Letrozole step-up protocol for ovulation induction in infertile women with polycystic ovary syndrome – a randomized controlled trial

Polycystic ovary syndrome (PCOS) is the largest single cause of anovulatory infertility. Letrozole, an aromatase inhibitor, has been regarded as the first-line drug for ovulation induction in PCOS patients. The conventional protocol of letrozole includes the administration of a fixed dose of letrozole (2.5–7.5 mg) for 5 days. Few recent studies have shown that the step-up letrozole protocol causes more follicles to grow, induces more ovulation, and increases the pregnancy rate. This study aimed to compare the effect of the letrozole step-up and conventional fixed-dose protocol for ovulation induction in infertile women with PCOS. This open-label randomized controlled study was conducted on a total of 70 infertile PCOS women eligible for ovulation induction. Treatment with letrozole started from day 2–3 of menstruation or withdrawal bleeding. They were randomly allocated into two groups. The experimental group (n = 35) was given step-up letrozole for four days, starting with 2.5 mg and increasing by 2.5 mg daily for next three days. The comparator group (n = 35) received conventional fixed-dose letrozole, 5 mg daily for 5 days. The outcome variables were the presence of a mature follicle by day 12–16 of the cycle and the number of mature follicles on the day of trigger. The number of participants who achieved mature follicles by day 12th to 16th of menstruation was higher in the letrozole step-up protocol. All participants in the step-up letrozole group developed mature follicles in the second and third cycle, an effect achieved in the third cycle in conventional fixed-dose letrozole group. There was multifollicular development in the step-up letrozole group in all three cycles. The mean number of mature follicles was significantly higher in the step-up letrozole group compared to the conventional dose group in the 2nd (1.28 ± 0.45 vs. 1 ± 0.50) and 3rd cycle (1.45 ± 0.51 vs. 1.06 ± 0.23). Step-up letrozole group resulted in a higher cumulative pregnancy rate compared to the conventional fixed dose letrozole group (16.3% vs. 9.3%). Step-up protocol of letrozole improves ovarian response and cumulative pregnancy rate in infertile women with PCOS when compared to conventional fixed dose protocol, but the difference is not significant.