Learning Objectives:After participating in this CME/CNE activity, the provider should be better able to:

1. Explain the incidence and causes of miscarriage to patients.

2. Identify signs and symptoms of early pregnancy loss.

3. Diagnose and manage early miscarriage, including expectant, medical, and surgical approaches.

4. Provide appropriate emotional counseling for patients experiencing miscarriage.

Miscarriage, spontaneous abortion, and early pregnancy loss are all synonymous for the demise of a previable pregnancy, typically between the first and early parts of the second trimesters.1 Organizations disagree on the exact gestational age for the loss to be considered "early." The American College of Obstetricians and Gynecologists (ACOG) has the earliest threshold and defines the phenomenon as a loss within the first 13 weeks of pregnancy or the end of the first trimester.2 In this article, we discuss management of pregnancy loss in the first trimester within this definition and framework.

Understanding the signs symptoms, and sequelae of first-trimester pregnancy loss is vital to treating these patients appropriately and ensuring that their physical and mental health are cared for effectively and empathetically. Standards of care and practice for treatment of patients experiencing miscarriage have changed. This article aims to delineate these changes in practice and how they improve patient care in the management of early pregnancy loss.

Epidemiology

According to ACOG, early pregnancy loss is a common occurrence, which happens in about 10% of all pregnancies that are clinically recognized.3 Quantifying the incidence of early pregnancy loss is difficult and highly variable based on the diagnostic criteria used and whether the pregnancy is clinically recognizable at the time of miscarriage. Some studies differentiate between the percentage lost before and after the pregnancy becomes clinically recognizable. Given these inconsistencies, it is likely that miscarriage data may be misrepresenting true epidemiology and likely the proportion of patients with a history of miscarriage is higher than studies have predicted.

Wilcox and colleagues4 conducted a prospective cohort study of women attempting to conceive in 1988. They demonstrated that 22% of the pregnancies experienced in the time frame of the study were lost before being clinically recognizable; they defined "clinically recognizable" as any pregnancy capable of being "diagnosed by the woman's physician or a conventional pregnancy test."4 As this research was conducted in 1988 and continues to be one of the most frequently cited on incidence of miscarriage, new research should be conducted to update this data to more accurately reflect current statistics. Another study used a prospective cohort to investigate the incidence, not just prevalence, of early pregnancy loss.5 The definition of clinical pregnancy was any pregnancy that "lasted >= 6 weeks (42 days) after the onset of the last menstrual period and that was confirmed by [[beta]-human chorionic gonadotropin] [beta]-hCG assay."4 Here, the authors demonstrated that nearly 25% of all early pregnancy losses in this study could be categorized as before being clinically pregnant.

Etiology

One of the goals of modern maternal health care is to minimize the risk and ideally prevent spontaneous abortion in patients who desire pregnancy. Numerous potential causes and contributing factors to spontaneous abortion have been studied in various populations; these include but are not limited to maternal age, caffeine consumption, and obesity. A study looked at 497 chorionic villi samples from first-trimester spontaneous abortions to quantify the association between maternal age and fetal chromosomal abnormalities.6 The investigators stratified by maternal age and demonstrated that patients older than 40 years were statistically more likely to encounter a fetal chromosomal abnormality and subsequent miscarriage.6 Additionally, they demonstrated that trisomy 22 and trisomy 16, the most common aneuploidies associated with early pregnancy loss, were also tied to maternal age.

One study investigated ultrasound measurements of singleton pregnancies as predictive markers for early pregnancy loss.7 Fetal heart rate, yolk sac diameter, gestational sac diameter, and fetal crown-to-rump length were measured through transvaginal ultrasonography at 12 weeks and beyond. They demonstrated that fetal heart rates in the fifth percentile or below were more likely to be associated with spontaneous abortion; in fact, every fetus with a heart rate below 80 beats per minute (bpm) in this study ultimately miscarried.7 Every 10-bpm decrease from 130-bpm downward increased the risk of early pregnancy loss by more than 25%. Crown-to-rump length and gestational sac diameter were also shown to be strong predictors of spontaneous abortion.7 There are increased associations of subchorionic hemorrhage and decreased fetal heart rate (<100 bpm at <7 weeks) with early pregnancy loss, but these are not diagnostic at the initial presentation.8,9

