Epidemiology

Spontaneous abortion, also known as miscarriage, occurs when a pregnancy ends before the fetus has reached viability. Viability correlates to a fetus larger than 500 g—or approximately the size at 20 to 22 weeks of gestation. Miscarriage is common and occurs in 25% to 30% of all pregnancies. Eighty percent of miscarriages occur before the 12th week of gestation, and up to 25% occur in pregnancies that are not even recognized clinically; in such cases human chorionic gonadotropin (HCG) can be detected in urine but the patient has no missed menses.¹

Approximately 25% of patients will experience some bleeding in the first trimester of pregnancy, with half of these patients proceeding to miscarriage. Risks for spontaneous abortion include advanced maternal age, previous spontaneous abortion, and prolonged time from ovulation to implantation. Other risk factors are smoking, alcohol, cocaine, caffeine, and use of nonsteroidal antiinflammatory drugs.

Presenting Signs and Symptoms

Spontaneous abortion is classified as threatened, inevitable, incomplete, complete, missed, or septic. Table 119.1 lists characteristics of these categories. Symptoms of spontaneous abortion include vaginal bleeding, suprapubic cramping or pain, and passage of tissue. Bleeding can vary from minor spotting to severe hemorrhage.

Table 119.1 Classification of Spontaneous Abortion

Threatened abortion is defined by vaginal bleeding with or without mild suprapubic cramping or pain. It is the most common manifestation of spontaneous abortion seen in the emergency department (ED). Examination shows a closed cervix, uterine size that correlates to gestational age, and bleeding varying from scant to heavy. Ultrasound imaging confirms an intrauterine pregnancy and fetal heart tones in appropriate gestational ages. Threatened abortion may resolve with progression to normal pregnancy, or it may progress to other forms of miscarriage.

Before the 12th week of gestation, most spontaneous abortions will progress to completion with few complications. After this time, patients are more likely to have an incomplete abortion and require medical or operative intervention.

A septic abortion occurs when infection develops during any stage of the abortion process. Implicated agents include Staphylococcus aureus, gram-negative rods, gram-positive cocci, and anaerobes. Risk factors include elective abortion, cytomegalovirus infection, amniocentesis, and incomplete abortion.

Differential Diagnosis and Medical Decision Making

As mentioned previously, bleeding in early pregnancy is common. It may represent benign bleeding from implantation or marginal separation of the placenta. Many cases are idiopathic. Pathologic processes in the differential diagnosis include ectopic pregnancy, gestational trophoblastic disease, cervicitis, subchorionic hemorrhage, and cervical or vaginal malignancy. Vaginal lacerations from intercourse or trauma may be to blame. Occasionally, nongynecologic sources such as rectal bleeding or hematuria are mistaken for vaginal bleeding.

Pregnancy should be confirmed by a positive urine HCG test. A speculum examination should be performed to assess the degree of bleeding and cervical dilation, as well as to inspect for expelled products of conception. Bimanual examination can assess uterine size, cervical opening, and any abnormal masses or tenderness.

Laboratory studies include a complete blood count, quantitative HCG, and blood type with Rh status. With significant bleeding or other medical disease, coagulation parameters and typing and crossmatching for blood products should be ordered. Ultrasonography is essential for a full diagnosis and for guiding further management (Fig. 119.1). Even if it appears that the patient has passed the embryo, she should undergo ultrasound imaging to evaluate for any retained products.

Fig. 119.1 Algorithm for evaluation of vaginal bleeding in a pregnant patient.

D&C, Dilation and curettage; HCG, human chorionic gonadotropin; IUP, intrauterine pregnancy.

Treatment

Many patients with spontaneous abortion often need little or no intervention following accurate diagnosis and exclusion of other pathology. Expectant management is the only option for threatened abortion; education and ensuring adequate follow-up care are essential. The presence of fetal heart tones in women with symptoms of threatened abortion is reassuring; less than 5% of women younger than 36 years will miscarry, but this risk rises to 29% in those older than 40.³

Inevitable abortions may be managed either expectantly or by dilation and curettage. Both methods are generally acceptable. If products of conception are visible in the cervical os, gentle removal with ring forceps may allow the cervix to close and may control the bleeding. A complete abortion requires no further treatment as long as ultrasound scanning confirms that no retained products are present. Any retrieved tissue should be examined for villi, which will have a frondlike appearance.

