Recurrent miscarriage

Published on 10/03/2015 by admin

Filed under Obstetrics & Gynecology

Last modified 22/04/2025

Print this page

This article have been viewed 1483 times

Chapter 34 RECURRENT MISCARRIAGE

Theodore O’Connell

Miscarriage, or spontaneous abortion, is the spontaneous loss of a fetus at less than 20 weeks’ gestation in the absence of elective medical or surgical measures to terminate the pregnancy. Recurrent miscarriage is defined as three or more consecutive pregnancy losses, although many clinicians define recurrent miscarriage as two or more losses. According to the latter definition, recurrent miscarriage affects from 1% to 5% of all couples trying to conceive. Fetal demise after the sixth month of gestation is rare, occurring in fewer than 4 per 1000 pregnancies.

Maternal age at conception is a strong independent risk factor for miscarriage, because of an increase in chromosomally abnormal conceptions. Reproductive history is also an independent predictor of future pregnancy outcome. Primigravidae and women with a history of live births have a lower risk of miscarriage in their next pregnancy than do women whose most recent pregnancy ended in miscarriage. Cigarette smoking, cocaine use, and alcohol use all increase the risk of miscarriage. Caffeine consumption is associated with a dose-dependent risk of miscarriage, which increases when intake exceeds 300 mg (three cups) of coffee daily.

Fetal aneuploidy is the most important cause of miscarriage before 10 weeks’ gestation. At least 50% to 60% of all miscarriages are associated with cytogenetic abnormalities. Antiphospholipid syndrome is the most important treatable cause of recurrent miscarriage. Antiphospholipid antibodies, of which there are about 20, include lupus anticoagulant and anticardiolipin antibodies. The prevalence of antiphospholipid syndrome among women with recurrent miscarriage is 15%.

Causes of Recurrent Miscarriage

Endocrine causes

• Hyperprolactinemia

• Insulin resistance

• Polycystic ovary syndrome

Genetic and fetal causes

• Balanced reciprocal translocation

• Fetal aneuploidy, including trisomy, polyploidy, and monosomy X

• Congenital malformations

Immune causes (not conclusively proved)

• Maternal autoimmune disease

Infective causes

• Bacterial vaginosis

• Pathogens in the association of toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex (TORCH)

Rh incompatibility

Structural abnormalities

• Bicornate uterus

• Cervical incompetence

• Uterine fibroids (effect on reproductive outcome is controversial)

• Uterine septum

Thrombophilic disorders

• Acquired activated protein C resistance

• Antiphospholipid syndrome

• Antithrombin III deficiency

• Elevated factor VIII concentrations

• Factor V Leiden and activated protein C resistance

• Hyperhomocysteinemia

• Methylene tetrahydrofolate reductase C677T (MTHFR C677T)

• Protein C deficiency

• Protein S deficiency

• Prothrombin G20210A

Unexplained causes

Key Physical Findings

✓ General examination to evaluate for evidence of any systemic disease

✓ Pelvic examination to evaluate for uterine or adnexal abnormalities

Suggested Work-Up

Pelvic ultrasonography	To evaluate for uterine abnormalities and ovarian structure
Parental peripheral blood karyotype	To evaluate for an abnormal karyotype
Measurement of early follicular-phase follicle-stimulating hormone (FSH)	To assess ovarian reserve
Measurement of lupus anticoagulant antibody and anticardiolipin antibody	To evaluate for antiphospholipid syndrome
Test for Factor V Leiden	To evaluate for Factor V Leiden gene mutation
Test for prothrombin gene mutation	To evaluate for prothrombin G20210A gene mutation

Additional Work-Up

Measurement of protein S	If thrombophilia is suspected, to evaluate for protein S deficiency
Measurement of protein C	If thrombophilia is suspected, to evaluate for protein C deficiency
Measurement of antithrombin III	If thrombophilia is suspected, to evaluate for antithrombin deficiency
Measurement of homocysteine	If thrombophilia is suspected, to evaluate for hyperhomocysteinemia
Test for MTHFR C677T	If thrombophilia is suspected, to evaluate for point mutation in the methylene tetrahydrofolate reductase gene

FURTHER READING

Griebel CP, Halvorsen J, Golemon TB. Management of spontaneous abortion. Am Fam Physician. 2005;72:1243-1250.

Hogge WA, Byrnes AL, Lanasa MC, et al. The clinical use of karyotyping spontaneous abortions. Am J Obstet Gynecol. 2003;189:397-400.

Kujovich JL. Thrombophilia and pregnancy complications. Am J Obstet Gynecol. 2004;191:412-424.

Miller TE, Estrella E, Myerburg RJ, et al. Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome. Circulation. 2004;109:3029-3034.

Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601-611.

Rasch V. Cigarette, alcohol and caffeine consumption: risk factors for spontaneous abortion. Acta Obstet Gynecol Scand. 2003;82:182-188.

Walker ID. Thrombophilia in pregnancy. J Clin Pathol. 2000;53:573-580.

Related

Instant Work-ups A Clinical Guide to Obstetric and Gynecologic C