Recurrent abortion is defined as 3 or more consecutive pregnancy losses before 20 weeks gestation, each with a fetus weighing less than 500 g. Approximately .4-1% of women are habitual aborters. Recurrence risks are difficult to quantify and studies are conflicting. Although there is an increased risk of abortion after a previous abortion, no generally accepted recurrence risks exist (Table 14-1). The incidence of clinically-evident abortion when there is no previous history is approximately 15%. This increases to 25-50% when there have been 3 or more miscarriages.
The recurrence risk is higher if the embryo or fetus has a normal karyotype. It may be that maternal causes are responsible for this higher recurrence risk when the karyotype of the abortus is normal.
Despite these conflicting reports, the prognosis following repeated losses is good, with most couples having an approximately 60% chance of a viable pregnancy.
Chromosomal abnormalities and uterine malformations have been shown to play a role in repetitive miscarriages. Other causes, including hormonal abnormalities, infection, systemic disease, environmental agents, and/or immunologic factors may also play a role. Table 14-2 summarizes a diagnostic work-up for recurrent abortion.
A. Genetic Error
As described previously, there is a 50-60% incidence of abnormal karyotype in first-trimester spontaneous abortions. Possible causes of genetic errors include balanced rearrangements of parental chromosomes such as translocations, found in approximately 2-5% of patients with repetitive abortions.
A careful reproductive history and pedigree should be taken for both partners, and karyotype screening should be performed. It is also useful to know the karyotype of aborted material. If the defect is paternal, artificial insemination is available. For a maternal defect, a donor egg may be fertilized by the husband’s sperm. Preimplantation diagnosis is also an option. With this technique, a probe is made for the translocated region. Typically an embryo is allowed to reach the 8-cell stage. A few cells are aspirated and the probe is added. If no translocation is identified in the embryo, it is implanted in the uterus. Table 14-2 details possible therapies for recurrent abortion.
B. Uterine Abnormalities
Anatomic abnormalities were the first described causes of habitual abortion and account for up to 15% of recurrent pregnancy losses. Defects include congenital uterine anomalies, cervical incompetence, submucous leiomyomas, abnormalities due to diethylstilbestrol exposure in utero, and Asherman’s syndrome. A major difficulty in counseling couples is that approximately 50% of women with uterine defects have no reproductive problem. Unicornuate and bicornuate uteri each account for approximately one-third of spontaneous abortions due to anatomic abnormalities, and septate uteri account for another 20-25%. Submucous leiomyomas are responsible for a much smaller percentage of repeated losses. Generally, losses from anatomic abnormalities occur in the second trimester. Interference with implantation, lack of an adequate blood supply, or growth restriction are possible mechanisms for recurrent loss.
Diagnosis of uterine anatomic abnormalities is usually accomplished by hysterosalpingography or hysteroscopy. Treatment is primarily surgical, with reported success rates of 70-85% after surgical correction.
Cervical incompetence may be due to congenital abnormalities (eg, DES exposure), trauma from a vigorous D&C or cone biopsy, and/or possibly hormonal influences, and classically presents in mid-second or early third trimester with rapid, painless cervical dilatation. If other causes of recurrent losses are excluded and the presumed etiology is incompetent cervix, a cervical cerclage is recommended between 12 and 14 weeks’ gestation. Success rates with cerclage are 85-90%. Complications include risks from anesthesia, bleeding, infection, rupture of membranes, and miscarriage. Contraindications to cerclage placement include bleeding of unknown etiology, infection, labor, ruptured membranes, and congenital anomalies.
C. Hormonal Causes
Possible hormonal causes of habitual abortion include hypothyroidism and hyperthyroidism, progesterone insufficiency, and uncontrolled diabetes mellitus.
Progesterone deficiency or luteal phase defect (LPD) is felt by some to be an important cause of habitual abortion. A defective endometrium resulting in faulty implantation is the proposed mechanism. Inadequate hormonal support of the embryo may also be involved. Diagnosis is usually made by luteal phase endometrial biopsies. However, controlled studies demonstrating an improvement in pregnancy outcome with treatment are lacking, and thus LPD as a cause of recurrent miscarriage remains controversial. If a LPD is diagnosed by endometrial biopsy, however, most physicians advocate treatment with supplemental progesterone.
Infectious agents which have been implicated in repetitive losses include Mycoplasma, Ureaplasma urealyticum, Toxoplasma gondii, Chlamydia trachomatis, Treponema pallidum, Borrelia burgdorferi, Neisseria gonorrhoeae, Streptococcus agalactiae, Listeria monocytogenes, herpes simplex, and cytomegalovirus. Although these agents have been identified in early losses, a causal relationship has not been demonstrated.
E. Systemic Disease
Systemic causes of recurrent abortion include uncontrolled diabetes, uncontrolled thyroid disease, and collagen vascular disease. The incidence of systemic disease as a cause of habitual abortion is unknown, but is probably low. Therapy involves treatment of the specific disease.
F. Immunologic Factors
Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) may damage platelets and vascular endothelium, resulting in thrombosis. This may account for the relationship to miscarriage when found in combination with clinical features of antiphospholipid syndrome. Low-dose aspirin and/or heparin may be beneficial in this situation.
Compared to women who carry a pregnancy to term, women who are habitual aborters share more HLA antigens with their partners and have blunted responses to paternal antigen with lower levels of blocking antibodies or antileukocytotoxic antibodies. The maternal immunologic response may not be as effective in protecting the pregnancy, resulting in pregnancy loss.
Diagnostic tests for immunologic abnormalities are available in few centers. The efficacy of leukocyte immunotherapy is unknown, and treatment such as paternal leukocyte immunization is still experimental.
In up to 50% of women with recurrent abortion, a definitive cause may not be found. However, although the loss rate may be higher than that in the general population, the majority of these women will have a successful pregnancy in their reproductive lifetime.
Revision date: June 18, 2011
Last revised: by Andrew G. Epstein, M.D.
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