First-Trimester Spontaneous Abortion

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CHAPTER 18: Abortion
FIRSTTRIMESTER SPONTANEOUS ABORTION
Pathogenesis
More than 80 percent of spontaneous abortions occur within the first 12 weeks of gestation. With firsttrimester losses, demise 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. An anembryonic miscarriage
contains no identifiable embryonic elements. Less accurately, the term blighted ovum may be used (Silver, 2011). The others are embryonic
miscarriages, which often display a developmental abnormality of the embryo, fetus, yolk sac, and, at times, the placenta. In contrast, in later
pregnancy losses, the fetus usually does not die before expulsion, and other sources for abortion are sought.
Incidence
Rates for miscarriage vary according to the study population. In pregnancies aged 5 to 20 weeks’ gestation, the incidence ranges from 11 to 22 percent
and is higher in earlier weeks (Ammon Avalos, 2012). To evaluate rates starting at conception, Wilcox and colleagues (1988) studied 221 healthy women
trying to conceive through 707 menstrual cycles and found a miscarriage rate of 31 percent. This study found that two thirds of these losses are early
and clinically silent. Currently, certain factors are known to influence clinically apparent miscarriage. However, it is unknown if these same factors also
affect clinically silent pregnancy loss.
Fetal Factors
Of all miscarriages, approximately half are euploid abortions, that is, carrying a normal chromosomal complement. The other half has a chromosomal
abnormality. Initially determined by tissue karyotyping, this percentage appears to persist even when implementing newer cytogenetic techniques
(Jenderny, 2014). Notably, the American College of Obstetricians and Gynecologists (2016d) does not recommend routine use of chromosomal
microarray testing of firsttrimester fetal tissues. However, these organizations, and the American Society for Reproductive Medicine (2012), recognize
its value if cytogenetic analysis alters future care.
Both abortion and chromosomal anomaly rates decline with advancing gestational age (Ammon Avalos, 2012; Eiben, 1990). Kajii and associates (1980)
noted that 75 percent of chromosomally abnormal abortions occurred by 8 weeks’ gestation. Of chromosomal abnormalities, 95 percent are caused by
maternal gametogenesis errors, and 5 percent by paternal errors (Jacobs, 1980). Most common abnormalities are trisomy, found in 50 to 60 percent;
monosomy X, in 9 to 13 percent; and triploidy, in 11 to 12 percent (Eiben, 1980; Jenderny, 2014).
Trisomies typically result from isolated nondisjunction, rates of which rise with maternal age (Boué, 1975). Trisomies of chromosomes 13, 16, 18, 21,
and 22 are most common. In contrast, balanced structural chromosomal rearrangements may originate from either parent and are found in 2 to 4
percent of couples with recurrent pregnancy loss.
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 in Chapter 13 (Polyploidy). Conversely, autosomal monosomy is rare and incompatible with life.
Triploidy is often associated with hydropic or molar placental degeneration (Chap. 20, Epidemiology and Risk Factors). The fetus within a partial
hydatidiform mole frequently aborts early, and the few carried longer are all grossly deformed. Advanced maternal and paternal ages do not increase
the incidence of triploidy. Tetraploid fetuses most often abort early in gestation, and they are rarely liveborn.
Maternal Factors
In chromosomally normal pregnancy losses, maternal influences play a role. The causes of euploid abortions are poorly understood, but various
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FIRSTTRIMESTER SPONTANEOUS ABORTION,
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Euploid pregnancies abort later than aneuploid ones. Specifically, the rate of euploid abortion peaks at approximately 13 weeks (Kajii, 1980). In
addition, the incidence of euploid abortion rises dramatically after maternal age exceeds 35 years (Stein, 1980).
Triploidy is often associated with hydropic or molar placental degeneration (Chap. 20, Epidemiology and Risk Factors). The fetus within a partial
hydatidiform mole frequently aborts early, and the few carried longer are all grossly deformed. Advanced maternal and paternal ages do not increase
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the incidence of triploidy. Tetraploid fetuses most often abort early in gestation, and they are rarely liveborn.
