Continuing Education Activity

Early pregnancy loss, characterized by the spontaneous termination of an intrauterine pregnancy during the first trimester, presents a complex clinical scenario requiring multifaceted understanding and management. Detecting and addressing this condition effectively necessitates a personalized approach due to its various manifestations and stages. Accurate diagnosis, particularly in the early stages of gestation, can pose a significant challenge, and the lack of a comprehensive understanding of risk factors, differential diagnoses, and a failure to tailor management strategies to individual patient needs may result in suboptimal care. Counseling skills and enhanced empathy also contribute to better patient care and outcomes, as management needs to be personalized for each patient.

Healthcare professionals must recognize that early pregnancy loss encompasses multiple subtypes, each associated with distinct risk factors that demand thorough consideration. The healthcare team's ability to provide empathetic counseling is pivotal in delivering superior patient care and achieving favorable outcomes. In this context, fostering enhanced communication skills and empathy plays a vital role in improving patient experiences and outcomes, as management approaches must be precisely tailored to each patient's unique diagnosis and circumstances. This activity describes the evaluation and management of early pregnancy loss and highlights the role of the interprofessional team in improving patient care. 

Objectives:

• Identify the clinical findings typically found in the various stages of early pregnancy loss.

• Identify the essential steps to diagnose early pregnancy loss.

• Select the most appropriate management options based on the clinical situation and patient preferences.

• Collaborate and communicate with the healthcare team to improve outcomes in patients affected by early pregnancy loss.

Introduction

The terminology used to describe the loss of an intrauterine pregnancy before fetal viability (ie, a fetus likely to survive outside of the uterus) is inconsistent in the literature and has varied over time.[1][2] Traditionally, spontaneous abortion referred to a natural pregnancy loss before 20 weeks of gestation; however, more recently, the medical literature has been transitioning away from the phrase.[3] Patients prefer the term miscarriage, presumably to avoid the stigma associated with induced abortion.[1] The reVITALize gynecology definitions from the American College of Obstetricians and Gynecologists (ACOG), which are also endorsed by the American Academy of Nurse-Midwives, the American Academy of Family Physicians, and numerous other American professional organizations, now recommend the terms miscarriage or intrauterine pregnancy loss. Both terms are synonymous and are defined as the loss of a documented nonviable (ie, a pregnancy not expected to develop normally) intrauterine pregnancy.[4] 

Some organizations use the cut-off of <10 weeks of gestation to define an early miscarriage. The ACOG and the European Society of Human Reproduction and Embryology (ESHRE) use a similar term—early pregnancy loss. ACOG defines it as "an empty gestational sac or a gestational sac containing an embryo or fetus without fetal heart activity within the first 12 6/7 weeks of gestation," while the ESHRE considers an early loss as occurring before 10 weeks of gestation.[5][6] Although there is no consensus among societies concerning the correct terminology, early pregnancy loss will be used here, defined in concordance with ACOG as a nonviable intrauterine pregnancy ≤12 6/7 weeks of gestation.[5] 

Classification

Early pregnancy loss is a process and may be diagnosed at multiple stages.

• Biochemical pregnancy loss: A diagnosis entirely based on decreasing human chorionic gonadotropin levels without a pregnancy ever visualized on ultrasound. Generally, miscarriage occurs before 6 weeks of gestation in pregnancies achieved with the assistance of reproductive technology.[7]
• Asymptomatic pregnancy loss (ie, missed abortion): The missed death of the embryo or fetus without symptoms or expulsion of the products of conception (POC).[8]
• Threatened pregnancy loss: Symptoms (eg, bleeding and cramping) of an impending early pregnancy loss; however, the cervical os remains closed, and the embryo or fetus still appears viable on ultrasound.[9][10]
• Inevitable pregnancy loss: Similar to a threatened pregnancy loss, symptoms (eg, bleeding and cramping) are present; however, the cervical os is open. This term, in particular, is falling out of favor, as it can be clinically challenging to identify inevitable abortions with certainty.[3]
• Incomplete pregnancy loss: POC that remains within the uterus and the open cervical os after the diagnosis of an early pregnancy loss.[11]
• Complete pregnancy loss: The passage of all POC.[3]
• Recurrent pregnancy loss: The consecutive loss of multiple pregnancies. The American Society for Reproductive Medicine defines recurrent as ≥2 pregnancy losses; other organizations define it as ≥3 consecutive losses.[12][13]
• Septic miscarriage: An early pregnancy loss complicated by an intrauterine infection, which is rare. Alternatively, septic abortion has traditionally been used to mean any pregnancy loss, spontaneous or induced, complicated by infection. Septic abortions occur most often in the setting of nonsterile abortion procedures.[14]

