Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome
Background: Clomiphen citrate (CC) is the first line therapy for women with infertility and poly cystic ovary syndrome( PCOS).However, 20-25% of women are resistant to CC and do not ovulate.
Objective: The objective of this study was to evaluate the efficacy of sequential treatment of metformin and incremental doses of letrozole in induction of ovulation in cases of CC- resistant PCOS patients.
Material and Methods:In this propective before-after study, we enrolled 106 anovulatory PCOS women who failed to ovulate with CC alone from Amir-Almomenin University Hospital in Semnan, Iran from June 2005 to December 2008. After an initial 6- 8 weeks of metformin treatment, they received 2.5 mg letrozole daily on days 3-7 after menes. If they did not ovulate with 2.5 mg letrozole, the doses were increased to 5 to 7.5 mg daily in subsequent cycles. The main outcomes were ovulatory rate , pregnancy rate and cumulative pregnancy rate. The mean number of follicles≥ 18 mm, the mean of follicular size and endometrial thickness on the day of HCG administration were secondary outcome measures.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT201109073386N3
Registration date:2011-10-09, 1390/07/17
Registration timing:retrospective
Last update:
Update count:0
Registration date
2011-10-09, 1390/07/17
Registrant information
Name
Azam Azargoon
Name of organization / entity
Semnan University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 23 1446 3401
Email address
a-azargoon@sem-ums.ac.ir
Recruitment status
Recruitment complete
Funding source
Semnan University of Medical Sciences
Expected recruitment start date
2005-06-01, 1384/03/11
Expected recruitment end date
2008-11-30, 1387/09/10
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome
Public title
Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria: women who were 19-42 years of age with period of infertility more than 1.5 years; normal serum prolactin and thyroid function tests; having documented patent tubes by hysterosalpingography; no other infertility factor and failed to ovulate with a dose of CC of 150 mg/day for 5 days from day 3 of the period.The women were excluded from the study if they were diabetic; taking any medication that could influence carbohydrate metabolism; had hypertension or abnormal renal or liver function tests; and undergone ovarian drilling.Hirsutism was diagnosed when the Ferriman and Gallway score is >8
The diagnosis of PCOS was according to the Rotterdam Criteria.
Age
From 19 years old to 42 years old
Gender
Female
Phase
N/A
Groups that have been masked
No information
Sample size
Target sample size:
106
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Deputy research
Street address
Semnan university of medical sciences-Basij Blvd-Semnan
City
Semnan
Postal code
Approval date
2011-09-27, 1390/07/05
Ethics committee reference number
90/100019
Health conditions studied
1
Description of health condition studied
Poly cystic ovarian syndrome
ICD-10 code
E28.2
ICD-10 code description
Polycystic ovarian syndrome
Primary outcomes
1
Description
Ovulation, Pregnancy and Cumulative pregnancy rates in different doses of letrozole
Timepoint
During and the end of treatment
Method of measurement
Sonography and BHCG
Secondary outcomes
1
Description
The mean number of follicles≥ 18 mm, the mean of follicular size and endometrial thickness on the day of HCG administration
Timepoint
During treatment
Method of measurement
Sonograhy and BHCG
Intervention groups
1
Description
Metformin was started after two months of CC to allow for the washout of the latter. All women were examined clinically and their weight, height and body mass index (BMI) recorded. All patients received 1500 mg metformin (Glocophage, Merck, West Drayton, UK) daily for 6- 8 weeks.
The dose of metformin was built up gradually over a 3 weeks period, beginning at 500 mg daily with main meal for 1 week, followed by 500 mg twice daily for 1 week and increased to 500 mg three times daily to minimize side effects. If pregnancy occurred, metformin was continued for another 8 weeks. In case of failure of pregnancy after the end of this period, metformin was continued and patients were given 2.5 mg letrozole (Femara, Novartis, Quebec, Canada) for 5 days starting from day 3 of their menstrual cycle.