Incomplete or missed abortions can be managed expectantly as long as shock, fever, or significant ongoing bleeding are absent. The time course for completion of a spontaneous abortion is highly variable, and patients will need education and routine gynecologic care to plan for dilation and curettage if tissue does not pass spontaneously or if the bleeding becomes heavy. Patients should attempt to collect the products of conception for examination and should undergo subsequent ultrasonography to assess whether all products of conception have passed. Studies have proved the safety of this practice.⁴ Approximately 90% of patients with incomplete and 76% of those with missed abortions require no surgical treatment when managed expectantly for 4 weeks. Complications occur in 1%, less than in those managed medically.⁵

Prostaglandins such as misoprostol can effectively induce abortion for pregnancy failure of longer than 12 weeks and may help control bleeding in patients with inevitable or incomplete abortions. The dose of misoprostol is 800 mcg administered vaginally or rectally, but this drug should be given only after consultation with a gynecologist. One large study showed an 84% success rate.⁶ Misoprostol induces spontaneous abortion, so any possibility of a desired viable pregnancy must be excluded.

Surgical management includes dilation and curettage or dilation and evacuation. Indications are listed in Box 119.1. Risks associated with surgical management are small and include uterine perforation, infection, adhesions, and anesthetic complications.

Women with significant hemorrhage or hemodynamic instability should first receive crystalloid volume replacement. If no response is seen or if the bleeding persists, either type-specific or type O-negative blood should be administered. Patients with septic abortions should be given broad-spectrum antibiotics in addition to dilation and curettage.

Next Steps in Care and Follow-Up

Emergency gynecologic consultation is needed for patients with significant hemorrhage or signs of infection. Others may be managed expectantly or with close follow-up as long as adequate outpatient care is ensured. Patients with missed abortions may ultimately need surgical management if they do not spontaneously pass tissue.

Patients should be instructed to contact their physician or return to the ED if heavy bleeding, severe pain, or fever develops. Bleeding should resolve over the course of a few weeks, and menses will generally resume within 6 weeks. Pelvic rest (no vaginal intercourse, tampons, or douching) for 2 weeks is often recommended because of the theoretic risk for infection, although no studies support this risk. Patients are often advised to not become pregnant for 2 to 3 months, but again no studies show worse outcomes if another pregnancy is achieved during this interval.

Psychosocial issues surrounding miscarriage are common, including feelings of guilt and sadness. Reassuring women that most miscarriages are due to genetic abnormalities and are not the result of their actions is essential. Women with substance abuse leading to abortion should be counseled appropriately. Referral for grief counseling may be appropriate. Patients with recurrent miscarriages should be offered referral for fertility treatment and genetics counseling.

Epidemiology

Ectopic pregnancy, in which the developing embryo implants outside the uterine cavity, is responsible for the greatest morbidity and mortality in early pregnancy. The incidence of ectopic pregnancy in the United States has increased over the past 30 years, and it now accounts for 2% of all pregnancies.⁷ This increase has been attributed to rising rates of pelvic inflammatory disease, as well as the advent of assisted reproductive technologies.

At the same time there has been a decrease in the morbidity and mortality associated with ectopic pregnancy because of more widespread use of ultrasound and methotrexate. Despite advances in diagnosis and management, ruptured ectopic pregnancy remains responsible for 10% of pregnancy-related deaths.

Pathophysiology

Risk factors for ectopic pregnancy are outlined in Box 119.3. Tubal pathology, the most significant risk factor, leads to abnormal transport and implantation of the embryo. The majority of cases arise in women with a history of pelvic inflammatory disease, and women with a previous ectopic pregnancy have a 15% recurrence rate. However, up to 50% of patients with an ectopic pregnancy have no identifiable risk factor.⁸

Genetic abnormalities in the embryo have not been found to be a risk factor for abnormal implantation. Although women using an intrauterine device or those who have undergone a sterilization procedure are at decreased overall risk for pregnancy, the incidence of ectopic pregnancy is increased in those who do become pregnant. For example, the pregnancy rate after tubal ligation is 0.1% to 0.8%, but as many as one third of these pregnancies are ectopic.