Etiology

In more than 60% of pregnancy losses between 6 to 10 weeks of gestation, the etiology is believed to be fetal chromosomal abnormalities, including trisomies, monosomy, and polyploidy.[5][15][16] Additionally, inflammatory and immunologic dysregulation is thought to play a role in some cases, likely due to the effect on trophoblastic invasion.[17][18][19]

Risk Factors

The most common risk factor for early pregnancy loss is advanced maternal age.[5] For example, the incidence of early pregnancy loss in women aged 20 to 30 years is only 9% to 17%, while the incidence at 45 years of maternal age is 75% to 80%.[5] A prior history of pregnancy loss also increases the risk of recurrent pregnancy loss, with the risk increasing after each additional loss. For example, the risk of miscarriage in a future pregnancy is approximately 20% after one miscarriage, 28% after 2 consecutive miscarriages, and 43% after ≥3 consecutive miscarriages.[20] Additionally, first-trimester vaginal bleeding, which occurs in up to 25% of pregnancies, is associated with a higher risk of pregnancy loss.[21][3]

Several chronic diseases can predispose a pregnant patient to early pregnancy loss, including obesity, diabetes, hyperprolactinemia, celiac disease, thyroid disease, and autoimmune conditions, particularly antiphospholipid syndrome.[22][23][24] Furthermore, some infections are associated with an increased risk of early pregnancy loss, such as syphilis, parvovirus B19, Zika virus, and cytomegalovirus infections.[25] Structural uterine abnormalities (eg, congenital Müllerian anomalies, leiomyoma, and intrauterine adhesions) and intrauterine pregnancies with an intrauterine device still in place also have been shown to increase the risk of early pregnancy loss.[16] Chronic stress secondary to social determinants of health (eg, racism, housing or food insecurity, or living under threats of violence) is also associated with an increased risk of pregnancy loss.[17] Additional modifiable risk factors include alcohol consumption, smoking, cocaine use, and high caffeine consumption (eg, drinking >3 cups of coffee daily).[22] Finally, environmental contaminants, including arsenic, lead, and organic solvents, have also been associated with early pregnancy loss. 

Epidemiology

Overall, 10% to 20% of clinically recognized pregnancies will end in early pregnancy loss.[5][26] However, these statistics likely underestimate the true incidence of spontaneous loss, as many miscarriages remain undiagnosed, with the resulting bleeding being mistaken as heavy, late menses. Studies that have tracked pregnancies using daily measurements of serum β-hCG levels estimate a higher incidence of approximately 38%.[16] Additionally, 12% to 57% of pregnancies with first-trimester bleeding end in miscarriage.[27]

History and Physical

General Principles

The approach to evaluating a pregnant patient with first-trimester bleeding for possible pregnancy loss depends on knowing the location and viability of the pregnancy. Therefore, assessment of a pregnant patient with suspected or threatened early pregnancy loss primarily involves:

• Determination of the stability of the patient
• Exclusion of differential diagnoses (eg, ectopic or molar pregnancies) 
• Confirmation of the viability of the pregnancy or, if nonviable, the stage of pregnancy loss [5]

Clinical Features

Symptoms of early pregnancy loss depend on the type or stage of loss. An asymptomatic pregnancy loss (ie, missed abortion) may only be notable due to the regression of common pregnancy signs and symptoms (eg, nausea or fatigue).[21][8] Patients with threatened, incomplete, or complete pregnancy losses commonly report pelvic cramping and vaginal bleeding symptoms. A thorough history of the patient's vaginal bleeding (eg, the first day of the last menstrual period, the onset of abnormal uterine bleeding, the number of soaked pads in an hour, and the number and size of clots, if present) should be documented.[3] In addition to these symptoms, septic miscarriages are typically also accompanied by uterine tenderness, purulent cervical and vaginal discharge, and in severe cases, systemic signs (eg, fever, tachycardia, and hypotension).[14] 

