Metformin Use in Preconception and Pregnancy

Safety and Efficacy

The American Diabetes Association recommends that metformin can be used in women with insulin resistance when trying to conceive, particularly in the context of PCOS, but should be discontinued once pregnancy is confirmed unless the woman has type 2 diabetes requiring ongoing treatment 1
Metformin appears safe when trying to conceive and may improve ovulation rates in women with PCOS and insulin resistance 1
The medication is not teratogenic based on available evidence, but there is no evidence-based need to continue metformin unless the woman has type 2 diabetes or gestational diabetes requiring treatment 1

Randomized controlled trials comparing metformin with other therapies for ovulation induction in women with PCOS have not demonstrated benefit in preventing spontaneous abortion or gestational diabetes 2, 3, 1
The American Diabetes Association explicitly states there is no evidence-based need to continue metformin in women with PCOS once pregnancy is confirmed 1

Metformin readily crosses the placenta, resulting in umbilical cord blood levels equal to or higher than maternal levels 4, 3, 5
Long-term follow-up studies reveal concerning metabolic effects in children exposed to metformin in utero, including higher weight, waist-to-height ratio, and waist circumference compared to those exposed to insulin 4, 3
Follow-up studies at 4-10 years showed offspring had higher BMI, weight-to-height ratios, and borderline increases in fat mass 4, 3, 5
Meta-analyses demonstrate metformin exposure results in smaller neonates with acceleration of postnatal growth, leading to higher BMI in childhood 4, 3, 5

The American College of Obstetricians and Gynecologists recommends weight control and regular exercise as first-line interventions for women with insulin resistance trying to conceive 1
If ovulation induction is needed for PCOS, clomiphene citrate is recommended as first-line treatment, with metformin added to improve ovulation frequency in women with documented insulin resistance 1
Metformin should be discontinued at the end of the first trimester if it was used solely for ovulation induction in PCOS, unless the woman has type 2 diabetes requiring ongoing treatment 1, 6

Metformin should not be continued during pregnancy if the woman develops hypertension, preeclampsia, risk factors for intrauterine growth restriction, or suspected placental insufficiency 3, 5, 6

Metformin should not be continued throughout pregnancy simply because it helped the woman conceive, as the preconception benefits do not translate to pregnancy benefits for PCOS patients without diabetes 1
Metformin does not prevent gestational diabetes, even in high-risk women 6