Background: Although clomiphene citrate is the first line in ovulation induction in anovulatory infertile women, but some of polycystic ovarian syndrome (PCOS) patients are clomiphene-resistant. This study was carried out to compare the combined effect of letrozole and clomiphene with gonadotropins on pregnancy rate in clomiphene-resistant PCOS patients.

Materials and Methods: This clinical trial study was carried out on 120 clomiphene-resistant PCOS patients. The patients were randomly divided into two groups: group 1 received clomiphene (100 mg/day) and group 2 received letrozole (5 mg/day) on the 3–7 th days of menstrual cycle. Both groups received (150 IU/im) HMG on the 5–8 th days of menstrual cycle. On 10-11 th days of menstrual cycle, transvaginal sonography was performed to determine endometrial thickness, dominant follicle number and increase HMG dose, if required. HCG at a dose of 5000 IU was administered when at least one mature follicle was observed. β-HCG level was evaluated 2 weeks after HCG administration. The two groups were compared for mature follicles numbers, endometrial thickness, gonadotropin consumption and pregnancy rate. Chi–square, Kolomogrov–Smirnov, t-test, Levene, Mann-Whitney tests were used to analyze data.

Results: Although the pregnancy rate in letrozole group was higher than in the clomiphene one, the difference was not significant (36.7% vs 33.3%, P=0.702). The mean endometrial thickness in letrozole and clomiphene group was 7.47 mm and 7.49 mm, respectively (P=0.685). In letrozole and clomiphene group the mean of dominant follicles numbers was 2.18 and 2.83, respectively (P=0.087) while the gonadotropin level mean in both groups was 6.78 (p=0.941).

Conclusion: In clomiphene resistant PCOS patients, similar to clomiphene, letrozole in combined regimens with gonadotropin can be effective for the induction of ovulation.