randomized trial of metformin-letrozole versus metformin-clomiphene citrate in patients with polycysytic ovary syndrome resistant to clomiphene

ABSTRACT

To compare the effects of the combination of aromatase inhibitor Letrozole [2.5 mg] and metformin vs. clomiphene citrate [CC 100 mg] and metformin in clomiphene resistant PCO women. In a prospective randomized trial, a total of 120 cycles in 60 women with clomiphene resistant polycystic ovary syndrome were studied. Patients were randomized into treatment with 2.5 mg of Letrozole daily [29 patients, 53 cycles] or 100 mg of CC daily [30 patients, 67 cycles]. Number of mature follicles, endometrial thickness, estradiol level, pregnancy rate, and miscarriage rate were measured. The mean age, BMI, infertility duration, ovulation rate and the number of mature follicles [>18 mm] in both groups of patients were similar. Total and per follicle estradiol concentrations were significantly lower in the Letrozole group than in the CC group on the day of HCG administration [1664.63 +/- 1350 vs. 981.35 +/- 648 and 783.38 +/- 251 vs. 447.60 +/- 133.36 picomol/L], and the endometrial thickness was significantly higher [0.82 +/- 0.1 vs. 0.55 +/- 0.28 cm]. No difference was found in metformin side effects between both groups. There was no significant difference in pregnancy rate between Letrozole and CC groups [10 cases or 34.5% vs. 5 pregnancies or 16.67% respectively]. Two miscarriages of the 5 pregnancies [40.0%] occurred in the CC group with no abortion in Letrozole group. In comparison to the CC group term pregnancies were also significantly higher in the Letrozole group [10 cases or 34.5% vs. 3 pregnancies or 10.00% respectively]. In women with clomiphene resistant polycysytic ovary syndrome, the combination of Letrozole and metformin is associated with higher pregnancy, and lower miscarriage rates in comparison to CC and metformin