The most common location for ectopic implantation is the fallopian tube, which accounts for 95% of all ectopic pregnancies. The growing blastocyst leads to tubal distention and bleeding into the peritoneal cavity. If the pregnancy continues and is undetected, it can lead to rupture of the tube with subsequent hemorrhage. Less commonly, ectopic pregnancies implant on the ovary, abdominal viscera, or cervix. In these cases, significant hemorrhage or perforation of abdominal structures may occur. See Figure 119.2 for sites of ectopic implantation.

Fig. 119.2 Sites and rate of occurrence at each site of ectopic implantation.

Presenting Signs and Symptoms

Most ectopic pregnancies are detected 6 to 8 weeks after missed menses, and significant tubal distention and bleeding have usually occurred by that point. Symptoms may mimic the signs of spontaneous abortion. The classic triad consists of abdominal pain, vaginal bleeding, and a missed menstrual period, although these symptoms vary with the stage of the pregnancy. Patients with early ectopic pregnancies may have no abdominal tenderness or vaginal bleeding, and the ectopic implantation may be found only incidentally on ultrasonography.

In contrast, a woman with tubal rupture may display hemodynamic instability and signs of a surgical abdomen. Approximately one half of patients are asymptomatic before tubal rupture. Of those with rupture, 99% have abdominal pain, 74% have amenorrhea, and 56% have vaginal bleeding.

An interstitial, or cornual, pregnancy occurs when the embryo is implanted in the proximal portion of the tube that is embedded in the muscle of the uterus. The tube at this location is more distensible, so the embryo may grow undetected for a longer period. It may not be discovered until 12 weeks or later. Ultrasonography demonstrates an asymmetric uterine thickness surrounding the gestational sac. However, a skilled ultrasonographer is required, and in the early stages it may be mistaken for a normal intrauterine pregnancy. Cornual pregnancy is associated with a 2% to 2.5% maternal mortality rate and is more likely than other tubal pregnancies to require hysterectomy.

A heterotopic pregnancy occurs when an intrauterine pregnancy is present simultaneously with an ectopic gestation. Its incidence was at one time estimated to be 1 in 30,000, but the true incidence is unknown. Thus an ectopic gestation can essentially be excluded if an intrauterine pregnancy is demonstrated by ultrasonography. Patients using assisted reproductive techniques have up to a 1% incidence of ectopic pregnancy, highest in patients with transfer of multiple embryos. In these patients, an ectopic gestation should not be excluded solely on the basis of the presence of an intrauterine pregnancy.⁹

Differential Diagnosis and Medical Decision Making

The differential diagnosis of ectopic pregnancy is listed in Box 119.4. Because of the high potential for morbidity, any patient with abnormal vaginal bleeding or abdominal or pelvic pain should be considered to have an ectopic pregnancy until proved otherwise (see Fig. 119.1).

Treatment

Ruptured ectopic pregnancy may have dramatic findings, with the patient in hemorrhagic shock. Rapid stabilization with intravenous fluids and packed red blood cells is essential. Unstable patients may require O-negative blood until a full crossmatch is performed. Laboratory studies include a complete blood count, quantitative HCG, and coagulation studies. The gynecology department should be consulted for operative management. Rh-negative patients should receive Rh₀ IG.

In stable patients, treatment of confirmed unruptured ectopic pregnancy may be medical, surgical, or expectant.

Next Steps in Care and Follow-Up

In consultation with the patient’s gynecologist, patients with a confirmed ectopic pregnancy should receive methotrexate or be transferred for operative management. Low-risk patients with an indeterminate work-up who are clinically stable may be discharged with appropriate follow-up in 48 to 72 hours for repeated HCG testing and ultrasonography. Patients without access to follow-up may be admitted for observation. Patients with a pregnancy of unknown location should be counseled about the possibility of an ectopic pregnancy.

