 20% to 4%). There were no significantdifferences in either rate of ongoing pregnancy (40% v 46%;- 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%;1%, - 7% to 10%). A significantly larger proportion of womenin the metformin group discontinued treatment because of sideeffects (16% v 5%; 11%, 5% to 16%).

Conclusion Metformin is not an effective addition to clomifenecitrate as the primary method of inducing ovulation in womenwith polycystic ovary syndrome.

Trial registration Current Controlled Trials ISRCTN55906981 [controlled-trials.com] [controlled-trials.com].

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Rapid Responses:

Read all Rapid Responses

Good Work, but not the end of the PCOS/Metformin Saga.: William U Atiomo
bmj.com, 23 Jun 2006 [Full text]
Metformin still has its place.: Jeevan P Marasinghe
bmj.com, 24 Jun 2006 [Full text]
Re: Good Work, but not the end of the PCOS/Metformin Saga.: Etelka Moll, et al.
bmj.com, 28 Jun 2006 [Full text]
Re: Metformin still has its place.: Etelka Moll, et al.
bmj.com, 28 Jun 2006 [Full text]
Not All Faith In Metformin Lost: Spyros Papaioannou, et al.
bmj.com, 30 Jun 2006 [Full text]
Re: Not All Faith In Metformin Lost: Etelka Moll, et al.
bmj.com, 14 Jul 2006 [Full text]
Necessity to assess the clinical predictors for driving the best strategy of treatment in infertile anovulatory patients with polycystic ovary syndrome: Stefano Palomba, et al.
bmj.com, 1 Aug 2006 [Full text]