ABORTION

The word abortion derives from the Latin aboriri—to miscarry. Abortion is defined as the
spontaneous or induced termination of pregnancy before fetal viability. It thus is appropriate that

miscarriage and abortion are terms used interchangeably in a medical context. But because

popular use of abortion by laypersons implies a deliberate intact pregnancy termination, many

prefer miscarriage for spontaneous fetal loss. Newere terms made possible by widespread use of

sonography and human chorionic gonadotropin measurements that identify extremely early
pregnancies include early pregnancy loss, wastage, or failure. Throughout this book, these are all
used at one time or another.
NOMENCLATURE
Terminology used to define fetal viability and thus an abortus has tremendous medical,
legal, and social import. Viability lies between the lines that separate abortion from preterm
birth. It is usually defined by pregnancy duration and fetal birthweight for statistical and legal
purposes (Chap. 1, p. 2). This has led to incongruities in definitions from authoritative
organizations. Importantly, the National Center for Health Statistics, the Centers for Disease
Control and Prevention, and the World Health Organization all define abortion as pregnancy
termination before 20 weeks’ gestation or with a fetus born weighing < 500 g. These criteria,
however, are somewhat contradictory because the mean birthweight of a 20-week fetus is 320 g,
whereas 500 g is the mean for 22 to 23 weeks (Moore, 1977). Further confusion may derive from
criteria set by state laws that define abortion even more widely.
As indicated above, technological developments have revolutionized current abortion
terminology. Transvaginal sonography (TVS) and precise measurement of serum human
chorionic gonadotropin (hCG) concentrations are used to identify extremely early pregnancies as
well as those with an intrauterine versus ectopic location. Ubiquitous application of these
practices makes it possible to distinguish between a chemical and al clinical pregnancy. An ad
hoc internationall consensus group has proposed the term pregnancy of unknown location—PUL
—with the goal of early identification and management of ectopic pregnancy (Barnhart, 2011;
Doubilet, 2013). Management options for ectopic gestation are described in Chapter 19 (p. 384).
Uterine pregnancies that eventuate in a spontaneous abortion are also termed early pregnancy
loss ors early pregnancy failure.
 Terms that have been in clinical use for many decades are generally used to describe later
pregnancy losses. These include:
1. Spontaneous abortion—this category includes threatened, inevitable, incomplete,
complete, and missed abortion. Septic abortion is used to further classify any of these that
are complicated further by infection.
2. Recurrent abortion—this term is variably defined, but it is meant to identify women with
repetitive spontaneous abortions so that an underlying factor(s) can be treated to achieve
a viable newborn.
3. Induced abortion—this term is used to describe surgical or medical termination of a live
fetus that has not reached viability
FIRST-TRIMESTER SPONTANEOUS ABORTION
 Pathogenesis
More than 80 percent of spontaneous abortions occur within the first 12 weeks of gestation. With
first-trimester losses, death of the embryo or fetus nearly always precedes spontaneous
expulsion. Death is usually accompanied by hemorrhage into the decidua basalis. This is
followed by adjacent tissue necrosis that stimulates uterine contractions and expulsion. An intact
gestational sac is usually filled with fluid and may or may not contain an embryo or fetus. Thus,
the key to determining the cause of early miscarriage is to ascertain the cause of fetal death. In
contradistinction, in later pregnancy losses, the fetus usually does not die before expulsion, and
thus other explanations are sought.
 Incidence
Statistics regarding the incidence of spontaneous abortion vary according to the diligence used
for its recognition. Wilcox and colleagues (1988) studied 221 healthy women through 707
menstrual cycles and found that 31 percent of pregnancies were lost after implantation. They
used highly specific assays for minute concentrations of maternal serum β - hCG and reported
that two thirds of these early losses were clinically silent. Currently, there are factors known to
influence clinically apparent spontaneous abortion, however, it is unknown if these same factors
affect clinically silent miscarriages. By way of example, the rate of clinical miscarriages is
almost doubled when either parent is older than 40 years (Gracia, 2005; Kleinhaus, 2006). But, it
is not known if clinically silent miscarriages are similarly affected by parental age.
  Fetal Factors
As shown in Table 18-1, approximately half of miscarriages are anembryonic, that is, with no
identifiable embryonic elements. Less accurately, the term blighted ovum may be used (Silver,
2011). The other 50 percent are embryonic miscarriages,c which commonly display a
developmental abnormality of the zygote, embryo, fetus, or at times, the placenta. Of embryonic
miscarriage, half of these—25 percent of all abortuses—have chromosomal anomalies and thus
are aneuploid abortions. The remaining cases are euploid abortions, that is, carrying a normal
chromosomal complement.

FIGURE 18-1 Frequency of chromosomal anomalies in abortuses and

stillbirths during each trimester. Approximate percentages for each
group are shown. (Data from Eiben, 1990; Fantel, 1980; Warburton,
1980.)

Aneuploid Abortion
Both abortion rates and chromosomal anomalies decrease with advancing gestational age.
As shown in Figure 18-1, 50 percent of embryonic abortions are aneuploid, but chromosomal
abnormalities are found in just a third of second-trimester fetal losses and in only 5 percent of
third-trimester stillbirths. Aneuploid abortion occurs at earlier gestational ages. Kajii and
associates (1980) noted that 75 percent of aneuploid abortions occurred by 8 weeks. Of these, 95
percent of chromosomal abnormalities are caused by maternal gametogenesis errors, and 5
percent by paternal errors (Jacobs, 1980). Some found most common are listed in Table 18-1.
