First Trimester Bleeding
First Trimester Bleeding
First Trimester Bleeding
Approximately one-fourth of pregnant women will experience bleeding in the first trimester. The differential diagnosis
includes threatened abortion, early pregnancy loss, and ectopic pregnancy. Pain and heavy bleeding are associated with
an increased risk of early pregnancy loss. Treatment of threatened abortion is expectant management. Bed rest does not
improve outcomes, and there is insufficient evidence supporting the use of progestins. Trends in quantitative β subunit of
human chorionic gonadotropin (β-hCG) levels provide useful information when distinguishing normal from abnormal early
pregnancy. The discriminatory level (1,500 to 3,000 mIU per mL) is the β-hCG level above which an intrauterine pregnancy
should be visible on transvaginal ultrasonography. Failure to detect an intrauterine pregnancy, combined with β-hCG levels
higher than the discriminatory level, should raise concern for early pregnancy loss or ectopic pregnancy. Ultrasound find-
ings diagnostic of early pregnancy loss include a mean gestational sac diameter of 25 mm or greater with no embryo and
no fetal cardiac activity when the crown-rump length is 7 mm or more. Treatment options for early pregnancy loss include
expectant management, medical management with mifepristone and misoprostol, or uterine aspiration. The incidence of
ectopic pregnancy is 1% to 2% in the United States and accounts for 6% of all maternal deaths. Established criteria should
be used to determine treatment options for ectopic pregnancy, including expectant management, medical management
with methotrexate, or surgical intervention. (Am Fam Physician. 2019;99(3):166-174. Copyright © 2019 American Academy
of Family Physicians.)
Approximately 25% of pregnant women experience bleeding. Bleeding equal to or heavier than a menstrual
bleeding before 12 weeks’ gestation.1,2 The differential diag- period and bleeding accompanied by pain are associated
nosis includes nonobstetric causes, bleeding in a viable with an increased risk of early pregnancy loss.2,7 Patients
intrauterine pregnancy, early pregnancy loss, and ectopic should be assessed for signs and symptoms of hypovole-
pregnancy. Physical examination findings, laboratory test- mia. Vital signs indicating hemodynamic instability or
ing, and ultrasonography can be used to diagnose the cause peritoneal signs on physical examination require emergent
of first trimester bleeding and provide appropriate manage-
ment. A glossary of terms used in this article is available in
Table 1.3-6 WHAT IS NEW ON THIS TOPIC
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FIRST TRIMESTER BLEEDING
evaluation. A speculum examination can help identify non- abortion. A 50- or 120-mcg dose is recommended before
obstetric causes of bleeding, such as vaginitis, cervicitis, 12 weeks’ gestation, although 300 mcg can be administered
or a cervical polyp. If products of conception are visible if lower doses are not available.3 After 12 weeks, a 300-mcg
on speculum examination, the diagnosis of incomplete dose should be given.12
abortion can be made and treatment offered. Further eval-
uation is needed unless a definitive nonobstetric cause PROGESTERONE
of bleeding is found or products of conception are seen Measurement of serum progesterone may be useful in
(Figure 1).8 distinguishing between an early viable or nonviable preg-
nancy, especially in the setting of inconclusive ultrasonog-
Laboratory Testing raphy. A meta-analysis evaluating the accuracy of a single
β-HUMAN CHORIONIC GONADOTROPIN progesterone test to predict pregnancy outcome in women
The β subunit of human chorionic gonadotropin (β-hCG) with first trimester bleeding showed that a level less than
can be detected in the plasma of a
pregnant woman as early as eight days
after ovulation.9 Quantitative β-hCG TABLE 1
levels can provide useful information
in early pregnancy. The rate of β-hCG Definition of Terms Related to First Trimester Bleeding
increase is less rapid as the level and Early Pregnancy Loss
increases. For symptomatic women Term Definition
with a viable intrauterine pregnancy,
Anembryonic gestation Ultrasonography shows gestational sac with mean
initial β-hCG levels of less than 1,500 diameter ≥ 25 mm and no yolk sac or embryo
mIU per mL, 1,500 to 3,000 mIU per
