Amer SA, et al. – The objectives of this study are to test the hypothesis that letrozole as a primary ovulation induction (OI) agent will generate higher pregnancy rates than clomiphene citrate (CC) in anovulatory women with polycystic ovarian syndrome (PCOS) and to test the effectiveness of each drug as a secondary OI agent. Participants receiving letrozole as a primary treatment achieved a significantly (P = 0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%).

Methods

• For this study, they conduced a double–blind randomized controlled trial (RCT).
• Total 159 participants were included in this study between April 2007 and June 2014.
• All the participants were randomly allocated to either CC (n = 79) or letrozole (n = 80) in a 1:1 ratio.
• Both drugs were encapsulated to look identical.
• Randomization was performed in mixed blocks and stratified by patients’ BMI (<30 and 30–35 kg/m²).
• Subfertile women diagnosed with PCOS were included in this trial.
• Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non–responders and continuing until pregnancy or for up to six ovulatory cycles.
• Non–responders were crossed over to the other treatment after a 6–week break.
• Cycles were initially monitored with ultrasound follicle tracking then mid–luteal serum progesterone measurement in subsequent cycles.

Results

• Among the 159 participants incorporated into the intention–to–treat analysis, four women conceived before treatment and six were lost–to–follow–up.
• The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment.
• Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3–33%]) higher pregnancy rate (61.%) than those on CC (43%).
• The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3–5] cycles) compared to CC (6[4–7] cycles).
• LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%).
• After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%).