Recurrent Miscarriages

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Recurrent miscarriageis the pregnancy loss of three or more consecutive pregnancies before the fetus reaches viability (20 - 24 weeks gestation depending on the country). About 1% of couples trying to have children have recurrent miscarriage.

Miscarriage occurs in 15-20% of recognized pregnancies.

1% of couples trying to conceive have recurrent miscarriages.

Following three consecutive miscarriages, the risk of further miscarriage is about 40%.

 

A woman may develop recurrent miscarriage after a successful pregnancy.

Risk factors

Increasing maternal age affects ovarian function and increases rates of aneuploidy in association with older oocytes.

 

There are a higher number of conceptions that are chromosomally abnormal and do not develop.

As the number of miscarriages increases, the risk of chromosomal abnormalities decreases and the risk of underlying maternal cause increases.

 

Causes of recurrent miscarriages:

A. Genetic abnormalities:

Recurrent miscarriage may be linked to chromosomal abnormality in 2-5% of couples.

A balanced reciprocal or Robertsonian translocation is the most common type.

 

B. Anti-phospholipid syndrome (APS):

This is the most important treatable cause of recurrent miscarriage.

The anti-phospholipid antibodies, lupus anticoagulant, anticardiolipin antibodies and anti-B2-glycoprotein I antibodies may be associated with recurrent miscarriage before ten weeks.

Anti-phospholipid antibodies are present in 15% of women with recurrent miscarriage.

APS is the only proven thrombophilia that is associated with adverse pregnancy outcomes.

 

C. Structural:

Uterine abnormalities (arcuate or septum) are seen in between 10-25% of cases of recurrent miscarriage. Only 50% of pregnancies where there is a uterine structural abnormality achieve term delivery.

Uterine fibroids are present in up to 30% of women, but they affect reproductive loss depending on their place in the uterus.

 

D. Cervical incompetence (late miscarriage preceded by spontaneous rupture of membranes or painless cervical dilatation) may often be a cause of mid-trimester recurrent miscarriage.

Second-trimester miscarriages may be linked to uterine malformations such as the presence of a uterine septum or a bicornuate uterus.

 

E. Endocrine:

Women with polycystic ovarian syndrome are at higher risk of miscarriage, which may be related to insulin resistance and hyper-insulinemia.

There is insufficient evidence to support the use of metformin during pregnancy to reduce this risk.

Uncontrolled diabetes mellitus is risk factors for recurrent miscarriage.

 

F. Inherited thrombophilia:

Inherited thrombophilia, such as protein C and S deficiency may have a role in recurrent miscarriage, because of an increased risk of thrombosis in the utero-placental circulation.

Women with second-trimester miscarriage should be screened for inherited thrombophilia.

 

Infections:

Bacterial vaginosis in the first trimester is a risk factor for second-trimester miscarriage and preterm delivery.

 

Investigations

Anti-phospholipid antibodies:

The presence of these is associated with early miscarriages and maternal morbidity and is referred to as primary APS. There is requirement for two tests at least six weeks apart showing either lupus anticoagulant or anticardiolipin antibodies at significant levels.

 

Women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriages should be screened for antiphospholipid antibodies before pregnancy.

 

Women with second-trimester miscarriage should be screened for inherited thrombophilia including factor V Leiden, factor II (prothrombin) gene mutation and protein S.

 

All women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriages should have pelvic ultrasound to assess uterine anatomy.

If uterine anomalies are detected then further investigations, such as hysteroscopy and/or laparoscopy, may be required.

 

Karyotyping

Karyotyping of products of conception should be undertaken on the products of conception from the third (and any subsequent) miscarriages. If an unbalanced structural chromosomal abnormality is found, referral to genetics is indicated.

 

Parental peripheral blood karyotyping of both partners should be performed in couples with recurrent miscarriage where testing of products of conception reports an unbalanced structural chromosomal abnormality.

 

Management:

Reassurance should be given about the high probability of a successful outcome. 

Pharmacological treatment

In primary APS patients, heparin combined with low-dose aspirin improves live birth rate to 70%.

 

There is some evidence suggesting that use of metformin during pregnancy is associated with a reduction in the miscarriage rate in women with polycystic ovarian syndrome.

 

A Cochrane review found evidence of benefit for progestogen therapy in women with a history of recurrent miscarriage.    

Surgical

 

Cervical cerclage is used where cervical incompetence is suspected. However, it is diagnosed as a cause of second-trimester miscarriage. The cerclage procedure also carries a risk of stimulating uterine contractions.

 

Cerclage benefit increases as the cervix shortens to less than 25 mm. It has also been shown to be beneficial in those women with a shortened cervical length of less than 25 mm.

 
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