13.1 Contraception, Preconception Care & Teratogenicity
Key Takeaways
- Family planning and reproductive health is a named blueprint subsection, and hormonal therapy is enumerated under ovarian disorders and female reproductive health.
- Combined hormonal contraception is contraindicated in women 35 or older who smoke, and in migraine with aura, because of stroke and thromboembolic risk.
- Long-acting reversible contraception has the lowest typical-use failure rates and few medical contraindications.
- Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, valproate, isotretinoin, methotrexate and warfarin are teratogens that must be changed before conception.
- Folic acid supplementation should begin before conception, at higher doses for women with prior neural tube defect or on antiseizure medication.
Last updated: August 2026
Internal medicine physicians frequently manage women of reproductive age who present with complex chronic medical conditions requiring effective contraception, preconception counseling, or acute obstetric-medical co-management during pregnancy. Mastery of the CDC Medical Eligibility Criteria, teratogenic pharmacology, hypertensive disorders of pregnancy, gestational diabetes, gestational thyroid physiology, and peripartum anticoagulation is essential for the ABIM examination.
1. Contraception Selection & CDC Medical Eligibility Criteria (US MEC)
The Centers for Disease Control and Prevention (CDC) publishes the United States Medical Eligibility Criteria for Contraceptive Use (US MEC) to guide safe contraceptive prescribing across diverse medical comorbidities:
- Category 1: A condition for which there is no restriction for the use of the contraceptive method.
- Category 2: A condition where the advantages of using the method generally outweigh the theoretical or proven risks.
- Category 3: A condition where the theoretical or proven risks usually outweigh the advantages of using the method; method not recommended unless more suitable methods are unavailable or unacceptable.
- Category 4: A condition that represents an unacceptable health risk if the contraceptive method is used (absolute contraindication).
Absolute Contraindications to Combined Hormonal Contraception (US MEC Category 4)
Combined hormonal contraceptives (CHCs)—including combined oral contraceptive pills (COCPs), the transdermal norelgestromin/ethinyl estradiol patch, and the etonogestrel/ethinyl estradiol vaginal ring—contain an estrogen component (typically ethinyl estradiol) that increases hepatic synthesis of clotting factors (fibrinogen, factors VII, VIII, X) and decreases antithrombin III, substantially amplifying the baseline risk of venous thromboembolism (VTE), stroke, and myocardial infarction.
| Clinical Condition | Rationale & Pathophysiology | Safe Alternative Methods |
|---|---|---|
| Age >= 35 and smoking >= 15 cigarettes/day | Synergistic, exponential increase in myocardial infarction, stroke, and arterial thrombosis | Progestin-only pills (POPs), Nexplanon implant, LNG-IUD, Copper IUD |
| Migraine with Aura (at any age) | 2- to 4-fold elevated baseline risk of ischemic stroke multiplied up to 7-fold by exogenous estrogen | POPs, Progestin implant, LNG-IUD, Copper IUD |
| Current or prior Venous Thromboembolism (DVT / PE) | High risk of recurrent thrombosis due to estrogen-induced hypercoagulability | Copper IUD, LNG-IUD, Etonogestrel implant, POPs |
| Known Thrombogenic Mutations (Factor V Leiden, Prothrombin G20210A, Protein C/S/Antithrombin deficiency, Antiphospholipid Syndrome) | Profound prothrombotic state; high risk of fatal PE or extensive venous infarction | Copper IUD (preferred non-hormonal), LNG-IUD, Nexplanon, POPs |
| Ischemic Heart Disease, Stroke, or Complicated Valvular Heart Disease | Estrogen increases arterial thrombosis, vasospasm, and volume retention; high risk in pulmonary HTN or SBE history | Copper IUD, LNG-IUD, Nexplanon, POPs |
