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Recurrent miscarriage, spontaneous abortion, or recurrent pregnancy loss occurs in 15% of clinically diagnosed pregnancies in women in the United States who are. Approximately 3-4% experience recurrent spontaneous abortions, defined as the loss of three or more consecutive pregnancies recurrent miscarriage and spontaneous abortion. Most spontaneous abortions occur because of abnormalities in the fetus. Almost 70% of first-trimester abortuses, 30% of second-trimester abortuses, and 3% of stillbirths are karyotypically abnormal. The remaining nongenetic causes are anatomic, environmental, hormonal, immune.
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 increases to 30%.
The prevalence of spontaneous abortion increases with increasing maternal age, although not with gravidity per se. The risk begins to increase rapidly at age 35 years. The risk of spontaneous abortion at age 40 years.
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 likely to be normal.
Translocations, inversions, and deletions may be found in patients experiencing recurrent spontaneous abortions. The yield is increased if the couple has a history of a child with anomalies or a stillbirth.
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 the implantation site. A higher term pregnancy rate has been reported.
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 adhesions may interfere with implantation or placentation. As many as 90% of patients conceive.
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 decidualization.
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 menses and amenorrhea remain indications for testing.
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 with diabetes mellitus do not have an increased risk of pregnancy loss.
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.
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 (Ureaplasrna urealyticum). Women who have T-strain mycoplasma endometritis have a higher prevalence of spontaneous abortion. Furthermore, controlled prospective data indicate that doxycycline therapy improves resultant term pregnancy rates.
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.
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.
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.
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.
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.
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.
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 diagnostic doses, X-rays have not been proven to cause fetal demise, but it would be prudent to perform X-ray examinations during pregnancy.
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 independent of maternal age and alcohol consumption.