Recurrent Pregnancy Loss

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What is recurrent pregnancy loss?

Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies and is considered distinct from infertility. When the cause is unknown, each pregnancy loss merits careful review to determine whether specific evaluation may be appropriate, and after three or more losses, a thorough evaluation is warranted.

Patients may experience either primary RPL, in which a pregnancy has never led to a viable birth, or secondary RPL, in which a live birth has resulted at some point in the patient’s history.

Spontaneous abortion (SAB), or miscarriage, is the most common complication of early pregnancy, and the risk of miscarriage increases as the age of the mother increases. Risk factors related to miscarriage include

  • Advanced maternal age
  • Smoking
  • Alcohol consumption, especially moderate to high alcohol consumption
  • Use of illicit drugs such as cocaine
  • Use of nonsteroidal anti-inflammatory medications (NSAIDs)
  • High caffeine consumption
  • Extremes of maternal weight (BMI25 kg/m2)

What causes recurrent pregnancy loss?

  • Parental chromosomal abnormality: In approximately 5% of couples with at least two miscarriages, a structural chromosomal abnormality will be found. Usually, the chromosomal abnormality will be a reciprocal translocation (50%), a Robertsonian translocation (25%), or mosaicism (10%), with the rest being chromosomal inversions or sporadic abnormalities.
  • Uterine abnormalities: Uterine abnormalities can be present in 10-50% of women with RPL and can be congenital (present from birth), acquired, or develop over time. Congenital uterine abnormalities refer to structural changes in the development and shape of the uterus at birth, (including uniconuate (single horn), bicornuate (double horn), uterus didelphys (complete duplication), and uterine septum.) Acquired uterine abnormalities relate primarily to scarring resulting from surgical procedures, dilation & curettage procedures, or fibroid removal, which may destroy the uterine lining and lead to scar formation. Abnormalities which develop over time include fibroids and/or polyps.
  • Immunologic dysfunction: Immunologic dysfunction represents a less well-characterized reason for RPL. Theoretically, it is believed to be due to a disregulation of the normal maternal immune mechanism at the maternal-fetal interface.
  • Antiphospholipid syndrome (APS): This syndrome is an autoimmune disease characterized by blood clots involving the arteries or veins and/or multiple pregnancy losses (first or second trimester), and/or premature birth (before 34 weeks) due to placental abnormalities or eclampsia/preeclampsia. Diagnosis is based on the above clinical history and the presence of elevated antibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and anit-beta2-glycoprotein. The diagnosis of APS is complex, and certain lab criteria must be met before the diagnosis can be confirmed.
  • Medical conditions: Untreated medical conditions such as diabetes mellitus and hyper/hypothyroidism are linked to an increased risk of both pregnancy loss and poor obstetric outcome. The increased risk in poorly controlled diabetic women is felt to be due to high blood glucose levels and maternal vascular disease.
  • Inherited thrombophilia: A relationship between early pregnancy loss and inherited abnormalities in the blood clotting cascade has been hypothesized, but there is no clearly defined association as yet. It is believed that clot formation within the arteries that feed the placenta may impair circulation between the uterus and the placenta and lead to early pregnancy loss.
  • Genetic factors: Sporadic aneuploidy (abnormal chromosome number) of the early conceptus is believed to be responsible for up to 50% of early pregnancy losses. The risk of these aneuploidies increases with both maternal and paternal age.

How is recurrent pregnancy loss diagnosed?

The diagnosis of RPL requires targeted testing to rule out various causes:

  • Karyotype blood testing of couples is done to rule out chromosomal abnormalities.
  • Uterine evaluation to rule out anatomic abnormalities, either congenital or acquired, leading to RPL can be accomplished utilizing a hysterosalpingogram (HSG), sonohysterogram (SHG), 3-D ultrasonography, or magnetic resonance imaging (MRI). At this time HSG and SHG represent the most cost-effective, simplest, and most accurate diagnostic testing.
  • Blood testing: evaluation of thyroid function with a serum TSH level, evaluation of ovarian reserve utilizing a serum AMH level, and elimination of possible immunologic factors utilizing anticardiolipin antibodies and lupus anticoagulant.
  • Screening for diabetes mellitus should be reserved for those women with clinical manifestations of the disease.

A couple with a history of RPL should undergo thorough evaluation and testing. Clinical history should touch on the salient points of each miscarriage including:

  • Time to conception
  • Gestational age of the pregnancy when the loss occurred
  • Characteristics of the pregnancy at the time the miscarriage was discovered
  • Any data obtained from testing, including ultrasound results and/or genetic testing done on the fetal tissue

It is also important to obtain pertinent gynecologic history regarding previous pregnancies that were viable, history of uterine surgeries, history of irregular menstrual cycles, history of medical illnesses/endocrine abnormalities, and/or non-gynecologic surgeries.

Each couple should be questioned about any exposure, either previously or ongoing, to chemical or environmental toxins, any personal or family history of venous or arterial thrombosis (blood clots), any family history of recurrent pregnancy loss, stillbirths, mental retardation, and/or congenital abnormalities.

A general, as well as targeted, physical examination should be performed on the patient, with any signs or symptoms related to endocrine and/or gynecologic abnormalities thoroughly documented and investigated.

How is RPL treated?

The treatment of RPL should be based upon clinical, radiologic, and laboratory findings. Couples in which one of the partners carries a chromosomal rearrangement or abnormality should be referred for genetic counseling to discuss the probability of viable pregnancy based on the chromosomes involved.

Women possessing a uterine septum, intrauterine adhesions, and uterine fibroids (especially submucosal fibroids) can choose surgical correction, which has been shown to be associated with a reduced risk of miscarriage.