Spontaneous Pregnancy
Loss
Any
pregnancy that implants outside of the uterine endometrial cavity is called an ectopic
pregnancy. Despite improved diagnostic and therapeutic approaches to this
disorder, ectopic pregnancy remains the most common cause of pregnancy-related
maternal death in the first 12 weeks of pregnancy. A ruptured ectopic preganacy
is a medical emergency. Overall, ectopic pregnancies cause 4–10% of
pregnancy-related deaths with maternal hemorrhage the ultimate fatal pathway.
The incidence of ectopic pregnancy rose in the USA from the 1950s through the
1990s when national recording was halted. At that time the best estimate for
the incidence of ectopic pregnancy was 2 in 100 pregnancies.
The known
risk factors for ectopic pregnancy focus on alterations in appropriate function
of the fallopian tube. The fallopian tube is not simply a conduit for sperm and
embryo passage but rather a delicate microenvironment in which cilia help to
move the fluids within the fallopian tubes that transport gametes and
blastocysts. Decreased ciliary movement due to exposure to elevated levels of
progesterone or direct damage, ciliary and cellular destruction as the result
of trauma or infectious disease, and tubal blockage from surgical interruption
or scarring all promote abnormal embryo transport. Over 90% of ectopic
pregnancies can be directly related to tubal pathologies. From highest to
lowest risk, these include: (i) previous ectopic pregnancy; (ii) tubal sterilization
or reconstructive surgery; (iii) in utero exposure to diethyl
stilbesterol (DES); (iv) prior genital tract infection (often silent, particularly
with chlamydia); (v) infertility; (vi) multiple sexual partners; (vii)
cigarette smoking; (viii) young age at initiation of sexual activity; (ix)
maternal age at conception of >35 years; and (x) the practice of vaginal
douching. The remaining 10% of ectopic pregnancies are of unknown etiology.
They may result from embryonic factors, although there is no increase in
embryonic or fetal karyotypic abnormalities when ectopic gestations are compared
with intrauterine gestations. Two commonly cited risk factors for ectopic
pregnancy are frequently misinterpreted. The use of assisted reproductive
techniques, including in vitro fertilization, has recently been shown to
have little effect on the overall incidence of ectopic pregnancies, although
the rate of the otherwise rare heterotopic pregnancy (an ectopic gestation
coexisting with an intrauterine gestation) is increased. The use of an
intrauterine contraceptice device (IUD) protects against all pregnancies and
thereby decreases the overall ectopic pregnancy rate. However, when pregnancy
does occur with an IUD in place, the gestation is more likely to be ectopic.
Almost all
ectopic pregnancies (∼95%)
occur in the fallopian tube (Fig. 36.1). The most common site of implantation
of an ectopic gestation within the fallopian tube is in its ampullary portion.
Ampullary and fimbrial ectopic gestations frequently dislodge and abort prior
to rupture. As the interstitial portion of the fallopian tube has thick muscular
support, interstitial ectopic gestations may develop to relatively late
gestational ages prior to clinical presentation. Cervical, interstitial and heterotopic
(intrauterine + ectopic) ectopic pregnancies are rare but appear to be more
frequent after in vitro fertilization. Ovarian ectopic gestations are
random events without documented risk factors. Abdominal ectopic pregnancies
are exceedingly uncommon.
Miscarriage
A miscarriage is defined as a
spontaneous pregnancy loss before 20 weeks’ gestation; the medical term
is spontaneous abortion.
Miscarriages occur in 15% of clinically recognized pregnancies. The total
number of human conceptions far exceeds the number of births. It is estimated that
at least 60% of all human conceptions do not result in a viable pregnancy, with
the majority of these being spontaneously lost before or shortly after an
expected menses. These pregnancies can be documented by the appearance and
disappearance of a pregnancy-specific hormone (human chorionic gonadotropin,
hCG; Chapter 18) from the maternal bloodstream. It is clear that there is a
sensitive and effective mechanism in the maternal system that can detect
abnormal pregnancies and prevent survival of the overwhelming majority.
It is
impossible to know the causes of those pregnancy losses that occur around the
time of the expected menses, the so-called biochemical pregnancies. They
probably result from a myriad of abnormalities and pregnancy loss represents the
final common clinical outcome. Abnormalities may occur in the conceptus or in
the microenvironment of the maternal reproductive tract at the time of
conception. The latter may result from congenital or acquired anatomic defects
in the uterus. They may also be caused by endocrine abnormalities that alter
the maturation of
the ova prior to ovulation, the development of the embryo during transit to the
intrauterine cavity or the growth and maturation of the endometrium as it
prepares for implantation.