With first-trimester miscarriages, autosomal trisomy is they most frequently identified
chromosomal anomaly. Although most trisomies result from isolated nondisjunction, balanced
structural chromosomal rearrangements are found in one partner in 2 to 4 percent of couples with
recurrent miscarriages. Trisomies have been identified in abortuses for all except chromosome
number 1, and those with 13, 16, 18, 21, and 22 are most common. A previous miscarriage
increases the baseline risk for aneuploidy in a subsequent fetus from 1.4 to 1.7 percent (Bianco,
2006). With two or three previous miscarriages, the risk increases to 1.8 and 2.2 percent,
respectively.
Monosomy X (45,X) is the single most frequent specific chromosomal abnormality. This
is Turner syndrome, which usually results in abortion, but liveborn females are described (Chap.
13, p. 264). Conversely, autosomal monosomy is rare and incompatible with life.
Triploidy is often associated with hydropic or molar placental degeneration (Chap. 20, p.
398). The fetus within a partial hydatidiform mole frequently aborts early, and the few carried
longer are all grossly deformed. Advanced maternal and paternal age do not increase the
incidence of triploidy. Tetraploid fetuses most often abort early in gestation, and they are rarely
liveborn. Last, chromosomal structural abnormalities infrequently cause abortion.
Euploid Abortion
Chromosomally normal fetuses abort later than those that are aneuploid. Specifically, the
rate of euploid abortions peaks at approximately 13 weeks (Kajii, 1980). In addition, the
incidence of euploid abortions increases dramatically after maternal age exceeds 35 years (Stein,
1980).
 Maternal Factors
The causes of euploid abortions are poorly understood, but various medical disorders,
environmental conditions, and developmental abnormalities have been implicated. One example
is the well-known influence of maternal age just described.
Infections
Some common viral, bacterial, and other infectious agents that invade the normal human
can cause pregnancy loss. Many are systemic and infect the fetoplacental unit by bloodborne
organisms. Others may infect locally through genitourinary infection or colonization. However,
despite the numerous infections acquired in pregnancy, these uncommonly cause early abortion.
Brucella abortus, Campylobacter fetus, and Toxoplasma gondii infections cause abortion in
livestock, but their role in human pregnancy is less clear (Feldman, 2010; Hide, 2009;
Mohammad, 2011; Vilchez, 2014). There appear to be no abortifacient effects of infections
caused by Listeria monocytogenes, parvovirus, cytomegalovirus, or herpes simplex virus
(Brown, 1997; Feldman, 2010). One possible exception is infection with Chlamydia trachomatis,
which was found to be present in 4 percent of abortuses compared with < 1 percent of controls
(Baud, 2011). Another is polymicrobial infection from periodontal disease that has been linked
with a two- to fourfold increased risk (Holbrook, 2004; Moore, 2004; Xiong, 2007).
Data concerning a link between some other infections and increased abortion are
conflicting. Examples are Mycoplasma and Ureaplasma (Quinn, 1983a,b; Temmerman, 1992).
Another is an association with human immunodeficiency virus (HIV) (Quinn, 1983a,b; van
Benthem, 2000). Oakeshott and coworkers (2002) reported an association between second-, but
not first-, trimester miscarriage and bacterial vaginosis.
Medications
Only a few medications have been evaluated concerning a role with early pregnancy loss.
Oral contraceptives or spermicidal agents used in contraceptive creams and jellies are not
associated with an increased miscarriage rate. Similarly, non steroidal antiinflammatory drugs or
ondansetron are not linked (Edwards, 2012; Pasternak, 2013). A pregnancy with an intrauterine
device (IUD) in situ has an increased risk of abortion and specifically of septic abortion (Chap.
38, p. 700). With the newer IUDs, Moschos and Twickler (2011) reported that only 6 of 26 intact
pregnancies aborted before 20 weeks. Finally, studies have shown no increase in pregnancy loss
rates with meningococcal conjugate or trivalent inactivated influenza vaccines (Irving, 2013;
Zheteyeva, 2013).
Cancer.
Therapeutic doses of radiation are undeniably abortifacient, but doses that cause abortion
are not precisely known (Chap. 46, p. 930). According to Brent (2009), exposure to < 5 rads does
not increase the risk.
Cancer survivors who were previously treated with abdominopelvic radiotherapy may
later be at increased risk for miscarriage. Wo and Viswanathan (2009) reported an associated
two- to eightfold increased risk for miscarriages, low-birthweight and growth-restricted infants,
preterm delivery, and perinatal mortality in women previously treated with radiotherapy. Hudson
(2010) found an associated increased risk for miscarriage in those given radiotherapy and
chemotherapy in the past for a childhood cancer.
The effects of chemotherapy in causing abortion are not well defined (Chap. 12, p. 248).
Particularly worrisome are women with an early normal gestation erroneously treated with
methotrexate for an ectopic pregnancy (Chap. 19, p. 384). In a report of eight such cases, two
viable-size fetuses had multiple malformations. In the remaining six cases, three each had a
spontaneous or induced abortion (Nurmohamed, 2011).
Diabetes Mellitus
The abortifacient effects of uncontrolled diabetes are well- known. Optimal glycemic
control will mitigate much of this loss and is discussed in Chapters 8 (p. 157) and 57 (p. 1128).
Spontaneous abortion and major congenital malformation rates are both increased in women with
insulin-dependent diabetes. This is directly related to the degree of periconceptional glycemic
and metabolic control.
