Metformin to Prevent Late Miscarriage and Preterm Delivery in Women With Polycystic Ovary Syndrome

Conditions

Polycystic Ovary Syndrome, Pregnancy

Keywords

miscarriage, preterm birth, prevention

Brief summary

The overall aim of the PregMet 2 Study is to investigate whether metformin prevents late miscarriages and preterm deliveries in PCOS women treated with metformin from first trimester of pregnancy to delivery in a large, randomized, controlled, multi-centre trial setting. The investigators hypothesis is that metformin compared to placebo treatment from the first trimester to term, reduces the prevalence of late miscarriage (gestational week 13-22) and preterm birth (gestational week \< 37) in PCOS women diagnosed according to Rotterdam 2003 consensus criteria, with singleton pregnancy.

Mariell Ryssdal, Johanne E. Skage, Anders Hagen Jarmund, Liv Guro Engen Hanem, Tone Shetelig Løvvik et al. (8 authors)

BJOG An International Journal of Obstetrics & Gynaecology2025-08-11

10.1111/1471-0528.18320

Placental and cerebral circulation in fetuses of mothers with polycystic ovary syndrome and the effect of Metformin exposure

Emma Nordtvedt, Jörg Kessler, Cathrine Ebbing, Ganesh Acharya, Tone Shetelig Løvvik et al. (9 authors)

BMC Pregnancy and Childbirth2025-07-101 citations

10.1186/s12884-025-07866-9

Childbirth experiences in women with polycystic ovary syndrome: A cohort study

Anne Engtrø Husby, Melanie Rae Simpson, Rebecka Dalbye, M. Larsen, Eszter Vanky et al. (6 authors)

Acta Obstetricia Et Gynecologica Scandinavica2024-02-172 citations

10.1111/aogs.14800

Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial.

Løvvik TS, Carlsen SM, Salvesen Ø, Steffensen B, Bixo M, Gómez-Real F, Lønnebotn M, Hestvold KV, Zabielska R, Hirschberg AL, Trouva A, Thorarinsdottir S, Hjelle S, Berg AH, Andræ F, Poromaa IS, Mohlin J, Underdal M, Vanky E.

2019-02-18111 citations

10.1016/s2213-8587(19)30002-6

Interventions

DRUGMetformin

Metformin 500 mg tablets, 1 tablet x 2 daily the first week and then 2 tablets x 2 daily from the second week to delivery

DRUGplacebo

identical placebo tablets, 1 tablet x 2 daily the first week and then 2 tablets x 2 daily from the second week to delivery

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 45 Years

Healthy volunteers

No

Inclusion criteria

* Age: 18-45 years * PCOS diagnosed or reconfirmed according to Rotterdam 2003 criteria, not more than 5 years prior to inclusion * Mode of conception: Any * Single, viable fetus, diagnosed by vaginal ultrasound * Gestational week at inclusion: week 6 + 0 to 12 + 0 * Wash out for metformin: at least 7 days * Able to communicate fluently in the official language at the study cite or English

Exclusion criteria

* Any type of diabetes (except GDM in former pregnancy) * Known liver disease or ALAT \> 100 IU/L * Known kidney disease or creatinine \> 110 μmol/L * Known alcohol or drug abuse * Use of drugs interfering with metformin: erytromycin (or other macrolides), cimetidine, anticoagulation therapy * Unsuitable for participation of other reasons

Design outcomes

Primary

Measure	Time frame	Description
combined incidence of late miscarriages and preterm births	at delivery	This includes spontaneous births, induced vaginal deliveries and operative deliveries on medical indications.

Secondary

Measure	Time frame	Description
number of patients hospitalized	at delivery	—
Total number of hospitalization days/ hospitalized participant	2 months	—
NICU admissions and total number of days in NICU/baby	2 months	—
Prevalence of preeclampsia	up to delivery	—
SNP	at delivery	SNP analysis (genetic analysis)
Prevalence of gestational diabetes	up to delivery	—

Countries

Iceland, Norway, Sweden

Outcome results

None listed