comparison of the effectiveness of clomiphene citrate, tamoxifen and letrozole in ovulation induction in infertility due to isolated unovulation

background: unovulation is the most common cause of infertility. the first line oral treatment has been clomiphene citrate. another anti-estrogen used for ovulation induction is tamoxifen. many unovulatory infertile women are resistance to anti-estrogens and need another treatment. alternative treatments are aromatas inhibitors. objective: this study was designed to compare the effectiveness of clomiphene, tamoxifen and letrozole in ovulation induction outcomes in isolated non pcos unovulatory patients. materials and methods: 150 unovulatory infertile women who had isolated non- polycystic ovarian syndrome (pcos), randomized to 3 groups. group a received clomiphene 50 mg to maximum 150 mg for 5 days, group b received tamoxifen 10mg to maximum 30 mg for 5 days, group c received letrozole 2.5 mg for 5 days, to maximum 7.5 mg until ovulation was induced. if ovulation failed to occur with 5 days treatments, drug continued for 7 days. treatment has been stopped if they became pregnant or if patient didn’t ovulate with maximum dose for 7 days (resistant to treatment) or failed to concept after six months despite ovulation (failure of treatment). main outcome measures were: number of mature follicles, endometrial thickness, pregnancy rate, multiple pregnancy rate, live birth and miscarriage. results: overall ovulation rate was 60 (73.4%), this rate in group a was 39 (78%), in group b it was 24 (68%) and in group c was 37 (74%). pregnancy rate in groups a, b and c were, 32 (64%), 20 (40%), and 25 (50%) respectively, and live birth rate was 22 (44%) in a, 17 (34%) in b and 21 (42%) in c. miscarriage rate with clomiphene was 10 (20%) while this was 3 (6%) in tamoxifen and 4 (8%) in letrozole group (p=0.05). one twin pregnancy was occurred with clomiphene and one with tamoxifen, while all pregnancies with letrozole were singleton. conclusion: because of higher pregnancy rate with clomiphene citrate than tamoxifen and letrozole, clomiphene citrate is still the first-line therapy for ovulation induction. surprisingly, pregnancies after tamoxifen and letrozole have lower miscarriage rate than clomiphene.