Key points

Introduction

Early pregnancy loss (EPL) is defined as an intrauterine pregnancy in the first trimester that cannot result in a live birth. EPL occurs in 15% to 25% of all clinically recognized pregnancies. ^, Determining the exact incidence of EPL is difficult, as many losses occur before patients become aware of their pregnancy. However, an estimated 1 in 4 pregnancy-capable patients will experience EPL in their lifetime. Societal stigma hampers discussion of loss despite the high incidence.

Throughout this review, the authors use the term EPL to refer to pregnancy losses through 13 weeks and 6/7 days gestation, second-trimester loss for losses occurring from 14 to 20 weeks, and stillbirth for losses after 20 weeks. Patients may use or prefer different terms to describe their individual losses. Emotional responses during and after an EPL can vary and may not be directly related to whether the initial pregnancy was desired or intended. The amount of control patients have over the process is most predictive of how they will feel afterward. ^,

The primary focus of this review is on diagnosis, management, and aftercare of EPL, with limited discussion of second-trimester losses and stillbirth.

Making the diagnosis

EPL can present diagnostic uncertainty, as the common symptoms of EPL, vaginal bleeding, and abdominal pain or cramping, are also frequently present in normally developing intrauterine pregnancies. In addition, some patients may be completely asymptomatic at the time of EPL diagnosis. A single ultrasound can be diagnostic for EPL when it meets specific and conservative criteria ( Box 1 ). These criteria strive to ensure with 100% certainty that a normal intrauterine pregnancy will not be intervened upon preemptively. The authors of these guidelines achieve this by adding an additional buffer to the evidence-based diagnostic criteria for EPL, in part to account for interobserver variation in ultrasound measurements of early pregnancy structures. For example, a crown-rump length (CRL) of 5.3 mm without cardiac activity has 100% positive predictive value for EPL. The published diagnostic criteria increase the required CRL measurement for definitive diagnosis of EPL to 7 mm. Similarly, an empty gestational sac with a 21 mm mean sac diameter (MSD) has 100% specificity for EPL, but the diagnostic criteria increase the required MSD measurement to 25 mm. With counseling, patients may weigh the stringency of these criteria against their own desires for expedited management or for avoidance of the spontaneous passage of pregnancy tissue while awaiting a definitive diagnosis. Similarly, clinicians can feel confident that if these criteria are met, then the diagnosis of EPL is a certainty.

When the diagnosis of EPL is unclear by ultrasound, additional testing is required. Some ultrasound findings are suggestive of but not definitive for EPL and a follow-up ultrasound is recommended to confirm the diagnosis ( Box 2 ). Many patients who present with vaginal bleeding or abdominal pain will have a pregnancy of unknown location and require serial human chorionic gonadotropin (hCG) trending, follow-up ultrasonography, and/or diagnostic uterine aspiration (in the case of undesired pregnancy or an abnormal hCG trend) to confirm the pregnancy location and rule out ectopic pregnancy. Others may have a probable intrauterine pregnancy ( Table 1 ) but require follow-up ultrasound to ensure that a yolk sac and ultimately an embryo develop, confirming an intrauterine pregnancy. For these patients, follow-up ultrasonography in 14 days will facilitate definitive diagnosis of EPL if no embryo with cardiac activity is detected at that time. In the case of a pregnancy of unknown location or a clinical scenario suggestive but not diagnostic of EPL, the uncertainty surrounding the pregnancy’s outcome and the waiting for a definitive diagnosis can be troubling and anxiety provoking for patients. Thorough counseling is crucial, complete with a clear follow-up plan and contingency planning for emergency care in the case of heavy bleeding or severe pain.

Once an intrauterine pregnancy with embryonic cardiac activity is seen on ultrasound, the risk of subsequent pregnancy loss diminishes. In pregnancies where a fetal pole with embryonic electrical activity is seen on ultrasound between 6 and 10 weeks’ gestation, the rate of subsequent pregnancy loss is 7.5%. The later the gestational age at the time of the ultrasound, the lower the rate of subsequent pregnancy loss.

