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Recurrent Spontaneous Abortion

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.



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


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


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


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