Miscarriage (early pregnancy loss)

Introduction

Miscarriage is the spontaneous loss of an intrauterine pregnancy before 24 weeks gestation. It occurs in approximately 10 – 24% of all clinical pregnancies.¹

The major risk factors for miscarriage are increasing maternal age and the number of previous miscarriages.¹

Most miscarriages (~80%) are diagnosed under 13 weeks, with the risk of miscarriage decreasing as gestational age increases.

Aetiology

In the first trimester, the most common cause of miscarriage is a chromosomal abnormality (50-60%). Autosomal trisomy is the most common abnormality (e.g. trisomy 16). The most common single chromosomal anomaly is 45X karyotype.

Maternal age is related to aneuploidy risk, with increasing maternal age increasing aneuploidy risk (and therefore increasing the risk of miscarriage).

In the second trimester miscarriage is commonly due to an incompetent cervix (e.g. due to previous cervical surgery) or systemic maternal illness. 

Other causes of miscarriage include:

• Fetal malformations (e.g. neural tube defects)
• Uterine structural abnormalities (e.g. uterine septum, Asherman’s syndrome, fibroids, bicornuate uterus)
• Chronic maternal health factors: thrombophilia, antiphospholipid syndrome, systemic lupus erythematosus, PCOS, poorly controlled diabetes mellitus, thyroid dysfunction
• Active maternal infection: rubella, CMV, herpes simplex virus, Listeria infection, toxoplasmosis, parvovirus B19
• Iatrogenic causes: amniocentesis and chorionic villus sampling
• Lifestyle factors: tobacco, alcohol and cocaine
• Exposure to environmental toxins
• Advanced paternal age

Classification of miscarriage²

Miscarriage can be classified as early (before 13 weeks) and late (between 13 and 24 weeks). Miscarriage can be further classified depending on the history and examination findings. 

Threatened miscarriage

A threatened miscarriage occurs when there is vaginal bleeding but the cervical os is closed, and ultrasound shows a viable intrauterine pregnancy.

The term ‘threatened’ refers to the threat of a miscarriage occurring. 

Minor vaginal bleeding is common in early pregnancy. Most threatened miscarriages do not result in the loss of the pregnancy. 

Inevitable miscarriage

An inevitable miscarriage refers to vaginal bleeding with an open cervical os, either with or without cramping abdominal pain. In this situation, pregnancy loss will occur (i.e. inevitable).

Incomplete miscarriage

An incomplete miscarriage occurs when there is vaginal bleeding, an open cervical os and products of conception are seen on examination. 

Complete miscarriage

A complete miscarriage is when the products of conception have passed, the cervical os is closed and ultrasound shows an empty uterine cavity. 

Other types of miscarriage

Other types of miscarriage include:

• Missed miscarriage: the presence of a nonviable intrauterine pregnancy that has not yet resulted in symptoms or the passage of the products of conception. 
• Recurrent miscarriage: the occurrence of three or more miscarriages.

Clinical features

History

Typical symptoms of miscarriage include:

• Vaginal bleeding
• Cramping abdominal pain
• Passage of any fetal tissue or clots

Other important areas to cover in the history include:

• Symptoms of, and risk factors for, ectopic pregnancy
• Menstrual history: last menstrual period (LMP), cycle length, days bleeding, severity & nature of bleeding
• Pregnancy history (if known): dating based on LMP/ultrasound results
• Past obstetric history: outcomes from previous pregnancies and complications
• Past gynaecological history: cervical/uterine surgery, sexual history
• Social history: smoking, alcohol, illicit drug use

Clinical examination

All patients with miscarriage should have basic observations (vital signs) recorded using an obstetric or maternal early warning chart.

A thorough abdominal examination should be performed to assess for signs of an acute abdomen (e.g. rebound tenderness and guarding), which may be suggestive of an ectopic pregnancy. 

A speculum examination should be performed to assess the cervical os, rule out other sources of bleeding (e.g. cervical/vaginal pathology), quantify the bleeding and assess for visible products of conception.

If an ectopic pregnancy is suspected, a bimanual examination should also be performed. Adnexal tenderness or a mass, and cervical motion tenderness, may be present in an ectopic pregnancy.

