I became pregnant using letrozole 7.5 mg and metformin 500 mg daily for PCOS; should I increase metformin to 1500–2000 mg per day (divided BID/TID) for metabolic and lipid control, or stay at 500 mg daily now that I’m pregnant?

Should You Continue Metformin During Pregnancy After Conceiving with Letrozole and Metformin for PCOS?

You should discontinue metformin now that you are pregnant, as there is no evidence-based justification for continuing it throughout pregnancy when used solely for PCOS-related ovulation induction. 1, 2

Why Metformin Should Be Stopped

No Pregnancy Benefit for PCOS Without Diabetes

• The American Diabetes Association explicitly states there is no evidence-based need to continue metformin in women with PCOS once pregnancy is confirmed 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 1, 2
• Metformin does not prevent gestational diabetes, even in high-risk women with obesity or PCOS 1, 2

Concerning Long-Term Effects on Your Baby

• Metformin readily crosses the placenta, resulting in umbilical cord blood levels equal to or higher than maternal levels 1, 2
• Long-term follow-up studies at 4-10 years 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 1, 2
• Meta-analyses demonstrate metformin exposure results in smaller neonates with acceleration of postnatal growth, leading to higher BMI in childhood 1, 2

When Metformin Should Be Continued

Metformin should only be continued during pregnancy in these specific situations:

• You have pre-existing type 2 diabetes that requires ongoing treatment (not just PCOS) 1, 2, 3
• You develop gestational diabetes and cannot safely or effectively use insulin due to cost barriers, language barriers, comprehension problems, or cultural factors 2, 3

The Metabolic/Lipid Question You Asked

Do not continue metformin for PCOS metabolic or lipid features during pregnancy. 1, 2

• The preconception benefits of metformin for insulin resistance and metabolic features do not translate to pregnancy benefits for PCOS patients without diabetes 1
• Pregnancy is not the time to treat metabolic syndrome or lipid abnormalities with metformin—these should be addressed before conception or after delivery 1, 2

Common Pitfall to Avoid

The most common error is continuing metformin throughout pregnancy simply because it helped you conceive. 1, 2 The medication served its purpose by improving ovulation and helping you achieve pregnancy, but that role is now complete.

What About the Miscarriage Concern?

While one recent review suggested continuing metformin to the end of the first trimester at 1000-2000 mg/day may help reduce miscarriage rates 4, this conflicts with higher-quality guideline evidence:

• The American Diabetes Association guidelines state metformin should be discontinued at the end of the first trimester if used solely for ovulation induction 1, 2
• Multiple randomized controlled trials have not demonstrated that metformin prevents miscarriage in women with PCOS 1, 2

Given the lack of proven benefit for preventing miscarriage and the documented long-term metabolic concerns for offspring, discontinuation is the evidence-based recommendation. 1, 2