Thyroid Disorders
These have long been suspected to cause early pregnancy loss and other adverse
pregnancy outcomes. Severe iodine deficiency, which is infrequent in developed countries, has
been associated with increased miscarriage rates (Castañeda, 2002). Varying degrees of thyroid
hormone insufficiency are common in women. Although the worst—overt hypothyroidism—is
infrequent in pregnancy, subclinical hypothyroidism has an incidence of 2 to 3 percent (Casey,
2005; Garber, 2012). Both are usually caused by autoimmune Hashimoto thyroiditis, in which
both incidence and severity accrue with age. Despite this common prevalence, any increased
risks for miscarriage due to hypothyroidism are still unclear (Krassas, 2010; Negro, 2010). That
said, De Vivo (2010) reported that subclinical thyroid hormone deficiency may be associated
with very early pregnancy loss.
The prevalence of abnormally high serum levels of antibodies to thyroid peroxidase or
thyroglobulin is nearly 15 percent in pregnant women (Abbassi-Ghanavati, 2010; Haddow,
2011). Although most of these women are euthyroid, those with clinical hypothyroidism tend to
have higher concentrations of antibodies. Even in euthyroid women, however, antibodies are a
marker for increased miscarriage (Benhadi, 2009; Chen, 2011; Thangaratinam, 2011). This has
been confirmed by two prospective studies, and preliminary data from one suggest that thyroxine
supplementation decreases this risk (Männistö, 2009; Negro, 2006). Effects associated with
thyroid disorders in women with recurrent miscarriage are considered further on page 359.
Surgical Procedures
The risk of miscarriage caused by surgery is not well studied. There is extensive interest
in pregnancy outcomes following bariatric surgery, because as discussed on page 353, obesity is
an uncontested risk factor for miscarriage. However, currently, it is not known if this risk is
mitigated by weight-reduction surgery (Guelinckx, 2009).
It is likely that uncomplicated surgical procedures performed during early pregnancy do
not increase the risk for abortion (Mazze, 1989). Ovarian tumors can generally be resected
without causing miscarriage (Chap. 63, p. 1227). An important exception involves early removal
of the corpus luteum or the ovary in which it resides. If performed before 10 weeks’ gestation,
supplemental progesterone should be given. Between 8 and 10 weeks, a single 150-mg
intramuscular injection of 17-hydroxyprogesterone caproate is given at the time of surgery. If
between 6 to 8 weeks, then two additional 150-mg injections should be given 1 and 2 weeks after
the first. Other progesterone regimens include: (1) oral micronized progesterone (Prometrium),
200 or 300 mg orally once daily, or (2) 8-percent progesterone vaginal gel (Crinone) given
intravaginally as one premeasured applicator daily plus micronizeds progesterone 100 or 200 mg
orally once daily continued until 10 weeks’ gestation.
Trauma seldom causes first-trimester miscarriage, and although Parkland Hospital is a
busy trauma center, this is an infrequent association. Major trauma—especially abdominal— can
cause fetal loss, but is more likely as pregnancy advances (Chap. 47, p. 950).
Nutrition
Extremes of nutrition—severe dietary deficiency and morbid obesity—are associated
with increased miscarriage risks. Dietary quality may also be important, as this risk may be
reduced in women who consume fresh fruit and vegetables daily (Maconochie, 2007).
Sole deficiency of one nutrient or moderate deficiency of all does not appear to increase
risks for abortion. Even in extreme cases—for example, hyperemesis gravidarum—abortion is
rare (Maconochie, 2007). Other examples discussed on page 352 are anorexia anda bulimia
nervosa. Importantly, Bulik and colleagues (2010) reported that half of pregnancies in women
with anorexia nervosa were unplanned.
Obesity is associated with a litany of adverse pregnancy outcomes (Chap. 48, p. 965).
These include subfertility and an increased risk of miscarriage and recurrent abortion (Jarvie,
2010; Lashen, 2004; Satpathy, 2008). In a study of 6500 women who conceived with in vitro
fertilization (IVF), live birth rates were reduced progressively for each body mass index (BMI)
unit increase (Bellver, 2010a). As noted earlier, although the risks for many adverse late
pregnancy outcomes are decreased after bariatric surgery, any salutary effects on the miscarriage
rate are not clear (Guelinckx, 2009).
Social and Behavioral Factors
Lifestyle choices reputed to be associated with an increased miscarriage risk are most
commonly related to chronic and especially heavy use of legal substances. The most common
used is alcohol, with its potent teratogenic effects discussed in Chapter 12 (p. 245). That said, an
increased miscarriage risk is only seen with regular or heavy use (Floyd, 1999; Maconochie,
2007). In fact, low-level alcohol consumption does not significantly increase the abortion risk
(Cavallo, 1995; Kesmodel, 2002).
At least 15 percent of pregnant women admit to cigarette smoking (Centers for Disease
Control and Prevention, 2013). It seems intuitive, but unproven, that cigarettes could cause early
pregnancy loss by a number of mechanisms that cause adverse late-pregnancy outcomes (Catov,
2008).
Excessive caffeine consumption—not well defined—has been associated with an
increased abortion risk. There are reports that heavy intake of approximately five cups of coffee
per day—about 500 mg of caffeine—slightly increases the abortion risk (Armstrong, 1992;
Cnattingus, 2000; Klebanoff, 1999). Studies of “moderate”—less than 200 mg daily—did not
increase the risk (Savitz, 2008; Weng, 2008). Currently, the American College of Obstetricians
and Gynecologists (2013b) has concluded that moderate consumption likely is not a major
abortion risk and that any associated risk with higher intake is unsettled. Adverse effects of illicit
drugs are discussed in Chapter 12 (p. 253).
