Vaginal bleeding during pregnancy is common and can cause significant distress in patients. Light spotting is a normal finding in many pregnancies in the first trimester, but heavier bleeding, often resembling menses, is associated with a greater risk of pregnancy loss (Figure 1).1 About one-third of pregnancies end in a loss, and most of these losses occur during the first trimester, often before a woman even knows she is pregnant.2 About 25% of women will have first-trimester bleeding, and about half of those women will have a spontaneous abortion.1,3 Through vigilant attention to vital signs, history, physical examination, laboratory analyses, and pelvic ultrasonography, clinicians can develop a working differential diagnosis, definitively rule out potentially life-threatening pathologies, and effectively treat women who present with vaginal bleeding in early pregnancy.
The most important first step in evaluating a patient with vaginal bleeding is to assess the patient's vital signs. Heavy vaginal bleeding with unstable vital signs necessitates rapid intervention with two large-bore IV access devices, supplemental oxygen, appropriate fluid resuscitation, and emergency gynecologic consultation. If the patient's vital signs are stable, the next step is to conduct a thorough history and physical examination.
The history of present illness should include the date of the patient's last menstrual period (LMP), any history of irregular menses, history and confirmation of pregnancy (including previous beta-hCG results, ultrasound, and medical records, if available), a description of bleeding (amount, color, whether any tissue is present), and any associated symptoms such as dizziness, nausea, abdominal pain, or pelvic pain.
The past medical history should include an obstetric history including gravida and para status; history of infertility, including infertility treatment; information on previous pregnancy loss or ectopic pregnancy; contraceptive history; previous sexually transmitted infections; and history of blood dyscrasias, seizure disorders, or autoimmune diseases. Obtain a list of any medications, including over-the-counter and herbal supplements, that the patient is taking or has taken since the LMP.
The social history should include information about illicit drug use, tobacco use, intimate partner violence or abuse, and an assessment of the patient's social support system.
The aim of the physical examination is to identify any findings that could support the differential diagnosis and to help rule out any emergent findings. Perform a cardiac examination for murmurs; skin examination for bruises, petechiae, and signs of other bleeding diatheses; an abdominal examination; and a pelvic examination. Be aware of an abdominal examination that reveals diffuse tenderness, rigidity, or peritoneal signs, which can be associated with intra-abdominal bleeding from a ruptured ectopic pregnancy. If it has been at least 10 weeks since the patient's LMP, attempt to auscultate fetal heart sounds with handheld Doppler.3 External bleeding must be ruled out with a physical examination of the perineum, vulva, and rectum for signs of trauma or significant bleeding.
The pelvic examination consists of the speculum and bimanual examinations. Using the speculum lets the clinician visualize the cervix and assess for cervical dilation, presence of polyps, cervicitis, and possible lesions. If products of conception are visualized, the tissue can be removed using gentle traction with ring forceps and sent to pathology for evaluation.3 The bimanual examination lets the clinician estimate the size, shape, and position of the uterus and identify the presence or absence of adnexal masses or tenderness. Sometimes the cervix will appear closed on visual inspection but is open when palpated on bimanual examination. The presence of palpable and/or visual cervical dilation indicates inevitable abortion.
Laboratory testing and ultrasonography help to further refine the differential diagnosis of first trimester bleeding. A qualitative beta-hCG only provides a positive or negative result without any quantitative, numerical information. The quantitative beta-hCG is a serum blood test that provides a numerical level of the hormone. The beta subunit of hCG should at least double every 48 hours in the first 6 weeks of pregnancy, so follow the hCG curve to assess pregnancy viability.4 The quantitative beta-hCG also is used to correlate sonographic findings in the first trimester (Table 1).
In addition to beta-hCG, obtain a complete blood cell count with differential, blood type, and Rh factor.
Ultrasonic evaluation should be accomplished transvaginally by an experienced ultrasonographer, and findings should be correlated with beta-hCG results. The discriminatory level is the level of beta-hCG at which specific sonographic findings should be visualized. The threshold level is the lowest beta-hCG at which sonographic findings should be visualized. If the beta-hCG falls within any of the zones, but visualization of a gestational sac, yolk sac, or fetal pole cannot be accomplished, repeat the ultrasound in 7 to 10 days before diagnosing pregnancy loss.
By 6 weeks gestation, beta-hCG levels are between 3,500 and 115,000 mIU/L. At this point in pregnancy, the fetal pole should be visualized, but the beta-hCG discriminatory zone is wide (Table 1). Cardiac activity may not be seen until the beta-hCG reaches about 17,500 IU/mL, or around 7 weeks.5 A solitary transvaginal ultrasound that does not reveal a gestational sac, a fetal pole, or fetal cardiac activity within the above parameters should be repeated within 1 week for confirmation.5 However, a gestational sac with a mean diameter of 20 mm or larger without a fetal pole, or a crown-rump length of 5 mm or greater without cardiac activity indicates a nonviable pregnancy.6
The differential diagnosis of first-trimester bleeding can be divided into emergent and nonurgent causes.
