A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS).

DESIGN: Open-label randomized controlled trial.

SETTING: Academic medical center using two clinic sites.

PATIENT(S): Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility.

INTERVENTIONS(S): Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle.

MAIN OUTCOME MEASURE(S): Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL.

RESULT(S): Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups.

CONCLUSION(S): The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate.

CLINICAL TRIAL REGISTRATION NUMBER: NCT02802865.