Appendix AScope

Publication Details


1. Guideline title

Pain and bleeding in early pregnancy: assessment and initial management of ectopic pregnancy and miscarriage in the first trimester

Short title

Pain and bleeding in early pregnancy

2. The remit

The Department of Health has asked NICE: ‘to produce a clinical guideline on the assessment and initial management, both physical and emotional, of pain and bleeding in the first trimester of pregnancy’.

3. Clinical need for the guideline


  1. Approximately 137,000 women in England each year experience pain and bleeding in early pregnancy.
  2. Pain and bleeding in early pregnancy occur in about one in five clinically confirmed pregnancies. In 50–60% of these the pregnancy will continue and will have a successful outcome (‘threatened miscarriage’) but the symptoms may indicate impending miscarriage (25–30%) or ectopic pregnancy (10–15%).
  3. There is variation in the presentation of pain and bleeding with a spectrum ranging from severe pain and light or no bleeding (typically an ectopic pregnancy) to bleeding with no pain (typically a threatened miscarriage).
  4. In approximately 8–31% of women presenting to secondary care with pain and bleeding in the first trimester, the location of the pregnancy may be not clear at the first assessment (‘pregnancy of unknown location’). This figure may be higher in units that do not have specialised scanning units. Subsequent assessment reveals the many of these to be viable intrauterine pregnancies. The remainder are either non-viable intrauterine pregnancies or ectopic pregnancies.
  5. Between 15 and 20% of clinically confirmed pregnancies spontaneously end before the 13th week.
  6. Early pregnancy loss accounts for approximately 50,000 inpatient admissions in the UK annually.
  7. From 2008 to 2009 in England, the hospital data for the rate for miscarriage was 66 in every 1000 inpatient deliveries and the rate for ectopic pregnancies was 16 in every 1000 inpatient deliveries.
  8. Between 2003 and 2005 there were 10 deaths from ectopic pregnancy in the UK, giving a maternal mortality rate of 0.47 per 100,000 maternities. Two thirds of these were associated with substandard care.
  9. Early pregnancy loss, particularly in couples affected by recurrent miscarriage or ectopic pregnancy, can have a significant impact on the woman's physical health (for example resulting from blood loss, infection or subsequent subfertility), mental health (for example, depression, anxiety and post-traumatic stress disorder) and emotional wellbeing, as well as that of her partner and family.
  10. Certain groups are at higher risk of miscarriage, including older women and those with medical conditions such as connective tissue disorders or diabetes.
  11. Recurrent miscarriage (three or more consecutive miscarriages) affects approximately 1% of couples, and can lead to great distress. A cause is found in a minority of cases.

Current practice

  1. There is a belief that an efficient early pregnancy assessment unit (EPAU) service improves outcomes for women with pain and bleeding in early pregnancy compared with more ‘traditional care ’ (for example, an emergency department and gynaecological ward), by prompt and timely diagnosis and appropriate management. Treatment in an early pregnancy assessment unit may mean that admission to hospital can be avoided.
  2. There is evidence of widespread variation in availability of facilities and provision of care. For example, in a more ‘traditional’ setting care will be provided on an ad hoc basis by on-call medical staff as part of the emergency gynaecology service within a hospital. In contrast, a dedicated early pregnancy assessment unit run by a specialist multidisciplinary team will deal exclusively with women with pain and bleeding in pregnancy. However, there may be variation in resources available and practices undertaken in both settings, for example not all EPAUs will offer out-of-hours care.
  3. The majority of women presenting with pain and bleeding up to the beginning of the 13th week of pregnancy will have a threatened miscarriage and the pregnancy will continue. There is no agreement on how best to manage symptoms for these women.
  4. Management of miscarriage may be expectant (no intervention and awaiting natural passage of tissue), medical (the use of drugs to expel tissue from the uterus), or surgical (the removal of tissue from the uterus), and in many cases women are given a choice of treatments.
  5. Ectopic pregnancy is often managed surgically by laparoscopy and/or laparotomy but in some cases women are treated medically. Very occasionally no active treatment is needed. There is variation in practice in the way women with ectopic pregnancy with the same ultrasound and biochemical characteristics are managed.
  6. In a significant proportion of women with pain and bleeding in the first trimester, the pregnancy is of unknown location at the first assessment. In the majority of cases a conservative approach of repeated investigation is followed, but the ideal timing and nature of these assessments is not clear.
  7. There are certain aspects of management for which there is widespread variation in practice. These include:
    • Use and interpretation of investigations such as serial serum human chorionic gonadotrophin (hCG) measurements
    • expertise in trans-vaginal ultrasound scanning
    • proportion of miscarriages managed expectantly, medically and surgically
    • proportion of ectopic pregnancies managed medically and surgically
    • provision of information for women and their partners
    • counselling services.
  8. Pain and bleeding in early pregnancy are common problems with significant consequences, but there is wide variation in clinical practice. There is a need for guidance on optimum care in terms of diagnosis and treatment.