Epidemiology

The incidence of gestational trophoblastic disease (GTD) varies from 1 per 1000 pregnancies in the United States to 2 per 1000 pregnancies in Japan.¹⁹ Well-established risk factors include nulliparity, personal history of GTD, and maternal age younger than 20 or older than 35 years. Heavy smoking, oral contraceptive use, infertility, and maternal blood types AB or B are also risk factors. Although the disease carried significant morbidity in the past, earlier diagnosis with ultrasonography and more sensitive HCG measurements have led to more successful treatment in recent years.

Pathophysiology

GTD is a disorder of abnormal proliferation of trophoblastic tissue. The benign form is a hydatidiform mole, whereas the malignant forms are grouped as gestational trophoblastic neoplasia, which includes choriocarcinoma, placental site trophoblastic tumor, and persistent or invasive GTD. Although GTD is classically associated with molar pregnancy, it may result from any gestational event, such as spontaneous abortion or term pregnancy.

The most common form of GTD is a hydatidiform mole, either partial or complete. A partial mole contains fetal tissue and arises from fertilization of a haploid ovum by two sperm or by a single sperm that then duplicates. In contrast, a complete mole has no fetal tissue or maternal DNA and results from fertilization of an enucleate egg. Up to 15% of complete moles result in malignancy, whereas malignant transformation of a partial mole is less common. Table 119.2 lists the typical characteristics of molar pregnancies.

Table 119.2 Characteristics of Molar Pregnancies

HCG, Human chorionic gonadotropin.

The abnormal trophoblastic tissue in GTD secretes HCG, thereby resulting in quantitative serum levels much higher than predicted in normal pregnancy. Patients with GTD have an increased incidence of hyperemesis gravidarum and early preeclampsia. Hyperthyroidism may result because of the structural similarity of HCG and thyroid-stimulating hormone. Theca lutein cysts seen in patients with GTD are bilateral, multiloculated ovarian cysts that are present in 15% to 25% of patients with complete moles.

Trophoblastic hyperplasia causes uterine enlargement abnormal for the stage of pregnancy. Deeper uterine invasion may result and lead to severe hemorrhage from destruction of the myometrium or uterine vasculature. Malignant forms of GTD may spread into the pelvis or be manifested as distant metastases, most commonly to the liver, lungs, vagina, and brain.

Presenting Signs and Symptoms

The most common complaint with molar pregnancy is first trimester vaginal bleeding. Patients may also complain of pelvic pain or pressure, and there may be passage of hydropic vesicles from the vagina.

Complete moles have a more striking clinical manifestation, with uterine size larger than expected at the stage of pregnancy, absent fetal heart tones, and markedly elevated HCG levels. Vaginal bleeding may be heavy. Medical complications include pregnancy-induced hypertension, early preeclampsia, hyperthyroidism, anemia, and hyperemesis gravidarum.²⁰

In contrast, the manifestation of a partial mole is subtle. Symptoms are similar to those of spontaneous abortion, with mild to moderate bleeding and cramping. Patients typically do not have significant uterine enlargement, and the diagnosis is made only when the abnormal placental tissue is visualized on ultrasonography. Patients with partial moles are less likely to have the medical complications associated with complete moles because HCG levels are lower.

As mentioned earlier, GTD may also develop after a nonmolar pregnancy, such as spontaneous and elective abortion, ectopic pregnancy, and term gestation. These patients have prolonged bleeding after delivery or miscarriage, with subsequent HCG levels that fail to return to undetectable measurements. Up to 75% of cases of malignant GTD occur after nonmolar pregnancies. Because placental site trophoblastic tumors may occur years after pregnancy, GTD should be considered in a woman with metastatic disease from an unknown primary site.²¹

Differential Diagnosis and Medical Decision Making

Molar pregnancy should be included in the differential diagnosis of any patient with first trimester bleeding (see Box 119.4). Abnormally elevated quantitative HCG levels suggest the diagnosis, although there is no absolute level that identifies molar pregnancy. Pelvic ultrasonography is diagnostic in almost all cases. Tissue obtained from uterine evacuation provides histologic confirmation.