mL, or more than 3,000 mIU per mL Complete abortion Complete passage of all products of conception
will increase over 48 hours by at least Early pregnancy loss Nonviable intrauterine pregnancy within the first
49%, 40%, or 33%, respectively.10 A 12 6/7 weeks of gestation
slower rate of increase suggests early
pregnancy loss or ectopic pregnancy. Ectopic pregnancy A pregnancy outside the uterine cavity (most com-
monly in a fallopian tube)
By approximately 10 weeks’ gestation,
the β-hCG level typically plateaus or Embryonic demise Ultrasonography shows embryo with crown-rump
decreases, after which serial ultraso- length ≥ 7 mm and no cardiac activity
nography is the preferred diagnostic Incomplete abortion Some, but not all, of the products of conception
tool.11 have passed
Physical examination
6 ng per mL (19.1 nmol per L) reliably excludes viable preg- DISCRIMINATORY LEVEL
nancy, with a negative predictive value of 99%.13 A low pro- The discriminatory level is the β-hCG level above which an
gesterone level cannot distinguish intrauterine pregnancy intrauterine pregnancy is expected to be seen on transvag-
from ectopic pregnancy.13 inal ultrasonography.14 When combined with β-hCG lev-
els greater than the discriminatory level, ultrasonography
HEMOGLOBIN that does not show an intrauterine pregnancy should raise
A baseline hemoglobin level should be documented for concern for early pregnancy loss or ectopic pregnancy. The
all women with bleeding during pregnancy. All patients discriminatory level varies with the type of ultrasound
should be instructed to seek care if they have symptoms of machine used, the sonographer, and the number of gesta-
anemia or heavy bleeding, quantified as soaking through tions. A recent study found a 99% probability that an intra-
more than two sanitary pads per hour for two consecutive uterine gestational sac will be detected at a β-hCG level of
hours.3 3,510 mIU per mL.14 Currently, a discriminatory level of
1,500 to 3,000 mIU per mL is typically used.10,15 However,
Ultrasonography ultrasonography can be diagnostically useful in symptom-
The embryologic events of early pregnancy occur in a pre- atic women at any β-hCG level. Signs of ectopic pregnancy
dictable, stepwise fashion. Deviations from this established (e.g., adnexal mass, fluid in the cul-de-sac) can be seen on
pattern should raise suspicion for early pregnancy loss or ultrasonography well below the discriminatory level.
ectopic pregnancy (Table 2).4,5 Guidelines have been estab-
lished for ultrasound diagnosis of early pregnancy loss to Pregnancy of Unknown Location
decrease the risk of false diagnosis and intervention in a Pregnancy of unknown location describes the scenario in
desired viable intrauterine pregnancy. which a pregnancy test is positive, but neither intrauterine
168 American Family Physician www.aafp.org/afp Volume 99, Number 3 ◆ February 1, 2019
FIRST TRIMESTER BLEEDING
TABLE 2
Gestational Appears four to five Mean sac diameter of 16 to 24 mm and no Mean sac diameter ≥ 25 mm
sac (measured weeks after last men- embryo and no embryo
by mean sac strual period Absence of embryo with cardiac activity Absence of embryo with
diameter) seven to 13 days after ultrasonography cardiac activity ≥ 2 weeks after
shows gestational sac without yolk sac ultrasonography shows gesta-
Small gestational sac relative to size of tional sac without yolk sac
embryo (< 5 mm difference between mean
sac diameter and crown-rump length)
Yolk sac Appears 5.5 weeks Absence of embryo with cardiac activity Absence of embryo with
after last menstrual seven to 10 days after ultrasonography cardiac activity ≥ 11 days after
period shows gestational sac and yolk sac ultrasonography shows gesta-
Enlarged yolk sac (> 7 mm) tional sac and yolk sac
Embryo (measured Appears six weeks Crown-rump length < 7 mm and no Crown-rump length ≥ 7 mm
by crown-rump after last menstrual embryonic cardiac activity and no embryonic cardiac
length and period; embryonic Absence of embryo ≥ 6 weeks after last activity
embryonic cardiac cardiac activity menstrual period
activity) appears at 6.5 weeks
Empty amnion (amnion seen adjacent to
yolk sac with no visible embryo)
Embryonic heartbeat ≤ 85 beats per minute
nor ectopic pregnancy is shown on ultrasonography. In Threatened abortion should be managed expectantly.
