Recurrent Miscarriage

Question 1

What is recurrent miscarriage?

Answer 1

Miscarriage is relatively common. Recurrent miscarriage is classed as three or more consecutive miscarriages.

Question 2

How does the risk of miscarriage change with age?

Answer 2

The risk of miscarriage increases with age, with the rate of miscarriage approximately:

• 10% in women aged 20 – 30 years
• 15% in women aged 30 – 35 years
• 25% in women aged 35 – 40 years
• 50% in women aged 40 – 45 years

Question 3

When are investigations offered for recurrent miscarriage?

Answer 3

Investigations are initiated after:

• Three or more first-trimester miscarriages
• One or more second-trimester miscarriages

Question 4

What are the causes of recurrent miscarriage?

Answer 4

• Idiopathic (particularly in older women)
• Antiphospholipid syndrome
• Hereditary thrombophilias
• Uterine abnormalities
• Genetic factors in parents (e.g. balanced translocations in parental chromosomes)
• Chronic histiocytic intervillositis
• Other chronic diseases such as diabetes, untreated thyroid disease and systemic lupus erythematosus (SLE)

Question 5

What is antiphospholipid syndrome?

Answer 5

Antiphospholipid syndrome is a disorder associated with antiphospholipid antibodies, where blood becomes prone to clotting. The patient is in a hyper-coagulable state. The main associations are with thrombosis and complications in pregnancy, particularly recurrent miscarriage.

Antiphospholipid syndrome can occur on its own, or secondary to an autoimmune condition such as systemic lupus erythematosus.

Question 6

In women with antiphospholipid syndrome, how is the risk of miscarriage minimised?

Answer 6

The risk of miscarriage in patients with antiphospholipid syndrome is reduced by using both:

• Low dose aspirin
• Low molecular weight heparin (LMWH)

Question 7

Give examples of hereditary thrombophilias that can cause recurrent miscarriage

Answer 7

The key inherited thrombophilias to remember are:

• Factor V Leiden (most common)
• Factor II (prothrombin) gene mutation
• Protein S deficiency

Question 8

Give examples of uterine abnormalities that can cause recurrent miscarriage

Answer 8

Several uterine abnormalities can cause recurrent miscarriages:

• Uterine septum (a partition through the uterus)
• Unicornuate uterus (single-horned uterus)
• Bicornuate uterus (heart-shaped uterus)
• Didelphic uterus (double uterus)
• Cervical insufficiency
• Fibroids

Question 9

What is chronic histiocytic intervillositis?

Answer 9

Chronic histiocytic intervillositis is a rare cause of recurrent miscarriage, particularly in the second trimester. It can also lead to intrauterine growth restriction (IUGR) and intrauterine death.

The condition is poorly understood. Histiocytes and macrophages build up in the placenta, causing inflammation and adverse outcomes. It is diagnosed by placental histology showing infiltrates of mononuclear cells in the intervillous spaces.

Question 10

What investigations are used for recurrent miscarriage?

Answer 10

Patients should be referred to a specialist in recurrent miscarriage for further investigation. Investigations include:

• Antiphospholipid antibodies
• Testing for hereditary thrombophilias
• Pelvic ultrasound
• Genetic testing of the products of conception from the third or future miscarriages
• Genetic testing on parents

Question 11

Briefly describe the management of recurrent miscarriage

Answer 11

Management of recurrent miscarriage depends on the underlying cause.

There is new evidence from the PRISM trial that suggests a benefit to using vaginal progesterone pessaries during early pregnancy for women with recurrent miscarriages presenting with bleeding. This may become part of guidelines in the future. At present, the RCOG guidelines on recurrent miscarriage (2011) state there is insufficient evidence for progesterone supplementation.