Ultrasonographic findings in a patient with a complete mole include diffuse hydatidiform swelling of chorionic villi (“snowstorm pattern”), bilateral theca lutein cysts, and absence of fetal tissue or amniotic fluid. The ultrasonographic appearance of a partial mole is not as striking and may be misinterpreted by an inexperienced ultrasonographer. There is only focal hydatiform swelling with absence of theca lutein cysts. Growth-restricted embryonic tissue or amniotic fluid may also be seen.

Laboratory tests should include a complete blood count, blood typing and antibody screen, clotting function analysis, renal and liver studies, and measurement of the serum HCG level. For patients with malignant disease, additional work-up includes chest radiography to search for metastases. Other appropriate studies include computed tomography of the chest and magnetic resonance imaging of the abdomen, pelvis, and brain.

Treatment

GTD is likely to be diagnosed only incidentally in the ED during evaluation for spontaneous abortion or ectopic pregnancy. Most patients have few or mild symptoms. Initial ED management includes supportive care for significant hemorrhage, including intravenous fluids and blood products. Rh₀ IG should be administered to Rh-negative women. Patients with rupture or torsion of theca lutein cysts may require operative management, although rupture is rare.²²

Next Steps in Care and Follow-Up

Any woman with suspected or diagnosed GTD should be referred to a gynecologic oncologist urgently because the disease may progress quickly. Definitive management of molar pregnancy includes dilation and curettage. As long as serial HCG levels decline appropriately, no further treatment is needed. Persistent local disease is usually treated with chemotherapy, although hysterectomy may be performed in women with locally invasive disease who no longer desire fertility.

Posttreatment monitoring for malignant or persistent disease consists of serial HCG measurements. Patients should have frequent pelvic examinations to monitor for local recurrence or vaginal metastases. Patients should be instructed to use contraceptive methods for 12 months because an increase in HCG levels as a result of pregnancy would obscure the monitoring results. Affected patients have an approximately 1% chance for a recurrent mole in future pregnancies, although this risk increases to as high as 28% after two molar pregnancies.²³

Epidemiology

Estimates of the incidence of hyperemesis gravidarum range from 0.3% to 2% of all pregnancies. Risk factors include multiple gestations, GTD, personal or family history of hyperemesis, and female sex of the fetus. Protective factors include advanced maternal age, cigarette smoking, and anosmia. Hyperemesis gravidum is responsible for the highest percentage of hospital admissions during the first half of pregnancy.^24,25

Pathophysiology

Up to 85% of pregnant patients experience nausea and vomiting to some degree. Hyperemesis gravidarum has no strict diagnostic criteria, but it is generally defined as nausea and vomiting that results in loss of 5% or more of prepregnancy weight, as well as ketonuria. In addition, the symptoms must not be attributable to another medical condition.

Hormonal factors are believed to be the pathogenesis. Studies have shown that women with higher HCG and estradiol concentrations have an increased incidence of hyperemesis, but the mechanism is unknown.²⁶ In contrast, no correlation of progesterone levels and symptoms has been shown. Other potential causes such as vitamin deficiencies, gastric motility, and Helicobacter pylori infection have not been consistently linked to the disease. The belief in the past that psychologic issues were causative has no supporting data.

Presenting Signs and Symptoms

Hyperemesis classically begins early in the first trimester, with symptoms peaking at 9 to 10 weeks and generally resolving by 16 to 18 weeks. Most patients report more severe symptoms in the morning hours, often made worse by noxious smells. Frequently, multiple ED visits or interactions with a primary care provider occur because of the persistence of symptoms.

Symptoms of abdominal pain and tenderness are usually minimal; such findings suggest another pathology. The physical examination confirms varying levels of dehydration.

Complications include dehydration, weight loss, and vitamin deficiencies. Esophagitis, Mallory-Weiss tears, and Wernicke encephalopathy have been reported in patients with persistent vomiting and malnutrition. Anxiety, as well as depressive symptoms, may occur in response to the illness.

Differential Diagnosis and Medical Decision Making

The diagnosis of hyperemesis gravidarum is one of exclusion given the lack of confirmatory testing available. A careful history should confirm that the symptoms began in the first trimester, with review of systems negative for symptoms consistent with coexistent pathology. Physical examination is aimed at identifying these other conditions. Box 119.6 outlines the differential diagnosis of hyperemesis.

