I RECURRENT PREGNANCY LOSS ^709

Recurrent pregnancy loss, defined by the American Society for Reproductive Medicine as two or more pregnancy losses, occurs in approximately 1% of women who desire to bear children.

Recurrent early pregnancy loss can be a difficult and frustrating problem for patients and clinicians. The following factors should be considered in the evaluation of women with recurrent pregnancy loss:

• Characteristics of prior pregnancy losses

• Exposure to toxins and drugs

• Genetic abnormalities

• Pelvic infections

• Endocrine or metabolic dysfunction

• Immunologic disorders

• Uterine abnormalities

• Psychologic stress of the associated loss

• Age of the patient

For couples with recurrent pregnancy loss, it is reasonable to offer a basic evaluation. Tests commonly offered to couples with recurrent preg­nancy loss are as follows:

• Karyotyping of both partners to look for balanced chromosome abnormalities

• Hysterosalpingography, ultrasonography, sonohysterography, or hysteroscopy to look for uterine abnormalities

Couples affected by balanced translocations should be counseled regarding the risk of recurring spontaneous abortion, offered prenatal genetic studies, and offered the use of newer assisted reproductive technologies in future pregnancies. Corrective surgery for uterine defects may be reasonable when such defects appear to interfere with implantation or pregnancy growth.

Other appropriate tests may depend on the timing of the pregnancy loss. For example, antibody testing for antiphospholipid syndrome (lupus anticoagulant, anticardiolipin, and anti-β₂-glycoprotein I antibody test­ing) are not indicated in most cases of fetal loss. Obstetric indications for antiphospholipid antibody testing include a history of one unexplained loss of a morphologically normal fetus at or beyond the 10th week of gestation or of three or more unexplained consecutive spontaneous preg­nancy losses before the 10th week of pregnancy (with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded).

Testing for inherited thrombophilias in women who have experienced recurrent fetal loss in the first trimester is not recommended because it is unclear if anticoagulation therapy reduces recurrence. However, tests for thrombophilia should be considered in cases of otherwise unexplained fetal death in the second trimester or third trimester. Some of the older evaluations and treatments of recurrent pregnancy loss have been based on poorly designed clinical studies and unproven hypotheses. Patients and physicians in search of a solution have sometimes explored less-well- accepted etiologies and empirical or alternative treatments. Although the assessment of luteal phase progesterone production or effect is firmly entrenched in the traditional evaluation of recurrent pregnancy loss, the evidence that supports this is scant. Treatment for luteal phase defect is of unproven efficacy. Cultures for bacteria or viruses and tests for glucose intolerance, antibodies to infectious agents, antinuclear antibodies, pater­nal human leukocyte antigen status, and maternal antipaternal antibodies are not beneficial. Immunoglobulin and paternal leukocyte therapies are not effective in preventing recurrent pregnancy loss and are no longer rou­tinely recommended in the evaluation of women with recurrent pregnancy loss. There is conflicting literature regarding the role of thyroid abnormali­ties in recurrent pregnancy loss.

It now appears that more than 50% of couples who complete evaluation will not have an identifiable cause. Informative and supportive counseling plays an important role and may lead to the best pregnancy outcomes. Couples with unexplained recurrent pregnancy loss should be counseled regarding the potential for successful pregnancy without treatment.

Bibliography

Antiphospholipid syndrome. Practice Bulletin No. 132. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:1514-21. [PubMed] [Obstetrics & Gynecology]

Definitions of infertility and recurrent pregnancy loss: a committee opinion.

Inherited thrombophilias in pregnancy. Practice Bulletin No. 138. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:706-17. [PubMed] [Obstetrics & Gynecology]

Intravenous immunoglobulin (IVIG) and recurrent spontaneous pregnancy loss. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril 2006;86:S226-7. [PubMed] [Full Text]

Resources

American College of Obstetricians and Gynecologists. Repeated miscarriage. Patient Education Pamphlet AP100. Washington, DC: American College of Obstetricians and Gynecologists; 2013.

Family history as a risk assessment tool. Committee Opinion No. 478. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;117:747-50. [PubMed] [Obstetrics & Gynecology]

Preimplantation genetic screening for aneuploidy. ACOG Committee Opinion No. 430. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;113:766-7. [PubMed] [Obstetrics & Gynecology]

RESOLVE: The National Infertility Association. Available at: http://www.resolve.org. Retrieved August 9, 2013.