Maternal Factors
In chromosomally normal pregnancy losses, maternal influences play a role. The causes of euploid abortions are poorly understood, but various
medical disorders, environmental conditions, and developmental abnormalities have been implicated.
Euploid pregnancies abort later than aneuploid ones. Specifically, the rate of euploid abortion peaks at approximately 13 weeks (Kajii, 1980). In
addition, the incidence of euploid abortion rises dramatically after maternal age exceeds 35 years (Stein, 1980).
Infections
Some common viruses, bacteria, and parasites that invade the normal human can infect the fetoplacental unit by bloodborne transmission. Others
may infect locally through genitourinary infection or colonization. However, despite the numerous infections acquired in pregnancy and discussed in
Chapters 64 and 65, these uncommonly cause early abortion.
Medical Disorders
Some disorders are possibly linked with higher rates of early pregnancy loss and are discussed in their respective chapters. Prominent risks are
associated with poorly controlled diabetes mellitus, obesity, thyroid disease, and systemic lupus erythematosus. In these and others, inflammatory
mediators may be an underlying theme (Kalagiri, 2016; Sjaarda, 2017). Although thrombophilias were initially linked to various pregnancy outcomes,
most putative associations have been refuted (American College of Obstetricians and Gynecologists (2017e).
Cancer
Therapeutic doses of radiation are undeniably abortifacient. Doses that cause abortion are not precisely known, but suggested parameters are found
in Chapter 46 (XRay Dosimetry). Similarly, the effects of chemotherapy exposure in causing abortion are not well defined (Chap. 12, Antimicrobial
Drugs). Particularly worrisome are women with an ongoing pregnancy after early exposure to methotrexate, described later (Medical Abortion). Of
cancer survivors, those who were treated with abdominopelvic radiotherapy or chemotherapy may later be at greater risk for miscarriage, as discussed
in Chapter 63 (Reproductive Tract Neoplasms).
Surgical Procedures
The risk of miscarriage caused by surgery is not well studied. But, as discussed in Chapter 46 (Medications and Surgeries), uncomplicated surgical
procedures performed during early pregnancy are unlikely to increase the abortion risk (Mazze, 1989). Of indications, ovarian tumors can generally be
resected without inciting miscarriage. 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, and supplementation is enumerated in Chapter 63 (Diagnosis).
Trauma seldom causes firsttrimester 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, Trauma).
Nutrition
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. Dietary quality may play a role, as miscarriage risk may be reduced in women who consume a diet rich in
fruits, vegetables, whole grains, vegetable oils, and fish (Gaskins, 2015). With regard to maternal weight, underweight is not associated with a greater
miscarriage risk (Balsells, 2016). However, as noted in Chapter 48 (Pregnancy and Obesity), obesity does raise pregnancy loss rates.
Social and Behavioral Factors
Lifestyle choices reputed to be associated with a higher miscarriage risk are most often related to chronic and especially heavy use of legal substances.
The most commonly used is alcohol, with its potent teratogenic effects discussed in Chapter 12 (Known and Suspected Teratogens). That said, an
increased miscarriage risk is only seen with regular or heavy use (Avalos, 2014; Feodor Nilsson, 2014).
Approximately 10 percent of pregnant women admit to cigarette smoking (Centers for Disease Control and Prevention, 2016). It seems intuitive that
cigarettes could cause early pregnancy loss (Pineles, 2014). Adverse effects of illicit drugs are discussed in Chapter 12 (Tobacco).
Excessive caffeine consumption—not well defined—has been associated with a higher abortion risk. Reports link heavy intake of approximately five
cups of coffee per day—about 500 mg of caffeine—with a slightly greater abortion risk (Cnattingius, 2000; Klebanoff, 1999). Studies of “moderate”
FIRSTTRIMESTER SPONTANEOUS ABORTION, Page 2 / 9
intake—less than 200 mg daily—did not indicate increased risk (Savitz, 2008; Weng, 2008). In contrast, in one prospective cohort of more than 5100
gravidas, caffeine was linked to miscarriage but not in a doseresponse relationship (Hahn, 2015). Currently, the American College of Obstetricians and
Gynecologists (2016e) has concluded that moderate consumption likely is not a major abortion risk and that any associated risk with higher intake is
The most commonly used is alcohol, with its potent teratogenic effects discussed in Chapter 12 (Known and Suspected Teratogens). That said, an
increased miscarriage risk is only seen with regular or heavy use (Avalos, 2014; Feodor Nilsson, 2014). Access Provided by:
Approximately 10 percent of pregnant women admit to cigarette smoking (Centers for Disease Control and Prevention, 2016). It seems intuitive that
cigarettes could cause early pregnancy loss (Pineles, 2014). Adverse effects of illicit drugs are discussed in Chapter 12 (Tobacco).
