The use of GnRH antagonist protocol nowadays is the slandered protocol of controlled ovarian stimulation in patients with poly cystic ovarian syndrome (PCOS) because it decreases the incidence of OHSS(1, 2). However, this protocol may lead to asynchronous growth of follicles with an early dominant follicle specially in PCOS patients(3). In most of cases this phenomenon will affect the IVF outcomes(2, 4) Aromatase inhibitors (AIs) nowadays is recommended to be used for ovulation induction in patients with PCOS (5, 6).It has fewer side effects, and a shorter half-life than clomiphene citrate(CC), and no effect ON the endometrial receptivity. It is used in treating patients with chronic anovulation, unexplained infertility and poor ovarian reserve(7). It acts through decreasing estrogen levels and allows follicle stimulating hormone (FSH) release from the hypothalamus (8, 9). It could be used alone or with combination with human menopausal gonadotropin (HMG) specially in patients with CC resistant(10-13). It also improves the ovarian response to FSH when they are used in combination and it decreases the risk of OHSS (14).

This study aims to evaluate the effect of uses of letrozole in combination with HMG during ovarian stimulation in patients having PCOS undergoing IVF/ICSI on the follicular growth pattern, synchronized growth of follicles, maturity of oocyte and the quality of embryos.

Participants in this study will be group of subfertile women undergoing IVF/ ICSI trial and having polycystic ovarian syndrome Inclusion criteria

1. Ages ≥20 and <40 years old

2. Women having the diagnosis of polycystic ovarian syndrome according to Rotterdam criteria (15)

3. Women who have at least one of the following indications for IVF or ICSI:

   1. Resistance to slandered ovulation induction and life style modification
   2. Tubal factors: unilateral or bilateral tubal obstruction, unilateral or bilateral salpingectomy or tubal ligation
   3. Male factors: oligoasthenozoospermia or obstructive azoospermia Exclusion criteria

1. Women with unexplained infertility. 2. women with poor ovarian reserve according to Bologna criteria (16). 3. Couples with known chromosomal abnormalities. 4. Women who refuse to participate in this study.

Methods

• patients will be randomly assigned into two groups (100 patients in each group): letrozole group (study group) and non letrozole group (control group). Treatment assignment will be blinded to patients, physicians, and nursing staff.
• All patients will receive combined oral pills before stimulation.
• letrozole 2.5mg twice daily (Femara; Novartis Pharma Services, Basel, Switzerland) will be given for 5 days starting from the second day of menstruation in combination with low dose step up stimulation with recombinant FSH in the study group.
• Allocated patients will be randomized into either of two groups.

Inclusion Criteria:

• 1. Ages ≥20 and <40 years old 2. Women having the diagnosis of polycystic ovarian syndrome according to Rotterdam criteria (15) 3. Women who have at least one of the following indications for IVF or ICSI:

  1. Resistance to slandered ovulation induction and life style modification
  2. Tubal factors: unilateral or bilateral tubal obstruction, unilateral or bilateral salpingectomy or tubal ligation
  3. Male factors: oligoasthenozoospermia or obstructive azoospermia

Exclusion Criteria:

• 1. Women with unexplained infertility. 2. women with poor ovarian reserve according to Bologna criteria (16). 3. Couples with known chromosomal abnormalities. 4. Women who refuse to participate in this study.

subfertile women undergoing IVF/ ICSI trial and having polycystic ovarian syndrome

double blinded clinical trial