Podcast Summary: Dr. Chapa’s OBGYN Clinical Pearls

Episode: Continue Metformin in 1st T for PCOS?
Host: Dr. Chapa
Date: December 11, 2025

Episode Overview

In this engaging and clinically focused episode, Dr. Chapa dives deep into the latest evidence around the use of metformin in the first trimester of pregnancy for women with polycystic ovary syndrome (PCOS). Building on prior discussions about PCOS management and international guidelines, Dr. Chapa explores new findings from a December 2025 systematic review and meta-analysis published in the American Journal of OB/GYN ("the Gray Journal"). With characteristic energy, humor, and clear language, he translates technical data into practical takeaways and clinical pearls for medical students, residents, and practicing providers.

Key Discussion Points & Insights

1. Context: Metformin Use in PCOS and Pregnancy

[00:37 – 06:25]

• Metformin is commonly used in PCOS patients either for metabolic indications (e.g., elevated BMI, blood pressure, dyslipidemia) or in combination with ovulation induction agents (notably with clomiphene, less so with letrozole).
• Clinical question: Should metformin be discontinued at the positive pregnancy test or continued through the first trimester?
• 2023 International Guidelines (ASRM and others) previously stated metformin did not prevent gestational diabetes, hypertension in pregnancy, preeclampsia, macrosomia, or "late miscarriage" (>12 weeks).

"Or some patients with PCOS are on metformin in combination with clomiphene for ovulation induction, which is totally fine... Now, Letrozole doesn't seem to need a partner like metformin, unlike Clomid."
— Dr. Chapa [00:37]

2. Evidence Update: The December 2025 Meta-Analysis

[06:56 – 14:04]

• Source: Gray Journal, December 2025; systematic review + meta-analysis
• Included: 12 high-quality ("trustworthy") studies; n=1,708 women with PCOS.
• Key focus: Outcomes when metformin was continued through the first trimester vs stopped after conception.

Main Findings:

• Higher clinical pregnancy rates: Odds ratio (OR) 1.57 (95% CI: 1.1–2.23)
• Possible reduction in miscarriage: OR 0.64 (95% CI: 0.32–1.25)
• Possible increase in live births: OR 1.24 (95% CI: crosses 1)
• None of the data definitive; all confidence intervals crossed 1, but the trend favored benefit.

"It seems to say that in those women...who conceived and continued the metformin throughout the first trimester...showed higher clinical pregnancy rates and a possible reduction in miscarriage compared to placebo or those without treatment."
— Dr. Chapa [11:32]

Clarification on Miscarriage:

• Prior guidelines said metformin did not help with "late miscarriage" (>12 weeks).
• New data hints it might lower risk of early miscarriage (<12 weeks), which guideline statements did not specifically address.

"Notice what it says. It doesn't say anything here about early miscarriage. This is where this new publication fills the gap. Beautiful."
— Dr. Chapa [08:23]

What Metformin Does Not Do (per guidelines and new review):

• Does not prevent gestational diabetes, preeclampsia, hypertensive disorders, macrosomia, or late miscarriage.

3. Risk-Benefit Considerations and Counseling

[14:04 – 18:27]

• Potential concern: Offspring exposed to metformin in utero may have higher BMI at ages 5–10 (suggested in the PREGMET and PEDMET studies), but causality not established. Data is "suggestive" and confounded by multiple factors (diet, lifestyle, genetics).
• No evidence of increased malformations or neurodevelopmental issues with first-trimester metformin exposure.
• Imprinting risk ("metabolic imprinting" of the child) is a theoretical concern, mainly seen with later/more prolonged exposure (e.g., gestational diabetes).

"It didn't seem to hurt and it might help. Although the imprinting issue is something we can't ignore..."
— Dr. Chapa [16:10]

4. Practical Recommendations and Shared Decision-Making

[15:55 – 20:45]

• Shared decision-making is key: Counsel patients that metformin continuation through the first trimester may have small potential benefit for reducing early miscarriage, but the overall benefit is likely modest; allow patient preference to guide.
• Typical practice: Dr. Chapa is comfortable allowing patients to continue metformin until 10–12 weeks, then stop if desired.
• Metformin is not harmful in this context, but benefits remain suggestive.

"This is a perfect example...of shared decision making...If you're gonna ask me when to stop it, it really depends on what you want to do."
— Dr. Chapa [16:50]

Notable Quotes & Memorable Moments

• Scottish PCOS Joke Segment:
  A humorous interlude breaks up the clinical content, with Dr. Chapa noting the difference between PCOS-associated mood issues and the exaggerated claims in the joke:

  "No, PCOS does not cause psychosis. It's just a joke. Yeah. Causes mood swings, low sex drive, and psychosis, so it's hard to detect. Just a joke."
  — Dr. Chapa [05:01]

• On Evidence Quality:

  "Only 12 trustworthy studies with an N of 1708. At least it's not harmful and it may possibly be helpful..."
  — Dr. Chapa [20:24]

• Practical Clinical Pearl:

  "The point is you don't need to stop it immediately with a positive pregnancy test unless the patient wants to. This is a perfect example...of shared decision making."
  — Dr. Chapa [16:35]

Timestamps for Important Segments

• Intro & Clinical Question: [00:37–06:25]
• Guideline Review & What Metformin Does (and Doesn’t) Do: [06:56–11:32]
• Meta-Analysis Results Breakdown: [11:32–15:55]
• Statistical Interpretation (Odds Ratios, CIs): [14:04–15:55]
• Counseling & Decision-Making Advice: [15:55–20:45]
• Metabolic Imprinting and Pediatric Outcomes: [17:36–20:55]
• Final Clinical Pearls & Summary: [20:24–21:50]

Practical Clinical Takeaways

• Continuation of metformin through the first trimester may modestly reduce risk of early miscarriage and slightly increase clinical pregnancy and live birth rates for women with PCOS.
• No evidence of benefit for prevention of gestational diabetes, hypertensive disorders, preeclampsia, macrosomia, or late miscarriage.
• No shown risk of congenital malformations or neurodevelopmental issues, though some data suggest offspring may be at higher risk of metabolic imprinting/higher BMI—causality not proven.
• Shared decision-making is best: Continue metformin until 12 weeks if patient desires; otherwise, stopping at positive pregnancy test is also acceptable.
• Data remain limited: Further research is needed; current findings support individualized, patient-centered counseling.

Closing Thought

"This is fast. You know, our commitment here is to try to let you know quicker what's going on. This just came out in the Gray Journal..."
— Dr. Chapa [20:50]

Episode provides timely, evidence-based insight—delivered with personality—for counseling PCOS patients about metformin use during early pregnancy.