Excessive caffeine consumption—not well defined—has been associated with a higher abortion risk. Reports link heavy intake of approximately five
cups of coffee per day—about 500 mg of caffeine—with a slightly greater abortion risk (Cnattingius, 2000; Klebanoff, 1999). Studies of “moderate”
intake—less than 200 mg daily—did not indicate increased risk (Savitz, 2008; Weng, 2008). In contrast, in one prospective cohort of more than 5100
gravidas, caffeine was linked to miscarriage but not in a doseresponse relationship (Hahn, 2015). Currently, the American College of Obstetricians and
Gynecologists (2016e) has concluded that moderate consumption likely is not a major abortion risk and that any associated risk with higher intake is
unsettled.
Occupational and Environmental Factors
Environmental toxins suggested to have a possible link to miscarriage include bisphenol A, phthalates, polychlorinated biphenyls, and
dichlorodiphenyltrichloroethane (DDT) (Krieg, 2016). Even fewer studies implicate occupational exposures. In a followup of the Nurses Health Study II,
Lawson and associates (2012) reported slightly increased miscarriage risks in nurses exposed to sterilizing agents, xrays, and antineoplastic drugs.
Also, a higher miscarriage risk was found for dental assistants exposed to more than 3 hours of nitrous oxide daily if there was no gasscavenging
equipment (Boivin, 1997).
Paternal Factors
Increasing paternal age is significantly associated with an greater risk for abortion (de La Rochebrochard, 2003). In the Jerusalem Perinatal Study, this
risk was lowest before age 25 years, after which it progressively increased at 5year intervals (Kleinhaus, 2006). The etiology of this association is not
well studied, but chromosomal abnormalities in spermatozoa likely play a role (Sartorius, 2010).
Spontaneous Abortion Clinical Classification
Threatened Abortion
This diagnosis is presumed when bloody vaginal discharge or bleeding appears through a closed cervical os during the first 20 weeks. This bleeding in
early pregnancy must be differentiated from that with implantation, which some women have at the time of their expected menses. Aside from this,
almost one fourth of women develop bleeding during early gestation that may persist for days or weeks. It may be accompanied by suprapubic
discomfort, mild cramps, pelvic pressure, or persistent low backache. Of symptoms, bleeding is by far the most predictive risk factor for pregnancy
loss.
Even if miscarriage does not follow threatened abortion, rates of later adverse pregnancy outcomes are increased as shown in Table 181. Of these,
highest risks are for preterm delivery. Weiss and coworkers (2004) noted greater risks for adverse outcomes in later pregnancy if early bleeding was
heavy rather than light. Compared with those without bleeding, women with firsttrimester bleeding in an initial pregnancy have higher recurrence
rates in their second (Lykke, 2010).
TABLE 181
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 Lowbirthweight infant
Cesarean delivery Fetalgrowth restriction
Fetal and neonatal death
From Lykke, 2010; Saraswat, 2010; Weiss, 2004; Wijesiriwardana, 2006.
Every woman with an early pregnancy, vaginal bleeding, and pain should be evaluated. The primary goal is prompt diagnosis of ectopic pregnancy, and
serial quantitative serum βhCG levels and transvaginal sonography are integral tools. Because these are not 100percent accurate to confirm early
embryo death or location, repeat evaluations are often necessary. With a robust uterine pregnancy, serum βhCG levels should rise at least 53 to 66
Even if miscarriage does not follow threatened abortion, rates of later adverse pregnancy outcomes are increased as shown in Table 181. Of these,
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highest risks are for preterm delivery. Weiss and coworkers (2004) noted greater risks for adverse outcomes in later pregnancy if early bleeding was
heavy rather than light. Compared with those without bleeding, women with firsttrimester bleeding in an initial pregnancy have higher recurrence
rates in their second (Lykke, 2010).