stable patients, close monitoring of symptoms, serial quan- There is insufficient evidence to support the use of proges-
titative β-hCG testing, and ultrasonography are recom- tin for the prevention of early pregnancy loss.3,18 Bed rest
mended 4 (Figure 2 8,10,14,15). Pregnancy of unknown location does not improve outcomes and may cause psychological
can be diagnostically challenging because the increase in harm in patients with subsequent early pregnancy loss.19
β-hCG level can be similar among women with an early Patients should be reassured that nothing they did caused
viable pregnancy, ectopic pregnancy, or early pregnancy the bleeding.
loss.10 Because pregnancy of unknown location does not
exclude ectopic pregnancy, and because rupture of ectopic Early Pregnancy Loss
pregnancy can occur at any β-hCG level, serial measure- Expectant management, medical management, and uterine
ments should be obtained until a definitive diagnosis is aspiration are safe and effective treatments for early preg-
made or until the level is undetectable.16 Patients should nancy loss. Patient satisfaction, mental health outcomes,
be counseled about warning signs of ectopic pregnancy, infection rates, and future fertility are similar between
including shoulder pain, pelvic pain, and dizziness. these treatments.20-22 Mental health outcomes are better
when patients are included in the decision-making process,
Threatened Abortion and shared decision making should guide management.23
The diagnosis of threatened abortion should be made in
patients with bleeding and an ultrasound-confirmed via- EXPECTANT MANAGEMENT
ble intrauterine pregnancy. The rate of early pregnancy loss Watchful waiting is recommended as first-line treatment for
is approximately 11% after a live fetus has been detected patients with incomplete abortion;more than 90% of these
on ultrasonography.17 The risk of early pregnancy loss is patients will complete the process spontaneously within four
increased when subchorionic hemorrhage (Figure 3 6) and weeks.24 Watchful waiting is less effective in patients with
bleeding are present. When an intrauterine pregnancy is an anembryonic gestation or embryonic demise, with com-
detected on ultrasonography but viability is uncertain, pletion rates at one month of 66% and 76%, respectively.24
repeat ultrasonography should be performed in seven to Patients who choose expectant management over uterine
10 days to confirm viability.3,5 In these cases, a normal aspiration experience more days of bleeding, longer time to
increase in the β-hCG level or a normal progesterone level completion, and higher rates of unplanned surgical inter-
can be reassuring. vention.20,21 Serious complications are rare, and patients who
Yes No
Initial β-hCG level > 3,000 mIU per mL* Initial β-hCG level < 3,000 mIU per mL*
*—The β-hCG level at which an intrauterine pregnancy should be seen on transvaginal ultrasonography is called the discriminatory level and varies
from 1,500 to 3,000 mIU per mL.10,14,15
†—In a viable intrauterine pregnancy, there is a 99% chance that the β-hCG level will increase at least 33% to 49% in 48 hours, depending on the
initial level.6 Ectopic pregnancy can also present with this rate of increase, so use clinical judgment in combination with β-hCG values.
‡—The β-hCG level should be followed to zero only if ectopic pregnancy has not been excluded. If definitive diagnosis of complete abortion has
been made, there is no need to obtain additional β-hCG levels.
Evaluation of first trimester bleeding in pregnancy of unknown location. (β-hCG = β subunit of human chorionic
gonadotropin.)
