Effectiveness of bromocriptine monotherapy or combination treatment with clomiphene for infertility in women with galactorrhea and normal prolactin: A systematic review and meta-analysis.

BACKGROUND Among women with unexplained infertility, 28% to 55% of patients with galactorrhea are normoprolactinemic. Bromocriptine, a common treatment for infertile women with hyperprolactinemia, has been used in the treatment of unexplained subfertility in women with galactorrhea and normal prolactin; however, its effectiveness and safety profile have never been determined. OBJECTIVE The aim of this study was to determine the relative effectiveness and safety profile of bromocriptine monotherapy or as an adjunct to clomiphene citrate in women with galactorrhea and normal prolactin levels. METHODS We conducted a search of the Cochrane Subfertility Review Group specialized register of controlled trials (March 2010), CENTRAL (The Cochrane Library, Issue 3, 2010), MEDLINE (1950-March 2010), EMBASE (1980-March 2010), and the China Biological Medicine Database (inception to March 2010) for relevant randomized controlled trials (RCTs) using the following terms: controlled, randomized, blinded, clinical trials, humans, galactorrhea, prolactin, bromocriptine, infertility, and subfertility. Additionally, reference lists of identified articles were searched for relevant articles. RESULTS Of the 8 studies identified, 5 were excluded after full-text review for the following reasons: lack of a placebo group (2); difference in cointerventions (1); difference in end points (1); and systematic review (1). Therefore, 3 RCTs were included in this review. Bromocriptine administered in combination with clomiphene was found to be associated with a higher accumulative pregnancy rate compared with clomiphene monotherapy (fixed odds ratio [OR], 5.33; 95% CI, 2.62-10.88), and a lower miscarriage rate (fixed OR, 0.20; 95% CI, 0.05-0.76). Only 1 trial reported live birth as an outcome, and multiple pregnancy rates were poorly reported. Patient-reported adverse effects were mentioned in the studies, but reports were often incomplete. CONCLUSIONS This review suggests the effectiveness of bromocriptine with clomiphene for infertility in women with galactorrhea and normal prolactin levels. Further RCTs of adequate power and of high methodologic quality are required to confirm these findings.