TABLE 181
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 Lowbirthweight infant
Cesarean delivery Fetalgrowth restriction
Fetal and neonatal death
From Lykke, 2010; Saraswat, 2010; Weiss, 2004; Wijesiriwardana, 2006.
Every woman with an early pregnancy, vaginal bleeding, and pain should be evaluated. The primary goal is prompt diagnosis of ectopic pregnancy, and
serial quantitative serum βhCG levels and transvaginal sonography are integral tools. Because these are not 100percent accurate to confirm early
embryo death or location, repeat evaluations are often necessary. With a robust uterine pregnancy, serum βhCG levels should rise at least 53 to 66
percent every 48 hours (Barnhart, 2004c; Kadar, 1982). Although a lessused marker, serum progesterone concentrations <5 ng/mL suggest a dying
pregnancy. Values >20 ng/mL support the diagnosis of a healthy one (Daily, 1994).
Transvaginal sonography is used to locate the pregnancy and determine viability. If this cannot be done, then a PUL is diagnosed, and serial
surveillance is implemented for clinically stable women. The gestational sac—an anechoic fluid collection that represents the exocoelomic cavity—may
be seen by 4.5 weeks (Fig. 93). At this same time, βhCG levels generally measure 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. However, they also noted that a threshold as high as 3500 mIU/mL may
be needed to identify the gestational sac in some cases that ultimately yield a viable singleton IUP.
Another caveat is that a gestational sac may appear similar to other intrauterine fluid accumulations—the socalled pseudogestational sac (Fig. 194).
This pseudosac may be blood derived from a bleeding 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 gestationalsac diameter of 10 mm. Thus, the diagnosis of an IUP should be made cautiously if the yolk sac is not
yet seen (American College of Obstetricians and Gynecologists, 2016h).
For management of threatened abortion, observation is the norm. Acetaminophenbased analgesia will help relieve discomfort from cramping. Bed
rest is often recommended but does not improve outcomes. The hematocrit and blood type is determined. If anemia or hypovolemia is significant,
then pregnancy evacuation is generally indicated. In cases in which there is a live fetus, some instead may choose transfusion and further observation.
Incomplete Abortion
During abortion, bleeding follows partial or complete placental separation and dilation of the cervical os. Before 10 weeks’ gestation, the fetus and the
placenta are frequently expelled together, but later, they deliver separately. Thus, tissue may remain entirely within the uterus or partially extrude
through the cervix. Products lying loosely within the cervical canal can be easily extracted with ring forceps. In contrast, with incomplete expulsion,
three management options include curettage, expectant management, or misoprostol (Cytotec), which is prostaglandin E1 (PGE1) (Kim, 2017). The last
two are deferred in clinically unstable women or those with uterine infection.
Each option has its own risks and benefits. With all three, infection and need for transfusion are uncommon. However, misoprostol and expectant care
are associated with unpredictable bleeding, and some women will undergo unscheduled curettage. Expectant management of spontaneous
incomplete abortion has failure rates that approximate 25 percent in randomized trials (Nadarajah, 2014; Nielsen, 1999; Trinder, 2006). Some
observational studies have shown failure rates of 10 to 15 percent (Blohm, 2003; Casikar, 2012; Luise, 2002). Medical therapy carries failure rates of 5 to
30 percent (Dao, 2007; Shochet, 2012; Trinder, 2006). In many studies for this, an oral misoprostol dose of 600 μg has been used (American College of
Obstetricians and Gynecologists, 2009). Alternatively, an 800μg vaginal or a 400μg oral or sublingual misoprostol dose is suitable. Last, curettage
usually results in a quick resolution that is 95 to 100percent successful. However, it is invasive and not necessary for all women.
