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.

Keywords
Infertility, Unovulation, Non-polycystic ovarian syndrome, Ovulation induction, Clomiphene, Tamoxifene, Letrozole.