Physical Examination

In addition to assessing for signs of pregnancy loss, a focused physical examination, including vital signs and a thorough abdominal and pelvic examination, will assist in determining if hemodynamic instability and/or possible ectopic pregnancy need to be emergently addressed. Findings from an abdominal exam may include peritoneal signs of an ectopic pregnancy or extra-uterine extension of a septic abortion.[3] A pelvic exam, which should include speculum-facilitated visualization of the cervix and bimanual palpation, is central to evaluating suspected miscarriage.[3] Findings of early pregnancy loss on pelvic examination may include an open or closed cervix, the presence or absence of pregnancy tissue within the cervical os, vaginal bleeding, and signs suggestive of a septic abortion (eg, purulent discharge, uterine or cervical motion tenderness).[3][27] Alternatively, an adnexal mass finding suggests an ectopic pregnancy rather than an early pregnancy loss. An estimation of the volume of vaginal bleeding should be obtained during the pelvic examination as part of the assessment for hemodynamic stability by noting how quickly blood fills the vaginal vault, which can be significant even in the absence of sepsis. Bleeding similar to or greater than typical menses suggests a diagnosis of early pregnancy loss.[3][27]

Evaluation

Diagnostic Studies

Verifying the location of a pregnancy within the uterus and assessing viability are the next steps in evaluating early pregnancy loss. Accurate diagnosis of early pregnancy loss is essential before initiating any treatment to prevent unintended consequences, including termination of a normally developing early pregnancy or engineering birth defects.[5] Differentiating viable from nonviable pregnancies, in addition to excluding differential diagnoses (eg, pregnancy complications or pelvic infection), typically begins with the following:

• Pelvic ultrasound
• Quantitative serum β-hCG level [5]

The first day of the last menstrual period (LMP) and findings from any prior ultrasound imaging performed during the current pregnancy should be reviewed. The LMP is used to initially calculate the estimated gestational age of the pregnancy, and ultrasound imaging, when available, can be used to confirm this dating and determine the location of the pregnancy (eg, intrauterine or ectopic).[3] Trending β-hCG levels with the findings from pelvic ultrasound assist in assessing the viability of the pregnancy.[3]

Additional Studies

• Hemoglobin and hematocrit: to assess acute blood loss anemia; large volumes of acute blood loss may not be accurately reflected in lab values [5][3]
• Maternal ABO blood type and Rh status: to prepare for possible blood transfusion or determine the need for anti-Rh immunoglobulin [5][3]
• Wet mount examination; bacterial and viral cultures (eg, of cervical, urine, blood, and evacuated gestational tissue): to evaluate suspected septic abortion [28][14]

Early Intrauterine Pregnancies

Pregnancy location can be definitively established once embryonic or fetal structures (eg, a yolk sac or fetal pole) are visible within an intrauterine gestational sac. For individuals with previously diagnosed intrauterine pregnancies, the diagnosis of early pregnancy loss can easily be made based on characteristic clinical features and the absence of any POC on ultrasound.[5] For pregnancies at gestational ages too early to visualize fetal cardiac activity, typically less than 6 weeks of gestation, documentation of falling hCG levels over 48 to 72 hours may assist with diagnosis.[5] The stages of early pregnancy loss and their possible associated findings are detailed in the Table.

Table. Diagnostic Findings Associated With Different Types of Early Pregnancy Loss [27]

FCA, fetal cardiac activity, IUP, intrauterine pregnancy; PE, physical exam; POC, products of conception.

^aSee Early Intrauterine Pregnancies of Unknown Viability.

Early Intrauterine Pregnancies of Unknown Viability

For pregnancies at gestational ages too early to visualize fetal cardiac activity (FCA), typically less than 6 weeks of gestation, documentation of falling β-hCG levels over 48 to 72 hours may assist with the diagnosis of early pregnancy loss.[5] Even before FCA develops, ultrasound can help establish pregnancy viability, though it may require multiple scans over several weeks. Early pregnancy events follow a sequential pattern, and any variation from this sequence may suggest early pregnancy loss. For example, on ultrasound, the visualization of the yolk sac follows the appearance of the gestational sac, which is then closely followed by the presence of an embryo with cardiac activity. Therefore, ultrasound imaging of a gestational sac with a mean sac diameter (MSD) of at least 25 mm, a demonstration of an embryo would be expected. Moreover, a detectable fetal heart rate should be present with an embryo with a crown-rump length (CRL) of at least 7 mm.[5]

