What are the recommendations for a woman experiencing early pregnancy loss, particularly those with a history of recurrent losses and potential underlying conditions such as thyroid dysfunction or polycystic ovary syndrome (PCOS)?

Management of Early Pregnancy Loss

Women experiencing early pregnancy loss, including those with recurrent losses and underlying conditions such as thyroid dysfunction or PCOS, should receive immediate diagnostic evaluation with transvaginal ultrasound, Rh immunoglobulin if Rh-negative, and comprehensive preconception optimization addressing their specific endocrinopathies before attempting subsequent pregnancy. 1, 2

Immediate Diagnostic and Therapeutic Actions

Diagnostic Evaluation

• Perform transvaginal ultrasonography immediately to confirm fetal viability, detect subchorionic hematoma, and rule out ectopic pregnancy—do not delay imaging based on β-hCG thresholds, as ectopic pregnancies can rupture at very low β-hCG levels 1, 2
• Obtain serial ultrasound examinations when viability is uncertain to assess fetal growth and development 1, 2
• Consider serial quantitative hCG measurements or symptom-based diagnosis using shared decision-making 3

Critical Rh Management

• Administer 50 μg of anti-D immunoglobulin to all Rh-negative women with documented first-trimester loss of established pregnancy 1, 2
• This is essential because fetomaternal hemorrhage occurs in 48% of threatened abortion cases and 32% overall in spontaneous abortion 1, 2
• Note: The Society of Family Planning suggests against routine Rh testing before 12 weeks for medication management specifically, though this conflicts with ACOG guidance 3

Management Options for Current Loss

Treatment Approaches

• Offer all three equally acceptable options: expectant management, medication management (mifepristone 200 mg orally followed 7-48 hours later by misoprostol 800 mcg vaginally or buccally), or surgical management (suction curettage under general anesthesia, typically <30 minutes with same-day discharge) 1, 2, 3
• Use shared decision-making to select the approach based on patient preference, gestational age, and clinical circumstances 3, 4
• Provide ibuprofen 800 mg orally for pain control during medication management 3

Venous Thromboembolism Risk Assessment

• Stratify VTE risk before surgical management, particularly after 15 weeks when risk increases to 135.6 per 100,000 women versus 27.1 per 100,000 for early gestations 1
• The baseline VTE risk after surgical termination is 30.1 per 100,000 women within 42 days, compared to 13.5 per 100,000 in non-pregnant women 1, 2
• Consider LMWH thromboprophylaxis for high-risk patients with: personal/family history of VTE, known thrombophilia, BMI >30 kg/m², age >35 years, parity >3, active smoking, medical comorbidities, or immobility 1, 2

Management of Underlying Conditions for Future Pregnancies

Thyroid Dysfunction

• For hypothyroidism: initiate or optimize levothyroxine therapy to achieve euthyroidism before conception, as hypothyroidism in the first trimester is associated with cognitive impairment in children, preterm birth, low birth weight, placental abruption, and fetal death 5
• Monitor thyroid function closely, as replacement dosages typically need to increase by 30% or more by 4-6 weeks' gestation 5
• Screen TSH preconceptionally in women with risk factors and symptoms, and treat subclinical hypothyroidism 5
• For hyperthyroidism: achieve euthyroidism before pregnancy using propylthiouracil in the first trimester (due to methimazole's possible teratogenicity), then switch to methimazole in subsequent trimesters to avoid propylthiouracil-associated hepatotoxicity 5

Polycystic Ovary Syndrome (PCOS)

• Normalize weight through lifestyle modification before conception, as women with PCOS have increased risk of pregnancy loss 6
• Consider metformin therapy, which reduces the risk of pregnancy loss in women with PCOS 6
• Metformin may be continued in the preconception period even when transitioning other diabetes medications to insulin 5
• Address associated metabolic complications including insulin resistance, hyperlipidemia, and hypertension 5

