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

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. This study was designed to compare the effectiveness of clomiphene, tamoxifen and letrozole in ovulation induction outcomes in isolated non PCOS unovulatory patients. 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. 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. 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.