4. The guideline

The guideline development process is described in detail on the NICE website (see section 6, ‘Further information’).

This scope defines what the guideline will (and will not) examine, and what the guideline developers will consider. The scope is based on the referral from the Department of Health.

The areas that will be addressed by the guideline are described in the following sections.


4.1.1. Groups that will be covered

  1. Women with pain and bleeding in the first trimester of pregnancy (that is, less than 13 completed weeks). These women may also present with additional clinical features such as diarrhoea.
  2. Women who do not have pain and bleeding in pregnancy but who are found to have a missed miscarriage (i.e. women who are noted to have a non-viable pregnancy as confirmed by an ultrasound scan).
  3. No subgroups of women with pain and bleeding in early pregnancy have been identified as needing specific consideration.

4.1.2. Groups that will not be covered

  1. Women with pain and/or bleeding after the first trimester (13 or more completed weeks of pregnancy).
  2. Women with tumours of the placenta (molar pregnancy or trophoblastic disease) after the initial diagnosis.
  3. Women with pain and/or bleeding unrelated to pregnancy.

Healthcare setting

Primary and secondary care settings that provide care for women with complications in early pregnancy.

Clinical management

4.1.3. Key clinical issues that will be covered

  1. Initial management. ‘Initial’ is defined as the interval between presentation to a healthcare professional and either: the spontaneous loss or removal of pregnancy tissue following a miscarriage or ectopic pregnancy; suspicion or diagnosis of trophoblastic disease; or confirmation of a viable intrauterine pregnancy.
  2. The accuracy of clinical features (including uncommon features such as diarrhoea) in leading to a diagnosis.
  3. The accuracy and interpretation of biomarkers (human chorionic gonadotrophin [hCG], progesterone) and ultrasound in diagnosis, and identifying both the location and the viability of the pregnancy. This will also address the approach to pregnancies of unknown location.
  4. Pharmacological interventions to prevent miscarriage in women with threatened miscarriage.
  5. Effectiveness of early pregnancy assessment units in improving physical and emotional outcomes.
  6. Management strategies for miscarriage (expectant, medical and surgical management options).
  7. Management strategies for ectopic pregnancy (medical and surgical management options).
  8. Emotional and psychological support for women with pain and bleeding in early pregnancy, and those who experience pregnancy loss
  9. The provision of anti-D rhesus prophylaxis for women with miscarriage or ectopic pregnancy
  10. Note that guideline recommendations for drugs will normally fall within licensed indications; exceptionally, and only if clearly supported by evidence, use outside a licensed indication may be recommended. The guideline will assume that prescribers will use a drug's summary of product characteristics to inform decisions made with individual patients.'

4.1.4. Clinical issues that will not be covered

  1. Emergency management of women with acute presentations of shock and collapse.
  2. Management of other problems in the first trimester unrelated to pain and bleeding caused by miscarriage or ectopic pregnancy.
  3. Ongoing management of the pregnancy after the first trimester (that is, 13 completed weeks or more).
  4. Additional treatment and management required by women with recurrent miscarriage.

Main outcomes

  1. Maternal mortality.
  2. Measures of blood loss (measured loss, transfusion needs, coagulation problems and haemoglobin).
  3. Measures of pain.
  4. Need for further interventions.
  5. Continuation of the pregnancy.
  6. Neonatal outcome
  7. Subsequent pregnancy rates.
  8. Recurrence risk.
  9. Emotional and psychological outcomes of woman and her partner (including depression, anxiety and post-traumatic stress disorder).
  10. Women's experience of care and initial follow-up.
  11. Length of stay.
  12. Number of outpatient visits
  13. Adverse effects of treatment.
  14. Subsequent pregnancy complications.

Economic aspects

Developers will take into account both clinical and cost effectiveness when making recommendations involving a choice between alternative interventions. A review of the economic evidence will be conducted and analyses will be carried out as appropriate. The preferred unit of effectiveness is the quality-adjusted life year (QALY), and the costs considered will usually be only from an NHS and personal social services (PSS) perspective. Further detail on the methods can be found in ‘The guidelines manual’ (see ‘Further information’).


4.1.5. Scope

This is the final scope.

4.1.6. Timing

The development of the guideline recommendations will begin in November 2010.

5. Related NICE guidance

Published guidance

Guidance under development

NICE is currently developing the following related guidance (details available from the NICE website):

  • Fertility (update). NICE clinical guideline. Publication date to be confirmed.

6. Further information

Information on the guideline development process is provided in:

  • ‘How NICE clinical guidelines are developed: an overview for stakeholders the public and the NHS’
  • ‘The guidelines manual’.

These are available from the NICE website ( Information on the progress of the guideline will also be available from the NICE website (