Complete Abortion
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Each option has its own risks and benefits. With all three, infection and need for transfusion are uncommon. However, misoprostol and expectant care
are associated with unpredictable bleeding, and some women will undergo unscheduled curettage. Expectant management of spontaneous
incomplete abortion has failure rates that approximate 25 percent in randomized trials (Nadarajah, 2014; Nielsen, 1999; Trinder, 2006). Some
observational studies have shown failure rates of 10 to 15 percent (Blohm, 2003; Casikar, 2012; Luise, 2002). Medical therapy carries failure rates of 5 to
30 percent (Dao, 2007; Shochet, 2012; Trinder, 2006). In many studies for this, an oral misoprostol dose of 600 μg has been used (American College of
Obstetricians and Gynecologists, 2009). Alternatively, an 800μg vaginal or a 400μg oral or sublingual misoprostol dose is suitable. Last, curettage
usually results in a quick resolution that is 95 to 100percent successful. However, it is invasive and not necessary for all women.
Complete Abortion
At times, complete expulsion of the entire pregnancy may ensue, and the cervical os subsequently closes. A history of heavy bleeding, cramping, and
passage of tissue is typical. Patients are encouraged to bring in passed tissue, in which a complete gestation should be discerned from blood clots or a
decidual cast. The latter is a layer of endometrium in the shape of the uterine cavity that when sloughed can appear as a collapsed sac (Fig. 192).
If an expelled complete gestational sac is not identified, transvaginal 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 found to have an ectopic
pregnancy. Thus, a complete abortion cannot be surely diagnosed unless: (1) true products of conception are seen grossly or (2) unless sonography
confidently documents first an intrauterine pregnancy and then later an empty cavity. In unclear settings, serial serum hCG level measurements aid
clarification. With complete abortion, these levels drop quickly (Table 182).
TABLE 182
Percentage Decline of Initial Serum βhCG Levels Following Complete Spontaneous Abortion
Percentage Declinea
Initial hCG (mIU/mL) by day 2 Expected % (Minimum %) by day 4 Expected % (Minimum %) by day 7 Expected % (Minimum %)
50 68 (12) 78 (26) 88 (34)
100 68 (16) 80 (35) 90 (47)
300 70 (22) 83 (45) 93 (62)
500 71 (24) 84 (50) 94 (68)
1000 72 (28) 86 (55) 95 (74)
2000 74 (31) 88 (60) 96 (79)
3000 74 (33) 88 (63) 96 (81)
4000 75 (34) 89 (64) 97 (83)
5000 75 (35) 89 (66) 97 (84)
aThe percentage decline is given as the expected decline. The minimum expected decline in parentheses is the 95th percentile value. Declines less than this
minimum may reflect retained either intrauterine or extrauterine trophoblast.
Data from Barnhart, 2004a; Chung, 2006.
Missed Abortion
This describes dead products of conception that have been retained for days or weeks in the uterus with a closed cervical os. Diagnosis is imperative
prior to intervention and avoids interruption of a potentially live IUP. Transvaginal sonography is the primary tool.
At 5 to 6 weeks’ gestation, a 1 to 2mm embryo adjacent to the yolk sac can be seen (Daya, 1993). As listed in Table 183, absence of an embryo in a sac
with a mean sac diameter (MSD) ≥25 mm signifies a dead fetus (Fig. 181). Fetal cardiac activity can typically be detected at 6 to 6.5 weeks with a crown
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Data from Barnhart, 2004a; Chung, 2006.
Missed Abortion
This describes dead products of conception that have been retained for days or weeks in the uterus with a closed cervical os. Diagnosis is imperative
prior to intervention and avoids interruption of a potentially live IUP. Transvaginal sonography is the primary tool.
At 5 to 6 weeks’ gestation, a 1 to 2mm embryo adjacent to the yolk sac can be seen (Daya, 1993). As listed in Table 183, absence of an embryo in a sac
with a mean sac diameter (MSD) ≥25 mm signifies a dead fetus (Fig. 181). Fetal cardiac activity can typically be detected at 6 to 6.5 weeks with a crown
rump length (CRL) of 1 to 5 mm and an MSD of 13 to 18 mm (Goldstein, 1992; Levi, 1990). A threshold CRL ≥7 mm with absent cardiac activity is also used
to diagnose nonviability (Doubilet, 2013). Preisler and associates (2015) implemented the guidelines in Table 183 and confirmed these CRL and MSD
thresholds. However, for cases in which a gestational sac had no embryo or yolk sac and measured <12 mm, they recommended that to diagnose
nonviability after 2 weeks, in addition to the lack of an embryo with a heartbeat, the MSD should have failed to double.