Occupational and Environmental Factors
It is intuitive to limit exposure of pregnant women to any toxin. That said, although some
environmental toxins such as benzene are implicated in fetal malformations, data with
miscarriage risk is less clear (Lupo, 2011). The major reason is that it is not possible to
accurately assess environmental exposures. Earlier reports that implicated some chemicals as
increasing miscarriage risk include arsenic, lead, formaldehyde, benzene, and ethylene oxide
(Barlow, 1982). More recently, there is evidence that DDT—dichlorodiphenyltrichloroethane—
may cause excessive miscarriage rates (Eskenazi, 2009). In fact, use of DDT-containing
insecticides had been suspended. But in 2006, it was again and is still endorsed by the World
Health Organization (2011) for mosquito control for malaria prevention.
 There are even fewer studies of occupational exposures and abortion risks. In a follow-up
of the Nurses Health Study II, Lawson and associates (2012) reported slightly increased
miscarriage risks in nurses exposed to antineoplastic drugs, sterilizing agents, and x-rays. Some
of these found that exposure to video display terminals or tos ultrasound did not increased
miscarriage rates (Schnorr, 1991; Taskinen, 1990). Increased miscarriage risk was found for
dental assistants exposed to more than 3 hours of nitrous oxide daily if there was no gas-
scavenging equipment (Boivin, 1997; Rowland, 1995). Conclusions from a metaanalysis were
that there is a small incremental risk for spontaneous abortion in women who worked with
cytotoxic antineoplastic chemotherapeutic agents (Dranitsaris, 2005).
Immunological Factors
The immune tolerance of the mother to the paternal-haploid fetal combination remains
enigmatic (Calleja-Agius, 2011; Williams, 2012). This is discussed in greater detail in Chapter 5
(p. 97). There is, however, an increased risk for early pregnancy loss with some immune-
mediated disorders. The most potent of these are antiphospholipid antibodies directed against
binding proteins in plasma (Erkan, 2011). These along with clinical and laboratory findings
provide criteria for the antiphospholipid antibody syndrome—APS (American CollegeS of
Obstetricians and Gynecologists, 2012). Because associated pregnancy loss can be repetitive,
recurrent miscarriage due to APS is discussed on page 359.
Inherited Thrombophilias
Although thrombophilias were initially linked to various pregnancy outcomes, most
putative associations have been refuted. Currently, the American College of Obstetricians and
Gynecologists (2013a) is of the opinion that there is not a definitive causal link between these
thrombophilias and adverse pregnancy outcomes in general, and abortion in particular.
Uterine Defects
Various inherited and acquired uterine defects are known to cause both early and late
recurrent miscarriages, and they are considered on page 358.
 Paternal Factors
These factors in the genesis of miscarriage are not well studied. Chromosomal abnormalities in
sperm reportedly had an increased abortion risk (Carrell, 2003). Increasing paternal age was
significantly associated with increased risk for abortion in the Jerusalem Perinatal Study
(Kleinhaus, 2006). This risk was lowest before age 25 years, after which it progressively
increased at 5-year intervals.
 Clinical Classification of Spontaneous Abortion
Threatened Abortion
The clinical diagnosis of threatened abortion is presumed when bloody vaginal discharge or
bleeding appears through a closed cervical os during the first 20 weeks (Hasan, 2009). Bleeding
in early pregnancy must be differentiated from implantation bleeding, which some women have
at the time of the expected menses (Chap. 5, p. 90). Almost a fourth of women develop clinically
significant bleeding during early gestation that may persist for days or weeks. With miscarriage,
bleeding usually begins first, and cramping abdominal pain follows hours to days later. There
may be low-midline clearly rhythmic cramps; persistent low backache with pelvic pressure; or
dull and midline suprapubic discomfort. Bleeding is by far the most predictive risk factor for
pregnancy loss (Eddleman, 2006). Overall, approximately half will abort, but this risk is
substantially less if there is fetal cardiac activity (Tongsong, 1995).
Even if miscarriage does not follow early bleeding, the risk for later adverse pregnancy
outcomes is increased as shown in Table 18-2. In the study of almost 1.8 million pregnancies
from the Danish National Patient Registry, there was a threefold risk for many of these
pregnancy complications.
Threatened Abortion versus Ectopic Pregnancy. Every woman with an early pregnancy, vaginal
bleeding, and pain should be evaluated. The primary goal is prompt diagnosis of an ectopic
pregnancy. As discussed in Chapter 19.
TABLE 18-2. Adverse Outcomes That are Increased in Women with Threatened Abortion
Maternal Perinatal
Placenta previa Preterm ruptured membranes
Placental abruption Preterm birth
Manual removal of placenta Low-birthweight infant
Cesarean delivery Fetal-growth restriction
Fetal and neonatal death
 FIGURE 18-2 Composite curve describing decline in
serial human chorionic gonadotropin (hCG) values
starting at a level of 2000 mIU/mL following early
spontaneous miscarriage. The dashed line is the
predicted curve based on the summary of data from
all women. The colored area within the dashed lines
represents the 95-percent confidence intervals. (Data
from Barnhart, 2004a.)