Investigations

Laboratory investigations

Relevant laboratory investigations may include:

• Full blood count: in patients who have significant blood loss and/or evidence of hypovolaemia
• Beta-HCG: provides an indication as to whether the pregnancy is progressing (see below)
• Group and save / cross-match: if significant bleeding
• Antibody screen: rhesus negative women undergoing a surgical procedure to manage miscarriage will require anti-D rhesus prophylaxis

Imaging

A transvaginal ultrasound should be performed in any patient presenting in early pregnancy with vaginal bleeding and/or abdominal pain. 

The aim of ultrasound scanning is to assess for an intrauterine pregnancy or evidence of an ectopic pregnancy (adnexal pathology or the presence of free fluid in the abdomen).

In addition, the ultrasound can assess fetal viability at that point in time. 

If the ultrasound scan is inconclusive for an intrauterine pregnancy (i.e. there is a pregnancy of unknown location), serial beta-HCG measurements are performed. Serum beta-HCG levels should increase by more than 63% in 48 hours in a progressing pregnancy. Ectopic pregnancy is not excluded, although it is unlikely. 

Beta-HCG levels that fall by more than 50% in 48 hours indicate a failing pregnancy (potential miscarriage). 

Beta-HCG levels that fall by less than 50%, or fail to rise by more than 63%, over 48 hours require clinical review to exclude an ectopic pregnancy. 

Management

All patients require an assessment of their haemodynamic status. 

Emergency management (haemodynamically unstable patient)

Patients who present with significant haemorrhage, and/or evidence of haemodynamic instability, require an ABCDE approach and urgent senior input from the obstetrics & gynaecology team.

A speculum examination should be performed and products of conception should be removed. Products of conception in the cervical os can lead to cervical shock due to vagal stimulation.

Continued bleeding in a haemodynamically unstable patient warrants surgical management. 

Surgical management

There are two options for the surgical management of miscarriage:

• Manual vacuum aspiration (MVA): can be performed under local anaesthetic on the ward, involves manual suction aspiration of the uterus
• Surgical evacuation: usually performed in theatre under general anaesthetic, an electronic suction device is used to remove products of conception

Surgical management should be performed in patients with significant bleeding who have retained products of conception. Surgical management is also used when medical management or expectant management has been unsuccessful. 

Rhesus negative patients undergoing surgical management of miscarriage should be given anti-D rhesus prophylaxis. 

Medical management

Medical management involves the use of a prostaglandin agent (misoprostol) to induce uterine contractions and effacement of the cervix. 

A pregnancy test should be performed three weeks after medical management. If positive, imaging for retained products of conception will be required.

Expectant management

Expectant management involves waiting for spontaneous passage of the products of conception, without any medical or surgical intervention.

A pregnancy test should be performed three weeks after expectant management providing pain and bleeding settles. If positive, imaging for retained products of conception will be required.

If no bleeding has occurred, or worsening pain or bleeding, women require repeat assessment and alternative management. 

Recurrent miscarriages

Recurrent miscarriage is defined as three or more miscarriages. These patients require a specialist review to assess for an underlying cause of miscarriage. 

Causes of recurrent miscarriage include:

• Increased maternal age
• Parental genetic factors (balanced translocations, mosaicism)
• Thrombophilic disorders
• Endocrine disorders (diabetes mellitus, thyroid disorders, PCOS)
• Structural uterine abnormalities

Relevant investigations for recurrent miscarriage include:

• Cytogenetic analysis performed on the products of conception of the third and any subsequent miscarriages
• Parental karyotyping and genetic counselling
• Blood tests: HbA1c, antiphospholipid/thrombophilia screen, thyroid function tests
• Pelvic ultrasound

The chance of subsequent success of an intrauterine pregnancy is still up to 75%.

Complications

Complications of miscarriage include:

• Infection
• Retained products of conception: may require surgical management
• Asherman’s syndrome (uterine adhesions): a complication of repeated surgical management
• Psychological impact: depression and/or anxiety

Risk of recurrence

There is no increased risk of having another miscarriage after having one miscarriage. 

After two miscarriages, the risk of having a subsequent miscarriage is 25%.

After three miscarriages, the risk is approximately 40%.

References

1. NICE Clinical Knowledge Summary. Miscarriage. Available from: [LINK]
2. BMJ Best Practice. Miscarriage. Available from: [LINK]
3. Miscarriage Association. Support Services. Available from: [LINK]