TABLE 183
Guidelines for Early Pregnancy Loss Diagnosisa
Sonographic Findings
CRL ≥ 7 mm and no heartbeat
MSD ≥ 25 mm and no embryo
An initial US scan shows a gestational sac with yolk sac, and after ≥ 11 days no embryo with a heartbeat is seen
An initial US scan shows a gestational sac without a yolk sac, and after ≥ 2 weeks no embryo with a heartbeat is seen
Modalities
Transvaginal preferable to transabdominal US
Mmode imaging used to document and measure heartbeat
Doppler US not used to evaluate a normal early embryo
aFrom the Society of Radiologists in Ultrasound ; American College of Radiology.
CRL = crownrump length; MSD = mean sac diameter; US = ultrasound.
From Doubilet, 2013; Lane, 2013.
FIGURE 181
Transvaginal sonogram displays a large anechoic sac consistent with an anembryonic gestation. Calipers measure uterine length and anteroposterior
thickness in a sagittal plane.
During scanning, because of theoretical temperature elevation in tissues exposed to pulsed Doppler beam, this modality is applied only when needed
FIGURE 181 Access Provided by:
Transvaginal sonogram displays a large anechoic sac consistent with an anembryonic gestation. Calipers measure uterine length and anteroposterior
thickness in a sagittal plane.
During scanning, because of theoretical temperature elevation in tissues exposed to pulsed Doppler beam, this modality is applied only when needed
for additional diagnostic purposes. Mmode should be used to document cardiac activity and measure the rate (Lane, 2013). Finding of an IUP and
cardiac activity lowers subsequent miscarriage rates (Siddiqi, 1988).
In addition to the diagnostic parameters of Table 183, other softer sonographic markers may portend early pregnancy failure. Values for yolk sac
diameters (measured innertoinner ring) for each gestational week in normal pregnancy have been established. Yolk sac diameters ≥6 mm in
pregnancies <10 weeks’ gestation are suspicious for pregnancy failure (Berdahl, 2010; Lindsay, 1992). The fetal heart rate in the first trimester rises
from 110 to 130 beats per minute (bpm) at 6 weeks’ gestation to 160 to 170 bpm at 8 weeks (Achiron, 1991; Rauch, 2009). A slower heart rate is
unfavorable, especially those <85 bpm (Laboda, 1989; Stefos, 1998). Even with cardiac activity, fetuses with a small MSD may presage embryonic loss.
Specifically, a difference <5 mm between the MSD and CRL values raises concern (Bromley, 1991; Dickey, 1992). Last, subchorionic hematoma, that is,
blood collected between the chorion and uterine wall, often accompanies threatened miscarriage. Studies are contradictory as to its association with
ultimate pregnancy loss (Pedersen, 1990; Stabile, 1989; Tuuli, 2011). Bennett and associates (1996) noted that miscarriage risk correlated with larger
hematoma size, older maternal age, and bleeding at a gestational age ≤8 weeks.
With rapid confirmation of embryonic or fetal death, surgical or medical evacuation or expectant observation is an option. As with induced abortion,
nonsurgical options balance their noninvasiveness against heavier procedural bleeding, longer completion times, and lower success rates. Of options,
expectant care underperforms medical or surgical options, and failure rates range from 15 to 50 percent (Luise, 2002; Trinder, 2006; Zhang, 2005).
Also, weeks may pass between pregnancy failure diagnosis and actual spontaneous miscarriage.
Alternatively, misoprostol can be given to hasten uterine evacuation. A single 800μg dose vaginally is a common standard (American College of
Obstetricians and Gynecologists, 2016c). It may be repeated in 1 to 2 days, and one large trial reported that 22 percent of women required a second
dose (Zhang, 2005). Overall, failure rates range from 15 to 40 percent (Petersen, 2014; Trinder, 2006). Unlike induced abortion, adding mifepristone
does not add value (Stockheim, 2006). Contraindications mirror those listed in the section describing induced abortion (Medical Abortion).