A multispecialty panel from the Society of Radiologists in Ultrasound released guidelines based on ultrasound findings for diagnosing intrauterine pregnancy failure. These guidelines, reaffirmed by ACOG, include findings diagnostic of pregnancy failure and those suspicious for, but not diagnostic of, pregnancy failure.[29][5]

Findings consistent with a pregnancy failure diagnosis

• CRL ≥7 mm without FCA
• MSD ≥25 mm without an embryo
• Absence of an embryo with FCA ≥14 days following an ultrasound demonstrating a gestational sac without a yolk sac
• Absence of an embryo with FCA ≥11 days following an ultrasound demonstrating a gestational sac with a yolk sac

Findings that raise suspicion of pregnancy failure but are not conclusive for diagnosis

• CRL of <7 mm without FCA
• MSD of 16 to 24 mm without an embryo
• Absence of an embryo with FCA 7 to 13 days following an ultrasound demonstrating a gestational sac without a yolk sac
• Absence of an embryo with FCA 7 to 10 days following an ultrasound demonstrating a gestational sac with a yolk sac
• Absence of an embryo ≥6 weeks since the LMP
• Empty amnion (ie, amnion seen adjacent to a yolk sac with no visible embryo)
• Enlarged yolk sac >7 mm
• Small gestational sac compared to the size of the embryo (ie, <5 mm difference between the MSD and CRL)

If the viability of an intrauterine pregnancy is uncertain (eg, ultrasound findings are nondiagnostic of pregnancy failure or signs of threatened pregnancy loss are present), the ultrasound should be repeated in 7 to 10 days.[5]

Early Pregnancies of Unknown Location

When the location of a fertilized egg is unknown at the time of presentation (ie, fetal or embryonic structures are not seen on the initial ultrasound), the immediate step is to determine the gestational age and location of the fertilized egg to exclude an ectopic pregnancy. This typically requires trending β-hCG levels over several days.[3]

Initially, the estimated due date (EDD) is determined based on an accurate LMP. This estimate is then compared to the EDD, calculated using ultrasound for confirmation. ACOG states that "accurate gestational age calculation, rather than an absolute β-hCG level, is the best determinant of when a normal pregnancy should be seen within the uterus with transvaginal ultrasonography" and notes that the gestational sac and yolk sac should be visible between 5 and 6 weeks of gestation, regardless of the number of embryos present.[30] Irregularities in the menstrual cycle, however, can impact the timing of ovulation and conception relative to the LMP, which is why it is crucial to consider the entire clinical picture during evaluation and not to rely solely on either the LMP-derived due date or a single β-hCG level. Therefore, the first β-hCG level primarily provides a secondary guide on the pregnancy development that should be expected on ultrasound. Serial β-hCG levels, if needed, can then be monitored for the average increase characteristic of a developing intrauterine pregnancy.[5]

The concept of a discriminatory level may be useful in assessing pregnancy location, but similarly, it should be applied with care and in the context of the full clinical picture. The discriminatory level refers to the β-hCG level at which the gestational sac should be visible on transvaginal sonography; if the β-hCG level is above the discriminatory level cut-off and a gestational sac is not seen in the uterus, ectopic pregnancy should be suspected.[5][3][29][28] To avoid misdiagnosis of a potentially viable intrauterine pregnancy, ACOG recommends using a cut-off with a conservatively high β-hCG level, such as 3,500 mIU/mL, which is a higher value than what has been recommended in the past, to aid in diagnosis.[30] Multiple gestations, for example, will have relatively higher β-hCG levels than singletons at a given gestational age.

While the location of the pregnancy remains uncertain, patients should be closely followed until the location is definitively identified (ie, a yolk sac and fetal pole are seen within the gestational sac). This is done by trending β-hCG levels every 48 to 72 hours, with periodic repeat ultrasound assessments (often done at the same time as the repeat β-hCG levels) until the location is confidently identified on ultrasound or β-hCG levels fall to nonpregnant levels (ie, 0).[5][3][29][28] It is important to remember that hormonal changes associated with ectopic pregnancy can result in the formation of an intrauterine fluid collection. However, this is not a true gestational sac; this is why visualization of embryonic structures is essential to identify the developing embryo's location accurately. 

