الفهرس 
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Abstract
Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy, it is the commonest endocrine disorder in women of reproductive age. The exact etiology of PCOS is unknown.
LH hypersecretion is a characteristic hallmark of PCOS. LH is secreted in a pulsatile manner. Women with PCOS have an increase in both the LH pulse frequency and amplitude.
While obesity and insulin resistance are not necessary features of PCOS, they are common and play a role in pathogenesis of many cases. It is also the most common hormonal disturbance that can underlie hirsutism (over half of cases).
Endocrine and metabolic factors appear to have an influence on the development of anovulation in women with PCOS, but these factors do not exclude the possibility of an intrinsic abnormality of folliculogenesis in PCOS.
The characteristic morphological feature of polycystic ovaries in anovulatory women is accumulation of antral follicles in the range of 2–8 mm in diameter. An enlarged stromal volume is invariably presents, and a total ovarian volume >10 cc is often witnessed.
The abnormal endocrine environment may therefore contribute to advancement of follicle maturation and premature arrest of development.
PCOS is associated with risks of diabetes mellitus and metabolic syndrome and their complications, in addition to the dermatologic manifestations, the gynecologic problems of menstrual irregularity, infertility, and predisposition to endometrial carcinoma.
The diagnosis of PCOS requires that clinicians exclude other conditions that are sufficiently common, are associated with importantly adverse natural histories, and are treatable (e.g., pregnancy, ovarian or adrenal neoplasm, endocrinopathies).
In the absence of knowledge of a root cause, the treatment of PCOS is symptomatic. It is directed at the patient’s main complaints, For those women not desiring pregnancy, the most common therapies are oral contraceptive pills, antiandrogens, and insulin lowering treatments.
For women with infertility the first-line treatment is ordinarily clomiphene citrate.
The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC), because the aim of ovulation induction for women with anovulatory PCOS is to restore fertility and achieve a singleton live birth, and approximately 80% ovulate and 40% become pregnant of PCOS women treated with CC which is reported to be highly effective with a cumulative singleton live-birth rate of 72%.
CC is used in anovulation, unexplained infertility, and luteal phase deficiency.
CC is a non-steroidal compound closely resembling estrogen, acts by blocking estrogen receptors, particularly in the hypothalamus, thereby signaling a lack of circulating estrogens and inducing a change in the pulsatile release of gonadotrophin-releasing hormone (GnRH). This induces release of FSH from the anterior pituitary and is often enough to set the cycle of events leading to ovulation into motion.
The starting dose of CC generally used to be 50 mg/day, for 5 days, starting on days 2 to 5 after a spontaneous or progestin- induced withdrawal bleeding.
If there is no response, i.e. no evidence of ovulation, the dose may be increased in increments of 50 mg in subsequent cycles until ovulation is achieved, and the recommended maximum dose is 150 mg/day.
Although CC is very successful in inducing ovulation, there is usually a discrepancy between ovulation and pregnancy rates (PR) (CC failure), and also the lack of response found in a number of treated individuals (CC resistance).
Several studies made it evident that the earlier the day of starting CC the better the results.
Early administration of CC in patients with PCOS will lead to more follicular growth and endometrial thickness, which might result in a higher pregnancy rate (PR).
Hence this study had been done to compare between the effect of starting CC early on the luteal phase and starting CC late on the second day of menstrual cycle which was used for years, and the anti estrogenic effect of CC on ovulation, endometrium and pregnancy rate in the two regiments.
After collecting the data of the patients who agreed the inclusion and exclusion criteria, they were divided into two groups. Group I received the early treatment regiment, and group II received the late treatment regiment with CC.
This study has shown that the total number of follicles and the mean follicular diameter during stimulation was significantly more when starting CC early.
Endometrial receptivity is the period of time during which the uterine environment is conductive to the blastocyst acceptance and implantation. In this study we used two ultrasound parameters to assess endometrial receptivity, including endometrial thickness, and endometrial blood flow.
Color Doppler ultrasound equipment was added for monitoring the endometrial and subendometrial blood flow, because a good blood supply is usually considered to be an essential requirement for normal implantation, so an ability to identify receptive human endometrium would be of major clinical value.
When looking at the antiestrogenic effects of CC on endometrium, we see that early administration showed significantly higher mean endometrial thickness at time of HCG injection when compared to late administration of CC, and also the endometrial vascularity; this is an important results which reflects a good endometrial receptivity
When looking at the endometrial and subendometrial blood flow in both treatment regimens, the RI and PI was higher in late CC administration group. The results were statistically significant, and hence the blood flow was better in early CC administration at luteal phase, as it escaped the anti estrogenic effects of CC and hence better endometrial receptivity and pregnancy rate.
Although the Pregnancy rate was more in the early group, the difference was not statistically significant.
In conclusion, it is well documented that CC is very effective in inducing ovulation but the pregnancy rate, which is the main goal, is still lower than expected, this was explained by the anti estrogenic effects of CC on uterine receptivity and cervical mucus, hence this study suggests that early administration Of CC in patients with PCOS to decrease unfavorable anti estrogenic effects will lead to more follicular growth and endometrial receptivity, which might result in higher pregnancy rate and lower miscarriage rate.