Letrozole induction of ovulation in infertile women with Clomiphene Citrate resistance

  Background: Aromatase inhibitors have been recently advocated as an inexpensive, effective, and low risk treatment in clomiphene citrate (CC)-resistant patients.   Objective: To evaluate the efficacy of letrozole in induction of ovulation in CC- resistant patients.   Methods: This prospective clinical trial was carried out on 30 patients admitted to a private infertility clinic in Qazvin during 2009. Thirty patients with polycystic ovary syndrome (PCOS) and unexplained infertility who were resistant to CC entered the study. Inclusion criteria included age between 18-39, infertility more than 2 years, normal TSH, prolactin, spermogram, and FSH in the beginning of follicular phase and the exclusion criteria were history of pelvic surgery, presence of adhisions and every infertility factors except unovulation. After a washout period of 2 months, letrozole was given orally in doses of 2.5-7.5 mg on days 5-9 of the menstrual cycle. Dose increase was performed if there was no dominant follicle at lower dose. Follicular assessment was carried out by vaginal sonography on day 16 followed by administration of hCG if follicle>18mm was detected. Ovulation and pregnancy rate and the endometrial thickness on day of hCG administration were measured. Data were analyzed using chi-square test, paired t-test, and the Fischer’s exact test.   Findings: Following administration of letrozole in three doses of 2.5, 5, and 7.5 mg, 3 (10%), 12 (40%), and 5 (16.7%) patients had follicle>18mm, respectively. The overall ovulation rate was %66.6. Among these patients, 16 (80%) had one dominant follicle and 4 (20%) with 2 but no twin pregnancy was present. Pregnancy took place in 5 patients (16.7%). Endometrial thickness was 11.5, 11.5 and 11.4 in doses of 2.5, 5 and 7.5 mg of letrozole, respectively.   Conclusion: The findings of the present study showed that the induction of ovulation with letrozole in CC-failure is associated with ovulation and pregnancy in a significant number of patients. Regarding the low risk of multiple pregnancy and hyperstimulation syndrome, letrozole could be the first line treatment in CC- failure.