Recurrent Miscarriage: The 6 Causes Reproductive Endocrinologists Test for After Two or More Losses

Recurrent Pregnancy Loss: 6 Causes Reproductive Endocrinologists Test for After Two or More Losses

Experiencing more than one miscarriage can be heartbreaking and confusing. When you have two or more consecutive losses—clinically defined as recurrent pregnancy loss—it's reasonable to seek a deeper evaluation. Reproductive endocrinologists focus on six main areas to uncover causes and guide treatment. Knowing what's being tested can help you feel informed and empowered as you plan next steps.

---

1. Parental Chromosomal Abnormalities

Up to 5 percent of couples with recurrent pregnancy loss carry balanced chromosomal rearrangements (translocations or inversions) that don't affect the parents' health but can cause miscarriage.

• What's tested

• Peripheral blood karyotype for both partners
• Advanced options: microarray or next-generation sequencing (rarely needed)

• Why it matters

• Identifies balanced translocations or other structural rearrangements
• Helps estimate recurrence risk and guides options like preimplantation genetic testing (PGT)

---

2. Uterine Anatomic Issues

Structural problems in the uterus can interfere with embryo implantation or growth. About 10–15 percent of women with recurrent losses have a uterine anomaly.

• Common abnormalities

• Septate uterus (fibrous band divides the cavity)
• Bicornuate or arcuate uterus (abnormal shape)
• Intrauterine adhesions (Asherman's syndrome)
• Fibroids or polyps (especially in the lining)

• How it's evaluated

• Transvaginal ultrasound with 3D imaging
• Saline infusion sonohysterogram (SIS)
• Hysteroscopy (direct visualization)

• Treatment options

• Surgical correction (e.g., hysteroscopic septum resection)
• Removal of polyps or submucosal fibroids

---

3. Endocrine and Metabolic Disorders

Hormonal balance is critical for early pregnancy maintenance. Common endocrine factors include thyroid disease, diabetes, and luteal phase defects.

• Key tests

• Thyroid-stimulating hormone (TSH), free T4
• Anti-thyroid antibodies (anti-TPO, anti-TG)
• Fasting blood glucose and hemoglobin A1C
• Prolactin level
• Day-21 progesterone (luteal phase assessment)

• What to watch for

• Hypothyroidism or hyperthyroidism can increase miscarriage risk
• Thyroid autoimmunity (even with normal hormone levels)
• Uncontrolled diabetes (elevated A1C)
• Polycystic ovary syndrome (PCOS) and insulin resistance

• Management strategies

• Optimizing thyroid function with levothyroxine
• Blood sugar control via diet, exercise, or medication
• Progesterone supplementation in the luteal phase (select cases)

---

4. Thrombophilias and Coagulation Disorders

Clotting disorders can impair blood flow to the developing placenta. Both inherited and acquired thrombophilias are considered.

• Inherited thrombophilias

• Factor V Leiden mutation
• Prothrombin G20210A mutation
• Protein C, protein S, antithrombin deficiencies

• Acquired thrombophilias

• Antiphospholipid syndrome (APS): anticardiolipin antibodies, lupus anticoagulant, anti-β2 glycoprotein I

• Testing protocol

• Antiphospholipid panel (two tests at least 12 weeks apart)
• Genetic testing for Factor V and prothrombin mutations
• Protein C/S and antithrombin activity levels

• Treatment approaches

• Low-dose aspirin plus unfractionated or low-molecular-weight heparin in APS
• Individualized anticoagulation for inherited thrombophilias (controversial—discuss with your specialist)

---

5. Immune System Factors

The body's immune response must allow the embryo to implant and grow. While routine immune testing remains controversial, certain markers may guide therapy in select patients.

• Potential immune markers

• Natural killer (NK) cell levels and activity (peripheral vs. uterine)
• Th1/Th2 cytokine balance
• HLA compatibility between partners (rarely used)

• Current perspectives

• Evidence for immunologic testing and treatment is mixed
• Some centers offer intravenous immunoglobulin (IVIG), corticosteroids, or intralipid therapy—but these remain experimental
• Consultation with a reproductive immunologist can clarify whether immune work-up makes sense for you

---

6. Infectious and Environmental Contributors

Certain infections and environmental exposures can elevate miscarriage risk, though routine screening is limited to specific scenarios.

• Infections sometimes tested

• Listeria monocytogenes (if history of food-borne illness)
• Parvovirus B19, cytomegalovirus (CMV), toxoplasmosis (if indicated by symptoms or exposure)
• Bacterial vaginosis or untreated sexually transmitted infections (screen as part of routine prenatal care)

• Environmental factors

• Smoking, alcohol, recreational drugs
• High levels of caffeine (recommendation: ≤200 mg/day)
• Occupational exposures (e.g., solvents, heavy metals)

• Prevention tips

• Follow food safety guidelines to avoid Listeria
• Practice safe sex and complete STI screening
• Minimize environmental toxins whenever possible

---

Next Steps and When to Seek Help

If you've experienced two or more miscarriages, consider:

1. Talking to a reproductive endocrinologist to review your history and order appropriate tests.
2. Using a free AI-powered Miscarriage symptom checker to understand your symptoms and receive personalized guidance on when to seek care.
3. Addressing modifiable factors—optimizing thyroid health, controlling blood sugar, quitting smoking, and limiting caffeine.
4. Reviewing genetic testing results with a genetic counselor to understand implications for future pregnancies.

Throughout this process, remember that up to 50 percent of cases remain unexplained even after thorough evaluation. A normal work-up, however, does not mean future loss is inevitable. Many couples go on to have healthy pregnancies with targeted support and care.

---

Important: This information is intended to guide discussions with your healthcare provider. If you experience heavy bleeding, severe pain, fever or any life-threatening symptoms, seek medical attention immediately. Always speak to a doctor about any concerns, tests, or treatments to ensure the best possible outcome for you and your partner.