From the Guidelines
For a preliminary recurrent miscarriage workup, screening for Antiphospholipid antibodies (APLAs) is recommended for women with recurrent early pregnancy loss (three or more miscarriages before 10 weeks of gestation) 1. The following tests are also recommended as part of the preliminary workup:
- Karyotyping of both partners to identify genetic abnormalities that may cause recurrent miscarriages
- Thyroid function tests (TSH, free T4) to rule out thyroid dysfunction that can interfere with early pregnancy development
- Uterine cavity evaluation (hysteroscopy or sonohysterography) to identify uterine abnormalities that may impair implantation or fetal growth
- Hormonal profile (FSH, LH, estradiol, progesterone) to assess hormonal imbalances that can affect ovulation and early pregnancy maintenance
- Thrombophilia screening (Factor V Leiden, Prothrombin gene mutation) to identify disorders that increase the risk of blood clots, potentially affecting placental function These tests should be performed before attempting another pregnancy, with blood tests done at any time and uterine evaluation best performed in the follicular phase of the menstrual cycle. Additional considerations include lifestyle factors (smoking cessation, weight management) and folic acid supplementation (400-800 mcg daily) to optimize pregnancy outcomes. If no clear cause is identified, empiric treatments like low-dose aspirin (81 mg daily) and progesterone supplementation (200 mg vaginally daily) may be considered in subsequent pregnancies, starting as soon as pregnancy is confirmed, based on the latest guidelines and evidence-based practice.
From the Research
Preliminary Workup for Recurrent Miscarriage
The preliminary workup for recurrent miscarriage involves a comprehensive evaluation of the couple, including:
- Obstetric and family history, age, BMI, and exposure to toxins 2
- Basic investigations such as:
- Full blood count
- Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies)
- Parental karyotype
- Pelvic ultrasound and/or hysterosalpingogram 2
- Testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy 3
- Cytogenetic analysis of pregnancy tissue from the third and subsequent miscarriages, and in any second trimester miscarriage 3
- Assessment for congenital uterine anomalies, ideally with 3D ultrasound 3
- Thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies 3
Additional Investigations
Additional investigations may be considered in specific cases, such as:
- Testing for Factor V Leiden, prothrombin gene mutation, and protein S deficiency in women with second trimester miscarriage, ideally within a research context 3
- Parental peripheral blood karyotyping if testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality or if there is unsuccessful or no pregnancy tissue available for testing 3
Lifestyle Modifications
Lifestyle modifications that may be recommended for women with recurrent miscarriage include:
- Maintaining a BMI between 19 and 25 kg/m2
- Smoking cessation
- Limiting alcohol consumption
- Limiting caffeine to less than 200 mg/day 3