Aim of study: To investigate whether four months of metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytroplasmic-sperm-injection) might increase clinical pregnancy rate in normal-weight (BMI below 28 kg/m3) in PCOS (=polycystic ovarian syndrome)-women

Condition	Intervention	Phase
PCOS- polycystic ovarian syndrome = hormonal and metabolic disease filling at least 2 out of the following 3: 1. Hyperandrogenemiae, clinicalor biochemical 2. An- or oligoovulations ( cycle above 35 days) 3. Polycystic ovaries in ultrasound Often insulin resistance or a metabolic syndrome. Often sub-or infertility due to lack of ovulations.	Drug: Metformin / Placebo treatment for 4 months	Phase IV

Further Study Details: 

Primary Outcomes: To investigate whether four months of Metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmatic sperm injection) will increase clinical pregancy rate in normal weight PCOS-women
Secondary Outcomes: 1.Spontaneous pregnancy rates during the pretreatment period; 2. Spontaneous abortion rates (I or II trim.abortions); 3. Live birth rates; 4. Number of oocytes collected; 5. Embryo quality; 6. Number of days of gonadotrophin treatment; 7. Dose of gonadotrophin, total per cycle and daily; 8. s-estradiol on day of hCG-administration; 9.Occurrence of ovarian hyperstimulation syndrome (OHSS)
Expected Total Enrollment:  300

PCOS is an hormonal disease including hyperandrogenism, oligo-or anovulation and/or polycystic ovaries by ultrasound. PCOS women often suffer insulin resistance or even diabetes risk as well as a full blown metabolic disease.

This women often suffer infertility due to their lack of regular ovulations. Metformin is a well known anti-diabetic drug, and in some PCOS women metfomin might decrease the hyperandrogenism, improve insulin resistance and give more regular ovulations. Thereby increase chance of pregnancy. Our hypothesis is that metformin will increase clinical pregnancy rates both spontaneously and following IVF/ICSI

Ages Eligible for Study:  18 Years   -   38 Years,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Fulfilling Rotterdam criteriae for PCOS
• Infertility more than 1 year
• First or second cycle of IVF/ICSI treatment
• Age below 38 years at inclusion
• BMI below 28 kg/m3 at inclusion
• Willing to be randomised to 4 months metformin or placebo
• Signed written informed consenrt

Exclusion Criteria:

• Not suitable for starting dose 112.5 IE
• Basal FSH above 10IU/L
• Known renal disease or s-kreatinin above 110 umol/L
• Known liver disease or s-ALAT above 80 IU/L
• Known alcoholism or drug abuse
• Known diabetes mellitus or fasting plasma-glucosis above 7mmol/L
• Corticostereoid treatment (oral)
• Treatment with cimetidin, anticoagulants,erythromycin or other macrolides
• Hyperprolactinemiae (PRL above 700mIU/L)
• Abnormal thyroid function tests
• Known congenital adrenal hyperplasia
• Androgen secreting tumours
• Cushing syndrome
• Metformin treatment within the last one month prior to screening
• Unfit to participate for any other reason

Please refer to this study by ClinicalTrials.gov identifier  NCT00159575

Sigrun Beate Kjøtrød, MD      +47 73868359  Ext. +47 93458952    sigrun.kjotrod@stolav.no
Louise Reinertsen, study nurse      +47 73863941  Ext. +47 90034759    Louise.Reinertsen@stolav.no

Norway
      IVF-unit-St Olavs Hospital, Trondheim,  7046,  Norway; Recruiting
      Sigrun Kjøtrød, Trondheim,  7006,  Norway; Recruiting

Study chairs or principal investigators

Sven Carlsen, MD,PhD,  Study Chair,  St Olavs Hospital- Endocrinological section   

Study ID Numbers:  MET-AR study -PCOS 5; EUDRACTNR. 2004-001124-20
Last Updated:  September 11, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00159575
Health Authority: Norway: Norwegian Medicines Agency; Norway: Norwegian Social Science Data Services; Norway: Directorate for Health and Social Affairs
ClinicalTrials.gov processed this record on 2005-09-13