Aromatase Inhibitor for Ovulation Induction: a Comparative Study between Letrozole and Clomiphen Citrate in Anovulatory Infertile Women

The study was designed to compare the effectiveness of Letrozole and clomiphen citrate in the treatment of anovulatorv infertility. Thirty patients were selected randomly who had anovulatorv infertility. In letrozole group, fifteen patients got 5-7.5 mg of letrozole orally and in clomiphen citrate group, 100-150 mg of clomiphen citrate was given orally for maximum of six cycles and in both the groups the drugs were started from day 3 -7 of the menstrual cycle. There were no significant differences between the age, duration and type of fertility. But statistically significant increase of follicular development in letrozole group (ñ=0.020). Mean endometrial thickness was 8.33±1.54 and 5.36±1.84 respectively in letrozole and in clomiphen citrate group (ñ =0.048). There was no significant difference in ovulation in both the groups but pregnancy was more (33.3%) with the letrozole group. Letrozole is an effective agent for ovulation induction. It can be used as an alternative to CC as a first-line of treatment for ovulation induction. (Bangladesh J Physiol Pharmacol 2009; 25(1&2) : 10-12) Address of Correspondence: Dr. Rokshana Ivy, Senior Consultant, Department of Obstetrics & Gynecology, Maternal and Child Health Training Institute, Azimpur, Dhaka thinning of the endometrium, which is dose dependent9. It also appears that CC accumulates in the body because of its long half-life (2 weeks)10. Because of these problems, the concept of aromatase inhibition was proposed as a new method of ovulation induction that could avoid many of the adverse effects of CC11. Aromatase is a microsomal member of the cytochrome P450 hemoprotein-containing enzyme complex superfamily that catalyzes the rate limiting in the production of estrogen. Aromatase converts androstenedion to estrone and testosterone to estradiol12. Aromatase activity is present in many tissues, such as the ovaries, the brain, adipose tissue, muscle, liver, and breast, and in malignant breast tumors. The main sources of circulating estrogens are the ovaries in premenopausal women and adipose tissue in post menopausal women13. Letrozole is a third generation selective aromatase inhibitor14. It is an aromatase inhibitor that has been used in women with breast cancer15. In the late 1990s, Letrozole began to be used to induce ovulation by being administered in the early part of the menstrual cycle16. In this study, ovulation was induced in the infertile anovulatory women due to polycystic ovarian syndrome by letrozole and clomiphen citrate. MATERIALS AND METHODS The study was conducted in Bangladesh Infertility Management Center, Dhaka, a private infertility care center. The study period was from February 2008 to January 2009. Thirty infertile women of anovulatory polycystic ovarian syndrome (PCOS) were included in the study. The exclusion criteria were the tubal factor infertility, male factor infertility, endometriosis, hyperprolactinaemia and thyroid disorder. Once inclusion and exclusion criteria were met, alternate woman was selected either for letrozole group or for clomiphen citrate group. Before the study informed verbal consent was taken from all women. In letrozole group, 5-7.5 mg of letrozole and in clomiphen citrate group 100-150 mg of clomiphen citrate were given orally for maximum of six cycles and in both the groups the drugs were started from day 3-7 of the menstrual cycle. The main outcome measures were the follicular growth, endometrial thickness, occurrence of ovulation and pregnancy rate. Transvaginal ultrasounds were performed to document the follicular growth and the endometrial thickness on day 10 of the cycle and whenever necessary. Follicles were considered as mature when they attained the size of 18 mm or more. Endometrial thickness was measured as the maximal thickness of the endometrial lining in the plane through the central longitudinal axis of the uterine body. The tri-laminar endometrial pattern and the thickness of endometrium, 8 mm or more were considered satisfactory. When both the follicular growth and the endometrial thickness were satisfactory, 5000 IU HCG injection was given intramuscularly and advised for timed coitus. Ovulation was observed by transvaginal ultrasounds at 48 hours after the HCG injection and by day 21 progesterone. Pregnancy was confirmed by ultrasonography. The results were analyzed statistically by Statistical Program of Social Science (SPSS) version 11.5.