Spontaneous abortion: Risk factors, etiology, clinical

manifestations, and diagnostic evaluation

Spontaneous abortion: Risk factors, etiology, clinical manifestations, and diagnostic

evaluation
Authors
Togas Tulandi, MD, MHCM
Haya M Al-Fozan, MD
Section Editors
Deborah Levine, MD
Robert L Barbieri, MD
Deputy Editor
Sandy J Falk, MD
Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Oct 2013. | This topic last updated: Jul 17,
2012.

INTRODUCTION — Spontaneous abortion (SAb), also known as miscarriage,

refers to a pregnancy that ends spontaneously before the fetus has reached a
viable gestational age [ 1 ]. The World Health Organization defines it as expulsion
or extraction of an embryo or fetus weighing 500 g or less from its mother. This
typically corresponds to a gestational age of 20 to 22 weeks or less [ 2 ]. The term
"fetus" will be used throughout this discussion, although the term "embryo" is the
correct developmental term at ≤10 weeks of gestation.

Diagnostic issues relating to SAb will be reviewed here. Recurrent abortion and
management issues are discussed separately. (See"Evaluation of couples with
recurrent pregnancy loss" and "Spontaneous abortion: Management" .)

INCIDENCE — SAb is the most common complication of early pregnancy [ 1 ].

The frequency decreases with increasing gestational age. Eight to 20 percent of
clinically recognized pregnancies under 20 weeks of gestation will undergo SAb; 80
percent of these occur in the first 12 weeks of gestation [ 3-5 ]. The overall risk of
SAb after 15 weeks is low (about 0.6 percent) for chromosomally and structurally
normal fetuses, but varies according to maternal age and ethnicity [ 6 ].

Loss of unrecognized or subclinical pregnancies is even higher, occurring in 13 to

26 percent of all pregnancies [ 3-5,7-9 ]. Early pregnancy losses are unlikely to be
recognized unless daily pregnancy tests are performed. A study that compared
women's bleeding following a pregnancy loss before 6 weeks of gestation with their
typical menstruation found that mean bleeding length following a pregnancy loss
was 0.4 days longer than the woman's average menses and the amount of bleeding
was light [ 10 ].

These data were obtained from studies such as the following representative
examples:
  In a classic study in which daily urinary human chorionic gonadotropin (hCG)
assays were determined, the total rate of pregnancy loss after
implantation was 31 percent; 70 percent of these losses (22 percent of all
pregnancies) occurred before the pregnancy was detected clinically [ 4 ].
 In another study, daily urinary hCG assays were performed on 518
nulliparous, newly married women aged 20 to 34 years who were
attempting to conceive and had no known infertility [ 5 ]. Of the 586
conceptions with known outcome, loss of a preclinical pregnancy occurred
in 26 percent, loss of a clinically recognized pregnancy occurred in 8
percent, live birth occurred in 64 percent, with the remainder comprised
of induced abortion, ectopic pregnancy, molar pregnancy, and stillbirth.

If preimplantation losses are considered, 50 percent of fertilized oocytes do not

result in a live birth [ 11 ].

RISK FACTORS — Numerous risk factors are associated with an increased risk of
pregnancy loss:

Age — Advancing maternal age is the most important risk factor for spontaneous
miscarriage in healthy women. The effect of maternal age on pregnancy outcome
was illustrated in a review of over 1 million pregnancies of known outcome and with
admission to a hospital [12 ]. The overall rate of SAb was 11 percent and the
approximate frequencies of clinically recognized miscarriage according to maternal
age were: age 20 to 30 years (9 to 17 percent), age 35 (20 percent), age 40 (40
percent), and age 45 (80 percent) [ 12 ].

Previous spontaneous abortion — Past obstetrical history is an important

predictor of subsequent pregnancy outcome. The risk of miscarriage in future
pregnancy is approximately 20 percent after one miscarriage, 28 percent after two
consecutive miscarriages, and 43 percent after three or more consecutive
miscarriages [ 13 ]. By comparison, miscarriage occurred in only 5 percent of
women in their first pregnancy or in whom the previous pregnancy was successful.

