Recurrent miscarriage

Question 1

Definition

Answer 1

Three or more consecutive pregnancies before 24w with the same biological father and without a known cause

Question 2

What percentage of couples are affected?

Answer 2

1%

Question 3

Is the chance of miscarriage higher in fourth pregnancy?

Answer 3

Risk still only 40% but recurring cause is more likely (therefore should be investigated)

Question 4

Is age a factor?

Answer 4

Yes
Maternal age 35+
Paternal age 40+

Question 5

Causes?

Answer 5

Endocrine
Infection
Parental chromosomal abnormalities
Uterine abnormalities
Antiphospholipid syndrome
Thrombophilia
Alloimmune factors
Other causes

Question 6

Endocrine disease?

Answer 6

Well controlled disease (DM, thyroid) does not cause miscarriage, neither does PCOS; however, thyroid disease with presence of thyroid autoantibodies is related to miscarriage - so should be diagnosed and treated

Question 7

Infection?

Answer 7

Bacterial vaginosis assoc with second trimester loss and infection implicated in preterm birth. Infection generally not cause of recurrent early pregnancy loss (1st trimester)

Question 8

Parental chromosomal abnormalities?

Answer 8

2-5%. Typically reciprocal or robertsonian translocation. Parent may be phenotypically normal but karyotyping may show 50-75% abnormality. Refer to geneticist. Prenatal diagnosis with chorionic villus sampling/amniocentesis may be offered.
Use of donor gametes or preimplantation genetic diagnosis of IVF embryos may be offered (although this carries lower rates of successful outcome in pregnancy)

Question 9

Uterine abnormalities?

Answer 9

Diagnosed by USS. More common with late miscarriage. However, many are incidental findings - surgical correction may cause uterine weakness (inc chance uterine rupture) or adhesion formation.
Cervical problems - late (>16w) miscarriage and preterms

Question 10

Antiphospholipid syndrome antibodies?

Answer 10

Cause thrombosis in the uteroplacental circulation. Treat with Aspirin 75mg/24hr PO from day +ve pregnancy test and start LMW heparin 45mg/24hr SC from seeing foetal heart (5-6w) until delivery. Live birth rate 80%.

Consult specialist - future pregnancies at inc risk of recurrent miscarriage, pre-eclampsia, foetal growth restriction and preterm.

Question 11

What are the APL syndrome autoantibodies?

Answer 11

anti - Cardiolipin
Lupus anticoagulant
Phospholipid

Question 12

Thrombophilia?

Answer 12

In mothers with thrombophilia (factor V leiden, prothrombin gene mutations, protein c and s deficiency)
Heparin reduces risk of miscarriage

Question 13

Alloimmune causes?

Answer 13

Possible that mothers share HLA alleles with partners so mount insufficient protective response to foetus. Immunotherapy has no benefit, may be harmful to foetus, should not be offered.

Question 14

Other causes?

Answer 14

Obesity, smoking, excess caffeine intake should be reduced if possible.
Inc maternal age increases risk of spontaneous miscarriage so may be a factor in multiple failures.

Question 15

Investigating recurrent miscarriage

Answer 15

APL antibody screen (repeat at 6w if positive); positive if two tests return positive results, taken 12w apart
Karyotyping of foetal miscarriage tissue; if unbalanced, karyotype parents
TFTs
Pelvic USS (+MRI/hysterosaplingogram if abnormal); potential laparoscopy/hysteroscopy if abnormal.