Another study reviewed a cohort of pregnant patients enrolled in the Danish National Birth Cohort between 1996 and 2002 to first identify which risk factors of miscarriage could be altered to lessen their effects, and then estimated the number of spontaneous abortions attributable to these risk factors.10 They demonstrated that maternal age at conception and alcohol consumption during pregnancy were the most statistically significant risk factors for the occurrence of a spontaneous abortion. The authors concluded that approximately 25% of the miscarriages included in this study could be attributed to high levels of those risk factors.10

One study of the risk of miscarriage in women with antiphospholipid antibody syndrome demonstrated that recurrent pregnancy loss in the fetal period (>10 weeks' gestation) was markedly more frequent in patients with antiphospholipid antibodies than in patients without antibodies. Additionally, the authors demonstrated that 84% of patients with antiphospholipid antibodies had experienced at least one prior miscarriage, compared with 24% of patients without the antibodies.11,12

Diagnosis

Patients with early pregnancy loss generally present with a period of amenorrhea followed by vaginal bleeding and lower abdominal cramping. Although some patients may have suggestive symptoms such as pain and bleeding, many will present with only amenorrhea and/or a positive pregnancy test. The differential diagnosis typically includes early pregnancy loss, viable intrauterine pregnancy, ectopic pregnancy, or molar pregnancy. History should be obtained about all prior pregnancies, especially those resulting in miscarriage. Risk factors for early pregnancy loss such as described earlier should be elicited.

A thorough clinical examination, including vitals, abdominal, and pelvic examination, should be performed in all patients. Blood type and screen should be checked to evaluate for Rh status. A [beta]-hCG level and pelvic ultrasound are both useful in reaching a diagnosis, but a single one of each may not be enough to reach a diagnosis. If diagnosis is still unclear, follow-up ultrasound and/or [beta]-hCG may be needed in hemodynamically stable patients. Performing a transvaginal ultrasound is superior to an abdominal ultrasound for the diagnosis of intrauterine pregnancy and viability.13

The 2012 ultrasound guidelines from the Society of Radiologists in Ultrasound on location and viability of pregnancy indicate that certain findings are diagnostic of early pregnancy loss. These include a crown-to-rump length of 7 mm or more without heartbeat, mean sac diameter >= 25 mm without embryo, absence of embryo with heartbeat 2 weeks or more after an ultrasound that showed a gestational sac without a yolk sac, and absence of embryo with heartbeat 11 days or more after an ultrasound that showed a gestational sac with a yolk sac.14 There are certain findings that increase the likelihood of pregnancy failure but are not diagnostic at the initial scan.14 In these cases, a follow-up ultrasound at 1 to 2 weeks should be conducted for final diagnosis.

Counseling these patients appropriately is vital. In case of desired pregnancy, patients should be counseled that follow-up ultrasound will increase diagnostic accuracy, but there is a possibility of spontaneous passage of pregnancy and/or need for an emergency department visit and procedure in the interim. If the location of the pregnancy is unclear, patients will need repeat [beta]-hCG testing and ultrasound, with return precautions for possible ectopic pregnancy. An intrauterine pregnancy should not be interrupted with medical or surgical methods if diagnosis is not certain at the initial visit and the patient is clinically stable.15 For patients in whom this is an undesired pregnancy, active management is more straightforward and can be initiated at the time of initial presentation.

Management Options

After the diagnosis of early pregnancy loss is confirmed, patients should be informed about the diagnosis in an empathetic manner. The physician should communicate the different causes of early pregnancy loss, including chromosomal causes, advanced age, and others. Additionally, patients should be reminded that the risk of recurrent pregnancy loss is low and that most miscarriages are isolated events.

Medical professionals should avoid using medical jargon while communicating the diagnosis and should avoid phrases such as "this miscarriage was for the best" or "you can always have another pregnancy." For patients, this may be a significant loss; many women will undergo periods of grief and psychological distress.16 Support from both health care providers and family and friends is crucial for the healing process during this time.

