In approximately 50% of spontaneous abortions occurring during the first trimester, there is an abnormal karyotype. This incidence decreases to 20-30% in second trimester losses, and 5-10% in third trimester losses. As will be discussed below, the first trimester losses are typically autosomal trisomies or monosomy X, while later losses reflect chromosomal abnormalities seen in neonates.

Other suspected causes of spontaneous abortion account for a smaller percentage of losses. In a significant percentage of spontaneous abortions, the etiology is unknown. Infection, anatomic defects, endocrine factors, immunologic factors, and maternal systemic disease are felt to play a role in spontaneous abortion.

A. Morphologic and Genetic Abnormalities
Aneuploidy (an abnormal chromosomal number) is responsible for a large percentage of early spontaneous abortions, accounting for at least 50% of these losses.

Autosomal trisomies have been noted for every chromosome except chromosome number 1. Together, the autosomal trisomies make up just over 50% of all aneuploid losses. Trisomy 16 is the most commonly encountered trisomy in spontaneous abortions.

Monosomy X or Turner syndrome is the single most common aneuploidy in spontaneous losses, comprising approximately 20% of these conceptuses.

Polyploidy, usually in the form of triploidy, is found in approximately 20% of all miscarriages. Polyploid conceptions typically result in empty sacs or blighted ovums but occasionally can lead to partial hydatidiform moles.

The remaining half of early abortuses appear to have normal chromosomal complements. Of these, 20% have other genetic abnormalities which may account for the loss. Mendelian or polygenic factors resulting in anatomic defects may play a role. These tend to be more common in later fetal losses.

B. Maternal Factors
1. Systemic disease

a. Maternal infections - Organisms such as Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, Streptococcus agalactiae, herpes simplex virus, cytomegalovirus, and Listeria monocytogenes have been implicated in spontaneous abortion. Although these agents have been identified in early losses, a causal relationship has not been established.

b. Other diseases - Endocrine disorders such as hyperthyroidism or poorly controlled diabetes mellitus; cardiovascular disorders, such as hypertensive or renal disease; and connective tissue disease, such as systemic lupus erythematosus may also be associated with spontaneous abortion.

2. Uterine defects - Congenital anomalies that distort or reduce the size of the uterine cavity, such as unicornuate, bicornuate, or septate uterus, carry a 25-50% risk of miscarriage. A diethylstilbestrol (DES)-related anomaly, such as a T-shaped or hypoplastic uterus, also carries an increased risk of miscarriage. Acquired anomalies, particularly submucous or intramural myomas, have been associated with spontaneous abortions as well.

Previous scarring of the uterine cavity following dilatation and curettage (Asherman’s syndrome), myomectomy, or unification procedures has been implicated in spontaneous miscarriage, as have anatomic or functional incompetence of the uterine cervix.

3. Immunologic disorders - Blood group incompatibility due to ABO, Rh, Kell, or other less common antigens has been associated with spontaneous abortions. Furthermore, similar maternal and paternal HLA may enhance the possibility of abortion by causing insufficient maternal immunologic recognition of the fetus.

4. Malnutrition - Severe malnutrition has been implicated in spontaneous losses.

5. Emotional disturbances - Emotional causes of abortion are speculative. There is no valid evidence to support the concept that abortion may be induced by fright, grief, anger, or anxiety.

C. Toxic Factors
Agents such as radiation, antineoplastic drugs, anesthetic gases, alcohol, and nicotine have been shown to be embryotoxic. Other agents such as lead, ethylene oxide, and formaldehyde may also be toxic.

D. Trauma
Direct trauma, such as injury to the uterus from a gunshot wound, or indirect trauma, such as surgical removal of an ovary containing the corpus luteum of pregnancy, may result in spontaneous abortion.