Metformin in Assisted Reproduction-MET-AR-study

Study Overview
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Brief Summary
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Aim of study: To investigate whether four months of metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic-sperm-injection) might increase clinical pregnancy rate in normal-weight (body mass index [BMI] below 28 kg/m3) in PCOS (polycystic ovarian syndrome) women.

Detailed Description
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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. These women often suffer infertility due to their lack of regular ovulations. Metformin is a well known anti-diabetic drug, and in some PCOS women metformin 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.

Official Title
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Metformin Treatment Before IVF / ICSI in Non-obese Women With Polycystic Ovarian Syndrome

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin / Placebo treatment for 4 months


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfilling Rotterdam criteria 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 consent Exclusion Criteria: Not suitable for starting dose 112.5 IE Basal FSH above 10 IU/L Known renal disease or s-creatinine 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 glucose above 7 mmol/L Corticosteroid treatment (oral) Treatment with cimetidine, anticoagulants, erythromycin or other macrolides Hyperprolactinemia (PRL above 700 mIU/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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M: Metformin P: Placebo<br> | Drug: Metformin / Placebo treatment for 4 months<br>* M: Metformin 2000mg daily- 12-14 weeks of pretreatment + metformin 2000mg daily through conventional IVF ending on the day of pregnancy test; IE. 14 days after embryo transfer. P: Or identical placebo treatment for the same period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate whether four months of Metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic sperm injection) will increase clinical pregnancy rate in normal weight PCOS-women |  | Vaginal ultrasound in pregnancy week 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous pregnancy rates during the pretreatment period, Spontaneous abortion rates (I or II trim.abortions), Live birth rates, |  | Vaginal ultrasound in pregnancy week 7 | 
| Number of oocytes collected, Embryo quality, Number of days of gonadotrophin treatment, Dose of gonadotrophin, total per cycle and daily, s-estradiol on day of hCG-administration, Occurrence of ovarian hyperstimulation syndrome (OHSS) |  | All data evaluated at study end, from september 2009 onwards | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovarian syndrome, Clinical pregnancy rate, Oligo- or anovulation