Smoking — Heavy smoking (greater than 10 cigarettes per day) is associated with
an increased risk of pregnancy loss (relative risk 1.2 to 3.4) [ 14-18 ]. This
association is more pronounced when controlling for other causes of pregnancy
loss, such as limiting the analysis to chromosomally normal abortuses [ 19-21 ].
The mechanism is not known, but may be related to vasoconstrictive and
antimetabolic effects. Paternal smoking may also increase the risk of pregnancy
loss [ 22 ]. Smoking cessation should be recommended for its overall health
benefits (see "Smoking and pregnancy" and "Patterns of tobacco use" ).

Alcohol — Observational studies have generally, but not consistently, reported

that moderate to high alcohol consumption increases the risk of SAb [ 3,23-30 ]. As
an example, in one study there was an increased risk of miscarriage in women who
drank more than 3 drinks per week in the first 12 weeks of pregnancy [ 23 ].

Interpretation of studies of alcohol use in pregnancy is complicated by potentially

inadequate adjustment for confounders and underreporting of alcohol use. Women
planning pregnancy should avoid alcohol consumption since alcohol is a known
teratogen and a safe level of alcohol intake has not been established at any stage
of pregnancy. (See "Alcohol intake and pregnancy" and "Overview of illicit drug use
in pregnant women" .)
Gravidity — Some studies have shown an increased risk of miscarriage with
increasing gravidity [ 31,32 ], while others have not [ 33-35 ]. Possible reasons for
this association include (1) reproductive compensation behavior (pregnancy failure
is likely to be associated with repeated attempts at conception resulting in higher
gravidity) and (2) short interpregnancy intervals in multigravid women.
(See"Interpregnancy interval and pregnancy outcome" .)

Cocaine — Use of cocaine is associated with preterm birth, and may also be a risk
factor for spontaneous abortion [ 18 ]. In one study of 400 women who had a SAb
and 570 controls who remained pregnant through at least 22 weeks of gestation,
the presence of cocaine in hair samples was independently associated with an
increase in the occurrence of spontaneous abortion after adjustment for
demographic and drug-use variables (OR 1.4; 95% CI 1.0-2.1) [ 18 ].
(See "Overview of illicit drug use in pregnant women" .)

Nonsteroidal antiinflammatory drugs — The use of nonsteroidal

antiinflammatory drugs (NSAIDs), but not acetaminophen , may be associated with
an increased risk of miscarriage if used around the time of conception [ 36,37 ].
The postulated mechanism is that prostaglandin inhibitors interfere with the role
prostaglandins play in implantation, thus potentially leading to abnormal
implantation and pregnancy failure [ 38-41 ]. Although data are sparse, it is
reasonable to suggest that women who are trying to conceive should consider
avoiding use of NSAIDS to minimize the risk of miscarriage, especially when
alternative drugs (eg, acetaminophen) are available.

Fever — Fevers of 100°F (37.8°C) or more may increase the risk of miscarriage,
but the only two large studies have been contradictory and inconclusive.

 One study of women having euploid abortions, aneuploid abortions, and

delivering at 28 weeks of gestation or later (controls) hypothesized that if
fever was an antecedent (rather than a symptom) of SAb, there would be
an association between fever and euploid, but not aneuploid, abortions
[ 42 ]. Analysis of data supported this hypothesis: fevers were
significantly more frequent among women with euploid abortions than
among controls (18 versus 7 percent), but not more frequent among
women with aneuploid abortions. Their hypothesis was also strengthened
by the observation that the risk of abortion was highest proximate to the
febrile episode: the ORs for abortion when fever occurred in the same
calendar month, one month before, or two or more months before a
euploid abortion were 6.0, 3.3, and 1.4, respectively.
 By comparison, a second series interviewed over 24,000 Danish women in
the first 16 weeks of pregnancy and obtained information on the number
of fever episodes, highest temperature, duration, and gestational age at
occurrence [ 43 ]. This information was subsequently linked to a
pregnancy outcome registry. Fever occurred in 18.5 percent of
participants. There was no association between fever or any specific fever
characteristic and first, second, or third trimester fetal death, before or
after adjustment of risk factors. However, the low rate of first trimester
pregnancy loss (2.3 percent) suggests some women with spontaneous
abortions were not included, potentially masking an effect of fever on
early loss.

