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Administration of Single High Dose Letrozole for Ovulation Induction

Phase 4
Completed
Conditions
Anovulation
Interventions
Registration Number
NCT02703649
Lead Sponsor
Mount Sinai Hospital, Canada
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
36
Inclusion Criteria
  • Polycystic ovary syndrome (PCOS) patients
  • BMI (body mass index) of 18-35.
  • Proved one patent fallopian tube at least
Exclusion Criteria
  • Women with low ovarian response (According to Bologna criteria )
  • Blocked fallopian tubes
  • Pregnancy
  • Presence of any clinically significant health problem such that treatment with letrozole or pregnancy would not be in the subject's best interest.
  • Co-administration of other anti-estrogens
  • Hypersensitivity to Letrozole .

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Daily doseLetrozoleDaily dose of Letrozole 2.5 mg starting day 3 for 5 days.
Single doseLetrozoleSingle 20 mg dose of Letrozole on day 3 of the menstrual cycle.
Primary Outcome Measures
NameTimeMethod
number of follicles >15 mm at day of ovulationFirst day of monitoring will be on day 7 and the rest of monitoring will be appointed according to response up to 1month
Secondary Outcome Measures
NameTimeMethod
Pregnancy rate2 months

Trial Locations

Locations (2)

Mount Sinai Hospital, University of Toronto

🇨🇦

Toronto, Ontario, Canada

TRIO Fertility

🇨🇦

Toronto, Ontario, Canada

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