P-596 Comparative efficacy of Letrozole (5 mg) versus Clomiphene citrate (100 mg) for ovulation induction among infertile women

Field: Medicine (Health Sciences)

Abstract Study question Does Letrozole have better offerings while being compared to Clomiphene citrate as an Ovulation inducing agent in infertile women? Summary answer Compared to clomiphene, Letrozole - an aromatase inhibitor, is associated with higher live-birth and ovulation rates among infertile women. What is known already Anovulatory dysfunction is a common problem and is responsible for about 40% of female infertility and among causes; PCOS (polycystic ovarian syndrome) is the leading cause. Clomiphene citrate has been traditionally used as the drug of choice for treatment of women with anovulatory infertility. In the last decade, an aromatase inhibitor, letrozole, has emerged as an alternative ovulation induction agent among anovulatory women with polycystic ovarian syndrome. Letrozole has a definitive role in anovulatory women who have not responded to clomiphene citrate therapy, as confirmed by literature. Study design, size, duration Randomized double-blind study. Total 100 women were randomly assigned and divided into 2 groups of 50 patients each. The 2 groups were well matched at baseline. Study participants are of age 20 to 39 years. Study began in October 2019 and was completed in October 2021. Participants/materials, setting, methods Group 1: Clomiphene citrate (100 mg daily) and group 2: letrozole (5 mg daily), started from any day between 3-5 of the menstrual cycle and continued up to 5 consecutive days. Both groups have received Estradiol Valerate 4 mg on the 12th day of menstruation until 16th day of menstruation. All patients had USG monitoring of follicular and endometrium size with perifollicular flow and uterine scoring system for reproduction (USSR) score with timed intercourse. Main results and the role of chance Women who received letrozole as compared to those who received clomiphene citrate had more cumulative live births (36 of 50 [72%] vs. 28 of 50 [56%]). Number of women ovulated in Letrozole group was – 42 (84%) while in Clomiphene citrate (CC) Group it was 39 (78%). The ovulation rate was significantly higher with letrozole than with clomiphene citrate. Among the study participants who ovulated, there was a significantly greater chance of singleton pregnancy with letrozole compared to clomiphene citrate. The mean number of dominant follicles (18 mm) was 1.40 ± 0.58 for letrozole and 1.10 ± 0.86 for clomiphene citrate (P-value = &lt;0.05). The size of follicular development by day 14 was 17.6 ± 2.92 mm in Letrozole group while in Clomiphene citrate group it was 15.8 ± 3.84 mm (P-value = &lt;0.05). The mean endometrial thickness by day 14 was 7.2 ± 0.77 mm for Letrozole and 6.8 ± 0.92 mm for clomiphene citrate (P-value = &lt;0.05). Limitations, reasons for caution In our study, we have not considered lifestyle intervention before enrolment; although such interventions are recommended by experts, but there is currently no evidence from high quality clinical trials that they improve pregnancy outcomes in obese women. Wider implications of the findings Although Letrozole has still not gained universal acceptance as an ovulating agent for a variety of reasons, emerging evidences suggests that Letrozole could be an effective option and is non inferior to clomiphene citrate as an ovulating agent especially, in patients with non- responders to Clomiphene citrate and PCOS women. Trial registration number Not applicable