| Breast Cancer (current or past <5 years) | Estrogen and progestin stimulate hormone-receptor-positive neoplastic proliferation | Copper IUD (ParaGard) is Category 1; all hormonal methods are Category 4 |
| Severe Decompensated Cirrhosis, Hepatocellular Adenoma, or Malignant Liver Tumors | Impaired estrogen metabolism; hepatic adenomas are estrogen-dependent and risk rupture/hemorrhage | Copper IUD, LNG-IUD (Category 2 for cirrhosis, Category 3 for adenoma) |
| Uncontrolled Hypertension (SBP >= 160 or DBP >= 100 mmHg, or with vascular disease) | Estrogen stimulates angiotensinogen synthesis, worsening HTN and precipitating hemorrhagic/ischemic stroke | Copper IUD, LNG-IUD, Nexplanon, POPs |
| Diabetes Mellitus with Microvascular Complications (Nephropathy, Retinopathy, Neuropathy) or Duration > 20 years | Accelerated systemic endothelial dysfunction, microvascular damage, and heightened atherothrombotic risk | Copper IUD, LNG-IUD, Nexplanon, POPs |
Safe Contraceptive Alternatives in High-Risk Patients
- Progestin-Only Pills (POPs):
- Norethindrone (0.35 mg daily): Thickens cervical mucus and thins the endometrium. Requires strict compliance: taking a dose >3 hours late requires back-up barrier contraception for 48 hours.
- Drospirenone (4 mg daily, 24/4 regimen): Inhibits ovulation with a forgiving 24-hour missed-pill window. Has mild anti-mineralocorticoid activity (monitor potassium if co-administered with ACEi/ARBs or spironolactone).
- Subdermal Progestin Implant (Etonogestrel 68 mg / Nexplanon):
- Single rod inserted subdermally into the inner upper arm; highly effective (failure rate <0.05%), approved for 3 to 5 years.
- Primary mechanism: Suppresses ovulation and thickens cervical mucus. Most common side effect is unscheduled, irregular spotting.
- Levonorgestrel Intrauterine Devices (LNG-IUD: Mirena 52 mg, Kyleena 19.5 mg, Liletta 52 mg, Skyla 13.5 mg):
- Highly effective (failure rate <0.2%), provides 3 to 8 years of continuous contraception.
- Mechanism: Intense local endometrial decidualization and glandular atrophy, cervical mucus thickening. Mirena/Liletta 52 mg reduces menstrual blood loss by >80-90% and is FDA-approved for heavy menstrual bleeding.
- Copper Intrauterine Device (ParaGard T 380A):
- 100% non-hormonal, effective for up to 10 to 12 years.
- Mechanism: Continuous release of copper ions creates a sterile, inflammatory, spermicidal environment in the uterine cavity and fallopian tubes.
- Ideal for patients with breast cancer, active liver disease, or multiple cardiovascular comorbidities. May increase menstrual blood loss and dysmenorrhea in the first 3 to 6 months.
Emergency Contraception (EC) Comparison
- Copper IUD (ParaGard): Most effective emergency contraception (>99.8% efficacy). Must be inserted within 120 hours (5 days) of unprotected intercourse. Efficacy is completely unaffected by maternal body weight/BMI and provides ongoing long-term contraception.
- Ulipristal Acetate (Ella, 30 mg single oral dose): Selective progesterone receptor modulator (SPRM). Delays follicular rupture even after the luteinizing hormone (LH) surge has begun. Highly effective when taken within 120 hours (5 days). Superior efficacy compared to levonorgestrel in overweight and obese women (BMI >25-30 kg/m2). Requires holding hormonal contraception for 5 days after administration (to prevent competitive receptor antagonism).
- Oral Levonorgestrel (Plan B One-Step, 1.5 mg single oral dose): Over-the-counter progestin that prevents or delays ovulation if taken before the LH surge begins. Must be taken within 72 hours (3 days) of intercourse. Has significantly reduced efficacy in women with BMI >=25 kg/m2 and is largely ineffective in women with BMI >30 kg/m2.
