الفهرس 
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Abstract
Summary
Unexplained infertility refers to the absence of a definable cause for a couple’s failure to achieve pregnancy after 12 months of attempting conception despite a thorough evaluation, or after six months in women 35 and older .
Diagnosis of UI should be done after Exclusion of other Factors of infertility , Male factor, Ovulatory dysfunction , Tubal and Uterine Factors.
Management of UI could be expectant management with lifestyle Changes, ovulation induction with oral drugs as Clomiphene citrate or letrozole combined with or without IUI , ovulation induction with Gonadotropins injections combined with or without IUI and IVF.
Letrozole is used off-label in Ovarian stimulation , its mechanism of action is mainly aromatase enzyme inhibition thus reduction of circulating estradiol levels leading to release of inhibition of the hypothalamic–pituitary axis from estrogenic negative feedback, therefore follicle stimulating hormone (FSH) secretion is increased, resulting in stimulating effect on the growth of ovarian follicles.
Beside the conventional fixed dose protocol of letrozole in ovulation induction, many other regimens of letrozole were discussed in many studies , one of them is step-up protocol.
In our study we 180 patients diagnosed with UI were enrolled in the study and randomized in 2 groups 1st group stimulated with letrozole step up protocol, the 2nd group with conventional fixed dose protocol for 1 to 3 cycles .
CPR, LBR , Abortion Rate , Number of follicles, Endometrial layering, Endometrial thickness , Spiral artery doppler PI, RI , OHSS , Multifetal pregnancy and drug complications were recorded and statistically analyzed.
There is statistically significant difference between the two groups regarding ovulation rate. As ovulation rate was higher in group A (Step up protocol) = 95.3% (221 of 232 cycles) than group B (Fixed dose) =89.1% (212 of 238 cycles), with (P = 0.013). Also, As well, There was statistically significant difference between the two groups regarding Number of follicles ≥18 mm on day of HCG; the mean in group A (Step up protocol) was 2 ± 0.83 and 1.12 ± 0.33 in group B (Fixed dose protocol), with (P ≤0.001). There was no evidence of statistically significant difference between the two groups regarding the Endometrial thickness , trilaminar endometrial pattern or the spiral artery PI.
Although, spiral artery RI showed statistically significant difference between the two groups; the mean in group A (Step up protocol) was 0.56 ± 0.08 and 0.61 ± 0.08 in group B (Fixed dose), with (P = 0.001).
Regarding Pregnancy rate :Finally, there was no evidence of statistically significant difference between the two groups regarding cumulative pregnancy rate, which was higher in group A (36.7%) than group B (30%).
Seven out of 33 women (21.2%) had miscarriage in group A (Step-up) and 3 out of 27 (11.1%) women of pregnant women group B experienced miscarriage, with P-value=0.296. which statistically; of no significant difference.
There was no evidence of significant difference statistically regarding complications.
We concluded that Compared to the monofollicular development of the conventional protocol , letrozole step up protocol was associated with multifollicular development and better endometrial receptivity in the form of lower endometrial spiral artery RI with no significant increase in complications as OHSS, multifetal pregnancy or dug complications .