Confirmation of completion may include a history of heavy bleeding, cramping, and tissue passage followed by ebbing flow; a sonographically thin
endometrial thickness; and rapidly dropping serum hCG levels. That said, there is no consensus on an endometrial thickness threshold that mandates
additional intervention.
Inevitable Abortion
Preterm premature rupture of membranes (PPROM) at a previable gestational age complicates 0.5 percent of pregnancies (Hunter, 2012). Rupture may
be spontaneous or may follow an invasive procedure such as amniocentesis or fetal surgery. Risks for spontaneous rupture at a previable gestation
are prior PPROM, prior secondtrimester delivery, and tobacco use (Kilpatrick, 2006).
A gush of vaginal fluid that is seen pooling during sterile speculum examination confirms the diagnosis. In suspect cases, amnionic fluid will fern on a
microscope slide or will have a pH >7, or oligohydramnios will be seen on sonography (Sugibayashi, 2013). Also, amnionic fluid proteins placental
alpha microglobulin1 and insulin growth factor binding protein1, described in Chapter 22 (Identification of Labor), can be assayed (Doret, 2013).
In iatrogenic cases, defects are typically higher in the uterus and tend to self seal. Also, an occlusive plug—termed an amniopatch—can be created by
Inevitable Abortion
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Preterm premature rupture of membranes (PPROM) at a previable gestational age complicates 0.5 percent of pregnancies (Hunter, 2012). Rupture may
be spontaneous or may follow an invasive procedure such as amniocentesis or fetal surgery. Risks for spontaneous rupture at a previable gestation
are prior PPROM, prior secondtrimester delivery, and tobacco use (Kilpatrick, 2006).
A gush of vaginal fluid that is seen pooling during sterile speculum examination confirms the diagnosis. In suspect cases, amnionic fluid will fern on a
microscope slide or will have a pH >7, or oligohydramnios will be seen on sonography (Sugibayashi, 2013). Also, amnionic fluid proteins placental
alpha microglobulin1 and insulin growth factor binding protein1, described in Chapter 22 (Identification of Labor), can be assayed (Doret, 2013).
In iatrogenic cases, defects are typically higher in the uterus and tend to self seal. Also, an occlusive plug—termed an amniopatch—can be created by
intraamnionic instillation of autologous platelets and cryoprecipitate. Considered investigational, it is used to seal some surgical leaks (Richter, 2013).
Spontaneous rupture in the first trimester is nearly always followed by either uterine contractions or infection, and termination is typical. In some
secondtrimester 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 reasonable. 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 at home.
However, more typically with secondtrimester spontaneous PPROM at a previable age, 40 to 50 percent of women will deliver within the first week, and
70 to 80 percent will do so after 2 to 5 weeks (American College of Obstetricians and Gynecologists, 2016f). Average latency is 2 weeks (Hunter, 2012;
Kibel, 2016). Significant maternal complications attend previable PPROM and include chorioamnionitis, endometritis, sepsis, placental abruption, and
retained placenta (Waters, 2009). With bleeding, cramping, or fever, abortion is considered inevitable, and the uterus is evacuated.
Without these complications, expectant management is an option in the wellcounseled patient (American College of Obstetricians and Gynecologists,
2017f). Many will choose termination due to the justdescribed maternal risks and tenuous neonatal outcomes. In contemporary cohorts with PPROM
at <24 weeks’ gestation, only approximately 20 percent of fetuses survive until hospital discharge (Esteves, 2016; Everest, 2008; Muris, 2007). Of
surviving infants, 50 to 80 percent suffer longterm sequelae (Miyazaki, 2012; Pristauz, 2008). Further stratification of outcomes by gestational age is
described in Chapter 42 (Periviable Neonatal Survival). Overall, prognosis is improved if previable PPROM occurred at a later gestation, latency is
longer, and oligohydramnios is absent. Neonatal mortality predominantly stems from pulmonary dysfunction, which has higher rates when
oligohydramnios persists (Winn, 2000). Fetal deformations may also result from scant amnionic fluid. Amnioinfusion has been investigated but is
currently investigational (Roberts, 2014).
