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

Phase 4
20 Years
35 Years
Not Enrolling

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Trial Information

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

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.

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

- poor patient compliance

- complications with treatment

Type of Study:


Study Design:

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

Outcome Measure:

normal follicular size

Outcome Time Frame:

two years

Safety Issue:


Principal Investigator

Elham Rahmani, Dr

Investigator Role:

Principal Investigator

Investigator Affiliation:

Bushehr University of Medical Science


Iran: Ethics Committee

Study ID:




Start Date:

January 2008

Completion Date:

December 2010

Related Keywords:

  • Infertility
  • clomiphene citrate
  • infertility
  • letrozole
  • Infertility
  • Polycystic Ovary Syndrome