These causes, which include ectopic pregnancy, incomplete abortion, septic abortion, and gestational trophoblastic disease, require prompt medical intervention because of their association with significant morbidity and mortality.
- Ectopic pregnancy occurs when the zygote implants outside the uterus. Most (98%) of ectopic pregnancies occur in the fallopian tube, but implantation also can occur in the cervix or abdominal cavity.4,7 Without treatment, an ectopic pregnancy can lead to fallopian tube rupture and exsanguination. The death rate from ectopic pregnancy was 2.5 per 100,000 during 2009-2010 in Florida, the only state to have published mortality data on ectopic pregnancies since the 1990s.8 In general, women who are not white have a greater than threefold increase in death from ectopic pregnancy than white women, and teenagers from any racial or ethnic group have the highest mortality.9
Ectopic pregnancies occur at a rate of about 2% in the general population, but increase to 5% in women who have undergone assisted reproductive technologies, such as in vitro fertilization.10,11 A review of commercially insured women ages 15 to 44 years in the United States from 2002 to 2007 found the incidence rate of ectopic pregnancy to be 0.64%.12 Risk factors for ectopic pregnancy include pelvic inflammatory disease, history of Chlamydia trachomatis infection, cigarette smoking, conception with an intrauterine contraceptive device in situ, history of tubal sterilization, maternal age over 35 years, previous history of an ectopic pregnancy, and use of assisted reproductive technology.9,13 Other pelvic infections have been associated with a possible increased risk, including Neisseria gonorrhea and Mycoplasma.13 Nonwhite women have almost twice the incidence of ectopic pregnancy, and a nearly fourfold greater risk of ectopic mortality than white women.14,15
Early diagnosis and management of ectopic pregnancy often can be accomplished in the outpatient setting if the patient is hemodynamically stable and reliable to follow-up. Because the last normal menses in a patient with an ectopic pregnancy can be 4 to 12 weeks earlier, patients can present with either amenorrhea or irregular vaginal bleeding. The bleeding can be heavy or light, and the most common symptom is abdominal pain.9 The quantitative beta-hCG may not be as high as would be expected for the approximate gestational age, and the expected doubling of the quantitative beta-hCG in 48 hours will not occur.
Transvaginal ultrasound should be used to help identify an intrauterine gestational sac or fetal pole, but often these patients present too early for visualization to occur. If the beta-hCG is 1,500 mIU/L or greater and no intrauterine gestational sac is seen with ultrasound, the patient is considered to have an ectopic pregnancy until proven otherwise. An adnexal mass with echogenicity and free fluid in the cul-de-sac is diagnostic for ectopic pregnancy. An echogenic adnexal mass without free fluid in the cul-de-sac is an ectopic pregnancy about 70% of the time.9
Outpatient medical management with methotrexate is reserved for hemodynamically stable patients without contraindications to methotrexate, such as known hypersensitivity to the drug, no evidence of rupture, a mass less than 3.5 cm, and an initial beta-hCG level of less than 5,000 mIU/mL. The patient is given a single IM dose of 1 mg/kg of methotrexate and beta-hCG levels are monitored on the fourth and seventh days postinjection. Afterward, weekly beta-hCG levels are obtained until the level is undetectable.3 The beta-hCG should decline by at least 15% between days 4 and 7, and 15% every week until it is less than 5 mIU/mL.4 The process can take several weeks, so patient education and reassurance are important.
