Norway

• Trondheim, St. Olavs hospital

  • Tone Shetelig Løvvik, spesialist i kvinnesykdommer og fødselshjelp (lege)
  • Hilde Oksfjellelv, studiejordmor
  • Terese Skjemstad, studiejordmor

• Bergen, Haukeland Universitetssjukhus

  • Fransisco Real, overlege dr. med.
  • Marianne Lønnebotn, studiejordmor

• Skien, Sykehuset Telemark

  • Sally Almadhi, overlege
  • Paula Kinni, studiejordmor
  • Lena Aarestad Berg, studiejordmor

• Ålesund, Sykehuset Ålesund

  • Sissel Hjelle, overlege
  • Eva Kvassheim, studiejordmor

• Tønsberg, Sykehuset i Vestfold

  • Renata Zabielska, overlege dr. med
  • Britt Mari Korneliussen, studiejordmor
  • Drammen, Vestre Viken, Drammen sykehus
  • Sunniva Hochnowski, studielege
  • Maja Bonnichsen, studielege
  • Kristin Nordrum, studiejordmor

• Lillehammer, Sykehuset Innlandet, divisjon Lillehammer

  • Ann Hilde Berg, overlege
  • Elin Kjølgård Stjer, studiejordmor
  • Bodø, Nordlandssykehuset
  • Frida Andræ, overlege
  • Kristin Rist Jarnæs, studiejordmor

Sweden

• Uppsala, Uppsala Universitetsjukhus

  • Inger Sundström-Poroma, Professor, specialist i gynekologi och obstretik
  • Lena Moby, studie sjuksköterska

• Stockholm, Karolinska Universitetsjukhus

  • Angelica Lindèn-Hirschberg, Professor, specialist i gynekologi och obstretik
  • Anastasia Trouva, spesialist i hormonsykdommer
  • Berit Legerstam, studie barnmorska

• Umeå, Norrlands universitetssjukhus

  • Marie Bixo, Professor, specialist i gynekologi och obstretik
  • Anna-Carin Wihlbäck, overlege
  • Sigrid Nyberg, studiesjukskjöterska

Iceland

• Reykjavik, Landspitali Islands

  • Berglind Steffensen, Spesialist i gynekologi og obstretikk
  • Julia Omarsdottir, studiejordmor

The purpose of this study is to investigate if metformin prevents late miscarriage and preterm delivery in women with polycystic ovary syndrome (PCOS). We also want to find out as much as possible about pregnancy and pregnancy complications in PCOS women. We plan to follow up children of the women who participate in the study. This research project is initiated by the Faculty of Medicine at the Norwegian University of Science and Technology.

From Norwegian and international studies, we learn that PCOS women may have difficulties to become pregnant and have an increased incidence of various pregnancy complications. Many previous studies of pregnant PCOS women have weaknesses that make it difficult to draw reliable conclusions.

Between 2005-2009, 273 pregnant PCOS women from 10 Norwegian hospitals participated in a similar study. Half of the participants received metformin and half received placebo(fake drug).

We found that:

1. Metformin was well tolerated during pregnancy.
2. The incidence of pregnancy induced diabetes was high among the participants (about 25%).
3. There was no evidence of adverse effects of metformin in the mothers or the babies.
4. We found no convincing difference in the incidence of pregnancy complications between the metformin and placebo groups.
5. There was a tendency towards fewer late miscarriages and preterm deliveries in the metformin group. This was not statistically significant, and may be due to too few participants.
6. These may be promising results. But before routine use of metformin  can be considered for pregnant PCOS women, these results have to be proved in a large study. We have calculated that a study of 1000 pregnant PCOS women is necessary.

Metformin

Metformin is a drug that has been used to treat type 2 diabetes for more than 50 years. It does not induce "too low" levels of glucose such as insulin can do. Metformin is approved for use in pregnancy in the present study, but not for general  use in pregnancy. It may inhibit the absorption of folic acid and vitamin B12 from the intestines. Therefore,  supplementation of these vitamins should be used during the study.

As a participant you follow a programme which is the same either you receive metformin or placebo (fake drug).

1. You will receive written and verbal diet and lifestyle counselling.
2. You will receive either metformin or "placebo." Neither you nor the healthcare professionals performing the study will know what you receive, before the study is completed and all data is collected.
3. You follow the regular health checks as recommended for pregnant women in your country.
4. You will have 5 of these appointments at the maternity clinic of the study site.
5. You allow ultrasound examination at inclusion, week 19, week 28 and week 32.
6. We will perform an oral glucose tolerance test at inclusion and at week 28. This is done to detect possible diabetes in pregnancy.
7. Blood samples are drawn at inclusion, week 19, 28, 32 and 36. We aim to perform analysis that are relevant to various conditions and diseases during pregnancy.
8. We also want to take small tissue samples from the placenta and blood from the umbilical cord after the baby is born and the umbilical cord is detached.

Possible benefits of participating in the study are that participants receive a comprehensive, structured pregnancy follow-up, specially designed for women with PCOS. The doctors and midwives who are involved in the study have particular interest in and knowledge about PCOS.

Possible disadvantages are that you have to spend some more time on participation in the study compared to regular check-ups.  For all appointments you should attend fasting. Some might experience the drawing of blood samples a bit uncomfortable.

In case of normal liver and renal function (this is a prerequisite for participation) metformin carry no risk of serious side effects. Harmless, usually temporary side effects may be nausea, diarrhoea, mild abdominal discomfort and metallic taste in the mouth. The slow increase of metformin dosage and intake combined with food  reduces these effects. Metformin has never been reported to have teratogenic effect(damage/harm to the foetus).

Participation

Study participation is voluntary. You may at any time-point, without giving any reason, withdraw from the study.  This will have no negative consequences for you. If you withdraw from the study, you will return to your general practitioner/midwife  and will be followed up in accordance with the procedures in your home municipality.