Miscarriage is defined as spontaneous loss of pregnancy before fetal viability, so includes all pregnancy losses from conception to 24 weeks.1
Recurrent miscarriage is defined as the loss of three or more consecutive pregnancies. Up to 1% of couples may be affected.2
Spontaneous miscarriage may occur in up to half of all pregnancies before the first missed menstrual period; 10-20% of diagnosed pregnancies may result in early loss.3 After a single first-trimester miscarriage, no investigation is usually required.2
There is an increased risk of miscarriage with advancing maternal age and number of previous miscarriages. It is thought the number and quality of oocytes decline with advancing maternal age, in part related to an increase in chromosomal abnormalities that are due to an increased rate of meiotic errors.
With advanced maternal age, there is a greater chance of chromosomal abnormalities, such as Down's syndrome, trisomies 13 and 18, and sex chromosome aneuploidies.2
Following three consecutive miscarriages, the risk of further miscarriage is about 40%. A woman may develop recurrent miscarriage after a successful pregnancy. Excessive alcohol, smoking and drug abuse increase the risk of sporadic miscarriage.1
Uncontrolled diabetes mellitus, systemic lupus erythematosus and thyroid disease may be risk factors for recurrent miscarriage.
Women with polycystic ovary syndrome are at higher risk of miscarriage, which may be related to insulin resistance and hyperinsulinaemia. There is insufficient evidence to support the use of metformin during pregnancy to reduce this risk.
Antiphospholipid syndrome may be a treatable cause of recurrent miscarriage. The antiphospholipid antibodies, lupus anticoagulant, anticardiolipin antibodies and anti-B2-glycoprotein I antibodies may be associated with recurrent miscarriage before 10 weeks, with one or more morphologically normal fetal losses after the 10th week and one or more preterm births before the 34th week of gestation.4
Antiphospholipid antibodies are present in 15% of women with recurrent miscarriage. Women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriages should be screened before pregnancy for antiphospholipid antibodies.2
It is thought they may cause inhibition of trophoblastic function and differentiation in addition to a local inflammatory response. Moreover, there is increased risk of thrombosis as pregnancy advances.
Pregnant women with antiphospholipid syndrome should be considered for treatment with low-dose aspirin plus heparin to prevent further miscarriage. This may reduce pregnancy loss by 54%.4
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 uteroplacental circulation. Women with second-trimester miscarriage should be screened for inherited thrombophilia.1
Recurrent miscarriage may be linked to chromosomal abnormality in 2-5% of couples. A balanced reciprocal or Robertsonian translocation is the most common type.1
Cytogenetic analysis should be performed on products of conception of the third and subsequent miscarriages. If an unbalanced structural chromosomal abnormality is found, referral to genetics is indicated.1
Second-trimester miscarriages may be linked to uterine malformations such as the presence of a uterine septum or a bicornuate uterus.
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 anomalies are detected, further investigations, such as hysteroscopy and/or laparoscopy, may be required.
There is insufficient evidence to assess the effect of uterine septum resection in women with recurrent miscarriage.1
If there is a history of spontaneous rupture of membranes or painless cervical dilation causing second-trimester miscarriage, a diagnosis of cervical weakness may be considered. These patients may be offered cervical sonographic surveillance.
Any woman with a singleton pregnancy and a history of one second-trimester miscarriage related to cervical weakness should be offered ultrasound-indicated cerclage if a cervical length of 25mm or less is detected by a transvaginal scan before 24 weeks.3
Bacterial vaginosis in the first trimester is a risk factor for second-trimester miscarriage and preterm delivery.2
Treatment and support
Women with recurrent first and second-trimester miscarriage should be cared for in a recurrent miscarriage clinic in the setting of an early pregnancy assessment unit.
Information should be given to allow the woman to consider her future reproductive options.3
A woman may conceive after miscarriage after a normal menstrual cycle; however, emotional factors need to be considered in the timing of a future pregnancy. An important part of management is the role of support and counselling.2
- Dr Kochhar is a GP principal in St Leonards, East Sussex
1. RCOG. The Investigation and Treatment of Couples with Recurrent First-trimester and Second-trimester Miscarriage (Green-top guideline 17). London, RCOG, 2011.
2. Horne AW, Alexander CI.
Recurrent miscarriage. J Fam Plann Reprod Health Care 2005; 31: 103-7.
3. Rai R, Regan L. Recurrent miscarriage. Lancet 2006; 368: 601-11.
4. Empson M, Lassere M, Craig J et al. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev 2005; (2): CD002859.
Miscarriage Association. www.miscarriageassociation.org.uk