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Recurrent Early Pregnancy Loss

Practice Essentials

Early pregnancy loss is defined as the termination of pregnancy before 20 weeks’ gestation or with a fetal weight of below 500 g.

Genetic causes

Most spontaneous miscarriages are caused by an abnormal (aneuploid) karyotype of the embryo. At least 50% of all first-trimester spontaneous abortions (SABs) are cytogenetically abnormal.


Perform karyotype of parents with family or personal history of genetic abnormalities

Perform karyotype of the abortus in recurrent cases


For couples who have had an SAB due to a suspected genetic cause, the standard of care is to offer genetic counseling.

Although preimplantation genetic screening (PGS) of a removed blastomere for aneuploidy would theoretically increase the likelihood of embryonic implantation, reports in the literature have been conflicting with regard to the efficacy of this technique.

However, couples in whom pregnancy loss can be attributed to a balanced translocation may benefit from specific genetic testing by preimplantation genetic diagnosis (PGD).

Immunologic causes

Tests for antiphospholipid antibodies (APLAs), signaling the presence of the autoimmune disease antiphospholipid antibody syndrome (APS), have reportedly been positive in 10-20% of women with early pregnancy losses.

Three classes of clinically significant APL antibodies have been identified: anticardiolipin (aCL), lupus anticoagulant (LAC), and anti-β2 glycoprotein I antibodies.


Diagnosis of APS requires the presence of at least 1 of the clinical criteria and at least 1 of the laboratory criteria. The clinical criteria include the following:

Vascular thrombosis

3 or more consecutive unexplained miscarriages

At least 1 unexplained death of a morphologically normal fetus at or after 10 weeks’ gestation

At least 1 premature birth of a morphologically normal neonate at or before 34 weeks’ gestation, associated with severe preeclampsia or severe placental insufficiency

The laboratory criteria include the following:

aCL: Immunoglobulin G (IgG) and/or immunoglobulin M (IgM) isotype is present in medium or high titer on 2 or more occasions, 6 or more weeks apart

Prolonged phospholipid-dependent coagulation on screening tests

Inability to correct the prolonged screening test with normal platelet-poor plasma

Successful correction of the prolonged screening test with excess phospholipids

Exclusion of other coagulopathies as clinically indicated and heparin


Treatment options for APS include the following:

Subcutaneous heparin

Low-dose aspirin



Combinations of these therapies

Anatomic causes

Anatomic uterine defects can cause obstetric complications, including recurrent pregnancy loss, preterm labor and delivery, and malpresentation.


Imaging studies in the diagnosis of uterine defects include the following:


Hysterosalpingography (HSG)


Vaginal ultrasonography


Data from uncontrolled, retrospective reviews have suggested that resection of the uterine septum increases delivery rates, although a prospective, controlled trial did not show that surgical correction of uterine abnormalities benefits pregnancy outcomes.

Infectious causes

Infection is considered a rare cause of recurrent miscarriage. Most patients with a history of recurrent miscarriage do not benefit from an extensive infection workup.

Environmental causes

Approximately 10% of human malformations result from environmental causes. Clinicians should encourage life-style changes and counseling for preventable exposures to reduce the risk of environmentally related pregnancy loss.

Endocrine causes


Women with poorly controlled diabetes are at a significantly increased risk of miscarriage and fetal malformation. However, screening for occult diabetes in asymptomatic women is not necessary unless the patient presents with an elevated random glucose level or exhibits other clinical signs of diabetes mellitus or if there is an unexplained loss in the second trimester.

Thyroid dysfunction

Although the presence of antithyroid antibodies may represent a generalized autoimmune abnormality, which could be a contributing factor in miscarriages, screening for thyroid disease is not useful unless the patient is symptomatic.

Luteal phase defects

The criterion standard for the diagnosis of a luteal phase defect (LPD) is the finding that the histologic characteristics of a luteal phase endometrial biopsy are more than 2 days behind the findings expected in a normal cycle. However, the physician must be selective in deciding who should be screened for such defects, since there is no definitive treatment to make a difference in pregnancy outcomes in patients with an LPD.

Hematologic causes

Many recurrent miscarriages are characterized by defective placentation and microthrombi in the placental vasculature. In addition, certain inherited disorders that predispose women to venous and/or arterial thrombus formation are associated with pregnancy loss.


Aspirin and heparin therapy may be administered for proven diagnoses of thrombophilic disorders.

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