Treatment options

Patients vary in their readiness for management once a diagnosis of EPL is disclosed. Some may want an immediate plan in place for resolution of the pregnancy, while others may need days or weeks to process the diagnosis. Similarly, some patients may have difficulty understanding the diagnosis of a loss that does not present with “typical” EPL symptoms of bleeding and cramping. This spectrum of responses is appropriate and should be supported with clear outlining of the concerning symptoms that would require urgent evaluation.

EPL can be managed expectantly, with medication, or with procedural evacuation. These 3 options vary in process ( Table 2 ) and may vary in availability by practice setting but are all generally effective and safe. Most EPL management options are safe for most patients, making it primarily an individualized decision. Some patients may have certain clinical characteristics that make one management option preferable, safer, or recommended, or in contrast contraindicated. Patients consider many influences when making a decision about EPL treatment including their acceptance of the loss, their need for timing or control of the EPL process, their home or work responsibilities, pain and physical aversions, and their perceptions of health and safety. Centering the patient’s priorities and values around EPL management and allowing time for reflection and consultation with family and other members of their support system is essential. Given the variety of individual influences on EPL management decision-making, clinicians should offer all available management choices for which a patient is eligible, regardless of what might seem most expeditious from the clinician perspective.

Table 2

Management options for early pregnancy loss

Method	Expectant Management	Medication Management	Surgical/Procedural Management
Process	Watchful waiting	Mifepristone 200 mg (oral) 24–48 h later: Misoprostol 800 mcg (buccal or vaginal) If mifepristone not used: misoprostol 800 mcg every 3 h for up to 3 doses	Manual or electric uterine aspiration with suction curettage Sharp curettage not recommended
Effectiveness (without surgical intervention)	70% within 2 wk; 80% within 8 wk; higher for incomplete miscarriage	84% within 1 mo (mifepristone and misoprostol); 67% (misoprostol only)	N/A
Time to completion	Up to 8 wk	Between 1 d and 1 wk	<1 d
Location	Home	Home, with medications prescribed and dispensed in a health care setting (office, emergency department, or pharmacy)	Office, emergency department, surgical suite, or operating room
Bleeding amount at home	Up to 2 pads an hour at heaviest point with large clots	Same as expectant management	Similar to a period
Bleeding duration	Intermittent up to 6 wk	Intermittent up to 3 wk	Intermittent up to 2 wk
Follow-up	One or more visits over 8 wk, varies by patient	One or more visits in 1–2 wk	Not typically needed
Benefits	Avoid an invasive procedure Avoid medications with side effects Potentially lower cost of treatment	Avoid an invasive procedure Shorter time to completion than expectant management More control over timing than with expectant management	Less bleeding than with expectant or medication management More pain management options (paracervical block, moderate or deep sedation, or general anesthesia) Shortest time to completion More likely to be successful at later GA (10+ weeks)
Drawbacks	Heavy, prolonged bleeding Cramping pain Unpredictable timing	Heavy, prolonged bleeding Cramping pain GI side effects with misoprostol	Less patient control over timing and process
Risks	Hemorrhage Infection No passage of pregnancy tissue	Hemorrhage Infection No passage of pregnancy tissue	Hemorrhage Infection Injury to uterus, cervix, or surrounding structures Retained products of conception
Contraindications	Active infection or hemorrhage Hemodynamic instability Severe anemia Bleeding disorder Ectopic or suspected molar pregnancy	Active infection or hemorrhage Hemodynamic instability Severe anemia Bleeding disorder Chronic steroid use (if using mifepristone) Suspected molar pregnancy	No absolute contraindications Consider surgical risks associated with other medical conditions
Need for surgical intervention	∼20%	∼5%–20%	<1% chance of repeat procedure
Return to fertility	Ovulation as early as 10 d after completion No change in future fertility

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