Should a woman with polycystic ovary syndrome (PCOS) and metabolic risks, including hypertriglyceridemia and hypercholesterolemia, who is taking letrozole and metformin, discontinue metformin at the time of a positive pregnancy test or at the end of the first trimester?

Metformin Should Be Discontinued by the End of the First Trimester in Pregnant Women with PCOS

The American Diabetes Association recommends that metformin should be discontinued by the end of the first trimester when used for PCOS and ovulation induction, according to the most recent Standards of Care (2023). 1

Timing of Discontinuation

Discontinue metformin at the end of the first trimester (approximately 12-13 weeks gestation), not at the time of the positive pregnancy test. 1

Rationale for Continuing Through First Trimester

• Continuing metformin to the end of the first trimester at an effective dose (1000-2000 mg/day) may help reduce the rate of miscarriages in women with PCOS. 2
• The critical period for early pregnancy loss prevention appears to benefit from continued metformin exposure during the first trimester. 2

Why Not Continue Beyond First Trimester

Metformin readily crosses the placenta, with umbilical cord blood levels equal to or higher than maternal levels, raising concerns about fetal exposure. 1

• Long-term offspring data show concerning metabolic effects in children exposed to metformin in utero, including higher BMI, increased waist circumference, and increased obesity risk at ages 4-10 years. 1
• Follow-up studies at 9 years show children exposed to metformin have higher BMI, increased waist-to-height ratio, and greater waist circumference. 3

Evidence Against Continuing Metformin Throughout Pregnancy

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

• A 2023 meta-analysis of 11 randomized controlled trials demonstrated that metformin treatment in pregnancy does not reduce the risk of gestational diabetes in high-risk individuals with obesity, PCOS, or preexisting insulin resistance. 1
• While one older 2011 study suggested metformin reduced gestational diabetes and preeclampsia rates 4, this has not been confirmed by more recent, higher-quality meta-analyses. 1

Specific Contraindications During Pregnancy

The American College of Obstetricians and Gynecologists recommends that metformin should NOT be used in pregnant women with hypertension, preeclampsia, or those at risk for intrauterine growth restriction due to potential for growth restriction or acidosis with placental insufficiency. 1

Management of Your Metabolic Risks

For High Triglycerides and Cholesterol During Pregnancy

• Your metabolic risks (hypertriglyceridemia and hypercholesterolemia) should be managed primarily through lifestyle modifications during pregnancy, not metformin continuation. 3
• Statins are pregnancy category X and must be discontinued before conception. 5
• Regular exercise and weight control measures should be the first-line approach for metabolic management during pregnancy. 3

Monitoring During Pregnancy

• Screen for gestational diabetes with standard glucose tolerance testing at 24-28 weeks gestation. 3
• Monitor blood pressure regularly throughout pregnancy given your metabolic syndrome features. 3
• Continue fasting lipid monitoring as clinically indicated, though treatment options are limited during pregnancy. 3

Post-Pregnancy Considerations

• Metformin can be restarted postpartum if needed for metabolic management and PCOS treatment. 6
• Breastfeeding compatibility should be discussed with your provider if you plan to nurse. 6