Recurrent Pregnancy Loss Specific Evaluation

• Screen for antiphospholipid antibodies in women with three or more miscarriages before 10 weeks of gestation 5
• For women with antiphospholipid syndrome meeting laboratory criteria, use low-dose aspirin plus heparin during subsequent pregnancy 5, 7
• Do not routinely screen for inherited thrombophilia in women with history of pregnancy complications alone 5
• Do not use antithrombotic prophylaxis for inherited thrombophilia with history of pregnancy complications 5
• Do not use antithrombotic prophylaxis for women with two or more miscarriages but without antiphospholipid antibodies or thrombophilia 5

Diabetes Management

• Transition from oral antidiabetic agents to insulin before conception (metformin may be continued in the preconception period) 5
• Discontinue ACE inhibitors, ARBs, and statins due to associations with fetal renal anomalies and fetal death 5
• Achieve A1C <6% (42 mmol/mol) if possible without significant hypoglycemia, or relax to <7% (53 mmol/mol) if necessary 5
• Target fasting glucose <95 mg/dL (5.3 mmol/L), one-hour postprandial <140 mg/dL (7.8 mmol/L), and two-hour postprandial <120 mg/dL (6.7 mmol/L) 5
• Obtain comprehensive screening including foot exam, ophthalmologic exam, ECG (if age ≥35 years with cardiac signs/symptoms or risk factors), lipid panel, serum creatinine, TSH, and urine albumin-to-creatinine ratio 5

Hypertension Management

• Avoid ACE inhibitors, ARBs, and atenolol before conception due to associations with fetal renal anomalies, fetal death, and lower birth weight 5
• Assess for end-organ damage (retinopathy, renal disease, ventricular hypertrophy) in women with long-standing hypertension 5
• Treat severe hypertension (systolic ≥180 mm Hg or diastolic ≥110 mm Hg) to improve pregnancy outcomes 5

Universal Preconception Optimization

Essential Supplementation and Lifestyle Modifications

• Initiate folic acid supplementation at least 3 months before conception to reduce neural tube defects by two-thirds 5, 1, 2
• Achieve complete smoking cessation before or during early pregnancy, as only 20% of women successfully control tobacco dependence during pregnancy 5, 1, 2
• Achieve absolute alcohol cessation, as no time during pregnancy is safe to drink alcohol and harm can occur before pregnancy recognition 5, 1, 2
• Optimize weight before pregnancy in women with obesity to reduce risks of neural tube defects, preterm delivery, diabetes, cesarean section, and thromboembolic disease 5, 1, 2

Immunization and Infectious Disease Screening

• Verify rubella immunity and vaccinate if seronegative to prevent congenital rubella syndrome 5, 1, 2
• Provide hepatitis B vaccination for those at risk 5, 1, 2
• Screen for HIV to allow early antiretroviral treatment and prevention of mother-to-child transmission 5, 1, 2
• Screen for Neisseria gonorrhoeae/Chlamydia trachomatis, hepatitis C, syphilis, and obtain Pap smear 5
• Ensure current immunizations including inactivated influenza, Tdap, and COVID-19 (certain populations) 5

Contraceptive Planning

• Implement effective contraception until all glycemic targets and medical optimization are achieved in women with diabetes 5
• Use contraceptive planning to prevent pregnancy until thyroid dysfunction, hypertension, and other comorbidities are optimally controlled 5

Common Pitfalls to Avoid

• Never delay ultrasound imaging waiting for β-hCG to reach a discriminatory threshold—ectopic pregnancies can rupture at very low β-hCG levels 1, 2
• Never forget Rh immunoglobulin administration in Rh-negative women with first-trimester loss, as fetomaternal hemorrhage occurs in nearly half of threatened abortions 1, 2
• Never ignore VTE risk assessment before surgical management, particularly in women with multiple risk factors (personal/family history of VTE, thrombophilia, BMI >30, age >35, smoking, medical comorbidities) 1, 2
• Never continue ACE inhibitors, ARBs, statins, or atenolol in women planning pregnancy due to teratogenic effects 5
• Never assume thyroid replacement doses will remain stable in pregnancy—they typically increase by 30% or more by 4-6 weeks' gestation 5
• Never use antithrombotic prophylaxis for inherited thrombophilia or unexplained recurrent pregnancy loss without antiphospholipid syndrome 5