Dosage Optimization for Letrozole Treatment

Infertility Clinical Trial

Official title:

Dosage Optimization for Letrozole Treatment in Clomiphene Resistant Patients With Polycystic Ovary Syndrome: A Prospective Interventional Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01315912
• Other study ID #: bpums
• Secondary ID: bpums
• Status: Completed
• Phase: Phase 4
• First received: March 15, 2011
• Last updated: March 25, 2011
• Start date: January 2008
• Est. completion date: December 2010

Study information

• Verified date: January 2008
• Source: Bushehr University of Medical Science
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

In a prospective interventional study, 44 Clomiphene resistant infertile patients were selected from Abolfazl Infertility Clinic of Bushehr University of Medical Sciences. Letrozole was given orally in a dose of 2.5mg, 5mg and 7.5mg, respectively. If the patient displayed no response, the dosage was increased. The size of follicle, endometrial thickness, estradiol, complications and clinical pregnancy rate were evaluated as the final outcome.

Description:

In this prospective intervention, the investigators studied Abolfazle outpatients who were referred to us by Bushehr University of Medical Sciences in Iran between January 1, 2008 and December 30, 2010. The study was approved by the institutional Ethics Committee of Bushehr University of Medical Sciences and all patients were required to provide written informed consent before the study commenced.There were 3 steps in which the investigators prescribed letrozole (Femara,Novartis,Quebec,Canada). In all cases, daily administration began on the 3rd day of the menstrual cycle through to the 7th day (totaling 5 days). In the first step the investigators prescribed letrozole at a dose of 2.5 mg (one tablet) for one or two cycles according to the patient's response. Normal follicular size and endometrial thickness were considered 18-24 mm and 6 mm or more respectively.1 If the follicle was deemed not acceptable, the dose of letrozole was increased at the next cycle.

At the second and third steps the investigators prescribed letrozole at a dose of 5 mg daily and 7.5 mg/day,respectively and according to patient's response, repeat the same dose.

In the current study the investigators tested the hypothesis that prescribing letrozole as an ovulation induction agent in infertile women would increase pregnancy rate, ovulation and follicle number (at the normal size range of 18-24 mm), endometrial thickness (to normal thickness of 6 mm) and not have considerable side effects in the patients. The primary outcome measure was normal follicular size and the secondary outcome measure were the clinical and current pregnancy rates. Clinical pregnancy was considered as the presence of a gestational sac with fetal heart activity. Letrozole tablets were prescribed by an experienced nurse who throughly explained the method of use to the patients. Sonography was done by an experienced radiologist.

The nurse prescribed letrozole to the patients and the university hospital laboratory's technician did not know past medical history of clomiphene resistance of the patients. The radiologist did not have any knowledge about the drugs prescribed to the patients. Side effects and complications of Letrozole were detailed to all patients by an obstetrician. Statistical analysis was performed by the Statistical Package for Social Science version 11.5 for windows (SPSS Inc., Chicago. IL). The data was analyzed by student's t-test and chi-squared test for linear trend and comparing proportions. A P-value of <0.05 was considered to be statistically significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• The study group consisted of polycystic ovarian syndrome(PCOS) patients diagnosed according to the Rotterdam criteria. The investigators defined Clomiphene citrate (Clomid, Iran hormone,Tehran,Iran) resistance as anovulation after consumption of 3 cycles of cc at 150 mg/day, determined by serial estradiol monitoring and sonography. Patients resistant to Clomiphene citrate became candidates for letrozole (Femara,Novartis,Quebec,Canada) consumption at the step-up of the protocol. Patients were between 18 and 39 years of age, body mass index (BMI) was > 19 or < 30 kg/m2 and day 3 follicle-stimulating hormone (FSH) < 12Miu/Ml.

Exclusion Criteria:

• abnormal thyroid Function test

• hyperprolactinoma

• galactorrhea

• male-factor infertility

• tubal and uterine causes of infertility (hysterosalpingography)

• abnormal response in progesterone challenge test which implies no endogenous estrogen production

• poor patient compliance

• complications with treatment

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Letrozole
2.5 mg /day for 5 days

Locations

Country	Name	City	State
Iran, Islamic Republic of	Bushehr university of medical science	Bushehr

Sponsors (1)

Lead Sponsor	Collaborator
Bushehr University of Medical Science

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	normal follicular size		two years	Yes
Secondary	clinical and current pregnancy rates		two years	Yes