In this study clomiphene citrate-resistant patient had different response to letrozole in a way that 44.24% of the cycles had normal follicles and 23.89% of them resulted in pregnancy. Increasing the dosage can improve the chance of ovulation and pregnancy. Only 7 (15.9%) patients with 2.5 mg letrozole daily became pregnant while 11 patients were pregnant by increasing the dosage to 5 mg, and, among those who did not respond to these dosages, 9 patients became pregnant by increasing it to 7.5 mg. About 61.36% of the patients became pregnant with letrozole although letrozole is more expensive than clomid but cheaper than gonadotropins and so is more cost effective. The metformin-clomiphene citrate combination was seen to increase the ovulatory and pregnancy rate when compared with CC alone. Metformin increased the ovulatory rate in clomiphene citrate failures, also implying increased sensitivity to clomiphene citrate [14]. Akbary-Asbagh et al. and Begum et al. suggest letrozole as an effective treatment for clomiphene citrate-resistant (PCOS) patients [15, 16]. Two of 113 cycles resulted in twins; increasing the dosage improved the chance of two follicles in one cycle. In the first step, like Akbary-Asbagh et al. and Begum et al. study [15, 16], all the cycles had one follicle, but 31.25% and 30.43% of cycles had two follicles in 5 mg and 7.5 mg Letrozole regimen, respectively, even one patient had 3 follicles in a cycle. In Mitwally et al.'s study, for all PCO patients with a serial increase of letrozole dosage (set-up protocol) the same results were confirmed which may be due to the long-term inhibition of estrogen levels (E2) [17]. When a patient responds to clomiphene citrate, the E2 will increase considerably which will be greater than when she receives Letrozole [2, 4]. Because of clomiphene citrate resistance, E2 levels do not increase by clomiphene citrate consumption, and beside ovulation its level will be less than the acceptable level in letrozole groups [6]. Basal testosterone level is a good marker for pregnancy outcome and quantity of dominant follicles on HCG day in women with reduced ovarian reserve but not in women with normal range of serum FSH [18]. Letrozole is an effective ovulation induction drug in elevated-BMI women [19]. We had not any correlation between BMI, basal testosterone, LH/FSH, and number of mature follicle because according to inclusion criteria all of the patients had normal testosterone level, BMI, and LH/FSH ratio. The chance of AUB increased from 2.08% with 2.5 mg letrozole daily to 2.63% with 5 mg daily and 14.8% in the 7.5 mg regimen. No change was found in endometrial thickness according to the Cortines study [6]. So AUB could be due to a decrease in estrogen levels. Given these findings, it is required that more investigations be conducted with estrogen drugs like conjugated estrogens which can prevent AUB in cases with additional letrozole dosage. Letrozole can block estrogen (E) production, consequential in decreased negative feedback of E on pituitary for FSH secretion. Bentov et al., prove that a ratio of cycle day 7 to cycle day 3 postletrozole FSH level >1.5 is related with poor ovarian response. Letrozole challenge test can be a prediction of ovarian response [20]. We suggest that higher pregnancy rates during letrozole treatment can be achieved if antral follicular count, anti-Müllerian hormone, LH/FSH, and estradiol are checked and good patient selection is done [1]. The good pregnancy results and low multiple gestation rate of 2.5 mg letrozole for induction of ovulation is hopeful for letrozole user as a first-line drug [12]. The chances of multigestational pregnancy increases by increasing the number of follicles in a cycle which implies an appropriate response to letrozole. Cumulative pregnancy rates were considerable in clomiphene citrate resistant patients, but the pregnancy rate was not significantly different between the 2.5, 5, and 7.5 mg regimens while complications (multigestational pregnancy risk, irregular bleeding, and ovarian cyst) increased by dosage. Delivery rate was 25 live birth/cycles (22.12%) due to 2 abortions during the study.