Administration of Single High Dose Letrozole for Ovulation Induction

Sponsor

Mount Sinai Hospital, Canada (Other)

Overall Status

Completed

CT.gov ID

NCT02703649

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anovulation	Drug: Letrozole	Phase 4

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:

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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Administration of Single High Dose Letrozole for Ovulation Induction - A Randomized Controlled Trial

Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Jul 31, 2020

Actual Study Completion Date :

Jul 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single dose Single 20 mg dose of Letrozole on day 3 of the menstrual cycle.	Drug: Letrozole 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 Names: Femara
Active Comparator: Daily dose Daily dose of Letrozole 2.5 mg starting day 3 for 5 days.	Drug: Letrozole 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 Names: Femara

Arm

Intervention/Treatment

Experimental: Single dose

Single 20 mg dose of Letrozole on day 3 of the menstrual cycle.

Drug: Letrozole

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 Names:

Femara

Active Comparator: Daily dose

Daily dose of Letrozole 2.5 mg starting day 3 for 5 days.

Drug: Letrozole

Other Names:

Femara

Outcome Measures

Primary Outcome Measures

number of follicles >15 mm at day of ovulation [First 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

Pregnancy rate [2 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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 .

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Hospital, University of Toronto	Toronto	Ontario	Canada	M5G 1X5
2	TRIO Fertility	Toronto	Ontario	Canada	M5G 2K4

Sponsors and Collaborators

Mount Sinai Hospital, Canada

Investigators

Principal Investigator: Robert Casper, MD, University of Toronto

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mount Sinai Hospital, Canada

ClinicalTrials.gov Identifier:

NCT02703649

Other Study ID Numbers:

Siba0101

First Posted:

Mar 9, 2016

Last Update Posted:

Sep 17, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by Mount Sinai Hospital, Canada

Aromatase inhibitor

induction of ovulation

Additional relevant MeSH terms:

Anovulation

Letrozole

Study Results

No Results Posted as of Sep 17, 2021