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Spontaneous abortion occurs in 15% of diagnosed pregnancies in women who are 15-44 years of
age. Recurrent spontaneous abortions occur in about 3-4% of these women, defined as the loss
of three or more consecutive pregnancies. Most spontaneous abortions occur because of
abnormalities in the fetus recurrent pregnancy loss, misscarriage, misscariage, miscarriage, miscariage, habitual abortion.
Almost 70% of first-trimester abortuses, 30% of second-trimester
abortuses, and 3% of stillbirths have abnormal chromosome numbers. Nongenetic causes include
Recurrence Risk
The risk of pregnancy loss increases from 15-20% in the first pregnancy to 40% after one
spontaneous abortion, but does not increase thereafter. If a woman has at least one liveborn
child, the risk of her first spontaneous abortion is 15%; after one spontaneous abortion, it
The prevalence of spontaneous abortion increases with increasing maternal age, although not
with gravidity. The risk begins to increase rapidly at age 35 years. The risk of spontaneous
abortion at age 40 years is approximately twice that at age 20 years. Although one might suspect
that the reason for this increase is the known rise in aneuploid conception with increasing
maternal age, this does not wholly account for the rapid rise in spontaneous abortion. Indeed,
more euploid pregnancies are lost with increasing maternal age. This fact suggests that other
factors, such as decreased uterine blood supply, chronic infections, or deficient luteal phase, may
be involved. Furthermore, the endometrial lining contains glycoproteins and integrins important
in implantation that may change with age recurrent pregnancy loss, misscarriage, misscariage,
miscarriage, miscariage, habitual abortion.
Etiology
Genetics
Patients having a karyotypically abnormal abortus are more likely to have another abortus that is
abnormal. Conversely, if the first abortus has a normal karyotype, the subsequent abortuses are
Anatomic Anomalies
Müllerian Fusion Defects
Müllerian defects of all types are associated with a higher incidence of pregnancy loss. The
septate uterus, the most common anatomic abnormality, carries a risk of 70% spontaneous
abortion in the first trimester. This is believed to be due to the relatively less vascular nature of
Intrauterine Synechiae
Intrauterine synechiae (Asherman's syndrome) may cause oligomenorrhea, infertility, or
spontaneous abortion. Adhesions may follow overzealous curettage of the uterus during the
postpartum period, intrauterine surgery (eg, myomectomy), or endometritis. Dense, avascular
Leiomyomas
Uterine leiomyomas are usually multiple and may contribute to pregnancy loss, but the
pathophysiology is unknown. Location, rather than size, of the leiomyoma is probably the most
important factor. Submucous leiomyomas may result in fetal loss through several theoretical
mechanisms: 1) endometrial thinning over the surface of the myomas may impair
Endocrine Abnormalities
Thyroid Disease
The theory that thyroid disorders cause spontaneous abortion is now disproved. Although there
is no need to screen asymptomatic patients with spontaneous losses for thyroid disease, irregular
Diabetes Mellitus
When inadequately controlled, type 1 diabetes (formerly referred to as insulin-dependent
diabetes mellitus) may increase the risk of spontaneous abortion. However, euglycemic patients
Luteal-Phase Defect
The luteal-phase defect is presumably responsible for abnormal development of the
endometrium required for implantation and placentation. The luteal-phase defect results either
from a deficient secretion of progesterone or a poor endometrial response to adequate levels of
Infectious Agents
Almost every infectious agent except HIV has been implicated in causing recurrent spontaneous
abortion. However, prospective controlled studies are lacking. The only organism for which
prospective data are available is T-strain mycoplasma (Ureaplasma urealyticum). Women who
have T-strain mycoplasma endometritis have a higher prevalence of spontaneous abortion.
Immunologic Disorders
Autoimmune Disease
Patients with an autoimmune disease, such as systemic lupus erythematosus, have an increased
risk of spontaneous abortion. These patients seem to form antibodies not only against their own
tissue, but also against placental tissue, which ultimately causes rejection of early pregnancy.
Antiphospholipid Antibodies
The antiphospholipid antibodies, including lupus anticoagulant and anticardiolipin antibodies,
are aimed at cellular phospholipids, which were identified when testing patients with recurrent
spontaneous abortion suspected of having systemic lupus erythematosus. A prospective
longitudinal study performed by the National Institutes of Health revealed that patients who had
Shared Parental Histocompatibility Antigens
A fetal allograft that contains foreign paternal antigens theoretically should be rejected by the
mother. One theory suggests that the paternal antigens, which are foreign to the mother, invoke
protective blocking antibodies and prevent the normal maternal "immune cells of rejection" from
recognizing the fetus as a foreign organism. These protective antibodies form only when
maternal and paternal histocompatibility antigens are dissimilar; these antibodies account for the
formation of protective maternal antipaternal leukocyte antibodies. If antigenic similarity exists,
Passive Immunization
Embryo rejection in animal models depends on activated natural killer cells rather than antigen-specific
lymphocytes. A number of centers have suggested immunizing the mother with paternal
leukocytes to suppress natural killer cells. In one study, immunization with paternal lymphocytes
Active Immunization
Administration of IgG has been proposed to decrease overall maternal antibody production in an
attempt to reduce fetal rejection. Theoretically, treatment with IgG would decrease antibodies
against the phospholipids and foreign fetal antigen; however, it would also decrease any
Environmental Factors
A variety of environmental factors may result in spontaneous abortion. Many studies involving
spontaneous abortions are difficult to conclude because of the multiple confounding variables
that are difficult to control.
Irradiation and Antineoplastic Agents
X-irradiation and antineoplastic agents are known to be abortifacients. Therapeutic X-rays or
chemotherapeutic drugs are administered during pregnancy only to seriously ill women. In
Cigarette Smoking and Alcohol
Both cigarette smoking and alcohol ingestion are apt to increase the risk of first-trimester
spontaneous abortion. Cigarette smoking increases the risk of euploid pregnancy loss
Chemical Exposures
Exposure to various chemicals in the workplace has been shown to be associated with increased
risk of spontaneous abortion. Such chemicals include anesthetic gases, arsenic, aniline, benzene,
ethylene oxide, formaldehyde, and lead. Tetrachloroethylene, a compound frequently found in
dry cleaning and laundry establishments, has been shown to increase the risk of spontaneous
abortion more than threefold. Similarly, nurses mixing chemotherapeutic agents have an almost
Other Exposures and Trauma
Exposure to electromagnetic radiation from video display terminals does not increase the risk of
spontaneous abortion. Studies with women working at computers for months before their
Evaluation of Recurrent Pregnancy Loss
Patients experiencing recurrent pregnancy loss would benefit from a battery of the following
tests:
• Karyotype in husband and wife
• Karyotype in any subsequent abortus
• Endometrial biopsy --Histologic dating --U urealyticum culture
• Hysterosalpingography or hysteroscopy
• Fluorescent antinuclear antibodies
• Antiphospholipid antibodies --Lupus anticoagulant --Anticardiolipin antibodies
Follow-Up
Perhaps more important than evaluation and treatment in the patient experiencing spontaneous
pregnancy loss is the care for the patient during her next pregnancy. These patients will benefit