(p. 381), serial quantitative serum β-hCG and progesterone levels and transvaginal sonography
are used to ascertain if there is an intrauterine live fetus. Because these are not 100-percent
accurate to confirm early fetal death or location, repeat evaluations are often necessary. Serum
hCG levels in women with bleeding who went on to have an early miscarriage are shown in
Figure 18-2 and in Table 19-1 (p. 381). Values for women with early pregnancy bleeding who
went on to have a normal pregnancy are shown in Figure 18-3. Several predictive models have
been described (Barnhart, 2010; Condous, 2007; Connolly, 2013). With a robust uterine
pregnancy, serum β-hCG levels should increase at least 53 to 66 percent every 48 hours
(Barnhart, 2004a; Kadar, 1982). Serum progesterone concentrations < 5 ng/mL suggest a dying
pregnancy, whereas values > 20 ng/mL support the diagnosis of a healthy pregnancy.
FIGURE 18-3 Composite curve of increasing serum
levels of beta-human chorionic gonadotropin (β-hCG)
in women with early bleeding and subsequent normal
pregnancy. (Data from Barnhart, 2004b.)

Transvaginal sonography is used to locate the pregnancy and determine if the fetus is
alive. If this cannot be done, then pregnancy of unknown location is diagnosed (Chap. 19, p.
381). The gestational sac—an anechoic fluid collection that represents the exocoelomic cavity—
may be seen by 4.5 weeks (Fig. 9-3, p. 170). At this same time, β -hCG levels are generally
considered to be 1500 to 2000 mIU/mL (Barnhart, 1994; TimorTritsch, 1988). Connolly and
colleagues (2013) observed that this value could be as low as 390 mIU/mL, but also noted that a
threshold as high as 3500 mIU/mL may be needed to identify the gestational sac in 99 percent of
cases.
Another caveat is that a gestational sac may appear similar to other intrauterine fluid
accumulations—the so-called pseudogestational sac (Fig. 19-5, p. 382). This pseudosac may be
seen with ectopic pregnancy and is easier to exclude once a yolk sac is seen. Typically, the yolk
sac is visible by 5.5 weeks and with a mean gestational-sac diameter of 10 mm. Thus, the
diagnosis of a uterine pregnancy should be made cautiously if the yolk sac is not yet seen
(American College of Obstetricians and Gynecologists, 2011e).
At 5 to 6 weeks, a 1- to 2-mm embryo adjacent to the yolk sac can be seen (Daya, 1993).
Absence of an embryo in a sac with a mean sac diameter of 16 to 20 mm suggests a dead fetus
(Levi, 1988; Nyberg, 1987). Finally, fetal cardiac activity can be detected at 6 to 6.5 weeks with
an embryonic length of 1 to 5 mm and a mean sac diameter of 13 to 18 mm. A 5-mm embryo
without cardiac activity is likely dead (Goldstein, 1992; Levi, 1990).
There are various management schemes derived from these findings. At Parkland
Hospital, to ensure that live intrauterine pregnancies are not interrupted, we define the threshold
of embryo fetal death based on values two standard deviations from the mean. Thus, an
anembryonic gestation is diagnosed when the mean gestational sac diameter measures ≥ 20 mm
and no embryo is seen. Embryonic death is also diagnosed if an embryo measuring ≥ 10 mm has
no cardiac activity.
Management. Acetaminophen-based analgesia will help relieve discomfort from cramping. If
uterine evacuation is not indicated, bed rest is often recommended but does not improve
outcomes. Neither has treatment with a host of medications that include chorionic gonadotropin
(Devaseelan, 2010). With persistent or heavy bleeding, the hematocrit is determined. If there is
significant anemia or hypovolemia, then pregnancy evacuation is generally indicated. In these
cases in which there is a live fetus, some choose transfusion and further observation.
Anti-D Immunoglobulin. With spontaneous miscarriage, 2 percent of Rh D-negative women will
become alloimmunized if not provided passive isoimmunization. With an induced abortion, this
rate may reach 5 percent. The American College of Obstetricians and Gynecologists (2013c)
recommends anti-Rh0 (D) immunoglobulin given as 300 μg intramuscularly (IM) for all
gestational ages, or 50 μg IM for pregnancies ≤ 12 weeks and 300 μg for ≥ 13 weeks.
 With threatened abortion, immunoglobulin prophylaxis is controversial because of sparse
evidence-based data (American College of Obstetricians and Gynecologists, 2013c; Hannafin,
2006; Weiss, 2002). That said, some choose to administer anti-D immunoglobulin up to 12
weeks’ gestation for a threatened abortion and a live fetus. At Parkland Hospital, we administer a
50-μg dose to all Rh D-negative women with first-trimester bleeding.
Inevitable Abortion
In the first trimester, gross rupture of the membranes along with cervical dilatation is nearly
always followed by either uterine contractions or infection. A gush of vaginal fluid during the
first half of pregnancy usually has serious consequences. In some cases not associated with pain,
fever, or bleeding, fluid may have collected previously between the amnion and chorion. If this is
documented, then diminished activity with observation is a reasonable course. After 48 hours, if
no additional amnionic fluid has escaped and if there is no bleeding, cramping, or fever, then a
woman may resume ambulation and pelvic rest. With bleeding, cramping, or fever, abortion is
considered inevitable, and the uterus is evacuated.
Incomplete Abortion
Bleeding that follows partial or complete placental separation and dilation of the cervical os is
termed incomplete abortion. The fetus and the placenta may remain entirely within the uterus or
partially extrude through the dilated os. Before 10 weeks, they are frequently expelled together,
but later, they deliver separately. Management options of incomplete abortion include curettage,
medical abortion, or expectant management in clinically stable women as discussed on page 357.
With surgical therapy, additional cervical dilatation may be necessary before suction curettage.
In others, retained placental tissue simply lies loosely within the cervical canal and can be easily
extracted with ring forceps.
Complete Abortion
At times, expulsion of the entire pregnancy may be completed before a woman presents to the
hospital. A history of heavy bleeding, cramping, and passage of tissue or a fetus is common.