Caffeine — Meta-analyses of controlled studies have generally reported an

association between caffeine intake and spontaneous abortion, primarily at high
levels of consumption. However, these studies have multiple limitations, including
selection and recall bias, confounding, issues pertaining to exposure measurement
(ie, inability to accurately measure caffeine intake since it depends upon the size of
the cup, brand of coffee, and brewing method), as well as failure to account for
fetal karyotype, caffeine metabolism, timing of fetal demise, and the possibility that
an effect of caffeine may be gestational age-specific. The mechanism for the
increased rate of SAb with high caffeine intake might be related to maternal
metabolism and clearance of this substance. These issues are discussed in detail
separately. (See "The effects of caffeine on reproductive outcomes in women" .)

Prolonged ovulation to implantation interval — Early losses have also been

related to a prolonged interval (ie, >10 days) between ovulation and implantation
[ 44 ]. Such delays might result from fertilization of an older ovum, delayed tubal
transport, or abnormal uterine receptivity.

Prolonged time to pregnancy — Observational studies have reported that

prolonged time to achieving pregnancy correlates with an increased risk of
miscarriage [ 45-47 ].

Low-folate level — A well-designed, population-based, case-control study

showed low plasma folate levels (≤2.19 ng/mL [4.9 nmol/L])were associated with
an increased risk of SAb at 6 to 12 weeks of gestation, but only when the fetal
karyotype was abnormal [ 48 ]. Low folate levels with normal fetal karyotype and
high folate levels had no such adverse effect. In this population, less than 5 percent
of women received folate supplement. Whether low folate levels increase the risk of
abnormal karyotype in the embryo and subsequent abortion is under investigation.
Some investigators have suggested that maternal polymorphisms in the
methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTRR)
genes may increase the risk of meiotic nondisjunction. (See "Congenital cytogenetic
abnormalities", section on 'Trisomy 21 (Down syndrome)' .)

There is no evidence that vitamin supplementation prevents miscarriage [ 49 ].

There is no specific evidence that folate supplementation reduces the risk of
miscarriage in women with hyperhomocysteinemia, although this has been
suggested [ 50 ]. However, folate supplements are routinely recommended for all
pregnant women anyway for prevention of neural tube defects.

Maternal weight — Prepregnancy body mass index less than 18.5 or above
25 kg/m2 has been associated with an increased risk of infertility and SAB [ 51-
54 ]. (See "Optimizing natural fertility in couples planning pregnancy" and "The
impact of obesity on fertility and pregnancy" .)

Celiac disease — Untreated celiac disease may be associated with a higher risk of
SAb. (See "Definition and etiology of recurrent pregnancy loss", section on 'Celiac
disease' .)

ETIOLOGY — In one-third of imaging studies at or before 8 weeks of gestation, no

embryo or yolk sac is seen in the gestational sac. In the two-thirds of cases in
which an embryo is found, approximately 50 percent are abnormal, dysmorphic,
stunted, or too macerated for examination [ 55 ]. Abnormal embryos may result
from chromosomal abnormalities or exposure to teratogens.
Chromosomal abnormalities — Chromosomal abnormalities account for
approximately 50 percent of all miscarriages. Most of these abnormalities are
aneuploidies; structural abnormalities and mosaicism are responsible for relatively
few abortions.

The earlier the gestational age at abortion, the higher the incidence of cytogenetic
defects: the incidence of abnormal fetal karyotype is 90 percent in anembryonic
products of conception, 50 percent for abortuses at 8 to 11 weeks of gestation, but
decreases to 30 percent of abortuses at 16 to 19 weeks [ 56 ]. The frequency and
types of chromosomal abnormalities in early pregnancy loss were illustrated in a
review of 8841 spontaneous abortions in which 41 percent had chromosomal
abnormalities [ 57 ]. The most frequent types of abnormalities detected were:

 Autosomal trisomies — 52 percent

 Monosomy X — 19 percent
 Polyploidies — 22 percent
 Other — 7 percent

Trisomy 16 is the most common autosomal trisomy and is always lethal. Most
chromosomal abnormalities in the embryo arise de novo. Rarely, these defects are
inherited as a consequence of parental karyotypic abnormalities, such as balanced
translocations. (See"Definition and etiology of recurrent pregnancy loss", section on
'Genetic factors' .)