Surgical management is indicated for patients who are hemodynamically unstable, have contraindications to methotrexate, have a mass greater than 3.5 cm, have a beta-hCG level greater than 5,000 mIU/mL, have evidence of fetal cardiac activity, and who may not be reliable on follow-up.4,16 The preferred procedure for a hemodynamically stable patient without rupture who wishes to preserve future fertility is salpingostomy through laparoscopy.9 In patients with vascular compromise or extensive bleeding that results in difficult visualization through the laparoscope, laparotomy is suggested. Salpingectomy should be performed if the patient does not desire future pregnancy. However, salpingotomy is associated with an increased risk of persistent ectopic pregnancy. This risk can be mitigated with a single postoperative IM methotrexate injection.17 Patients who undergo salpingotomy will still need to have weekly beta-hCG levels until the levels become undetectable.16 Women who have had an ectopic pregnancy, regardless of how it was treated, are at high risk of future ectopic pregnancy.18
- Incomplete abortion occurs when a patient experiences vaginal bleeding, cramps, and the passage of tissue, but products of conception have not been fully expelled. Residual products of conception will be seen on ultrasound. Expectant management of patients with an incomplete abortion usually is successful, but the patient may take up to 2 weeks to completely expel remaining tissue.19 However, retained products of conception can cause significant bleeding, fever, pelvic pain, sepsis, and disseminated intravascular coagulation, so close follow-up is needed. If blood clots or products of conception are visualized in the cervical os, remove them carefully with a ring forceps. The tissue should be sent for histopathologic analysis. If severe bleeding occurs, administer 10 to 20 mcg/L of IV oxytocin or 0.2 mg of IM methylergonovine to help control hemorrhaging, and obtain blood crossmatching for possible blood transfusion.20 An immediate gynecologic consult is warranted, as the patient will likely require dilation and curettage in the OR under general anesthesia.12
- Septic abortion occurs when retained products of conception have not been adequately expelled and endometritis develops.7 A patient with septic abortion will most always present with pelvic pain, abdominal pain, bleeding, and most notably, fever. Assess the patient for hypotension and tachycardia, which can indicate hemorrhagic or septic shock that requires prompt referral to an ED if the patient has presented to an outpatient setting. The organisms associated with septic abortion are those commonly found in the vagina and include various aerobes, Gram-negative rods, and Gram-positive diplococci. Obtain cultures from the cervix or products of conception to rule out the presence of toxin-producing or antibiotic-resistant bacteria.7 Toxin-producing bacteria include Clostridium species, group A streptococcus, and Escherichia coli.21
If this early infection is not treated, pathogens can spread deeper into the myometrium and may progress to peritonitis and sepsis. Septic abortion causes a substantial number of maternal deaths in resource-poor countries, primarily due to illegal therapeutic or elective abortions.7
Treatment of septic abortion includes IV fluid resuscitation for hemodynamic stabilization, parenteral antibiotics, and surgical evacuation of retained products of conception. The antibiotics of choice are broad-spectrum and include combinations of gentamicin, clindamycin, metronidazole, levofloxacin, and ampicillin.22
- Gestational trophoblastic disease includes hydatidiform (molar) pregnancy, invasive mole (chorioadenoma destruens), and choriocarcinoma.7,21 Hydatidiform moles can further be classified into partial or complete moles. Partial moles have triploid karyotypes, usually have fetal tissue, and cause a smaller-than-expected uterus for gestational age.21 Fewer than 5% of patients with partial moles will develop malignant sequelae.21 Complete moles have diploid karyotypes and do not have fetal tissue. Patients with complete moles will have a uterus that is larger than expected for gestational age, and often have adnexal enlargement greater than 6 cm.21 Patients with complete moles have a 20% chance of developing malignant sequelae.21
The diagnosis of gestational trophoblastic disease is sonographic, classically identified as a mass with mixed echogenicity (Figure 2). The pathognomonic radiologic description is a snowstorm appearance or a cluster of grapes. Quantitative beta-hCG is often markedly elevated beyond what would be expected given the patient's LMP, and the patient often presents with hyperemesis gravidarum and preeclampsia. Management depends upon the histopathologic characteristics of the mass. Complete or partial moles require surgical evacuation and close follow-up with serial beta-hCG levels. Obtain a postevacuation baseline chest radiograph of a patient with a complete mole as gestational neoplastic disease can metastasize to the lungs once it extends outside the pelvic cavity.23 Refer patients to a gynecologic oncologist to ensure proper management and follow-up; some patients with partial molar pregnancies or complete moles can progress to gestational trophoblastic neoplasia. Women of Asian, Hispanic, and Native American backgrounds may have an increased risk of progression to gestational trophoblastic neoplasia.24-27 The management of invasive moles and choriocarcinomas is beyond the scope of this article.
First-trimester bleeding also can be caused by implantation, subchorionic hemorrhage, anembryonic pregnancy, and threatened or spontaneous abortion.
- Implantation bleeding can occur 4 to 6 weeks after the LMP. This type of bleeding typically presents as spotting or a light menses, and is thought to be caused by the fertilized ovum rupturing small blood vessels as it burrows into the endometrial lining of the uterus.1
- A subchorionic hemorrhage is a hematoma in the chorion, the outermost portion of the placenta. The subchorionic hemorrhage can cause bleeding resembling a menses, although other times no vaginal bleeding occurs and the mass is an incidental finding on a first-trimester ultrasound.3 A subchorionic hemorrhage can resemble a small uterine fibroid on ultrasound. A color Doppler can be used to differentiate the two: fibroids are hypoechoic with blood flow but subchorionic hemorrhages are avascular.22 A subchorionic hemorrhage in a woman over age 35 years is associated with a slightly elevated risk of spontaneous abortion, compared with women younger than age 35 years; a larger hematoma also is associated with elevated risk of spontaneous abortion.22 Patients with a subchorionic hemorrhage should be reevaluated in 7 to 10 days to ensure that bleeding has ceased and to reassess for pregnancy viability.28,29
- A spontaneous abortion is the loss of a fetus before 20 weeks gestation. The terms threatened abortion, inevitable abortion, anembryonic pregnancy, and incomplete abortion are all forms of spontaneous abortions (Table 2).