Importantly, during examination, the cervical os is closed. Patients are encouraged to bring in
passed tissue, which may be a complete gestation, blood clots, or a decidual cast. The last is a
layer of endometrium in the shape of the uterine cavity that when sloughed can appear as a
collapsed sac (Fig. 19-3, p. 379).
 If an expelled complete gestational sac is not identified, sonography is performed to
differentiate a complete abortion from threatened abortion or ectopic pregnancy. Characteristic
findings of a complete abortion include a minimally thickened endometrium without a
gestational sac. However, this does not guarantee a recent uterine pregnancy. Condous and
associates (2005) described 152 women with heavy bleeding, an empty uterus with endometrial
thickness < 15 mm, and a diagnosis of completed miscarriage. Six percent were subsequently
proven to have an ectopic pregnancy. Thus, unless products of conception are seen or unless
sonography confidently documents, at first an intrauterine pregnancy, and then later an empty
cavity, a complete abortion cannot be surely diagnosed. In unclear settings, serial serum hCG
measurements aid clarification. With complete abortion, these levels drop quickly (Connolly,
2013)
Missed Abortion
Also termed early pregnancy failure or loss, missed abortion, as originally defined, is
contemporaneously misused compared with its meaning many decades ago. Historically, the
term was used to describe dead products of conception that were retained for days, weeks, or
even months in the uterus with a closed cervical os. Early pregnancy appeared to be normal with
amenorrhea, nausea and vomiting, breast changes, and uterine growth. Because suspected fetal
death could not be confirmed, expectant management was the sole option, and spontaneous
miscarriage would eventually ensue. And because the time of fetal death could not be determined
clinically, pregnancy duration—and thus fetal age—was erroneously calculated from the last
menses. To elucidate these disparities, Streeter (1930) studied aborted fetuses and reported that
the mean death-to-abortion interval was approximately 6 weeks.
This historical description of missed abortion is in contrast to that defined currently based
on results of serial serum β-hCG assays and transvaginal sonography (Fig. 18-4). With rapid
confirmation of fetal or embryonic death, many women choose uterine evacuation. Although
many classify these as a missed abortion, the term is used interchangeably with early pregnancy
loss or wastage (Silver, 2011).
FIGURE 18-4 Transvaginal sonogram displays a large anechoic
sac consistent with an anembryonic gestation. Calipers measure
uterine length and anteroposterior thickness in a sagittal plane.
Septic Abortion
Horrific infections and maternal deaths associated with criminal septic abortions have become
rare with legalized abortion. Still, perhaps 1 to 2 percent of women with threatened or
incomplete miscarriage develop a pelvic infection and sepsis syndrome. Elective abortion, either
surgical or medical, is also occasionally complicated by severe and even fatal infections (Barrett,
2002; Ho, 2009). Bacteria gain uterine entry and colonize dead conception products. Organisms
may invade myometrial tissues and extend to cause parametritis, peritonitis, septicemia, and,
rarely, endocarditis (Vartian, 1991). Particularly worrisome are severe necrotizing infections and
toxic shock syndrome caused by group A streptococcus—S pyogenes (Daif, 2009).
During the last few years, rare but severe infections with otherwise low-virulence
organisms have complicated medical abortions. Deaths have been reported from toxic shock
syndrome due to Clostridium perfringens (Centers for Disease Control and Prevention, 2005).
Similar infections are caused by Clostridium sordellii and havei clinical manifestations that begin
within a few days after an abortion. Women may be afebrile when first seen with severe
endothelial injury, capillary leakage, hemoconcentration, hypotension, and a profound
leukocytosis (Cohen, 2007; Fischer, 2005; Ho, 2009). Maternal deaths from these clostridial
species approximate 0.58 per 100,000 medical abortions (Meites, 2010).
Management of clinical infection includes prompt administration of broad-spectrum
antibiotics as discussed in Chapter 37 (p. 685). If there are retained products or fragments, then
suction curettage is also performed. Most women respond to this treatment within 1 to 2 days,
and they are discharged when afebrile. Follow-up oral antibiotic treatment is likely unnecessary
(Savaris, 2011). In a very few women, severe sepsis syndrome causes acute respiratory distress
syndrome, acute kidney injury, or disseminated intravascular coagulopathy. In these cases,
intensive supportive care is essential (Chap. 47, p. 940).
To prevent postabortal sepsis, prophylactic antibiotics are given at the time of induced
abortion or spontaneous abortion that requires medical or surgical intervention. The American
College of Obstetricians and Gynecologists (2011b) recommends doxycycline, 100 mg orally 1
hr before and then 200 mg orally after a surgical evacuation. At Planned Parenthood clinics, for
medical abortion, doxycycline 100 mg is taken orally daily for 7 days and begins with
abortifacient administration (Fjerstad, 2009b)
  Management of Spontaneous Abortion
With embryofetal death now easy to verify with current sonographic technology, management
can be more individualized. Unless there is serious bleeding or infection with an incomplete
abortion, any of three options are reasonable—expectant, medical, or surgical management. Each
has its own risks and benefits—for example, the first two are associated with unpredictable
bleeding, and some women will undergo unscheduled curettage. Also, success of any method
depends on whether the woman has an incomplete or missed abortion. Some of the risks and
benefits are summarized as follows:
1. Expectant management of spontaneous incomplete abortion has failure rates as high as 50
percent.
2. Medical therapy with prostaglandin E 1 (PGE 1) has varying failure rates of 5 to 40
percent. In 1100 women with suspected first-trimester abortion, 81 percent had a
spontaneous resolution (Luise, 2002).
