What are the causes of recurrent pregnancy loss (RPL)?

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Last updated: April 18, 2025View editorial policy

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From the Guidelines

Recurrent pregnancy loss in women with myeloproliferative neoplasms (MPN) should be managed with a comprehensive evaluation and a risk-adapted therapeutic strategy, including aspirin therapy and close monitoring, to minimize the risk of fetal loss and pregnancy complications, as supported by the most recent evidence 1.

Key Considerations

  • A careful obstetric history is essential to identify high-risk features, such as prior pregnancy loss, gestational diabetes, hypertension, and thrombophilia, which can inform the management strategy 1.
  • Aspirin therapy is recommended for women with MPN, particularly those with essential thrombocythemia (ET) and a history of prior pregnancy loss or cardiovascular risk factors, as it has been shown to reduce the risk of fetal loss 1.
  • The presence of JAK2 mutation may be associated with a higher risk of late fetal loss, and women with this mutation should be closely monitored during pregnancy 1.
  • A multi-disciplinary team approach, including high-risk obstetrics, is crucial to ensure optimal management of women with MPN and recurrent pregnancy loss 1.

Management Strategy

  • Comprehensive evaluation, including genetic testing, uterine anatomy assessment, and testing for antiphospholipid syndrome and hormonal imbalances, to identify underlying causes of recurrent pregnancy loss.
  • Aspirin therapy, with or without low-molecular-weight heparin (LMWH), depending on the individual risk profile and presence of thrombophilia.
  • Close monitoring of fetal growth and well-being, as well as maternal health, to promptly identify and manage any complications that may arise during pregnancy.
  • Lifestyle modifications, such as maintaining a healthy weight, avoiding smoking and excessive alcohol, and taking prenatal vitamins with folic acid, to optimize pregnancy outcomes.
  • Psychological support to address the emotional distress associated with recurrent pregnancy loss.

From the Research

Definition and Incidence of Recurrent Pregnancy Loss

  • Recurrent pregnancy loss is a complex health challenge with no universally accepted definition 2
  • The true incidence of recurrent miscarriage is difficult to estimate due to the heterogeneity of definitions and criteria applied by international guidelines, but it is reported to range from 1% to 5% 2
  • Recurrent pregnancy loss is defined as the failure of two or more clinically recognized pregnancies before 20-24 weeks of gestation and includes embryonic and fetal losses 3

Etiology and Risk Factors

  • The exact etiology of recurrent pregnancy loss remains questionable and is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved 2
  • Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities 4
  • Other proposed etiologies include chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels, but these are still considered controversial 4
  • Up to 75% of cases remain unexplained, even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors 2, 5

Diagnosis and Management

  • The diagnostic approach and management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple 2
  • Evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss 4
  • Empiric treatments such as progesterone supplementation, anticoagulation, and/or immunomodulatory treatments are used for unexplained cases 4, 6
  • Preimplantation genetic testing may also play a role in the management of recurrent pregnancy loss 4

Prognosis and Psychological Impact

  • The long-term prognosis of couples with recurrent pregnancy loss is generally good, and most eventually achieve a healthy live birth 4, 3
  • However, multiple pregnancy losses can have a significant psychological toll on affected couples 4, 3
  • Accurate information and appropriate support should be offered to reduce the psychological burden associated with multiple miscarriages 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Recurrent pregnancy loss.

Nature reviews. Disease primers, 2020

Research

Recurrent pregnancy loss: current perspectives.

International journal of women's health, 2017

Research

Recurrent pregnancy loss: evaluation and treatment.

Obstetrics and gynecology clinics of North America, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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