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8/13/2023

Recurrent Pregnancy Loss

Pregnancy loss occurs in 15% to 25% of pregnancies, while recurrent pregnancy loss affects up to 2% of pregnancies. Recurrent pregnancy loss is defined by the loss of 2 or more ultrasound- or histopathologic-proven losses, not including self-reported losses.

Etiologies are divided into the following categories: cytogenetic abnormalities, antiphospholipid antibody syndrome, anatomic abnormalities, and hormonal/metabolic abnormalities. The following causes have not been shown to contribute and should not be included in the workup without other concerns: uterine and pelvic infections, sperm aneuploidy and fragmentation, alloimmune causes (eg, elevated cytokines or parental HLA mismatch, inherited thrombophilia, MTHFR pathogenic variants, chronic endometritis, and luteal phase deficiency).

To evaluate for cytogenetic causes, which affects 2% to 5% of couples, parental karyotype analysis should be done on a peripheral blood specimen, specifically looking for a balanced reciprocal or Robertsonian translocation. However, identified abnormalities may not always correlate with recurrent pregnancy loss. If a translocation is identified, patients should be counseled on options to undergo preimplantation genetic diagnosis.

Antiphospholipid antibody syndrome contributes to up to 20% of recurrent pregnancy loss. Patients should only be tested for this condition if they meet the following criteria: an unexplained loss after 10 weeks’ gestation with normal morphology, a baby delivered before 34 weeks because of a hypertensive disorder or placental insufficiency, or 3 or more consecutive spontaneous pregnancy losses with all other causes excluded. Testing includes lupus anticoagulant, anticardiolipin IgG and IgM, and anti-β₂- glycoprotein IgG and IgM. Patient with a positive test result should be retested 12 weeks later to confirm the diagnosis. The treatment plan is based on a history of a thrombotic event and includes prophylactic anticoagulation through 6 weeks postpartum.

Uterine anatomic abnormalities should be investigated with ultrasonography, hysterosalpingography, saline sonography, 3D ultrasonography, MRI, and/or hysteroscopy. Congenital malformations such as septate, with a loss rate up to 45%, or arcuate uterus are correlated with recurrent pregnancy loss. Surgical correction of septation is shown to improve pregnancy rates. Surgical intervention for fibroids and polyps is controversially beneficial but is usually recommended to maximize success.

The data also support correction of common hormonal and metabolic diseases. Patients should be screened for suboptimally controlled diabetes mellitus, thyroid disease, and hyperprolactinemia. If found to have a TSH concentration greater than 4.0 mIU/L, patients should be treated to achieve a goal value less than 2.5 mIU/L. Hyperprolactinemia should be treated with a dopamine agonist.

Finally, all patients should be screened for known lifestyle risks for miscarriage including tobacco use, obesity, cocaine use, alcohol intake exceeding more than 5 drinks per week, and caffeine use exceeding more than 3 cups of coffee per day.

Although recurrent pregnancy loss is an emotionally hard diagnosis, improved live birth rates are documented when patients are emotionally supported through this process. Patients should be offered behavioral health interventions and grief and guilt support.

Many other suggested causes of recurrent pregnancy loss are not supported in the literature. Up to 75% of couples do not have a definitive diagnosis after appropriate workup and should be sent to reproductive endocrinology and infertility specialists to discuss options. Patients should be reassured that after 2 or more losses, about 70% of couples eventually conceive and about 70% of those conceptions result in a live birth.  

Further Reading:

Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98(5):1103-1111. PMID: 22835448

Hennessy M, Dennehy R, Meaney S, et al. Clinical practice guidelines for recurrent miscarriage in high-income countries: a systematic review. Reprod Biomed Online. 2021;42(6):1146-1171. PMID: 33895080

Initial publication August 2023

Final editing of initial publication performed by The Medical Pen, LLC.

 

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This document is designed to aid practitioners in providing appropriate obstetric and gynecologic care. Recommendations are derived from major society guidelines and high-quality evidence when available, supplemented by the opinion of the author and editorial board when necessary. It should not be construed as dictating an exclusive course of treatment or procedure to be followed.

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