3. Curettage usually results in a quick resolution that is 95 to 100-percent successful. It is
invasive and not necessary for all women.
It is possible that patients and clinicians opt for surgical methods when there is not a strict
protocol for medical treatment (Kollitz, 2011).
Several randomized studies that compared these management schemes were reviewed by
Neilson (2010). A major drawback cited for between-study comparisons was varied inclusion
criteria and techniques. For example, studies that included women with vaginal bleeding reported
greater success for medical therapy than did studies that excluded such women (Creinin, 2006).
With these caveats in mind, selected studies reported since 2005 are listed in Table 18-3.
Importantly, Smith and coworkers (2009) reported that subsequent pregnancy rates did not differ
among these management methods
RECURRENT MISCARRIAGE
Other terms that have been used to describe repetitive early spontaneous pregnancy losses
include recurrent spontaneous abortion, recurrent pregnancy loss, and habitual abortion. It is
generally accepted that approximately 1 percent of fertile couples have recurrent miscarriages
classically defined as three or more consecutive pregnancy losses at ≤ 20 weeks or with a fetal
weight < 500 grams. Most of these are embryonic or early losses, and the remainder either are
anembryonic or occur after 14 weeks. Studies are difficult to compare because of
nonstandardized definitions. For example, some investigators include women with two instead of
three consecutive losses, and yet others include women with three nonconsecutive losses.
Documentation of pregnancy with β-hCG levels, sonography, and pathological examination also
varies widely.
At minimum, recurrent miscarriage should be distinguished from sporadic pregnancy loss
that implies intervening pregnancies that reached viability. Although women in the latter
category were thought to have a much lower risk of yet another abortion, there are reports such
as the one shown in Table 18-4 that question this assumption. In two studies, the risk for
subsequent miscarriage is similar following either two or three pregnancy losses. Remarkably,
the chances for a successful pregnancy are > 50 percent even after five losses (Brigham, 1999).
The American Society for Reproductive Medicine (2008) proposed that recurrent
pregnancy loss be defined as two or more failed clinical pregnancies confirmed by either
sonographic or histopathological examination. A thorough evaluation certainly is warranted after
three losses, and treatment is initiated earlier in couples with concordant subfertility (Jaslow,
2010; Reddy, 2007). Treatment considerations are beyond the scope of this book. The reader is
referred to Chapters 6 and 20 in the 2nd edition of Williams Gynecology (Cunningham, 2012;y
Doody, 2012).
 Etiology
There are many putative causes of recurrent abortion, however, only three are widely accepted:
parental chromosomal abnormalities, antiphospholipid antibody syndrome, and a subset of
uterine abnormalities. Other suspected but not proven causes are alloimmunity,
endocrinopathies, environmental toxins, and various infections. Infections seldom cause even
sporadic loss. Thus, most are unlikely to cause recurrent miscarriage, especially since maternal
antibodies usually have developed. For years, various inherited thrombophilia mutations that
include factor V Leiden, prothrombin G20210A, protein C and S deficiency, and antithrombin
deficiency were suspected. But, as discussed in Chapter 52 (p. 1029), large studies have refuted
an association between increased pregnancy wastage and these thrombophilias (American
College of Obstetricians and Gynecologists, 2013a).
TABLE 18-4. Predicted Miscarriage Rate in Scottish Women with Their Next Pregnancy
According to Number of Prior Miscarriagesa
Number of Prior Pregnancy Losses
0 1 2 3
Initial pregnancy 143,595 6577 700 115
with miscarriage (n)
Subsequent risk for 7% 14% 26% 28%
miscarriage
Nonconsecutive miscarriages showed the same pattern of risk as consecutive miscarriages.
a

Data from Bhattacharya, 2010

There is some evidence to support a role for various polymorphisms of gene expression
in miscarriages. Just a few examples include polymorphisms that alter VEGF-A expression,
those that exaggerate platelet aggregation, and those with a specific maternal type of Th1 and
Th2 immune response (Calleja-Agius, 2011; Corardetti, 2013; Eller, 2011; Flood, 2010).
The timing of recurrent loss may offer clues, and in some women, each miscarriage may
occur near the same gestational age (Heuser, 2010). Genetic factors usually result in early
embryonic losses, whereas autoimmune or uterine anatomical abnormalities more likely cause
second-trimester losses (Schust, 2002). As mentioned, first-trimester losses in recurrent
miscarriage have a significantly lower incidence of genetic abnormalities than sporadic losses—
25 versus 50 percent (Sullivan, 2004). That said, routine chromosomal evaluation of abortuses is
costly and may not accurately reflect the fetal karyotype.
 Parental Chromosomal Abnormalities
Although these account for only 2 to 4 percent of recurrent losses, karyotypic evaluation of both
parents is considered by many to be a critical part of evaluation. In an earlier study, balanced
reciprocal translocations accounted for half of chromosomal abnormalities, robertsonian
translocations for a fourth, and X chromosome mosaicism—47,XXY or Klinefelter syndrome—
foree 12 percent (Therapel, 1985). These chromosomal abnormalities are repetitive for
consecutive losses (van den Boogaard, 2010). Inheritance of translocation syndromes and their
sequelae are discussed in detail in Chapter 13 (p. 266).
After thorough genetic counseling, couples with an abnormal karyotype can usually be
managed with IVF followed by preimplantation genetic diagnosis. These techniques are
described in detail in Chapter 20 of Williams Gynecology (Doody, 2012).