Genetic abnormalities not detected by conventional cytogenetic analysis (G-banded

karyotype) account for an undefined proportion of spontaneous abortions. These
abnormalities include small deletions and duplications and point mutations.

Congenital anomalies — Congenital anomalies are caused by genetic or

chromosomal abnormalities, extrinsic factors (eg, amniotic bands), and exposure to
teratogens. Potential teratogens include maternal disorders (eg, diabetes mellitus
with poor glycemic control), drugs (eg, isotretinoin ), physical stresses (eg, fever),
and environmental chemicals (eg, mercury). (See "Genetic and environmental
causes of birth defects", section on 'Teratogens' and "Principles of teratology" .)

Trauma — Invasive intrauterine procedures/trauma, such as chorionic villus

sampling and amniocentesis, increase the risk of abortion. In contrast, the early
gestational age uterus is generally protected from blunt trauma to the maternal
abdomen [ 58 ]. (See "Chorionic villus sampling: Risks, complications, and
techniques" and "Diagnostic amniocentesis" .)

Host factors — Pregnancy loss may also be related to the host environment. As
an example, congenital or acquired uterine abnormalities (eg, uterine septum,
submucosal leiomyoma, intrauterine adhesions) can interfere with optimal
implantation and growth [59 ]. (See "Reproductive issues in women with uterine
leiomyomas (fibroids)" .)

Acute maternal infection with any of a large number of organisms (eg, Listeria
monocytogenes, Toxoplasma gondii, parvovirus B19, rubella, herpes simplex,
cytomegalovirus, lymphocytic choriomeningitis virus [ 60 ]) can lead to abortion
from fetal or placental infection.
Maternal endocrinopathies (eg, thyroid dysfunction, Cushing's syndrome, polycystic
ovary syndrome) can also contribute to a suboptimal host environment. Since
corpus luteum progesterone production is an integral component of successful
pregnancy, it is plausible that early pregnancy loss could be due to corpus luteum
dysfunction; however, this is controversial. Some well-designed studies did not
support this theory as they showed maternal serum progesterone levels proximate
to implantation (a time when corpus luteum progesterone production is critical)
were similar for continuing pregnancies and those subsequently lost [ 61,62 ]. The
use of progesterone to distinguish between a nonviable (missed abortion or ectopic
pregnancy) and a viable pregnancy when the location of the pregnancy is unknown
is addressed separately. (See "Clinical manifestations, diagnosis, and management
of ectopic pregnancy", section on 'Progesterone' .)

The effect of thyroid disease and thyroid peroxidase antibodies on abortion risk is
also reviewed separately. (See "Overview of thyroid disease in pregnancy" .)

A hypercoagulable state due to inherited or acquired thrombophilia and

abnormalities of the immune system (eg, systemic lupus erythematosus,
antiphospholipid syndrome) that lead to immunological rejection or placental
damage are active areas of investigation. (See "Inherited thrombophilias in
pregnancy" and "Obstetrical manifestations of the antiphospholipid syndrome" .)

Unexplained — The etiology of abortion of chromosomally and structurally

normal embryos/fetuses in apparently healthy women is unclear. As discussed
above, genetic abnormalities not detected by standard karyotype analysis (small
deletions and duplications and point mutations) account for an undefined proportion
of spontaneous abortions.

CLINICAL MANIFESTATION AND DIAGNOSIS — Women who are actively in

the process of having a spontaneous abortion usually present with a history of
amenorrhea, vaginal bleeding, and pelvic pain. On examination, the cervix is open
and the products of conception can be visualized in the vagina or cervical os, if they
have not already been passed.

The terminology for early pregnancy complications has not been standardized, thus
variations in the terms used to describe these events are common [ 63 ]. As an
example, a pregnancy in which no embryo is seen may be called an empty sac
(previous terms included blighted ovum or anembryonic pregnancy) [ 63 ]. A
missed abortion may be called an embryonic or early fetal demise, an early fetal
loss, or a delayed or silent miscarriage. Patients prefer the term "miscarriage" to
"abortion."