The most common risk factors for spontaneous abortion include chromosomal abnormalities, type 1 or type 2 diabetes requiring insulin with poor glucose control, severe maternal hypertension, autoimmune disease, renal disease, infections, and illicit drug use (particularly cocaine).30 Chromosomal abnormalities are present in more than 75% of fetuses spontaneously aborted in the first trimester, and the risk of a chromosomal abnormality increases with maternal age.30 Women over age 35 years have a significantly elevated risk of spontaneous abortion due to a chromosomal defect, with aneuploidies being the most common defect.22,30
A threatened abortion is defined as bleeding in the first 20 weeks of pregnancy without cervical dilation. The patient may or may not have pelvic pain. Ultrasound may reveal an intrauterine pregnancy with cardiac activity, but only if the patient is at least at 7 weeks gestation. If the patient presents with bleeding earlier than 7 weeks, obtain a quantitative beta-hCG and make ultrasound correlations (Table 1). Serum progesterone also may be obtained: a result less than 5 ng/mL is highly suggestive of a nonviable pregnancy, and a result of greater than 20 ng/mL has a 95% sensitivity of identifying a normal pregnancy.31
Provide emotional support to the patient and reevaluate gestational viability with ultrasound imaging in 1 week. Remember that up to 50% of threatened abortions will result in a pregnancy loss.5
In a patient with vaginal bleeding, a beta-hCG of greater than 1,500 IU/mL, and no gestational sac or yolk sac, a repeat beta-hCG should be checked in 48 hours. Decreasing beta-hCG levels indicate inevitable abortion, and management is expectant (closely monitor the patient for worsening vaginal bleeding and possible retained products of conception).32 About 80% of women will eventually expel the products of conception without any medical or surgical intervention.28
An anembryonic pregnancy, often referred to as a blighted ovum, is an ultrasonic diagnosis, although first-trimester bleeding may be an initial sign. The yolk sac should be visible when the gestational sac is greater than 8 mm, or about 5 weeks after the LMP (Figure 3). A mean gestational sac diameter of 20 mm without a yolk sac or fetal pole is diagnostic for an anembryonic pregnancy.22 Management can be medical, with the use of 800 mcg of misoprostol vaginally. Another dose of misoprostol may be administered in no sooner than 3 hours and up to 7 days if the patient is unresponsive to the initial dose. Patients should be counseled to expect heavy vaginal bleeding and cramping. Confirmation of complete abortion can be accomplished with ultrasound imaging or serial quantitative beta-hCG measurements.28 Surgical management is accomplished with suction aspiration. Both approaches have similar outcomes regarding evacuation of products of conception, but surgical management is quicker. Both medical and surgical approaches carry risk of bleeding and infection, but surgery is more costly and carries the extra risk of adhesion development.28 Any pregnant patient with bleeding who is Rh-negative and does not have anti-D antibodies should be given 300 mcg of Rho (D) immune globulin to prevent maternal sensitization and subsequent hemolytic disease of the newborn.30
Clinicians also must remember to thoughtfully address the patient's psychological and emotional needs during a potentially vulnerable life event, making appropriate referrals when necessary. Patients who desire another pregnancy should be counseled that no data support waiting to conceive, but they should abstain from intercourse or tampon use for the first 2 weeks after a pregnancy loss.22 In addition, patients who desire contraception may receive an intrauterine contraceptive device immediately after surgical or hormonal evacuation, or hormonal contraception immediately after medical or surgical evacuation.28
The diagnosis and management of first-trimester bleeding requires a differential diagnosis that includes the most commonly encountered emergent and nonemergent causes. Once the patient is deemed hemodynamically stable, the clinician can readily establish a diagnosis by performing a thorough history, physical examination, laboratory tests, and transvaginal ultrasound.
Signs of emergent causes, such as a ruptured ectopic pregnancy, missed abortion, septic abortion, or gestational trophoblastic disease, warrant a quick and focused history and physical and a consult with obstetrics. Nonemergent causes of first-trimester bleeding can be managed with a careful history, physical examination, quantitative beta-hCG, ultrasound correlations, and appropriate patient education on expectations and importance of follow-up.
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