Pregnancy and Infant Loss Awareness Month

Recurrent Miscarriage: Evidence to Accelerate Action

By: Alyssa M. Ensminger, DO

Editor’s Note: As Pregnancy & Infant Loss Awareness Month concludes, we are featuring a literature review on recurrent early pregnancy loss. Alyssa Ensminger, a former FACTS elective participant, summarized the 2021 study, published in The Lancet. The review includes recommendations for health care professionals on how to individualize care, offer treatments to couples who have had recurrent miscarriages, and urge policymakers to make these treatments more available.

Introduction

Recurrent early pregnancy loss, although common, presents a challenge for patients, clinicians, and researchers due to variable and evolving definitions, evaluation criteria, and management ideas. For example, the American Society for Reproductive Medicine defines the threshold for clinical evaluation as at least two early pregnancy losses. Yet, their recommended threshold for research purposes is at least three or more early pregnancy losses [1]. Researchers Coomarasamy et al. conducted a literature review to better understand the causes of recurrent pregnancy loss, identify tests to pinpoint patients at risk of recurrent pregnancy loss, and determine points of intervention significantly correlated with decreased risk of pregnancy loss [2]. The study also aimed to standardize the clinical approach to identifying, investigating, and managing recurrent pregnancy loss.

Methods

Coomarasamy et al. utilized MEDLINE and the Cochrane Database of Systematic Reviews to compile 30 systematic reviews of randomized controlled trials. For purposes of the study, recurrent pregnancy loss was defined as three or more consecutive pregnancy losses. The researchers also conducted a review of guidelines from several professional organizations, including committee consensus papers and practice bulletins from the National Institute for Health and Care Excellence, the European Society of Human Reproduction and Embryology, the American College of Obstetricians and Gynecologists, and the American Society for Reproductive Medicine. Recommendations from a 2019 consensus conference held in the United Kingdom were also examined.

Results

The primary goal of the literature review was to summarize the evidence for various clinical investigations for recurrent miscarriages. Each investigation evaluated the evidence for the association between a positive test result and miscarriage, causality of a positive result in relation to miscarriage risk, the predictive value of a test result, and treatments for a positive test result to improve outcomes. Test results most strongly associated with miscarriage included positive antiphospholipid syndrome, chromosomal abnormalities, hypothyroidism, uterine anomalies, and polycystic ovarian syndrome. Of these, hypothyroidism alone had strong evidence supporting improved outcomes following treatment.

The literature review also summarized several interventions used to prevent miscarriage in high-risk women, including women with recurrent pregnancy loss. The review highlighted progestogens, anticoagulants, levothyroxine, metformin, hCG, immunomodulators, and vitamin supplementation. Specifically, the study identified several interventions found to improve live birth outcomes. Moderate-quality evidence supports progesterone for women with diagnoses of recurrent pregnancy loss, while low-quality evidence supports the use of levothyroxine for subclinical hypothyroidism and a combination of baby aspirin and heparin for antiphospholipid syndrome. Unfortunately, there is no high-quality evidence to support existing treatments for the prevention of miscarriage among high-risk women.

“The study identified several interventions found to improve live birth outcomes. Moderate-quality evidence supports progesterone for women with diagnoses of recurrent pregnancy loss.”

Discussion

This literature review identified points of investigation and intervention for patients following a pregnancy loss. Specifically, researchers investigated many tests correlated with an increased risk of pregnancy loss. However, despite strong correlations, less evidence supports a causal relationship between a positive test result and a pregnancy loss. Many interventions have been examined, but there is insufficient evidence to conclusively identify the treatments most successful in preventing early pregnancy loss.

Further research is still needed to clarify preventable causes of pregnancy loss, but this article enables clinicians to maximize patient care following a loss. Some patients may simply want an answer, while others hope for an actionable solution to reduce future risk of loss. Although there remains a need for more research to identify evidence-based interventions, this study highlights the opportunity for clinicians to have an open and honest conversation about available tests and correlated outcomes. In addition, a comprehensive understanding of post-pregnancy loss care to identify the patient’s goals and needs is critical.

“Although there remains a need for more research to identify evidence-based interventions, this study highlights the opportunity for clinicians to have an open and honest conversation about available tests and correlated outcomes.”

The review concludes with the recommendation to implement a standardized, graded approach to post-pregnancy loss care. This approach considers the unique needs of a couple in their family-planning journey, while incorporating the evidence summarized in this review, to present a balanced picture of benefits and costs to patients. For patients who have experienced their first loss, this approach would direct them to online screening, preconception advice, and support groups. Patients with two losses would be connected with a mid-level practitioner to begin an appropriate clinical investigation. Finally, those with three or more losses would warrant a comprehensive investigation and intervention. Alongside this care, clinicians trained in fertility awareness-based methods (FABMs) may recommend a woman begin charting her cycle to identify potential abnormalities. This information can be utilized to tailor treatment and recommendations following a miscarriage.

Nearly half of all pregnancy losses are caused by non-preventable, sporadic, chromosomal abnormalities [1,3]. A couple may not require substantial workup or clinical investigation, but the approach detailed by Coomarasamy et al. ensures all patients receive care that recognizes the emotional impact of pregnancy loss as a significant health event. Given that prior approaches typically reserved care for patients with two or more losses, this is an important distinction: An estimated 20 to 30% of women will experience pregnancy loss during their reproductive years, while only 1% of women will have three or more losses [3]. Overall, the review emphasizes the need for care of all women who experience miscarriage to ensure they are not overlooked by our healthcare systems.

“A couple may not require substantial workup or clinical investigation, but a standardized, graded approach to post-pregnancy loss care ensures all patients receive care that recognizes the emotional impact of pregnancy loss as a significant health event.”

[1] Evaluation and treatment of recurrent pregnancy loss. A Committee Opinion. American Society for Reproductive Medicine. Fertil Steril. 2012;volume unknown:1-9.

[2] Coomarasamy A, Dhillon-Smith RK, Papadopoulou A, et al. Recurrent miscarriage: evidence to accelerate action. Lancet. 2021;297(10285):1675-82.

[3]  Early pregnancy loss. ACOG Practice Bulletin No. 200. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e197-207.

ABOUT THE AUTHOR

Alyssa M. Ensminger, DO

Alyssa M. Ensminger is a graduate of Des Moines University School of Osteopathic Medicine in Iowa. She plans to pursue a career as an Ob/Gyn and hopes to practice as a generalist with a focus on full-spectrum complex family planning. Alyssa took the FACTS elective to learn more about fertility awareness-based methods and plans to add them to her list of options she can offer her future patients.