الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Approximately 8-12% of women in general population have PCOS syndrome but it is the cause in about 30% of women with infertility.
Approximately 80% of PCOS women treated with clomiphene citrate; ovulate and approximately 20%-40% become pregnant. Clomiphene citrate is usually given in dose of 100mg daily for 5 days.
Clomiphene citrate is associated with higher than normal incidence of multiple births. CC is associated with thin endometrium, poor cervical mucous, reduction of the glandular density and slows down uterine blood flow during the early luteal phase and the implantation stage.
Recently the new aromatase inhibitor, letrozole has been used for induction of ovulation. Letrozole reversibly inhibits the enzyme responsible for estrogen biosynthesis. By decreasing the estrogen levels in the body it may release the hypothalamus and/or pituitary from the negative feed back of estrogen on the release of gonadotropins. This will result in an increase in endogenous FSH and LH, which stimulate the development of ovarian follicles. This mechanism is similar to the proposed mechanism of action of clomiphene citrate.
However, Letrozole may have another peripheral mechanism of action directly in the ovaries. Letrozole is eliminated from the body in a few days after last administration (in contrast to CC which may last up to few months). Also, it does not have a direct antiestrogen action by itself as in CC. So there should be no unwanted peripheral antiestrogen effects on the endometrium, and the cervix.
Letrozole (Femara®, Novartis) is available in 2.5 & 5 mg tablets. It is an approved drug that was developed to inhibit the estrogen production in postmenopausal women with breast cancer. Therefore, it has been tested and tolerated very well when administered continuously for several months.
Side effects of letrozole are usually mild in the form of headache, mild GIT upsets, hot flushes and easy fatigue.
Letrozole is associated with thicker endometrium favorable cervical mucous and better uterine blood flow.
The aim of this work was to compare the effects of Letrozole and Clomiphene Citrate on endometrial response in PCOS patients using subendometrial spiral artery Doppler.
This study included one hundred infertile women diagnosed as having PCOD. Women were randomized into two groups. Group I included 50 women who were given the aromatase inhibitor, letrozole (Femara, Novartis) orally in a dose of 5mg (two tablet) daily from day 5 to 9 of the menstrual cycle. Group II included 50 women who were given the CC orally in a dose of 100 mg (2 tablet) daily from day 5 to 9 of the menstrual cycle.
In this study, letrozole at a dose of 5 mg showed more effective in ovulation induction than Clomiphene citrate. In group I, the number of follicles 18 mm in diameter or more ranged from 1 to 4 with mean ± SD of 1.9 ± 1.01. in group II, the number of follicles 18mm or more ranged from 1 to 3 with a mean ± SD of 1.5 ± 0.77 mm. (p=0.0001). likewise, in group I, the endometrial thickness (measured by transvaginal ultrasonography) ranged from 5 to 15 with a mean ± SD of 8.93 ± 2.38mm. In group II, the endometrial thickness ranged from 4 to 10 with a mean ± SD of 5.60 ± 1.63mm. (p=0.001).
Doppler indices to endometrial- subendometrial vessels at the day of HCG administration shows decreased RI and PI in group I more than group II in which the mean RI and PI in both groups (0.77. 0.84 ) and (1.75, 2.08) respectively.
In the letrozole group the number of cycles showing good endometrial vascularity is 117 cycles with an incidence of 72.67% (117/161), while in CC group the number of cycles showing good endometrial vascularity is 45 cycles with an incidence of 26.01% (45/173). The difference between letrozole and CC groups was statistically significant (p=0.001).
The degree of vascular penetration summarized as, subgroup1, vessels penetrating the outer hypoechogenic area surrounding the endometrium but not entering the hyperechogenic outer margin; subgroup 2, vessels penetrating the hyperechogenic outer margin of the endometrium but not entering the
hypoechogenic inner area; and subgroup 3: vessels entering the hypoechogenic inner area in endometrial cavity.
Consequently, pregnancy was more significantly recorded after using Letrozole than CC, 20 cases (40%) in group I and 12 cases (24%) in group II respectively, this difference in the number of pregnant cases was highly significant between women of the two studied groups. The study also showed that pregnancy rates were significantly higher in patients with subgroup 3 penetration compared with subgroup 1 or subgroup 2 penetrations in both groups.
Comparison of the side effects of letrozole and CC showed that both drugs are generally tolerated with no significant difference in relative incidence of side effects.
In conclusion, our results indicate that the effect of letrozole on endometrial thickness in patients of anovulatory PCOS was significantly better compared to CC. Both RI and PI of subendometrial spiral artery showed significantly lower impedance compared to the CC group. Doppler velocimetry of spiral artery can be a useful supportive tool for evaluating endometrial response in the treatment of anovulatory PCOS patients with infertility.
Letrozole was also found to be superior in terms of number of pregnancy than CC. Therefore, letrozole is a safe and better alternative to CC in ovulation induction protocol for patients of anovulatory PCOS, and it may be considered as a first-line treatment for ovulation induction in these patients.