Threatened abortion — Bleeding through a closed cervical os in the first half of

pregnancy is quite common and is termed threatened abortion. The bleeding is
often painless, but may be accompanied by minimal/mild suprapubic pain. On
examination, the uterine size is appropriate for gestational age and the cervix is
long and closed. Fetal cardiac activity is detectable by ultrasound or Doppler
examination if the gestation is sufficiently advanced. The exact etiology of bleeding
often cannot be determined and is frequently attributed to marginal separation of
the placenta.
The term "threatened" abortion is used to describe these cases because pregnancy
loss does not always follow vaginal bleeding in early pregnancy, even after
repeated episodes or large amounts of bleeding. In fact, 90 to 96 percent of
pregnancies with both fetal cardiac activity and vaginal bleeding at 7 to 11 weeks of
gestation will result in an ongoing pregnancy, with the higher success rate
occurring at the later gestational ages [ 64 ].

A systematic review found a modest association (odds ratio ≤2) between first
trimester bleeding and various adverse outcomes (eg, miscarriage, preterm birth,
premature rupture of membranes, growth restriction, antepartum bleeding) later in
pregnancy [ 65 ]. The prognosis is worse when the bleeding is heavy or extends
into the second trimester [ 66-69 ]. As an example, in one large prospective series,
the frequency of preterm delivery with no, light, or heavy first trimester bleeding
was 6, 9.1 and 13.8 percent, respectively, and the frequency of spontaneous loss
before 24 weeks of gestation was 0.4, 1.0, and 2.0 percent, respectively [ 66 ]. Of
note, all of these pregnancies had cardiac activity at the time of enrollment at 10 to
14 weeks of gestation. Because these subjects were enrolled late in the first
trimester and with sonographically confirmed fetal cardiac activity, women with
very early bleeding that went on to miscarry had already been excluded. These
findings were further supported by a subsequent population-based study of almost
800,000 women, which also reported an association between first trimester
bleeding in a woman's first pregnancy with recurrent bleeding in a second
pregnancy [ 70 ].

No change in pregnancy management is indicated because of the low predictive

value for adverse outcome and the lack of effective interventions. (See "Risk factors
for preterm labor and delivery", section on 'Vaginal bleeding' .)

Inevitable abortion — When abortion is imminent, bleeding increases, painful

uterine cramps/contractions reach peak intensity, and the cervix is dilated. The
gestational tissue can often be felt or visualized through the internal cervical os.

Complete and incomplete abortion — When an abortion occurs before 12

weeks of gestation, it is common for the entire contents of the uterus to be
expelled, thereby resulting in a complete abortion. Over one third of all cases are
complete, rather than incomplete, abortions. If a complete abortion has occurred,
the uterus is small and well contracted with a closed cervix, scant vaginal bleeding,
and only mild cramping.

After 12 weeks, the membranes often rupture and the fetus is passed, but
significant amounts of placental tissue may be retained, leading to an incomplete
abortion, also called an abortion with retained products of conception. On
examination the cervical os is open, gestational tissue may be observed in
the vagina/cervix, and the uterine size is smaller than expected for gestational age,
but not well contracted. The amount of bleeding varies, but can be severe enough
to cause hypovolemic shock. Painful cramps/contractions are often present.

Ultrasonographic diagnosis of an incomplete miscarriage or retained products of

conception is problematic. Measurement of endometrial thickness and the
appearance of the midline echo have been used to make these diagnoses, but there
is no agreement on the appropriate cut-off for endometrial thickness (15 mm is
commonly used) and no threshold has been proven to be reliable [ 71 ].
When heterogeneous material is present in the endometrial cavity, Doppler
ultrasound can be helpful in distinguishing between retained products of conception
and blood clot. If blood flow to retained placental tissue is visualized, then it is
possible to make the diagnosis of retained products of conception. However, if
blood flow is absent, then either devascularized retained products of conception or
blood clot could be present.

Missed abortion — A missed abortion refers to in-utero death of the embryo or

fetus prior to the 20th week of gestation, with retention of the pregnancy for a
prolonged period of time. Women may notice that symptoms associated with early
pregnancy (eg, nausea, breast tenderness) have abated and they don't "feel
pregnant" anymore; vaginal bleeding may occur. The cervix is usually closed.

Septic abortion — Common clinical features of septic abortion include fever,

chills, malaise, abdominal pain, vaginal bleeding, and discharge, which is often
sanguinopurulent. Physical examination may reveal tachycardia, tachypnea, lower
abdominal tenderness, and a boggy, tender uterus with dilated cervix.

