Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome.

OBJECTIVE: To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS).

DESIGN: A multicenter randomized double-blinded placebo-controlled trial.

SETTING: Reproductive and developmental network sites.

PATIENT(S): Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups.

INTERVENTIONS(S): Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant.

MAIN OUTCOMES MEASURE(S): Cumulative live births.

RESULTS: The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group.

CONCLUSION(S): Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole.

CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000376 (https://apps.who.int/trialsearch/).