Use of clomiphene or letrozole for treating women with polycystic ovary
syndrome related subfertility in Hilla city
Suhaila F.M.H. Al-Shaikh ?, Entisar J. Al-Mukhatar, Adeeb A. Al-Zubaidy, Bushra J.U. Al-Rubaie,
Liqaa Al-Khuzaee
1. Introduction
Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in female, and it is one of the leading causes of sub-fertility in female [1]. Stein and Leventhal were the first who recognize an association between the presence of polycystic ovaries and signs of hirsutism, menstrual disturbances as amenorrhea and obesity [2,3]. According to Rotterdam Workshop Group in 2004, PCOS women must have two out of the following three criteria:
(1) oligo-ovulation or anovulation, (2) hyperandrogenism (clinical and/or biochemical), and (3) polycystic ovaries on sonographic examination [4]. Between 5–10% of females aged 18–44 are affected by PCOS [5] insulin resistance is a central, probably inherited, biochemical abnormality of PCOS, which lead to hyperinsulinemia [6]. While it can be found in up to 50% of women with PCOS [7], both lean and obese women with PCOS are found to be more insulin resistant than non affected weight-matched controls [8]. High levels of insulin in the blood stimulate the enzyme cytochrome
P450c 17-a in both ovaries and adrenal gland to produce increased amounts of male hormones [9].

Aim of the study
Evaluate and compare the therapeutic effect of CC and letrozole in the treatment of infertility in women with PCOS.
2. Patients and methods

Patients
This prospective clinical trial was conducted during the period from May to August 2011, approved by The Ethics Committee of the Al-Nahrain medical college. Women included in this study were among those who attended the infertility center of maternity and pediatrics teaching hospital and those who referred from outpatient clinics to the hospital in Hilla city, Babylon Province, Iraq.
All participants were given informed consent before they were included in this study. They were in reproductive age (18–
40 years), all of them had at least 2 out of 3 of Rotterdom criteria. Each one got detailed clinical history, physical examination and typical appearance of polycystic ovaries by ultrasound according to the criteria of Rotterdam consensus meeting 2003. Clinical assessment included menstrual cycle regularity (oligomenorrhea or amenorrhea), body mass index (BMI), type and duration of infertility and presence or absence of hirsutism. Hormonal studies were performed on day 2 (early follicular phase) of the menstrual cycle. A non heparinized venous blood sample was obtained to measure the circulating concentration of LH, FSH, LH:FSH ratio, total testosterone, Prolactin, TSH and Fasting blood sugar (FBS). BMI was calculated using the equation: weight (kilograms)/height (meters)2. All patients enrolled in the study fulfilled the following inclusion criteria: (1) diagnosed as PCOS in the presence of at least 2 of Rotterdam criteria, based on Rotterdam consensus meeting (2003). (2) Agreed to participate in the study. (3) Unable to achieve pregnancy in a period of last 12 months or more despite regular unprotected intercourse. (4) Had patent fallopian tubes proved by hysterosalpingography. (5) Evaluation of husband infertility by a specialist doctor revealed no abnormalities in the male side. (6) No history of heart, liver, or kidney disease, and un suspected
pregnancy.
The exclusion criteria include: (1) Patient’s refusal. (2) History of recent administration of hormonal therapy. (3) Male factor infertility. (4) Patients aged more than 40 years.
results and discussion:
Regarding Clomifene citrate, morphometric analysis of the endometrium from women with CC-treated cycles revealed abnormal endometrial development as demonstrated by a reduction in glandular density and an increase in the number of vacuolated cells [28]. In the present study the percentage of the responded cycles
(41.25%) after treatment with CC disagrees with that of Shamdeen and Mohammad [29] study in which only (27%) cycles were
responded to 200 mg CC daily for 5 days given to overweight PCOS infertile women who failed to respond to 150 mg CC, and this may explain the low number of responded cycles in our study as the CC treated women were overweight (BMI is 29.3 ± 4.3), moreover Legro et al. [2] found that indication of CC in women with PCOS and anovulation, has certain limitations in patients with BMI > 30 and advanced age. Also it disagrees with Badawy et al. [30], Atay et al. [31] and Bayar et al. [32] studies in which ovulatory cycles
According to the result of our study the use of CC alone for treatment of PCOS related infertility is insufficient and it should be combined with other infertility medication such as metformin as shown by a meta-analysis of randomized clinical trials which found that metformin plus CC superior to CC plus placebo for ovulation
induction [41].