What is more effective for Polycystic Ovary Syndrome (PCOS) and pregnancy, birth control or metformin (Glucophage)?

Management of PCOS for Women Attempting Pregnancy

For women with PCOS attempting to conceive, neither birth control nor metformin should be first-line therapy—clomiphene citrate is the recommended initial treatment, with metformin reserved as an adjunct or alternative option. Birth control has no role in fertility treatment as it prevents ovulation. 1

Treatment Algorithm for Women Attempting Pregnancy

First-Line Approach: Lifestyle Modification

• Weight loss of just 5% of initial body weight significantly improves both metabolic and reproductive abnormalities in PCOS. 1
• Implement regular exercise programs even without weight loss, as this likely provides positive metabolic effects. 1
• This foundational step should precede or accompany any pharmacologic intervention. 1

Second-Line: Clomiphene Citrate

• Clomiphene citrate is the recommended first-line medication for ovulation induction in PCOS based on good and consistent scientific evidence. 1
• Approximately 80% of women with PCOS ovulate on clomiphene, and about half of those who ovulate will conceive. 1
• This represents the standard of care endorsed by ACOG guidelines. 1

Role of Metformin in Fertility Treatment

Metformin improves ovulation frequency but should not be continued once pregnancy is confirmed, as randomized controlled trials show no benefit in preventing spontaneous abortion or gestational diabetes. 1

When to Consider Metformin:

• As combination therapy with clomiphene citrate in clomiphene-resistant cases (though recent evidence suggests letrozole may be superior to this combination). 2
• In women with significant insulin resistance or metabolic dysfunction alongside fertility goals. 1, 3
• Some older studies suggested metformin alone achieved higher pregnancy rates than clomiphene (68.9% vs 34.0% cumulative pregnancy rate), but this conflicts with guideline recommendations prioritizing clomiphene. 4, 5

Critical Safety Concerns with Metformin in Pregnancy:

• Metformin crosses the placenta, resulting in umbilical cord blood levels equal to or higher than maternal levels. 1
• Long-term offspring data show concerning trends: 4-9 year old children exposed to metformin in utero had higher BMI, increased obesity rates, higher waist-to-height ratios, and increased fat mass. 1
• The FDA label acknowledges limited data with metformin in pregnancy are insufficient to determine drug-associated risks for major birth defects or miscarriage. 6
• There is no evidence-based need to continue metformin once pregnancy is confirmed in PCOS patients. 1

Birth Control: Role in PCOS Management

Birth control pills are contraindicated for women actively attempting pregnancy, as they suppress ovulation. However, they serve important roles in PCOS management for women NOT attempting conception:

• Androgen suppression and menstrual cycle regulation in non-pregnant women. 1
• Management of hirsutism when combined with antiandrogen therapy. 1
• No evidence suggests increased cardiovascular events with oral contraceptive use in PCOS compared to the general population, despite increases in triglycerides and HDL cholesterol. 1

Common Pitfalls to Avoid

Do not continue metformin throughout pregnancy based on outdated protocols. 1 The 2021 American Diabetes Association guidelines explicitly state randomized controlled trials show no benefit in preventing spontaneous abortion or gestational diabetes when metformin is continued after conception. 1

Do not use metformin in pregnant women with:

• Hypertension or preeclampsia
• Risk factors for intrauterine growth restriction
• These conditions increase risk of growth restriction or acidosis with placental insufficiency. 1

Do not prescribe birth control to women actively trying to conceive—this seems obvious but the question's framing suggests potential confusion about treatment timing. 1

Evidence Quality Considerations

The strongest evidence comes from ACOG 2003 guidelines (though older, they represent consensus expert opinion) and the 2021 American Diabetes Association Standards of Care, which provide the most recent high-quality guideline recommendations. 1 The concerning offspring metabolic data from the MiG TOFU study represents important long-term safety information that should inform current practice. 1

Individual research studies show conflicting results on metformin versus clomiphene efficacy 4, 7, 5, but guideline-level recommendations consistently prioritize clomiphene citrate as first-line therapy. 1