Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study

Study Overview
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Brief Summary
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To investigate the effect of metformin on pregnancy complications and pregnancy outcome in the II. and III. trimester of pregnancy in women with polycystic ovary syndrome.

Official Title
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Metformin Treatment of Pregnant Women With Polycystic Ovary Syndrome: a Pilot Study

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis polycystic ovary syndrome (PCOS ) before pregnancy BMI 27-40 kg/m2 Human chorionic gonadotropin, beta subunit (HCG-beta) verified pregnancy week 5-8 At least one of the following criteria: (1) serum testosteron > 2,5 nmol/L; (2) Sex hormone binding globulin (SHBG) < 30 nmol; (3) Fasting C-peptid > 1,0 nmol/L; (4) Menstrual disturbances: oligo-/amenorrhea or metrorrhagia; (5) Hirsutism Exclusion Criteria: known liver disease or ALAT > 60 IU/L S-creatinin > 130 micromol/L diabetes mellitus alcohol or drug abuse peroral steroid treatment (except inhalation steroids) use of cimetidine, anticoagulant, erythromycin or other macrolides not suitable for other reasons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Metformin 850 mg x 2 daily | Drug: Metformin<br>* Metformin 850 mg x 1 per day for the first week, and 850 mg x 2 per day for the rest of the study period.. Orally. From inclusion (before gestational week 8) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study. In addition 1 mg tablet of folate and one daily multivitamin tablet.<br>* Other names: metformin from Weifa 425 mg / tablet;|
| Placebo Comparator: placebo<br>Placebo 1 tablet x 2 daily | Drug: Placebo<br>* Placebo, 2 tablets x 1 daily for the first week, and 2 tablets x 2 for the rest of the study period.Orally. From inclusion (that is before gestational week 12) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study. In addition 1 mg tablet of folate and one daily multivitamin tablet.<br>* Other names: Placebo from Weifa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dehydroepiandrosterone sulfate (DHEAS) | (µmol/l) Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. Measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA) | up to delivery | 
| Androstenedione | Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. measured by a double antibody technique on an Elecsys 2010 analyser (Roche Diagnostics GmbH, Germany) using reagents and calibrators supplied by the manufacturer | up to delivery | 
| Testosterone | Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. measured by a double antibody technique on an Elecsys 2010 analyser (Roche Diagnostics GmbH, Germany) using reagents and calibrators supplied by the manufacturer | up to delivery | 
| Sex hormone binding globulin (SHBG) | (nmol/l) Analysed in serum, from venous blood samples from the mother and venous and arterial umbilical cord blood (separately) collected within 1 h of birth. Measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA) | up to delivery | 
| Free testosterone index | Calculated as total testosterone divided by SHBG and multiplied by a factor of 100. SHBG measured using a competitive immunoassay on an Immulite 2000 analyser using the reagents and calibrators supplied by the manufacturer (Diagnostic Products Corp., USA) | up to delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of pregnancy complications | Gestational diabetes (GDM) defined according to World Health Organization (1998) criteria, i.e. 2 h plasma glucose values ≥7.8 mmol/l during an Oral Glucose Tolerance Test (OGTT) with 75 g. Uncomplicated GDM treated with dietary advice only was not ranked among the complications in this study. Pre-eclampsia defined as a blood pressure ≥140/90mmHg with concomitant albuminuria ≥0.3 g/24 h measured on two separate occasions after gestational week 20. Premature delivery was defined as delivery before gestational week 37 + 0 according to an estimated date of delivery, based on mid-trimester ultrasound scan | up to 6 weeks post partum | 
| Pregnancy outcome - gestational age | Gestational age at birth (days) | after delivery | 
| Pregnancy outcome - gestational length | Gestational length (cm) measured at birth | after delivery | 
| Pregnancy outcome - head circumference | Head circumference (cm) measured at birth. | after delivery | 
| Pregnancy outcome - birthweight | Birthweight (g) measured at birth | after delivery | 
| Pregnancy outcome - placental weight | Placental weight (g) measured at birth | after delivery | 
| Pregnancy outcome - Agpar score at 5 minutes | Apgar score at 5 minutes | after delivery | 
| Pregnancy outcome - Agpar score at 10 minutes | Apgar score at 10 minutes | after delivery | 
| Pregnancy outcome - umbilical artery pH | Umbilical artery pH measured in umbilical artery blood, immediately after delivery on a Rapidlab 248pH/Blood Gas Analyzer, using reagents and calibrators supplied by the manufacturer (Bayer Corp., USA) | after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Pregnancy outcome, Androgens