Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial

Abstract

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n = 102) received CC 100 mg and metformin 500 mg while the second group (n = 100) received letrozole 2.5 mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p < .001), more dominant follicles (p < .05), better endometrial thickness (p < .001), higher clinical pregnancy rate (36% versus 9.8%, p < .001), higher multiple pregnancy rate (p < .05), lesser adverse effects (p < .05) and higher acceptability (p < .001) compared to patients in the CC and metformin arm. In conclusion; letrozole is better and more acceptable than combined CC and metformin for inducing ovulation in patients with CC-resistant PCOS with higher clinical pregnancy rate and unexpectedly higher multiple pregnancy rate.

Clomiphene Citrate Combined with Tamoxifen Citrate versus Letrozole for Inducing Ovulation in Patients with Clomiphene Citrate -Resistant Polycystic Ovary Syndrome

“…Letrozole is effective for inducing ovulation in CC-resistant PCOS as demonstrated in previous studies and in recent reviews and guidelines [6,[8][9][10].…”

Simultaneous Letrozole and Clomiphene Citrate versus Letrozole Alone in Clomiphene Citrate Resistant Polycystic Ovary Syndrome: A Randomised Controlled Trial

“…There was a marked improvement in ovulation rate in patients with CCR-PCOS after administration of either letrozole alone or letrozole + CC; the ovulation rate in the first cycle of treatment was matched in both groups (19 These results were in accordance with Kamath et al [16], who studied the effect of letrozole versus placebo in CCR-PCOS patients, letrozole was better than placebo for ovulation rate per patient (6 of 18, 33.33% versus none of 18, 0%, p = 0.006). However, no difference in pregnancy rate per patient (1 of 18, 5.55%…”

“…But when both are combined with HMG, the ovulation rate was significantly higher than LE + HMG and CC + HMG, with lower risk of multiple pregnancy and OHSS [17]. Elnashar et al, studied the effect of letrozole on 44 patients with CCR-PCOS, and found that ovulation occurred 54.6% of patients, pregnancy occurred in 25% of patients and the mean endometrial thickness was 10.2 mm [18].Rezk et al, compare the effect of letrozole alone versus combination of clomiphene citrate and metformin in CCR-PCOS patients and found higher ovulation and clinical pregnancy rate with letrozole alone with unexpectedly higher multiple pregnancy rate[19].…”

Recent advances in the understanding and management of polycystic ovary syndrome

“…The major advantage of letrozole over CC is better ovulation-inducing response, especially in obese patients, which translates into higher pregnancy and live birth rates 60, 64 . Preliminary data also suggest that letrozole is superior to metformin plus CC to induce ovulation as assessed by the clinical pregnancy rate in an open-label randomized clinical trial 65 .…”