Adapted with permission from Reproductive Health Access Project. First trimester bleeding algorithm. November 1, 2017. https://www.reproductive-
access.org/resource/first-trimester-bleeding-algorithm/. Accessed November 10, 2017, with additional information from references 10, 14, and 15.
opt for expectant management should be informed that it does not improve rates of completed abortion or decrease
is safe to wait as long as they wish as long as there are no the need for unplanned surgical procedures compared with
signs of infection or hemorrhage. Patients may switch to expectant management.22 In contrast, medical management
medical management or uterine aspiration at any time. is more effective than expectant management for the treat-
ment of anembryonic gestation or embryonic demise.25 The
MEDICAL MANAGEMENT most effective regimen for medical management is 200 mg
A Cochrane review found that medical management with of oral mifepristone (Mifeprex) followed 24 hours later by
misoprostol (Cytotec) in women with incomplete abortion 800 mcg of vaginally administered misoprostol.26 Success
170 American Family Physician www.aafp.org/afp Volume 99, Number 3 ◆ February 1, 2019
FIGURE 3
rates at two days with this regimen are 84% vs. 67% in those
treated with misoprostol alone. Many regimens for using
misoprostol alone have been studied, and none has been
proven optimal.22 One common regimen is 800 mcg vagi-
nally, with a repeat dose in 24 to 48 hours if the first dose
is unsuccessful.27 Besides the expected cramping and vag-
inal bleeding, common adverse effects include nausea and
diarrhea.22
UTERINE ASPIRATION
Uterine aspiration is the preferred procedure for surgical
management of early pregnancy loss. Compared with sharp
Subchorionic hemorrhage (SCH) appears as a sonolu-
curettage, vacuum aspiration is associated with decreased
cent area adjacent to the gestational sac, which con- pain, shorter procedure duration, and less blood loss.28
tains an embryo (E) and yolk sac (YS). Office-based uterine aspiration is safe, less expensive, and
Reprinted with permission from Deutchman M, Tubay AT, Turok D.
often more convenient than treatment in the operating
First trimester bleeding. Am Fam Physician. 2009;79(11):989. room.29,30 Choices about analgesia during the aspiration
procedure should be made with the patient’s input.
Evidence
Clinical recommendation rating References
The initial β-hCG level should be considered when following the rate of β-hCG increase in early B 10
pregnancy. In viable intrauterine pregnancies with initial β-hCG levels of less than 1,500 mIU per
mL, 1,500 to 3,000 mIU per mL, or greater than 3,000 mIU per mL, there is a 99% chance that the
β-hCG level will increase by at least 49%, 40%, and 33%, respectively, over 48 hours.
Rh o(D) immune globulin (Rhogam) should be administered to Rh-negative women with early preg- C 12
nancy loss, especially when it occurs later in the first trimester.
Early pregnancy loss can be definitively diagnosed in women with ultrasound findings of a mean C 4, 5
gestational sac diameter of 25 mm or greater and no embryo or embryonic cardiac activity when
the crown-rump length is at least 7 mm.
Clinicians should expect to see a gestational sac on transvaginal ultrasonography when β-hCG B 10, 15
levels reach 1,500 to 3,000 mIU per mL.
Bed rest or progestins should not be recommended to prevent early pregnancy loss in patients with C 3, 18, 19
first trimester bleeding because these interventions have not been proven effective.
Expectant management, medical management, and uterine aspiration are safe methods for treating A 20-23, 28
anembryonic gestations and fetal demise. Patient preference should guide treatment decisions.
Oral mifepristone (Mifeprex), 200 mg, followed 24 hours later by misoprostol, 800 mcg vaginally, is A 26
the most effective regimen for medical management of early pregnancy loss and, when available,
should be recommended over misoprostol alone.
Treatment for incomplete abortion should rely on shared decision making. Patients should be A 22, 24
informed that expectant management is more than 90% effective.
172 American Family Physician www.aafp.org/afp Volume 99, Number 3 ◆ February 1, 2019
FIRST TRIMESTER BLEEDING
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