 Anatomical Factors
Several genital tract abnormalities have been implicated in recurrent miscarriage and other
adverse pregnancy outcomes, but not infertility (Reichman, 2010). According to Devi Wold and
colleagues (2006), 15 percent of women with three or more consecutive miscarriages will be
found to have a congenital or acquired uterine anomaly.
Of acquired abnormalities, uterine synechiae—Asherman—syndrome—usually result
from destruction of large areas of endometrium. This can follow uterine curettage or ablative
procedures. Characteristic multiple filling defects are seen with hysterosalpingography or saline-
infusion sonography. Treatment is done using directed hysteroscopic lysis of adhesions. In many
women, this lowers miscarriage rates and improves the “take home” pregnancy rate (Al-Inany,
2001; Goldenberg, 1995).
Uterine leiomyomas are found in a large proportion of adults women and can cause
miscarriage, especially if located near the placental implantation site. That said, data indicating
them to be a significant cause of recurrent pregnancy loss are not convincing (Saravelos, 2011).
Uterine cavity distortion is apparently not requisite for bad outcomes (Sunkara, 2010). But in
women undergoing IVF, pregnancy outcomes were adversely affected by submucous but not
subserosal or intramural leiomyomas (Jun, 2001; Ramzy, 1998). As discussed in Chapter 63 (p.
1226), most agree that consideration be given to excision of submucosal and intracavitary
leiomyomas in women with recurrent losses. Ironically, women undergoing uterine artery
embolization of myomas had an increased risk for miscarriage in a subsequent pregnancy
(Homer, 2010).
In contrast, congenital genital tract anomalies commonly originate from abnormal
müllerian duct formation or abnormal fusion. These have an overall incidence of approximately
1 in 200 women (Nahum, 1998). The distribution of anomalies and associated loss rates are
shown in Table 18-5. Depending on their anatomy, some may increase risks for early
miscarriage, whereas others may cause midtrimester abortion or preterm delivery. Unicornuate,
bicornuate, and septate uteri are associated with all three types of loss (Reichman, 2010). Looked
at another way, developmental uterine anomalies were found in approximately 20 percent of
women with recurrent pregnancy losses compared with about 7 percent of controls (Salim,
2003).
It has proven difficult to demonstrate that correction of uterine anomalies improves early
pregnancy outcome. Additional discussion regarding the incidence, clinical impact, and
treatment of anatomical abnormalities is found in Chapter 3 (p. 38), as well as in Chapter 18 of
Williams Gynecology (Bradshaw, 2012)

 Immunological Factors
In their analysis of published studies, Yetman and Kutteh (1996) determined that 15 percent of
more than 1000 women with recurrent miscarriage had recognized autoimmune factors. Two
primary pathophysiological models are the autoimmune theory—immunity directed against self,
and they alloimmune theory—immunity against another person.
As discussed on page 352, miscarriages are more common in women with systemic lupus
erythematosus, an autoimmune disease (Clowse, 2008; Warren, 2004). Many of these women
were found to have antiphospholipid antibodies, a family of auto-antibodies that bind to
phospholipid-binding plasma proteins (Erkan, 2011). Women with recurrent spontaneous
pregnancy loss have a higher frequency of these antibodies compared with normal controls—5 to
15 versus 2 to 5 percent, respectively (Branch, 2010). The antiphospholipid antibody syndrome
(APS) is defined by these antibodies found together with various forms of reproductive losses
along with substantively increased risks for venous thromboembolism (American College of
Obstetricians and Gynecologists, 2011d, 2013a). Mechanisms that cause pregnancy loss are
discussed along with treatment in Chapter 59 (p. 1173).
With regard to alloimmunity, a provocative theory suggests that normal pregnancy
requires formation of blocking factors that prevent maternal rejection of foreign fetal antigens
that are paternally derived (Chap. 5, p. 98). Factors said to prevent this include human leukocyte
antigen (HLA) similarity with the father, altered natural killer cell activity, regulatory T cell
stimulation, and HLA-G gene mutations (Berger, 2010; Williams, 2012). Various tests and
treatment options proposed to address this have not withstood rigorous scrutiny, and they are
currently investigational (Reddy, 2007). Proposed therapies using paternal or third-party
leukocyte immunization or intravenous immunoglobulin (IVIG) have not proved beneficial in
women with idiopathic miscarriage (American Society for Reproductive Medicine, 2006;
Stephenson, 2010).
 Endocrine Factors
According to Arredondo and Noble (2006), 8 to 12 percent of recurrent miscarriages are caused
by endocrine factors. Studies to evaluate these have been inconsistent and generally
underpowered. Two examples, both controversial, are progesterone deficiency caused by a
luteal-phase defect andt polycystic ovarian syndrome (Bukulmez, 2004; Cocksedge, 2008;
Nawaz, 2010).
In contrast, the well-known abortifacient effects of uncontrolled diabetes are detailed in
Chapter 57. Optimal periconceptional glycemic control will mitigate much of this loss. Likewise,
the effects on early pregnancy loss of overt hypothyroidism and severe iodine deficiency are well
known and discussed on page 353. Correction with supplementation reverses these effects. Also,
the effects of subclinical hypothyroidism and antithyroid antibodies are sporadic, and thus any
effects on recurrent miscarriage rates have been debated (Garber, 2012). That said, however, two
recent metaanalyses reported convincingly positive associations between these antibodies and an
increased risk for sporadic and recurrent miscarriages (Chen, 2011; Thangaratinam, 2011). Less
convincing are preliminary data regarding thyroid hormone treatment for antibody-positive
women.