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.
OBJECTIVE
To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome.


METHODS
Randomised clinical trial.


METHODS
Multicentre trial in 20 Dutch hospitals.


METHODS
228 women with polycystic ovary syndrome.


METHODS
Clomifene citrate plus metformin or clomifene citrate plus placebo.


METHODS
The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance.


RESULTS
111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences 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 women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%).


CONCLUSIONS
Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome.


BACKGROUND
Current Controlled Trials ISRCTN55906981 [controlled-trials.com].
Moll
Etelka
E
Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, PO Box 22700, 1100 DE, Amsterdam, Netherlands. e.moll@amc.uva.nl
Bossuyt
Patrick M M
PM
Korevaar
Johanna C
JC
Lambalk
Cornelis B
CB
van der Veen
Fulco
F
D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D006801:Humans; D008687:Metformin / Q000008:administration & dosage*; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
D005300:Fertility Agents, Female; D002996:Clomiphene; D008687:Metformin