Administration of Single High Dose Letrozole for Ovulation Induction
Condition: Anovulation
MeSH terms: Anovulation
Study type: Interventional
Phase: Phase 4

Summary: 
      Letrozole is considered an established treatment for ovulation induction.The most common
      protocol is daily dose of 2.5-7.5 mg starting day 3-5 of the cycle for 5 days.Another
      described protocol is single high dose 20mg Letrozole given on day 3 of the cycle.

      Our aim is to compare the single high dose Letrozole protocol to daily low dose protocol.
    

Detailed description: 
      Pre-study screening will be conducted before the enrolment in the study, routine fertility
      assessment: Physical history including fertility and fertility treatment history. Laboratory
      tests-cycle day 3 hormonal profile (Estradiol, Luteinizing hormone, Follicular stimulating
      hormone, progesterone), cycle day 3 antral follicular count.

      Pregnancy will be excluded by Human chorionic gonadotropin test at day 3 of the cycle, before
      starting the fertility treatment.

      Polycystic syndrome (PCOS) patients will be defined according to Rotterdam criteria 2003.

      A prospective randomized clinical trial. PCOS patients who require induction of ovulation
      will prospectively randomized into two groups:

        1. Single 20 mg dose of Letrozole on day 3 of the menstrual cycle. Monitoring for response
           will include the usual measurements of serum Estradiol (E2), Follicle stimulating
           hormone (FSH), Luteinizing Hormone (LH), Progesterone (P) and transvaginal ultrasound
           for follicular count and endometrial thickness measurement. First monitoring will be on
           day 7 of the cycle and the rest of the monitoring will be determined according to
           response.

        2. Daily dose of Letrozole 2.5 mg starting day 3 for 5 days. Monitoring for response will
           include serum Estradiol (E2), Follicule stimulating hormone (FSH), Luteinizing Hormone
           (LH ), Progesterone (P) and transvaginal ultrasound for follicular count and endometrial
           thickness measurement. First day of monitoring will be on day 7 and the rest of
           monitoring will be determined according to response.

      Statistical Analysis

        -  Primary Endpoint Analysis: Sample Size Selection In order to prove non-inferiority with
           significance level (alpha) 5% and power of 90%, standard deviation of outcome 1, and
           noninferiority limit 1; the sample size needed is 36 patients in both groups.
           Calculation based on Jolious SA formula.(7)

        -  Planned Analysis

      Primary Outcome Analysis:

      Comparison of the number of follicle >15 mm at day of ovulation

      Secondary Outcome Analysis:

      Pregnancy rate Comparison between the two groups Estradiol levels at day of ovulation
      triggering Ovarian hyperstimulation syndrome Clinical pregnancy rate

      Statistical analysis :

      The various outcome measures will be expressed as numbers and rates. The Student t test, χ2
      test and analysis of variance will be used where appropriate to analyze the various data
      among the study groups. P value less than .05 will be considered statistically significant.
    

Intervention name(s): Letrozole
Intervention type(s): Drug
Intervention description(s): After the decision to use Letrozole for induction of ovulation, we will obtain informed consent and randomize the patents into 2 groups Single 20 mg dose of Letrozole on day 3 of the cycle Daily dose of Letrozole 2.5 mg starting day 3 for 5 days.
Other intervention name(s): Femara
Intervention MeSH terms: Letrozole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Aromatase inhibitor; induction of ovulation