What investigations should be conducted in a 28-year-old woman with two consecutive spontaneous miscarriages and a history of preterm labor?

From the Guidelines

For a 28-year-old woman with two consecutive spontaneous miscarriages and a history of preterm labor, the most critical investigations to conduct include a transvaginal ultrasound to assess uterine anatomy and cervical length, as well as tests for underlying causes such as chromosomal abnormalities, endocrine disorders, autoimmune conditions, and thrombophilias. Given her history of preterm labor, a cervical length measurement is particularly important, as a short cervical length is associated with an increased risk of preterm delivery 1. The following investigations should be considered:

• A complete blood count
• Thyroid function tests (TSH, free T4)
• Antiphospholipid antibody testing (anticardiolipin antibodies, lupus anticoagulant, and anti-beta2 glycoprotein I)
• Karyotyping of both partners to detect chromosomal abnormalities
• Transvaginal ultrasound to assess uterine anatomy and identify structural abnormalities such as fibroids, polyps, or uterine septum
• Testing for inherited thrombophilias (Factor V Leiden, prothrombin gene mutation) may be considered, especially with a family history of thrombosis
• Screening for diabetes with hemoglobin A1C and testing for infections like bacterial vaginosis These investigations are crucial because recurrent pregnancy loss can result from various factors, and early identification of these factors allows for targeted interventions in subsequent pregnancies, potentially improving outcomes and reducing the risk of further pregnancy complications 1. It is also important to note that the management of a short cervix in individuals without a history of spontaneous preterm birth should follow the guidelines provided by the Society for Maternal-Fetal Medicine, which recommends the use of vaginal progesterone to reduce the risk of preterm birth in asymptomatic individuals with a singleton gestation and a transvaginal cervical length of 20 mm diagnosed before 24 weeks of gestation 1.

From the Research

Investigations for Recurrent Miscarriage

In a 28-year-old woman with two consecutive spontaneous miscarriages and a history of preterm labor, several investigations should be conducted to determine the underlying cause of recurrent miscarriage. These investigations include:

• Cytogenetic studies to check for genetic/chromosomal abnormalities 2
• Blood coagulation protein/platelet tests to check for thrombotic defects 2
• Hysterosalpingography to check for uterine abnormalities 2
• Sonography and magnetic resonance imaging to check for anatomic anomalies 2
• Tests for endocrine/hormonal abnormalities, such as thyroid function tests 3
• Tests for immunological disorders, such as antiphospholipid antibodies 3

Investigations for Preterm Labor

In addition to the investigations for recurrent miscarriage, the following tests can be conducted to predict preterm labor:

• Complete blood count (CBC) parameters, such as neutrophil-to-lymphocyte ratio, white blood cell count, red cell distribution width, absolute lymphocyte cell count, and absolute neutrophil cell count 4, 5, 6
• Lymphocyte values during the first trimester of pregnancy, which have been shown to be predictive of spontaneous preterm delivery 6

Diagnostic Procedures

The following diagnostic procedures can be considered:

• Parental karyotyping to check for genetic abnormalities 3
• Preimplantation genetic screening to check for genetic abnormalities 3
• Tests for natural killer cells, regulatory T cells, tumour necrosis factor α, cell-derived microparticles, leptin, certain glycoproteins, and cytokines to check for immunological disorders 3