If the patient is hemodynamically stable, expectant management, medical management, and surgical management are all acceptable options for the management of early pregnancy loss. The risks and benefits of each management option should be discussed with them, and the patient's preferences and priorities. Informed consent should be obtained before finalizing and beginning the management option.

Expectant Management

Expectant management is the process of waiting for several weeks to allow the body to naturally expel the products of conception, rather than medical or surgical intervention. For 81% of patients diagnosed with early pregnancy loss, a waiting period of up to 8 weeks from the initial diagnosis will result in complete expulsion.17 Further research suggests that expectant management is more successful in symptomatic women with incomplete passage of pregnancy tissue or ultrasound findings with retained products of conception as compared with asymptomatic women.17,18 Research has shown that expectant management is more successful for cases of incomplete abortion when compared with missed abortion or anembryonic pregnancy loss.19

Patients should be counseled about vaginal bleeding and abdominal cramping while undergoing expectant management. Most patients can achieve appropriate pain control with acetaminophen or nonsteroidal anti-inflammatory drugs, but some may require narcotics for adequate pain management. If there is continuous heavy bleeding (more than 2 maxi pads in an hour for more than 2 consecutive hours or other symptoms of excessive blood loss), they should return to an emergency department. Patients should also be counseled that they may need alternative management options should expectant management fail; however, there is no consensus definition for failure of expectant management. Follow-up ultrasound that shows absence of gestational tissue and an endometrial thickness of less than 3 cm is commonly accepted as complete expulsion of pregnancy tissue.3 If the ultrasound shows more than 3-cm endometrium and the patient is asymptomatic, there has been no evidence to support an increase in morbidity and therefore surgical intervention is not recommended.3

Medical Management

Medical management of early pregnancy loss decreases the time needed for complete expulsion and the need for surgical intervention when compared with expectant management; therefore, medical management is advised for patients who would prefer to avoid surgical intervention. Medical management can be considered if there is no evidence of infection, continuous heavy vaginal bleeding, presence of anemia, or other bleeding disorders.

Medical management has recently changed to include combined mifepristone-misoprostol-based regimens and misoprostol-only-based regimens. Misoprostol-only regimens have been studied in different dosages, intervals, and routes of administration with varying outcomes; vaginal or sublingual administration has been shown to be more effective than oral administration. A single dose of 800-[micro]g misoprostol given vaginally produced complete expulsion in 71% of cases by day 3. This improved to 84% after a repeat dose of 800-[micro]g misoprostol as needed within 3 days.20 If mifepristone is available, a single 200-mg oral dose of mifepristone 24 hours before 800-[micro]g vaginal misoprostol significantly increases complete expulsion rate without increasing side effects.3,21 The mifepristone-misoprostol combination decreases the need for surgical intervention as compared with misoprostol-only.3,21 ACOG now recommends a combined mifepristone-misoprostol dosing as the preferred medical management given these benefits; however, mifepristone has current restrictions based on the FDA Risk Evaluation and Mitigation Strategy criteria that makes utilization challenging.3,22

Follow-up ultrasound should be scheduled within 1 to 2 weeks to document complete expulsion of pregnancy tissue. Medical management is considered successful if ultrasound demonstrates no further evidence of gestational sac or continued pregnancy. In patients who had evidence of expelled gestational sac following misoprostol medication management, there is no correlation between the endometrial thickness and subsequent need for surgical intervention. If medical management fails, the patient may choose between expectant management and surgical intervention depending upon the clinical scenario. Patients should be counseled about return precautions and medications for pain, as discussed earlier in the Expectant Management section.

Surgical Management

Because surgical management provides complete evacuation in one visit and requires less follow-up, it is preferred by many patients to medical or expectant management. Additionally, if patients have evidence of infection, hemorrhage, altered hemodynamics, severe anemia, bleeding disorders, cardiovascular diseases, or suspicion of ectopic pregnancy with intrauterine pseudosac, surgical management is preferred. Suction curettage is always preferred over sharp curettage to avoid risk of Asherman syndrome.23 Surgical intervention can be performed in the office or emergency department setting with either manual vacuum aspirator or electronic vacuum. This can be performed under either local anesthesia or moderate sedation. Although surgical intervention can also be performed in the operating room under general anesthesia, it may not be the best use of resources considering the cost of operating room utilization. Surgical management of early pregnancy is effective in about 99% of patients regarding complete expulsion.20