Serum HCG measurements and ultrasonography can determine the time of gestation and rule out a hydatidiform mole. Urinalysis can rule out infection and may reveal ketonuria and high specific gravity. Laboratory evaluation can be helpful in excluding other pathology. Initial testing includes a complete blood count; basic chemistry panel; and liver, amylase, lipase, and thyroid function assays, including thyroid-stimulating hormone and free thyroxin levels.

As many as half of patients with hyperemesis will have mild elevations in transaminases; levels are usually in the low hundreds, with alanine transaminase levels being higher than aspartate transaminase levels. Amylase and lipase may be elevated, but much less so than with pancreatitis. Typical laboratory test results include hemoconcentration, electrolyte abnormalities, and mildly elevated hepatic and pancreatic function via urinalysis. The laboratory test abnormalities generally resolve by the 20th week of gestation, and no treatment is necessary.

Treatment

After coexistent pathology has been ruled out, treatment consists of rehydration, correction of electrolyte abnormalities, control of nausea, and reinstitution of nutrition. Volume resuscitation is accomplished with normal saline or lactated Ringer solution. Dextrose-containing solutions can then be used for maintenance fluids. Potassium, magnesium, and phosphorus supplements should be added to fluids as needed. Patients with prolonged vomiting should be given thiamine (100 mg/day) and multivitamins intravenously.

Pharmacotherapy is appropriate significant nausea, although patients may have reservations about using these medications. The combination of pyridoxine (10 mg) and doxylamine (12.5 mg) three to four times a day is considered safe; randomized, placebo-controlled studies have shown a 70% reduction in nausea and vomiting. This combination should be considered first-line therapy.^27,28

Various antiemetics (Table 119.3) have been used for hyperemesis with good results and reasonable safety data. Antihistamines have the best safety profile, but phenothiazines, metoclopramide, and ondansetron are considered safe as well. Gynecologists may prescribe oral corticosteroids for patients with refractory nausea and vomiting. Studies have shown conflicting results of effectiveness, and the incidence of cleft palate appears to be slightly increased in infants whose mothers received methylprednisolone in the first trimester of pregnancy. Steroids should thus be reserved as a last resort.^29,30

Table 119.3 Antiemetics for Hyperemesis Gravidarum

IM, Intramuscularly; IV, intravenously; PO, orally; PR, parenterally.

Many patients are reluctant to use pharmacotherapy because of a perceived fear of birth defects. These patients may be agreeable to adjunctive therapies such as acupuncture, hypnosis, and powdered ginger. Studies of acupuncture and acupressure have yielded conflicting results,³¹ whereas hypnosis has been shown to decrease vomiting in patients with hyperemesis. Powdered ginger (250 mg to 1 g/day) is as effective as pyridoxine, but its safety is not well established.³²

The ultimate goal of treatment is restoration of nutrition. Many patients are able to tolerate feeding after a short course of rehydration along with gut rest. The Patient Teaching Tips box outlines dietary suggestions.

Patients who cannot maintain their weight despite rehydration and antiemetics are candidates for enteral nutrition. Those who cannot tolerate enteral feedings should be given total parenteral nutrition. This regimen carries the usual risks of infectious and metabolic complications.

Next Steps in Care and Follow-Up

Patients with mild dehydration may be discharged home after fluid and electrolyte repletion. Antiemetics can be prescribed for home use after appropriate discussion with the patient and primary physician. Many patients come to the ED before they have established prenatal care; ensuring adequate outpatient care is essential. Patients with severe dehydration, significant electrolyte abnormalities, progressive weight loss, and intractable vomiting despite antiemetics should be admitted to the hospital.

Patients should be instructed to return to the ED if vomiting persists or if they experience new symptoms such as abdominal pain and fever. Patients with only mild nausea and vomiting are not at increased risk for low-birth-weight infants or birth defects. Although patients with true hyperemesis do have a higher incidence of low-birth-weight infants, appropriate weight gain later in pregnancy reduces this risk.³³