In the setting of a viable pregnancy, β-hCG levels increase at a relatively predictable rate. However, as the β-hCG level increases, its rate of increase gradually slows until it reaches a plateau around 10 weeks of gestation. The minimum rates of β-hCG rise expected over 48 hours are 49%, 40%, and 33% for initial β-hCG levels of <1,500 mIU/mL, 1,500 to 3,000 mIU/mL, and >3,000 mIU/mL, respectively.[31] If the β-hCG level fails to meet the minimum expected rate of rise, ectopic pregnancy should be strongly considered. Falling β-hCG levels typically indicate failing pregnancies. However, ectopic pregnancies can have an initial decrease in β-hCG followed by an abnormal increase. Therefore, if the pregnancy location has not been confidently identified on ultrasound, the β-hCG level should be monitored until nonpregnant levels are reached to ensure an ectopic pregnancy is not missed.[32]

Treatment / Management

Early pregnancy loss can be managed expectantly, medically, or surgically. Certain clinical factors may make one management strategy preferable, though all 3 modalities can often be considered. Studies show that patients managed according to their preferences have better mental health outcomes and are more satisfied with their care.[5][33] However, it is important to note that regional guidelines can vary, which is discussed in further detail below. 

Expectant and Medical Management

Contraindications: Hemorrhage and infection are contraindications to expectant and medical management. Additionally, expectant management is relatively contraindicated after the first trimester due to a lack of safety data. Expectant and medical management are typically less favored in patients who cannot tolerate heavier bleeding, including patients with severe anemia, bleeding disorders, and cardiovascular disease.[5] 

Efficacy: Expectant management may be continued safely for as long as the patient desires, provided infection and hemorrhage do not develop.[3] Approximately 70% of early pregnancy losses will have complete expulsion within one month and up to 80% within 2 months.[3][5] Expectant management appears more effective in symptomatic patients (eg, incomplete loss) than in asymptomatic patients (eg, missed abortion).[5] Furthermore, expectant and medical management are as effective as uterine aspiration in patients with first-trimester incomplete pregnancy losses.[11]

Medications: Misoprostol is the primary drug used to manage early pregnancy loss. Although numerous different misoprostol regimens have been used, the regimen currently recommended by ACOG consists of misoprostol 800 mcg vaginally once daily as a single dose; if the expulsion of POC does not occur, the dose may be repeated once, any time from 3 hours to 7 days after the first dose. Premedication with mifepristone 200 mg orally once daily as a single dose, 24 hours before the first dose of misoprostol, results in a higher success rate than misoprostol alone and is recommended by most experts, if available.[3][5]

A 2018 randomized controlled trial published in The New England Journal of Medicine included 300 women with early pregnancy loss compared with a combined mifepristone-misoprostol regimen (mifepristone 200 mg orally followed 24 hours later with misoprostol 800 mcg vaginally for 1-2 doses) to misoprostol alone (800 mcg vaginally for 1-2 doses). This study showed that adding mifepristone to misoprostol resulted in significantly higher rates of complete miscarriage resolution (91% vs 75%) and lower rates of needed surgical intervention (9% vs 24%). Rates of serious adverse events, defined as pelvic infection or bleeding resulting in blood transfusion, were similar in both groups.[34] Common adverse effects included vaginal bleeding, cramping, diarrhea, and nausea.[3] Oxytocin is ineffective for managing early pregnancy loss since oxytocin receptors are absent within the uterus until after the first trimester.[35] In addition to medications offered to assist in the expulsion of POC, patients should also be provided with appropriate pain control. Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically effective, though some patients may require additional agents. Antibiotics are not indicated unless an infection is present.[5]

Documenting completion: Although there is a lack of consensus, complete pregnancy loss is often defined as the absence of a gestational sac on ultrasound with an endometrial thickness of <30 mm. This ultrasound is usually performed 7 to 14 days after the initiation of medical management or at follow-up visits every 1 to 2 weeks in patients being managed expectantly. However, it is important to note that ACOG states, "surgical intervention is not required in asymptomatic women with a thickened endometrial stripe after treatment for early pregnancy loss. Thus, the use of ultrasound examination for any diagnostic purpose other than documenting the absence of the gestational sac is not recommended."[5] Patient-reported resolution of cramps and bleeding is also useful in confirming complete abortion.[5] β-hCG levels do not need to be followed to 0 mIU/mL unless the location of the pregnancy within the pelvis remains unknown or if persistent bleeding and constitutional symptoms of malignancy raise suspicion for gestational trophoblastic disease; however, serial levels may be used if ultrasound confirmation is not available.[5][36] Regardless of the management approach, patients should be counseled to return for evaluation if bleeding is excessive.[5] This is often defined as soaking more than one menstrual pad per hour for 2 consecutive hours.[5][3]