Infection is usually due to Staphylococcus aureus, Gram negative bacilli, or some

Gram positive cocci. Mixed infections, anaerobic organisms, and fungi, can also be
encountered. The infection may spread, leading to salpingitis, generalized
peritonitis, and septicemia.

Most spontaneous abortions are not septic. Septic abortion is, however, a common
complication of illegally performed induced abortion. Infrequently, septic abortion is
related to foreign bodies (eg, intrauterine contraceptive device, laminaria), invasive
procedures (eg, amniocentesis, chorionic villus sampling), maternal bacteremia, or
incomplete spontaneous or legally induced abortion. Septic deaths related to
Clostridium sordellii have been reported after medical termination of early
pregnancy. (See "Mifepristone for the medical termination of pregnancy" .)

DIFFERENTIAL DIAGNOSIS — The cardinal clinical sign of spontaneous abortion

is vaginal bleeding. Bleeding in the first trimester may be light, heavy, intermittent,
or constant and it may be painless or painful. The four major causes of bleeding
early in pregnancy are:

 Physiologic (ie, believed to be related to implantation)

 Ectopic pregnancy
 Impending or complete miscarriage
 Cervical, vaginal, or uterine pathology

These entities are reviewed in detail separately. (See "Overview of the etiology and
evaluation of vaginal bleeding in pregnant women" .)

Physical examination may reveal the source of bleeding (trauma, polyp, cervicitis,
neoplasia). Transvaginal ultrasonography is the cornerstone of evaluation of
bleeding and/or pelvic pain in early pregnancy ( algorithm 1 ). It is used for
distinguishing intrauterine from extrauterine (ectopic) and live from nonviable
pregnancies. Ultrasound examination may also reveal that the patient has
gestational trophoblastic disease. It is important when performing the transvaginal
examination to use a high frequency transducer, as this will improve visualization of
the yolk sac and early embryonic cardiac activity [ 72 ].
A single low human chorionic gonadotropin (hCG) concentration is only helpful if
ultrasonography is nondiagnostic, ie, the site and viability of the pregnancy are not
revealed. A single low hCG measurement is never diagnostic of a pregnancy
problem; serial measurements are always necessary. Serial hCG measurements
showing a falling beta-hCG concentration are consistent with both a nonviable
intrauterine pregnancy and a spontaneously resolving ectopic pregnancy, but do
not indicate whether the pregnancy is intrauterine or ectopic. The exception to this
is the finding of a markedly high hCG, which suggests a molar pregnancy. The
pattern of hCG change in normal and abnormal pregnancies and its correlation with
ultrasound findings is discussed in detail separately. (See"Clinical manifestations,
diagnosis, and management of ectopic pregnancy", section on 'Human chorionic
gonadotropin' .)

Other hormone assays (eg, progesterone, estrogen, inhibin A, PAPP-A) are less
useful.

DIAGNOSTIC EVALUATION OF THREATENED ABORTION

Clinical assessment — Clinical assessment of women with vaginal bleeding and a

closed cervix is insufficient for predicting prognosis because vaginal bleeding is
common in the first trimester, occurring in 20 to 40 percent of pregnant women,
and not always associated with impending abortion [ 73 ]. As discussed above,
even heavy, prolonged bleeding can be associated with a normal outcome.

Direct visualization of a dilated cervix or the gestational sac may be sufficient to

diagnose an inevitable, incomplete, or complete abortion clinically; however,
ultrasound examination can provide additional, sometimes unexpected, information
such as the presence of a multiple gestation or retained products of conception.

Loss of a previously detected fetal cardiac activity should raise suspicion that a
missed abortion has occurred, but often symptoms occur well before the fetal heart
has been detected with a hand-held Doppler device. Furthermore, inability to detect
fetal cardiac activity with these devices can be due to incorrect placement of the
device.

Ultrasonography — Ultrasonography is the most useful test in the diagnostic

evaluation of women with suspected SAb [ 74 ]. There is no role for monitoring hCG
levels once the presence of an intrauterine pregnancy has been established
sonographically.

