Following a pregnancy loss prior to the 20th week, patients are naturally concerned for their future prognosis.

And we reassure these patients that early pregnancy loss occurs in about one out of every six pregnancies, it is usually caused by isolated chromosome abnormalities or placental malformations, it is not preventable, and that the next time the patient becomes pregnant, she will again have a one out of six chance of having a miscarriage.

While all of that is true, it is also true that with increasing numbers of consecutive miscarriages, the likelihood of another miscarriage does go up, and the causes of these miscarriages change. And that’s because while in general, the vast majority of early pregnancy losses are caused by isolated, non-recurring events, a few of them are related to ongoing problems. So if these women continue to have pregnancies and pregnancy losses, they ultimately will make up a much larger proportion of the miscarriage population.

Understand that I’m not talking about large numbers of women. Only 2 percent of pregnant women will experience two miscarriages in a row, and only 0.4% will experience three miscarriages in a row.

Independently, as women age, their risk of a miscarriage increases, from around 13% between age 20 to 30, up to 40% at age 40.

Recurrent pregnancy loss is usually defined as 3 or more consecutive pregnancy losses prior to the 20th week.

There are a number of identifiable causes for these recurrences, although for about 40% of patients, no cause can be determined with our current knowledge. But we can identify one or more causes in 60% of these patients, and the causes include:

• Anatomic genital malformations
• Endocrine abnormalities
• Immunologic problems
• Microbiologic causes
• Genetic abnormalities

Because of the significant rise in risk of another miscarriage after three in a row, we usually initiate an evaluation to identify causes for recurrent pregnancy loss at that time, although some physicians in specific settings might begin the evaluation after two losses. The evaluation addresses each of the categories of causes for repetitive early pregnancy loss.

Chromosome evaluation

I obtain a blood karyotype from each partner, looking for such abnormalities as translocations, either balanced or Robertsonian, and mosaicism that might contribute to a lethal fetal defect. The yield on these tests is small, with about 4% of couples being positive for some significant structural abnormality. With some abnormalities, simply trying again for pregnancy may be the best option. With others, it may be wiser to pursue a course of donor insemination or donor eggs to avoid the chromosomal problem.

Anatomic Genital Malformations

Anything that distorts the normal uterine cavity shape and size can adversely affect conception and maintaining an early pregnancy. These abnormalities would include:

• Uterine fibroids
• Uterine didelphyc deformities such as a bicornuate or septate uterus
• Endometrial polyps

The best way to evaluate the patient for these problems will vary with their history, physical exam, and available resources, but some commonly-used techniques include:

• Sonohysterogram
• Hysterosalpingogram
• Transvaginal ultrasound
• Hysteroscopy
• Laparoscopy

Whenever a significant abnormality is identified, it usually can be surgically corrected.

Endocrine Abnormalities

Thyroid disorders, notably hypothyroidism, is associated with pregnancy loss, so a TSH and free T4 can rule out this problem. It may also prove useful to check the thyroid peroxidase antibody levels, since elevated TPO levels in euthyroid women have also been associated with pregnancy loss.

Diabetes, particularly poorly controlled diabetes has a significant association with early pregnancy loss, so it is valuable to rule out diabetes.

Polycystic ovary syndrome is associated with an increased risk of early loss. Screening for this may be helpful in identifying a cause for loss, but it is unclear whether such insulin-resistance modifiers as metformin will lead to improved outcome.

In contrast, hyperprolactinemia, also associated with early pregnancy loss, has been shown to be effectively reduced with bromcriptine, with an accompanying reduction in subsequent pregnancy loss rates.

Microbiologic Problems

Although infectious organisms can be associated with recurrent pregnancy loss in about 5% of cases, routine screening for Chlamydia, mycoplasma, bacterial vaginosis and toxoplasmosis has not been shown to be effective in lowering the recurrent loss rates.

For that reason, some physicians screen for these conditions while others do not. Whenever infectious agents are identified, specific antibiotics or antivirals can be prescribed. If no infectious organisms are identified, some physicians will provide a course of antibiotics to both partners empirically.

Immunologic issues

Both anticardiolipin antibodies and lupus anticoagulant are associated with recurring early pregnancy loss.

When identified, antiphospholipid syndrome can be treated with heparin or aspirin with an anticipated reduction in risk to future pregnancies.

Immunotherapy, in contrast, has not consistently demonstrated beneficial effects and its use in this setting would be considered experimental.

Progesterone Deficiency

For many years, patients with recurring early pregnancy loss were tested for the presence of a progesterone, or luteal phase deficiency. This was based on the observation that many miscarriages were preceded by a significant drop in serum progesterone. What is not clear is whether this drop is the cause of the miscarriage, or an effect of an abnormal pregnancy, destined to miscarry. Large, randomized, prospective studies are not available.

While some physicians continue to test for progesterone deficiency with luteal phase serum progesterones and endometrial biopsies and to prescribe progesterone to treat presumed deficiencies, others have abandoned this practice.