WITHDRAWN: Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea.
BACKGROUND
The administration of clomiphene citrate is followed by an enhanced release of pituitary gonadotropins resulting in follicular recruitment. After the drug is stopped, there is continuing secretion of estradiol, selection of the dominant follicle and, in successful cases, ovulation. Clomiphene is indicated as the initial treatment in the majority of women with amenorrhoea and oligomennorhoea. In women with irregular ovulation it seems to re-establish typical frequency of ovulation. Its effectiveness in oligo-amenorrhoeic women was tested in a number of randomised controlled trials at that time. These trials form the basis for the following review.


OBJECTIVE
Clomiphene citrate enhances the release of pituitary hormones, often resulting in ovulation. The objective of this review was to assess the effects of clomiphene citrate on ovulation and pregnancy in women with oligo-ovulatory subfertility.


METHODS
The Cochrane Subfertility Review Group specialised register of controlled trials was searched.


METHODS
Randomised trials of clomiphene compared with placebo or no treatment in women with oligo-ovulatory subfertility of at least 12 months duration.


METHODS
Trial quality was assessed and data were extracted independently by two reviewers.


RESULTS
Four studies were included. They were all of crossover design. Since it was not possible to separate data from the first and second phases of these trials, the effect of clomiphene may be overestimated. Compared with placebo, clomiphene citrate was associated with increased ovulation. The odds ratio for high doses (50-250 milligrams per day) was 6.82 (95% confidence interval 3.92 to 11.85). This dropped to a non-significant odds ratio of 1.29 (95% confidence interval 0.48 to 3.49) with low doses (10 milligrams per day). Clomiphene citrate (all doses) was associated with an increased pregnancy rate per treatment cycle (odds ratio 3.41, 95% confidence interval 4.23 to 9.48).


CONCLUSIONS
Clomiphene citrate (at doses between 50 to 250 milligrams per day) appears to be an effective method of inducing ovulation and improving fertility in oligo-ovulatory women. However adverse effects include possible ovarian cancer risk and risk of multiple pregnancy.
Hughes
E
E
McMaster University, Rm HSC-4F7, Dept of Obstetrics & Gynecol, 1200 Main St West, Hamilton, Ontario, Canada, L8N 3Z5. hughese@mcmaster.ca
Collins
J
J
Vandekerckhove
P
P
D000568:Amenorrhea / Q000150:complications*; D002996:Clomiphene / Q000627:therapeutic use*; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D009839:Oligomenorrhea / Q000150:complications*; D010062:Ovulation Induction; D011247:Pregnancy
D005300:Fertility Agents, Female; D002996:Clomiphene