A definite diagnosis of nonviable intrauterine pregnancy (missed abortion) can be

made based upon either of the following criteria:

 Absence of embryonic cardiac activity in an embryo with crown-rump length

greater than 5 mm [ 75 ].
 Absence of a yolk sac when the mean sac diameter is 13 mm [ 72,76 ].
 Absence of an embryonic pole when the mean sac diameter (average of
diameters measured in each of three orthogonal planes) is greater than
25 mm measured transabdominally or greater than 18 mm by the
transvaginal technique [ 77 ].

These measurements correspond to a gestational age of approximately 6 weeks.

Serial examinations four to seven days apart are helpful to assess viability of the
pregnancy when findings are equivocal or development appears to be lagging
behind that expected by dating criteria. The normal sequential development during
very early pregnancy, as noted sonographically, is shown in the table ( table 1 ).
(See"Prenatal assessment of gestational age" .)

Reassuring ultrasound findings — Ultrasound findings of a normal yolk sac and

fetal cardiac activity early in pregnancy are reassuring [ 64,78 ]. This was
illustrated by a study of consecutive pregnancies that were followed until ongoing
pregnancy or SAb could be documented [ 64 ]:

 The presence of a yolk sac between 22 and 32 days from in vitro fertilization
(IVF) was associated with the development of fetal heart motion in 94
percent of pregnancies, and the absence of the yolk sac by 32 days after
fertilization was always associated with a poor outcome.
 Valvular motion confirms a live pregnancy, but does not eliminate the
possibility of future pregnancy loss. When embryonic heart motion was
detected at 5 to 6 weeks of gestation in women less than 36 years of age,
the risk of subsequent SAb was 4.5 percent; however, the risk of
miscarriage despite previous detection of embryonic heart activity
increased to 10 percent in women aged 36 to 39 years and 29 percent in
women greater than or equal to 40 years of age [ 64 ]. In women with
recurrent pregnancy loss, the risk of spontaneous pregnancy loss after
observation of embryonic heart activity remains high, about 22 percent
[ 79 ].

Findings potentially predictive of pregnancy loss — The following ultrasound

findings are predictive of impending pregnancy loss. If any of these ominous
findings are noted, then a repeat ultrasound examination in about one week is
indicated because of the high likelihood of embryonic/fetal demise. When more
than one ominous finding is present, the risk of subsequent abortion increases
several-fold [ 80 ]:

 Abnormal yolk sac - An abnormal yolk sac may be large for gestational
age, irregular, free floating in the gestational sac rather than at the
periphery, or calcified. In one study, a yolk sac diameter more than two
standard deviations of the mean for the menstrual age had a sensitivity,
specificity, positive predictive value, and negative predictive value for
pregnancy loss of 65, 97, 71, and 95 percent, respectively [ 81 ]. In
another study, a mean sac diameter of 13 mm without a visible yolk sac
was diagnostic of a nonviable gestation in 100 percent of cases [ 76 ].
 Slow fetal heart rate - Embryonic heart rate below 100 beats per minute
(bpm) at 5 to 7 weeks of gestation is slow [ 82-84 ]. In one study, the
first trimester survival rate was 62 percent among 531 embryos with slow
early heart rates (less than 100 bpm at less than 6.2 weeks, less than 120
bpm at 6.3 to 7.0 weeks) compared to 92 percent survival among 1501
embryos with normal heart rates [ 84 ]. Higher rates of pregnancy loss
are associated with lower embryonic heart rates; survival is zero at heart
rates below 70 bpm at 6 to 8 weeks of gestation [ 83,85-88 ]. An
increased risk of first trimester embryonic demise persists in embryos with
a slow heart rate at 6.0 to 7.0 weeks but normal heart rate at follow-up
ultrasound at 8 weeks; one in four of these fetuses were lost [ 88 ]. If
slow cardiac activity is observed, it is prudent to perform a follow-up
sonogram (in five to seven days) to document loss of the cardiac activity
before proceeding to dilatation and curettage.
  Small sac - Small mean sac size (MSS) is diagnosed when the difference
between the MSS and crown-rump length (CRL) is less than 5 mm (MSS -
CRL < 5). In one series, 15 of the 16 patients (94 percent) with normal
embryonic heart rates and small sacs noted on first trimester sonogram
went on to spontaneously abort compared to only 4 of the 52 control
patients (8 percent) with normal sac sizes [ 89 ].

