Is metformin (metformin hydrochloride) safe to use when trying to get pregnant?

Metformin Safety When Trying to Get Pregnant

Metformin appears to be safe when trying to conceive, but there is no evidence-based need to continue it during pregnancy for women with polycystic ovary syndrome (PCOS) unless there are specific indications. 1

Safety Profile During Conception

• Metformin is considered safe for women attempting to conceive, with limited data showing no clear association with major birth defects or miscarriage risk 2
• The FDA label indicates that published studies with metformin use during pregnancy have not reported clear associations with major birth defects or miscarriage 2
• For women with PCOS specifically, metformin can improve ovulation rates, which may benefit those trying to conceive 1

Role in PCOS Management When Trying to Conceive

• For women with PCOS who wish to conceive, treatment should begin with weight control and regular exercise, followed by medication if needed 1
• Clomiphene citrate is recommended as first-line treatment for ovulation induction due to its effectiveness (about 80% ovulation rate) 1
• Metformin improves insulin sensitivity and can be beneficial in improving ovulation frequency in women with PCOS 1
• Metformin may be particularly helpful for women with PCOS who have insulin resistance or obesity 3

Important Considerations

• 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 mellitus 1
• There is no evidence-based need to continue metformin in women with PCOS once pregnancy is achieved unless there are other indications 1
• Metformin readily crosses the placenta, resulting in umbilical cord blood levels as high or higher than maternal levels 1
• Long-term follow-up studies of children exposed to metformin in utero have shown concerning trends:
  • Some studies show higher BMI, weight-to-height ratios, and waist circumferences in children exposed to metformin during pregnancy 1
  • A meta-analysis demonstrated that metformin exposure resulted in smaller neonates with acceleration of postnatal growth, resulting in higher BMI in childhood 1

Recommendations for Women Trying to Conceive

• For women with PCOS trying to conceive:

  • Metformin can be used to improve ovulation rates, particularly in those with insulin resistance 1, 3
  • Once pregnancy is achieved, there is generally no need to continue metformin unless there are specific indications such as type 2 diabetes 1
  • Discuss with your healthcare provider about discontinuing metformin once pregnancy is confirmed 1

• For women with type 2 diabetes:

  • The benefits of glycemic control during pregnancy may outweigh potential risks of metformin 1, 2
  • Insulin is still considered the preferred treatment for diabetes during pregnancy 1

Potential Benefits in Specific Situations

• Some evidence suggests metformin may reduce early pregnancy loss, miscarriage, and preterm birth in women with PCOS, though this remains controversial 4, 5
• One study showed continuous use of metformin throughout pregnancy in women with PCOS reduced rates of miscarriage, gestational diabetes requiring insulin treatment, and fetal growth restriction 5
• However, these potential benefits must be weighed against concerns about long-term effects on offspring 1

Cautions

• Metformin should not be used in women with hypertension, preeclampsia, or those at risk for intrauterine growth restriction due to potential for growth restriction or acidosis 1
• The effects of metformin on early pregnancy are not fully understood, and long-term offspring data continues to emerge 1
• Treatment failure with metformin monotherapy occurs in 14-46% of individuals 1