It is known
that the most frequent cause of overt miscarriage is a chromosomal
abnormality in the conceptus. At least 60% of miscarriages have a gross
chromosomal abnormality that can be detected in the expelled fetal material.
Table 36.1 lists the frequency of specific chromosomal abnormalities in
miscarried material. It is usually not possible to identify a specific etiology
for the remaining 40% of isolated spontaneous pregnancy losses, although some
are the result of an under- lying problem that can lead to recurrent pregnancy
losses.
Increasing
maternal age is accompanied by an increase in the frequency of chromosomal
abnormalities in embryos and fetuses and in the rate of spontaneous pregnancy
loss. Age-related egg abnormalities are thought to account for the majority of
this effect, consistent with the dramatic rise in spontaneous pregnancy loss
that is seen among mothers who are 35 or older. This effect is not noted in
association with paternal age until the father of the pregnancy has reached at
least 55 or 60 years. Even then, the effect is more subtle. Interestingly, an
increase in the frequency of certain psychiatric disorders among off- spring is
associated with paternal aging. Ovum deterioration is thought to explain most
of the decline in fertility after the maternal age of 40. Most spontaneous
pregnancy losses are heralded by vaginal bleeding and a fall in maternal
serum hCG during the first trimester of pregnancy.
These losses are subcategorized by clinical presentation a soutlined in Table 36.2. During
the first 12 weeks of pregnancy, maternal serum hCG normally rises with a
doubling time of about 48–72 h. The hCG level will typically plateau or drop
before tissue is passed in pregnancies with threatened miscarriages. Thus, it
would appear that the common signaling mechanism for abnormal pregnancies may
be a disruption in the expression of the hCG gene located on chromosome 19. How
trisomies and other chromosomal aneuploidies produce this effect on the hCG
gene is not known. Moreover, fetuses with trisomy 13, trisomy 18 and trisomy 21
(Down syndrome) can be carried to viability. It is equally puzzling how these
three trisomies escape the hCG signaling surveillance. Trisomy 21 is actually
associated with an increase in circulating hCG in the second trimester. This
finding is used during the first trimester of pregnancy in serum screening
regimens that determine Down syndrome risk.
Recurrent pregnancy loss
Because one
in every six pregnancies will result in a miscarriage, it is not uncommon for a
woman to experience one or more spontaneous losses during her pregnancy
attempts. A woman who has had two consecutive spontaneous losses, but has never
carried a pregnancy to full term, has a 35% chance of a loss in her next
pregnancy. If a woman has successfully carried a pregnancy in the past, she
will not reach a similar level of risk for spontaneous loss in a subsequent
pregnancy until she has experienced three losses. For this reason, diagnostic
work-up should be initiated in women with two losses if no successful
pregnancies have occurred in the past. Clinicians may choose to wait until a
third loss in patients who have had successful pregnancies. It is reasonable to
consider initiating diagnostic testing at an earlier point in the clinical
history among women with infertility or advanced maternal age.
Causes of
recurrent pregnancy loss (recurrent miscarriage) include parental chromosome
translocations; structural uterine abnormalities such as longitudinal septa and
intrauterine adhesions; endocrine disorders, including luteal phase defects,
polycystic ovary syndrome (PCOS), hyper prolactinemia, thyroid dysfunction and
poorly controlled diabetes mellitus; autoimmune conditions such as the
anti phospholipid antibody syndrome and a variety of heritable thrombophilias.
Couples experiencing recurrent pregnancy losses are appropriately anxious and
should be evaluated for an underlying cause in the hope that a specific
intervention may prevent future spontaneous pregnancy losses.
Stillbirth
The term stillbirth
is synonymous with fetal death or demise. All three terms refer to
the delivery of a fetus after 20 menstrual weeks that shows no signs of life.
Stillbirth rates vary widely between developed countries where the overall
rate is 6–7 in 1000 births and developing countries where the rate may be as
high as 30 in 1000 births. Similarly, the etiologies vary by environment and
resources; in developed countries fetal growth restriction, congenital or
karyotypic anomalies, and maternal medical diseases account for many
stillbirths whereas pre-eclampsia, obstructed labor and infection are more
common causes in less developed countries. Fetal death before the onset of
labor (antepartum fetal death) is much more common than fetal death during
labor or delivery (intrapartum fetal death).
There are
many causes of stillbirth. An etiology is never identified in at least 25%
of stillbirths (unexplained stillbirth) even after complete evaluation.
Fetal causes for stillbirth include chromosomal and genetic abnormalities and
congenital malformations. Placental causes include premature separation before
delivery (abruption), hemorrhage from the fetus into the maternal circulation
(fetomaternal hemorrhage) and umbilical cord complications. Other causes such
as intrauterine infection and fetal growth restriction are multifactoral, often
involving the mother and either placenta or fetus.
