Habitual abortion

Overview
Habitual abortion or recurrent pregnancy loss (RPL) is the occurrence of repeated pregnancies that end in miscarriage of the fetus, usually before 20 weeks of gestation. RPL affects about 0.34% of women who conceive.

Definition
Habitual abortion (recurrent pregnancy loss or recurrent miscarriage) is the occurrence of 3 consecutive spontaneous miscarriages (spontaneous abortions). The majority (85%) of women who have had two miscarriages will conceive and carry normally afterwards, so statistically the occurrence of three abortions at 0.34% is regarded as "habitual".

Causes
There are various causes for habitual abortions, and some are treatable. Some couples never have a cause identified, often after extensive investigations.

Uterine conditions
An uterine malformation is considered to cause about 15% of recurrent miscarriages. The most common abnormality is a uterine septum, a partition of the uterine cavity. The diagnosis is made by x-ray or ultrasound of the uterus. Also uterine leiomyomata could result in pregnancy loss.

Cervical conditions
In the second trimester a weak cervix can become a recurrent problem. Such cervical incompetence leads to premature pregnancy loss resulting in miscarriages or preterm deliveries.

Translocations
A balanced translocation or Robertsonian translocation in one of the partners leads to unviable fetuses that are aborted spontaneously. This explains why a karyogram is often performed in both partners if a woman has suffered repeated abortions. About 3% of the time a chromosomal problem of one or both partners can lead to recurrent pregnancy loss. Although patients which such a chromosomal problem are more likely to miscarriage, they can also deliver normal or abnormal babies.

Aneuploidy
Aneuploidy may be a cause of a random spontaneous as well as recurrent pregnancy loss. Aneuploidy is more common with advanced reproductive age reflecting decreased germ cell quality.

Endocrine disorders
Women with thyroid disorders, both hypo- or hyperactivity, have are at increased risk for pregnancy losses. Unrecognized or poorly treated diabetes mellitus leads to increased miscarriages. Women with polycystic ovary syndrome also have higher loss rates possibly related to hyperinsulinemia or excess androgens. Inadequate production of progesterone in the luteal phase may set the stage for RPL (see below).

Thrombophilia
An important example is the increased risk of abortion in women with thrombophilia (propensity for blood clots). The most common problem is the factor V Leiden and prothrombin G20210A mutation. Recent studies confirm that anticoagulant medication may improve the chances of carrying pregnancy to term. It explains about 15% of recurrent miscarriages.

Antiphospholipid syndrome
The antiphospholipid syndrome is a generally accepted cause of recurrent pregnancy loss.

Increased uterine NK cells
A controversial area is the presence of increased natural killer cells in the uterus. It is poorly understood whether these cells actually inhibit the formation of a placenta, and it has been noted that they might be essential for this process. A 2004 paper (Moffett et al) warned that determination of NK cells in peripheral blood does not predict uterine NK cell numbers, because they are a different class of lymphocytes, and state that immunosuppressive treatments are not warranted.

Parental HLA sharing
Earlier studies that perhaps paternal sharing of HLA genes would be associated with increased pregnancy loss have not been confirmed.

Reduced ovarian reserve
The risk for miscarriage increases with age, and women in the advanced reproductive age who have a reduced ovarian reserve are prone to higher risk of repeated miscarriages. Such miscarriages are due to decreased egg quality.

Luteal phase defect
The issue of a luteal phase defect is complex. The theory behind the concept suggests that an inadequate amount of progesterone is produced by the corpus luteum to maintain the early pregnancy. Assessment of this situation was traditionally carried out by an endometrial biopsy, however recent studies have not confirmed that such assessment is valid. Studies about the value of progesterone supplementation remain deficient, however, such supplementation is commonly carried out on an empirical basis.

Lifestyle factors
While lifestyle factors have been associated with increased risk for miscarriage in general, and are usually not listed as specific causes for RPL, every effort should be made to address these issues in patients with RPL. Of specific concern are chronic exposures to toxins including smoking, alcohol, and drugs.

Infection
A number of maternal infections can lead to a single pregnancy loss, including listeriosis, toxoplasmosis, and certain viral infections (rubella, herpes simplex, measles, cytomegalo virus, coxsackie virus). However, there are no confirmed studies to suggest that specific infections will lead to recurrent pregnancy loss in humans.

Assessment
Transvaginal ultrasonography has become the primary method of assessment of the health of an early pregnancy.

In non-pregnant patients who are evaluated for RPL the following tests are usually performed. Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood tests for thrombophilia, ovarian function, thyroid function and diabetes are performed.

Treatment
If the likely cause of recurrent pregnancy loss can be determined treatment is to be directed accordingly. In patients with unexplained RPL chances are about 60-70% that the next pregnancy is successful without treatment. In certain chromosomal situations, while treatment may not be available, IVF with preimplantation genetic diagnosis may be able to identify embryos with a reduced risk of another pregnancy loss which than would be transferred. Close surveillance during pregnancy is generally recommended for pregnant patients with a history of recurrent pregnancy loss. Even with appropriate and correct treatment another pregnancy loss may occur as each pregnancy develops its own risks and problems.