Alloimmunization: Finally, there is a risk of alloimmunization in unsensitized Rh(D)-negative patients, though this risk is low, especially in very early pregnancy before the development of fetal erythrocytes.[37] ACOG recommends giving Rh(D)-immune globulin to unsensitized Rh(D)-negative patients with early pregnancy loss, especially those later in the first trimester. The recommendations of professional societies from other countries, however, differ from those from the United States (US) slightly; for example, the National Institute for Health and Care Excellence (NICE) guidelines from the United Kingdom (UK) explicitly state that Rh(D)-immune globulin is not indicated for nonsurgical management of miscarriage in the first trimester.[5] If given, Rh(D)-immune globulin 50 to 120 mcg once is recommended in the first trimester and 300 mcg once in the second trimester.[37]

Surgical Management

Surgical management is indicated in all patients with contraindications to expectant and medical management, including patients with hemodynamic instability, uterine hemorrhage, or septic miscarriages, who all require emergent uterine evacuation. Nonemergent surgical management is indicated in patients who would not tolerate heavy bleeding, including those with severe anemia, cardiovascular disease, and bleeding disorders.[5] 

In the first trimester, surgical management consists of uterine aspiration or dilation and suction curettage, with sharp curettage as needed. These procedures may be performed in the operating room or office setting. There is evidence that suction curettage alone, without sharp curettage, is sufficient and decreases the risk of intrauterine adhesions as long as there is reasonable certainty that the uterus is empty.[5] Although rare, risks of surgical management include cervical laceration, uterine perforation, and the development of intrauterine adhesions, which are more common in the setting of infection. ACOG recommends a single preoperative dose of prophylactic antibiotics in patients managed surgically. A common regimen is doxycycline 200 mg orally once daily, as a single dose, 1 hour before uterine evacuation.[5] Additionally, all Rh(D)-negative patients undergoing surgical uterine evacuation should receive Rh(D)-immune globulin prophylaxis to prevent alloimmunization, regardless of gestational age, due to the higher risk of alloimmunization with uterine instrumentation.[5][37]

Choosing a Management Strategy

As previously discussed, certain patient-specific factors, such as hemorrhage or infection at presentation, or the presence of comorbidities, such as bleeding disorders or cardiovascular disease, are all indications for surgical management. Commonly, however, none of these factors are present. Generally, in these cases, all 3 options can be discussed with the patient, and her informed decision should be honored, though national guidelines can vary. For example, the UK NICE guidelines prefer to offer patients with first-trimester pregnancy loss a 1- to 2-week trial of expectant or medical management before offering them surgical management. In contrast, ACOG guidelines in the US note that all 3 management options are acceptable first-line treatments, and patient preference should guide management. Due to their uncertain nature, threatened and biochemical pregnancy losses should be managed expectantly.[5]

Regarding patient preference, some patients may prefer a more "natural" approach and be willing to wait up to 4 to 8 weeks for miscarriage resolution, while others may desire the immediate and definitive nature of surgical management. Some patients may prefer the control, expedited results, and higher success rates associated with medical management over expectant management. In multigravida patients, prior experience can also contribute significantly to their preferences. Additionally, the types of pregnancy loss (eg, asymptomatic or incomplete) should also be discussed with the patient, as differences in success rates with expectant versus medical management may also impact how a patient desires to proceed.[38][33]

Management of Septic Abortion

The first step is to assess hemodynamic stability and provide appropriate emergency resuscitation as needed. Initiate empiric broad-spectrum IV antibiotics and IV fluids as soon as possible. The selection of empiric IV antibiotics should be individualized, considering patient factors (eg, allergies, comorbidities), local susceptibility trends, and cost. Regimens include the following:

