From the Guidelines
A recurrent pregnancy loss workup should be initiated after two or more pregnancy losses, and the evaluation should include a thorough medical history, physical examination, and specific laboratory tests, as recommended by the American College of Radiology Appropriateness Criteria 1. The evaluation should include blood tests such as complete blood count, thyroid function tests (TSH, free T4), antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and beta-2 glycoprotein I antibodies), and parental karyotyping to identify chromosomal abnormalities.
- Uterine cavity assessment via hysteroscopy or sonohysterography is recommended to identify structural abnormalities like fibroids, polyps, or a septate uterus.
- Testing for inherited thrombophilias (Factor V Leiden, prothrombin gene mutation) may be considered in selected cases with a family history of thrombosis.
- Hormonal evaluations including prolactin, androgen levels, and glucose tolerance testing should be performed if clinically indicated.
- Genetic testing of pregnancy tissue (products of conception) can be valuable when available. Treatment depends on identified causes - for example, antiphospholipid syndrome may be treated with low-dose aspirin (81mg daily) and prophylactic heparin during pregnancy, thyroid disorders require appropriate medication adjustment, and uterine abnormalities may need surgical correction, as suggested by recent studies 1. This comprehensive approach is important because identifying specific causes allows for targeted interventions that can significantly improve the chances of a successful pregnancy. In cases of myeloproliferative neoplasms (MPN), preconception counseling and a multi-disciplinary team approach are crucial, with consideration of aspirin therapy, cytoreductive therapy, and strict hematocrit control, as recommended by recent guidelines 1.
From the Research
Recurrent Pregnancy Loss Workup
The workup for recurrent pregnancy loss (RPL) involves a comprehensive evaluation of the underlying causes of the condition. According to 2, the mainstays of RPL investigation include:
- A detailed personal history
- Screening for antiphospholipid syndrome
- Anatomical abnormalities of the uterus
Diagnostic Tests
The following diagnostic tests are not recommended as part of a routine RPL investigation:
- Inherited thrombophilias
- Vaginal infections
- Immunological and male factors of infertility However, some guidelines recommend testing for these factors in certain cases, as noted in 3.
Number of Pregnancy Losses
There is no consensus on when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing after two pregnancy losses, while others advise testing after three losses, as discussed in 3. The study found that the prevalence of abnormal test results for uterine abnormalities and antiphospholipid syndrome is similar in couples with two versus three or more pregnancy losses.
Management of RPL
The management of RPL depends on the underlying cause of the condition. According to 2, low-dose aspirin plus heparin is indicated for the treatment of antiphospholipid syndrome, and levothyroxine is recommended for overt hypothyroidism. Genetic counseling is required in cases of abnormal parental karyotype.
Evidence-Based Workup
An evidence-based workup for RPL is essential to provide best patient care and create a culture that permits rigorous research into potential tests and therapeutics, as emphasized in 4. The goal of the workup should be to optimize value and adhere to evidence-based care.
Challenges in RPL Workup
Despite the availability of various diagnostic tests and management options, up to 75% of RPL cases remain unexplained, as noted in 5. The exact etiology of RPL remains questionable, and the condition is considered polyetiological and multifactorial, with many modifiable and non-modifiable factors involved.