Complications

Infection can occur with any of the management options; overall infection rate for management of early pregnancy loss is about 1% to 2%. Expectant management has the lowest infection rate of the 3 options. There is no evidence that prophylactic antibiotics improve outcomes in patients undergoing medical management; however, antibiotic prophylaxis with a single dose of doxycycline 200 mg 1 hour before surgical management is recommended by the Society of Family Planning to prevent postoperative infection.24

Postabortion hemorrhage is the most common complication after early pregnancy loss in all 3 management options. Uterine perforation and intrauterine adhesion formation are rare complications of surgical management.25 The provider may consider intraoperative ultrasound during a surgical evacuation. Uterotonic agents such as misoprostol, methylergonovine maleate, or carboprost should be readily available and can be used as single agents or in combination, along with uterine massage.26 Communication between the surgeon, anesthesiologist, and blood bank is very important to ensure that blood products and hemodynamic support can be provided as needed. For uncontrolled bleeding after these measures, one may consider balloon tamponade with Foley or Bakri balloon and uterine artery embolization.26 If bleeding is not controlled by these measures, one should consider proceeding with laparotomy as one would if treating a postpartum hemorrhage. Hysterectomy should be used as a last resort to control life-threatening hemorrhage.26

Fetomaternal hemorrhage has been demonstrated in 3% to 11% of women with threatened abortion.26 Older data suggest that about 1.5% to 2% of Rh-negative women will become sensitized to the antigen after spontaneous abortion, whereas 4% to 5% women will become sensitized after dilation and curettage.27 However, there are emerging data that suggest that no fetal cells are detectable by flow cytometry after induced and spontaneous abortion up to 12 weeks.28 Additionally, rates of sensitization do not differ in countries that conservatively use Rhogam for all abortions in the first trimester as compared with those that use Rhogam less frequently.29 As such, the National Abortion Federation has recommended, in its new policy guidelines, that "forgoing Rh testing and anti-D immunoglobulin for medication abortion under 10 weeks may also be considered" because "medication abortion is more similar to spontaneous abortion with less risk of fetal-maternal hemorrhage" as compared with induced surgical abortion.30 Current clinical guidelines suggest that, if an Rh-negative patient presents with early pregnancy loss in the first 12 weeks, Rh immune globulin should be considered as either 50- or 120-mg doses to avoid the significant consequences of alloimmunization.31 If the early pregnancy loss occurs after the first 12 weeks, 300-[micro]g should be administered.32 Any Rh-negative patient who undergoes surgical management should be administered Rh immune globulin to prevent the risk of alloimmunization.

Follow-up Patient Counseling

Patients may start hormonal contraceptives immediately after successful completion of early pregnancy loss. Long-acting reversible contraception (LARC) including intrauterine devices can be placed immediately after surgical management of early pregnancy loss if there is no evidence of septic abortion.33

Generally, a workup is not recommended after the first early pregnancy loss. Having 2 or more failed clinical pregnancies, as confirmed by either ultrasonography or histopathology, is considered recurrent pregnancy loss. At this point, patients should be screened for cytogenetic abnormality, antiphospholipid syndrome, anatomic abnormalities of the uterus, and metabolic/hormonal causes. In case of cytogenetic abnormality in one or both parents, genetic counseling is advisable. Treatment using in vitro fertilization with embryo biopsy and preimplantation genetic testing for aneuploidy (PGT-A) followed by transfer of a euploid embryo or, alternately, use of donor gametes will increase the chance of successful pregnancy outcome. With antiphospholipid syndrome, combination of low-dose aspirin with heparin improves live-born rate. In patients with uterine anatomic abnormalities, case-by-case surgical correction is advised.34

There are no effective interventions to prevent early pregnancy loss in a subsequent pregnancy. Additionally, no data indicate a recommendation for pelvic rest or bed rest to prevent early pregnancy loss. Likewise, vitamins, [beta]-hCG, and uterine relaxants are not recommended for the prevention of early pregnancy loss.35 For those patients who have had 3 or more prior pregnancy losses, progesterone therapy may be beneficial.34

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