• Ampicillin 2 g IV every 4 hours, PLUS gentamicin 5 mg/kg daily IV PLUS metronidazole 500 mg IV every 8 hours 
• Ampicillin 2 g IV every 4 hours PLUS gentamicin 5 mg/kg daily IV PLUS clindamycin 900 mg IV every 8 hours
• Piperacillin + tazobactam 4.5 g IV every 8 hours with or without vancomycin
• Imipenem + cilastatin 500 mg IV every 6 hours
• Cefepime or ceftazidime 2 g IV every 8 hours PLUS metronidazole 500 mg IV every 8 hours
• Levofloxacin 500 mg IV daily PLUS metronidazole 500 mg IV every 8 hours [39][40]

Following stabilization and IV fluid resuscitation efforts and the initiation of antibiotics, the primary treatment of a septic abortion is the prompt surgical evacuation of the uterus, which is the source of the infection.[41] Septic abortion can be associated with significant complications, including sepsis, disseminated intravascular coagulation, toxic shock, acute renal injury, acute respiratory distress, and necrotizing fasciitis. Therefore, patients should be frequently monitored for evidence of clinical improvement (eg, decreasing uterine tenderness, afebrile for a minimum of 24 hours). Consultation with an infectious disease specialist is also recommended.[41] Once clinical improvement is documented, patients can be switched to oral antibiotic therapy for 10 to 14 days.[41]

Contraception

In patients who desire it, hormonal contraception may be initiated directly following the complete resolution of an early pregnancy loss. An intrauterine device may be placed immediately after surgical evacuation of the uterus, which is only contraindicated in the setting of intrauterine infection.[5]

Differential Diagnosis

The differential diagnosis of early pregnancy loss primarily involves consideration of the underlying etiologies of vaginal bleeding early in pregnancy, including:

• Ectopic pregnancy can also cause cramping, vaginal bleeding, and an abnormal rise of β-hCG in early pregnancy; an extrauterine mass may also be seen on ultrasound.
• Subchorionic hematoma, commonly presenting with vaginal bleeding, may cause threatened miscarriage and can progress to pregnancy loss.
• Gestational trophoblastic disease can present with signs and symptoms such as bleeding in pregnancy, a uterine size larger than expected for gestational age, abnormally high β-hCG levels, and hyperemesis gravidarum; ultrasound may demonstrate a diffuse mixed echogenic pattern within the uterus and cystic enlargement of the maternal ovaries.
• Cervical and vaginal pathologies (eg, infectious cervicitis, cervical polyps, ectropion, dysplasia, or trauma) should be considered, especially in the setting of postcoital or contact bleeding.
• Implantation or idiopathic bleeding of pregnancy should only be diagnoses of exclusion.

These differential diagnoses can usually be sufficiently evaluated through history, physical exam, and pelvic ultrasound.[5]

Prognosis

Severe complications of early pregnancy loss, including hypovolemic shock and septic miscarriage, are rare. Because complication rates are similarly low for expectant, medical, and surgical management, the prognosis of early pregnancy loss is typically good.[5] However, hemorrhage and infection due to miscarriage can contribute to maternal mortality, especially in low-income countries, where the social determinants of health decrease access to high-quality obstetrical care.[11] 

Additionally, the weeks to months after a miscarriage are often accompanied by feelings of grief, guilt, anxiety, and depression for both the patient and her partner, especially in cases of recurrent loss, fertility challenges, loss of a highly desired pregnancy, and in patients with pre-existing mental health concerns. Although there is limited evidence for the effectiveness of psychological counseling in this setting, patients and their families will likely experience better outcomes if these emotions and feelings are addressed early.[42] Attempting conception immediately after resolution of early pregnancy loss is safe, and couples who attempt conception within 3 months after miscarriage experience higher rates of successful pregnancy and live birth than those who postpone conception.[43][44] 

Recurrent pregnancy loss can vary slightly but is often defined as the spontaneous loss of 2 to 3 pregnancies. Fewer than 5% of patients are estimated to experience 2 consecutive losses, while only 1% will experience 3 or more.[45] A workup is recommended in these patients to look for an underlying cause. This workup generally includes genetic analysis of both parents and maternal assessment for hormonal anomalies, uterine anomalies, and antiphospholipid syndrome.[22] Recurrent pregnancy loss is discussed in more detail elsewhere.[46]

Complications

Complications of early pregnancy loss include the following:

• Retained POC
• Hemorrhage and subsequent complications secondary to hypovolemia
• Infection
• Traumatic complications of surgical management (eg, cervical laceration and uterine perforation)
• DIC
• Postabortion triad (ie, low-grade fever, pain, and bleeding)
• Hematometra
• Cervical shock 
  • A rare complication of incomplete pregnancy loss in which POC within the cervical canal causes a vagal response leading to clinically significant hypotension and bradycardia that does not respond to IV fluids.
  • Typically, it resolves quickly after the removal of POC from the cervix at the bedside.[47]
• Complications secondary to septic miscarriage (eg, sepsis syndrome, DIC, toxic shock syndrome, acute renal injury, acute respiratory distress syndrome, necrotizing fasciitis, and future infertility due to scarring of the fallopian tubes [14]

Deterrence and Patient Education

Pregnant individuals should be counseled on avoiding the modifiable risk factors for miscarriage, such as tobacco and cocaine use, and encouraged to optimize nutrition. However, limited evidence supports the use of any single prevention strategy. Pelvic rest, tocolytics, anticoagulants, and supplemental β-hCG have not been shown in studies to decrease the risk of early pregnancy loss. Aspirin and anticoagulants have only been shown to reduce the rate of spontaneous pregnancy loss in women with antiphospholipid syndrome. Likewise, supplemental progesterone has only been shown to prevent early pregnancy loss in patients with recurrent pregnancy loss.[5]

Pearls and Other Issues

Highlighted facts pertinent to early pregnancy loss are listed below.

• Early pregnancy loss is generally defined as a spontaneous pregnancy loss before 10 to 13 weeks of gestational age.[5]
• Approximately half of all early pregnancy loss is due to unknown genetic abnormalities.[5]
• The most common risk factors are advancing maternal age and previous early pregnancy loss. Alcohol or drug use, some infections, chronic disease, environmental exposures, and structural uterine abnormalities are other potential risk factors.[5]
• Symptoms and signs of early pregnancy loss depend on the type of pregnancy loss but generally include bleeding and menstrual-like cramping in the first half of pregnancy.[5]
• Types of pregnancy loss include missed, threatened, inevitable, incomplete, complete, recurrent, and septic miscarriage.
• The evaluation usually involves a thorough history and physical exam, pelvic ultrasound, and β-HCG measurement.[5]
• Although management also depends on the type of miscarriage, expectant, medical, and surgical approaches are generally equally effective. Patients are more satisfied with their care and have better mental health outcomes when managed in accordance with their preferences.[5]
• Medical management of early pregnancy loss is best achieved with a combination of misoprostol and mifepristone, though it can also be managed with misoprostol alone if mifepristone is unavailable.[5]
• Surgical management of miscarriage is indicated in cases of hemorrhage, infection, and patients with comorbidities that may lead to complications if significant heavy bleeding occurs (eg, severe anemia, cardiovascular disease, and bleeding disorders).[5]
• Only aspirin in the setting of antiphospholipid syndrome and supplemental progesterone in the context of recurrent miscarriage have demonstrated the potential for reducing the risk of early pregnancy loss.[5]
• Testing for genetic abnormalities and antiphospholipid syndrome should generally be reserved for recurrent early pregnancy loss cases.[5]
• Attempting pregnancy immediately following the complete resolution of early pregnancy loss is safe.[5]

Enhancing Healthcare Team Outcomes

Since early pregnancy loss can occur across multiple settings (eg, at home or in a clinic, urgent care, or hospital setting), team-based care is essential. Emergency department clinicians must ensure the seamless transfer of medical records, including relevant labs and imaging, to outpatient clinics for appropriate follow-up, which is often required. In the outpatient setting, convenient scheduling of frequent, appropriately timed appointments is critical, as well as providing patients with clear instructions on when to present to the clinic versus the emergency department for persistent symptoms. Finally, although the medical aspects of miscarriage management can be complicated, the patient's and her family's psychological well-being cannot be neglected.

Nursing staff often help with patient education, phone triage, scheduling, arranging follow-up, and emotional support at the bedside. Radiology technicians need to be familiar with the diagnostic criteria for early pregnancy loss to ensure all appropriate structures are adequately analyzed so that clinicians can make an accurate diagnosis. Frequently, patients have a follow-up β-hCG level drawn and then are seen by a clinician to review their results and discuss their care plan. Therefore, lab personnel must promptly process and report the findings to avoid delays in patient care. Medical assistants can assist clinicians by knowing that patients coming in for follow-up of early pregnancy loss may require a bedside ultrasound and have one readily available, as well as being emotionally supportive to patients during their visit.