Other findings suggestive of poor pregnancy outcome are a sac with an

irregular contour, mean sac diameter growth rate less than
1 mm/day, minimal decidual thickness/hypoechogenicity of the
choriodecidual area/absent double decidual sac, and low sac position in
the uterus [ 74 ].
 Subchorionic hematoma – A subchorionic hematoma is a risk factor for
SAb ( image 1 and image 2 ) [ 90 ]. A large subchorionic hematoma (ie,
comprising at least 25 percent of the volume of the gestational sac) is
concerning. A meta-analysis of seven comparative studies found that
women with a subchorionic hematoma versus women without had a
significantly increased risk of SAb (18 versus 9 percent; OR 2.18, 95% CI
1.29 –3.68) [ 91 ]. There was also an increased risk of placental abruption
(4 versus 1 percent; OR 5.71, 95% CI 3.91– 8.33) and preterm
premature rupture of membranes (4 versus 2 percent; OR 1.64, 95% CI
1.22– 2.21). Increased risks of preterm labor and stillbirth appeared to be
dependent upon the presence of vaginal bleeding.

Pregnancy outcome associated with subchorionic hematoma appears to

depend upon location, with worse outcomes for retroplacental than
marginal hematomas. The location, rather than the size, of a subchorionic
hematoma is the most salient characteristic in terms of pregnancy
outcome, in our experience. Women with retroplacental hematomas are
more likely to have an adverse outcome than those that are marginal
(only the margin of the placenta is separated) [ 92 ]. Data are mixed
regarding whether increasing size of the hematoma increases the risk of
adverse outcomes [ 93,94 ].

The only management option for subchorionic hematoma is expectant

management. Some clinicians repeat an ultrasound in two weeks to
confirm fetal viability and assess for change in size of the hematoma. This
is often reassuring to the patient, but does not alter management. A
subchorionic hematoma is not an indication for an evaluation for an
inherited thrombophilia.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient

education materials, “The Basics” and “Beyond the Basics.” The Basics patient
education pieces are written in plain language, at the 5 th to 6 th grade reading level,
and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the
10 th to 12 th grade reading level and are best for patients who want in-depth
information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on “patient info” and the
keyword(s) of interest.)

 Basics topics (see "Patient information: Miscarriage (The

Basics)" and "Patient information: Threatened miscarriage (The Basics)" )
 Beyond the Basics topics (see "Patient information: Miscarriage (Beyond the
Basics)" )

SUMMARY AND RECOMMENDATIONS

 Spontaneous abortion (SAb) (ie, a pregnancy that ends spontaneously

before the fetus has reached a viable gestational age) is the most
common complication of early pregnancy, occurring in 8 to 20 percent of
clinically recognized pregnancies and a comparable number of preclinical
pregnancies. (See 'Incidence' above.)
 The best documented risk factors for SAb are advanced maternal age,
previous spontaneous abortion, and maternal smoking. (See'Risk
factors' above.)
 Most SAbs are due to structural or chromosomal abnormalities of the
embryo. (See 'Etiology' above.)
 There are various stages and types of SAb. Women who are actively in the
process of having a spontaneous abortion usually present with a history of
amenorrhea, vaginal bleeding, and pelvic pain. The cervix is open and the
products of conception can be visualized in the vagina or cervical os, if
they have not already been passed. (See 'Clinical manifestation and
diagnosis' above.)
 The cardinal sign of impending abortion is vaginal bleeding. Differential
diagnosis included bleeding related to implantation, ectopic pregnancy,
and cervical, vaginal, or uterine pathology. (See 'Differential
diagnosis' above.)
 Ultrasonography is the most useful test in the diagnostic evaluation of
women suspected of SAb. A definite diagnosis of nonviable intrauterine
pregnancy can be made if either of the following criteria is present: (1)
absence of fetal cardiac activity in an embryo with crown-rump length
greater than 5 mm or (2) absence of a fetal pole when the mean sac
diameter is greater than 18 mm by the transvaginal technique. In the
absence of these findings, other parameters (eg, slow fetal heart rate,
abnormal yolk sac, small gestational sac) are predictive of pregnancy non-
viability, but follow-up should be obtained. (See 'Diagnostic evaluation of
threatened abortion' above.)

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