If expectant care is elected, management is described in Chapter 42 (LatePreterm Birth). Antibiotics are considered and given for 7 days to extend
latency. Other topics include lungmaturing corticosteroids, magnesium sulfate neuroprophylaxis, group B streptococcus antibiotic prophylaxis,
tocolytics, and neonatal resuscitation efforts. After initial hospitalization, the patient may be discharged home, with instruction for careful surveillance
for complications until viability, at which time readmission is usual (American College of Obstetricians and Gynecologists, 2016f). In subsequent
pregnancies, the risk for recurrent preterm birth is great, and in one cohort study, the rate neared 50 percent (Monson, 2016).
Septic Abortion
With abortion legalization, horrific infections and maternal deaths associated previously with criminal septic abortions are now rare. Still, with
spontaneous or induced abortion, organisms may invade myometrial tissues and extend to cause parametritis, peritonitis, and septicemia. Most
bacteria causing septic abortion are part of the normal vaginal flora. Particularly worrisome are severe necrotizing infections and toxic shock
syndrome caused by group A streptococcus—S pyogenes (Daif, 2009).
Rare but severe infections with otherwise lowvirulence organisms can complicate medical or spontaneous 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 have 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. Maternal deaths from these clostridial species approximate
0.58 per 100,000 medical abortions (Meites, 2010).
Management of clinical infection includes prompt administration of broadspectrum antibiotics as discussed in Chapter 37 (Pathogenesis and Clinical
Course). If there are retained products, then suction curettage is also performed. Most women respond to this treatment within 1 to 2 days and are
discharged when afebrile. Followup oral antibiotic treatment is likely unnecessary (Savaris, 2011). In a very few women, severe sepsis syndrome
develops, and intensive supportive care is essential. Although rare, clinical decline in the patient and widespread peritonitis despite curettage should
raise concerns. Imaging that shows free air or air within the uterine wall typically prompts laparotomy (Eschenbach, 2015). If the uterus is necrotic,
hysterectomy is indicated.
AntiD Immunoglobulin
With spontaneous miscarriage, 2 percent of Rh Dnegative 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 (2017g) recommends antiRho (D)
immunoglobulin given as 300 μg intramuscularly (IM) for all gestational ages. Doses may also be graduated, with 50 μg given IM for pregnancies ≤12
discharged when afebrile. Followup oral antibiotic treatment is likely unnecessary (Savaris, 2011). In a very few women, severe sepsis syndrome
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develops, and intensive supportive care is essential. Although rare, clinical decline in the patient and widespread peritonitis despite curettage should
raise concerns. Imaging that shows free air or air within the uterine wall typically prompts laparotomy (Eschenbach, 2015). If the uterus is necrotic,
hysterectomy is indicated.
AntiD Immunoglobulin
With spontaneous miscarriage, 2 percent of Rh Dnegative 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 (2017g) recommends antiRho (D)
immunoglobulin given as 300 μg intramuscularly (IM) for all gestational ages. Doses may also be graduated, with 50 μg given IM for pregnancies ≤12
weeks and 300 μg for ≥13 weeks. This is administered immediately following surgical evacuation. For planned medical or expectant management, the
injection is given within 72 hours of pregnancy failure diagnosis.
With threatened abortion, immunoglobulin prophylaxis is controversial because of sparse evidencebased data (Hannafin, 2006). That said, it is
reasonable to administer antiD immunoglobulin for a threatened abortion and a live fetus, and this is our practice.

First-Trimester Spontaneous Abortion

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Initial hCG (mIU/mL) by day 2 Expected % (Minimum %) by day 4 Expected % (Minimum %) by day 7 Expected % (Minimum %)

50 68 (12) 78 (26) 88 (34)

100 68 (16) 80 (35) 90 (47)

300 70 (22) 83 (45) 93 (62)

500 71 (24) 84 (50) 94 (68)

1000 72 (28) 86 (55) 95 (74)

2000 74 (31) 88 (60) 96 (79)

3000 74 (33) 88 (63) 96 (81)

4000 75 (34) 89 (64) 97 (83)

5000 75 (35) 89 (66) 97 (84)

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