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2. Preconception Optimization & Teratogenicity
Optimizing chronic medical therapy prior to conception is essential to prevent structural congenital malformations, fetal loss, and maternal decompensation. Organogenesis occurs primarily between weeks 3 and 8 post-conception, often before pregnancy is recognized.
Teratogenic Medications & Recommended Substitutions
| Drug Class / Medication | Teratogenic Effects / Fetal Toxicity | Recommended Safe Pregnancy Substitute |
|---|---|---|
| ACE Inhibitors & ARBs (e.g., Lisinopril, Losartan, Valsartan) | ACEi fetopathy: Renal tubular dysgenesis, oligohydramnios, neonatal anuria, pulmonary hypoplasia, calvarial/skull bone defects, fetal growth restriction | Labetalol, Extended-Release Nifedipine, or Methyldopa |
| HMG-CoA Reductase Inhibitors (Statins: Atorvastatin, Rosuvastatin) | Disruption of fetal cholesterol biosynthesis essential for cell membrane and steroidogenesis formation; potential skeletal/CNS anomalies | Discontinue preconception; bile acid sequestrants (Cholestyramine) if severe familial hypercholesterolemia |
| Methotrexate | Aminopterin-methotrexate syndrome: Craniofacial anomalies (craniosynostosis, hypertelorism), limb/skeletal hypoplasia, spontaneous abortion, neural tube defects | Azathioprine (<=2 mg/kg/day), Hydroxychloroquine, or Sulfasalazine (with 4 mg/d folic acid) |
| Mycophenolate Mofetil (MMF) | Mycophenolate embryopathy: Microtia/external ear canal atresia, cleft lip/palate, ocular coloboma, congenital heart defects | Switch to Azathioprine or Tacrolimus at least 3 to 6 months prior to conception |
| Valproic Acid / Divalproex | Fetal valproate syndrome: Neural tube defects (spina bifida in 1-2%), craniofacial clefts, cardiovascular malformations, dose-dependent autism spectrum and cognitive delay | Switch to Levetiracetam or Lamotrigine preconception; co-prescribe Folic Acid 4 mg daily |
| Warfarin | Warfarin embryopathy: Nasal hypoplasia, depressed nasal bridge, stippled epiphyses (chondrodysplasia punctata), optic atrophy, microcephaly, intracranial hemorrhage | Switch to Low-Molecular-Weight Heparin (LMWH) preconception or before 6 weeks gestation |
Glycemic Optimization
- Elevated maternal blood glucose during the first 8 weeks of gestation is directly teratogenic. Hyperglycemia increases the risk of caudal regression syndrome (sacral agenesis), transposition of the great arteries, ventricular septal defects, neural tube defects, and spontaneous abortion.
- Target: Preconception HbA1c < 6.5% (ideally <6.0% if achievable without severe hypoglycemia).
Folic Acid Supplementation Guidelines
- Average-Risk Women: 400 to 800 mcg (0.4 to 0.8 mg) daily orally starting at least 1 month prior to conception and continuing through the first trimester to prevent neural tube defects (anencephaly, spina bifida).
- High-Risk Women (4 mg [4,000 mcg] daily):
- Prior pregnancy complicated by a neural tube defect
- Personal history of neural tube defect (patient or partner)
- Patients taking antiseizure medications (valproate, carbamazepine)
- Pregestational diabetes mellitus (Type 1 or Type 2)
- Malabsorption syndromes (celiac disease, post-bariatric bypass surgery)
- High-dose folic acid (4 mg daily) should be initiated at least 1 to 3 months prior to conception and continued through 12 weeks gestation, then reduced to 0.4-0.8 mg daily.
Test Your Knowledge
A 36-year-old woman presents to your primary care clinic seeking advice on contraception. She smokes 1 pack of cigarettes daily (20 cigarettes/day). Her past medical history is notable for mild intermittent asthma and tension headaches. Her blood pressure is 124/78 mmHg, heart rate is 72 bpm, and BMI is 24 kg/m2. Which of the following contraceptive methods is the most appropriate and medically safe recommendation for this patient?
A
B
C
D