Cochrane Menstrual Disorders and Subfertility Group: Clomiphene citrate for unexplained subfertility in women

Plain English Summary: "Clomiphene citrate for unexplained subfertility in women Clomiphene citrate is a fertility drug that can increase the number of eggs released for possible fertilisation. It is used by women who do not ovulate regularly and by some who do but still have not become pregnant. Clomiphene citrate does not appear to increase the chance of pregnancy in women who ovulate regularly but have failed to conceive after more than a year of unprotected intercourse and so are considered to be subfertile. An associated risk of treatment with clomiphene citrate is a 10% chance of multiple pregnancy. The results of this review of trials should be used with caution due to the heterogeneity between some of the studies."



Editorial group: Cochrane Menstrual Disorders and Subfertility Group.  
Authors' 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.  


Some key items:

Adverse effects

• Battacharya 2008 was the only paper to report on adverse effects.
• The primary outcome of live birth was only reported in one study (Battacharya 2008).
• A case-cohort study has suggested a link with clomiphene when used for more than 12 months (Rossing 1994). Thus, if clomiphene has been unsuccessful after six to nine months it should probably be discontinued.