Clomiphene citrate for unexplained subfertility in women.
BACKGROUND
The effectiveness of clomiphene citrate has been demonstrated in the treatment of subfertility associated with infrequent or irregular ovulation. The physiologic effects and clinical benefits in ovulatory women with unexplained subfertility are less clear. The drug is associated with an increased risk of multiple pregnancy and a suggestion of potentially increased ovarian cancer risks. In light of these concerns, defining the effectiveness of clomiphene citrate for ovulatory women with unexplained subfertility is extremely important.


OBJECTIVE
To determine the effectiveness of clomiphene citrate in improving pregnancy outcomes in women with unexplained subfertility, used in a dose range of 50 to 250 mg for up to 10 days. The primary outcome was live births.


METHODS
We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (June 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009) and reference lists of articles.


METHODS
Only randomised controlled trials were included. Quasi-randomised designs were excluded.


METHODS
Fourteen potentially relevant trials were identified of which seven were included in this review. All trials were assessed for risk of bias using standardised Menstrual Disorders and Subfertility Group methodology.


RESULTS
Data relating to 1159 participants from seven trials were collated. There was no evidence that clomiphene citrate was more effective than no treatment or placebo for live birth (odds ratio (OR) 0.79, 95% CI 0.45 to 1.38; P = 0.41) or for clinical pregnancy per woman randomised both with intrauterine insemination (IUI) (OR 2.40, 95% CI 0.70 to 8.19; P = 0.16), without IUI (OR 1.03, 95% CI 0.64 to 1.66; P = 0.91) and without IUI but using human chorionic gonadotropin (hCG) (OR 1.66, 95% CI 0.56 to 4.80; P = 0.35). It should be noted that heterogeneity between studies ranged from 34% to 58% using the I(2) statistic.


CONCLUSIONS
There is no evidence of clinical benefit of clomiphene citrate for unexplained fertility. When making this treatment choice, potential side effects should be discussed. These include the increased risk of multiple pregnancy and the concern that use for more that 12 cycles has been associated with a three-fold increase in risk of ovarian cancer.
Hughes
Edward
E
Department of Obstetrics and Gynaecology, McMaster University, 1200 Main St West, Room 4D14, Hamilton, Ontario, Canada, L8N 3Z5.
Brown
Julie
J
Collins
John J
JJ
Vanderkerchove
Patrick
P
D002996:Clomiphene / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic
D005300:Fertility Agents, Female; D002996:Clomiphene