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Pregnancy Women's health

Miscarriage

Last revised in October 2023

Miscarriage is the spontaneous loss of a pregnancy before 24 weeks' gestation. Recurrent miscarriage is the consecutive loss of three pregnancies

Miscarriage: Summary

  • Miscarriage is the spontaneous loss of pregnancy before the fetus reaches viability. The term includes all pregnancy losses from the time of conception until 24 weeks of gestation.
  • Recurrent miscarriage is the loss of three or more pregnancies before 24 weeks of gestation.
  • The most common cause of spontaneous pregnancy loss in the first trimester is chromosomal abnormalities.
  • Risk factors for miscarriage include increasing parental age, endocrine disorders (such as polycystic ovary syndrome), and previous miscarriage.  
  • Miscarriage should be suspected if a woman who is pregnant, or has symptoms of pregnancy (such as amenorrhoea or breast tenderness), presents with vaginal bleeding, with or without pain, in the first 24 weeks of pregnancy.
  • If a miscarriage is suspected:
    • Pregnancy should be confirmed with a urine pregnancy test.
    • A detailed history and examination should be undertaken to assess the woman and to exclude differential diagnoses, such as ectopic pregnancy.
    • The possibility of ectopic pregnancy should be excluded even in the absence of risk factors (such as previous ectopic pregnancy) because about 30% of women with ectopic pregnancy will have no risk factors.
  • Immediate hospital admission should be arranged if there are signs of haemodynamic instability or significant concerns about the degree of bleeding or pain.
  • Immediate admission to an early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service should be arranged for women with a positive pregnancy test and one or more of the following:
    • Abdominal pain and tenderness.
    • Pelvic tenderness.
    • Cervical motion tenderness.
  • Referral to EPAU or out-of-hours gynaecology service should be arranged (urgency depending on the clinical situation) for women with bleeding or other symptoms and signs of early pregnancy complications who have one or more of the following:
    • Pain.
    • A pregnancy of 6 weeks gestation or more.
    • A pregnancy of uncertain gestation.
  • Expectant management should be used for women with a pregnancy of less than 6 weeks' gestation who are bleeding but not in pain, and who have no risk factors (such as previous ectopic pregnancy). The woman should be advised:
    • To return if bleeding continues or pain develops.
    • To repeat a urine pregnancy test after 7–10 days and return if it is positive.
    • That a negative pregnancy test means that the pregnancy has miscarried. 
  • Referral to EPAU or out-of-hours gynaecology service should be arranged: 
    • For women who return with worsening symptoms.
    • If there is doubt about the viability of a pregnancy.
  • Transvaginal ultrasound is the diagnostic tool of choice to assess the location and viability of the pregnancy. 
  • Secondary care treatment options include expectant management (watchful waiting), medical management, or surgery.
  • Following a miscarriage, women should be followed up in primary care and offered appropriate support, information, and advice.
  • Women with recurrent miscarriage should be offered referral for investigation and management. If no cause is found, the prognosis for a successful future pregnancy is about 75%. However, the prognosis worsens with increasing maternal age and the number of previous miscarriages.

Have I got the right topic?

From age 16 years onwards (Female).

This CKS topic covers the assessment and initial management of women with a suspected first-trimester miscarriage. It also briefly covers the management of women with recurrent miscarriage.

This CKS topic does not cover in great detail the management of women following referral to secondary care or other specialist services but makes recommendations on how the women should be followed up in primary care after a miscarriage.

There are separate CKS topics on Amenorrhoea, Ectopic pregnancy, and Pelvic inflammatory disease.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

October 2023 — reviewed. A literature search was conducted in August 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. No major changes to clinical recommendations have been made.

Previous changes

December 2022 — minor update. Information on secondary care management of threatened miscarriage has been added to this topic in line with the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management.  

November 2020 — minor update. A link to the reference for the American College of Obstetricians and Gynecologists (ACOG) guideline on early pregnancy loss was updated. 

May 2018 — reviewed. A literature search was conducted in March 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. No changes to clinical recommendations have been made, but the topic has been restructured.

July 2013 — revised. A literature search was conducted in June 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Based on recommendations in the NICE 2012 guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage, changes have been made regarding the following:

  • Assessment of a woman presenting with symptoms and signs of an early pregnancy complication.
  • The recommended urgency of referral to secondary care or other specialist services for assessment and management.

October 2009 to February 2010 — this is a new CKS topic. The evidence base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 October 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 October 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 October 2023.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 October 2023.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 October 2023.

New policies

No new national policies or guidelines since 1 October 2023.

New safety alerts

No new safety alerts since 1 April 2018.

Changes in product availability

No changes in product availability since 1 October 2023.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Assess a woman presenting with symptoms of a possible miscarriage.
  • Promptly recognize the symptoms and signs of a possible ectopic pregnancy.
  • Refer the woman appropriately to secondary care or other specialist services.
  • Manage the distress caused by miscarriage.
  • Offer referral for the investigation and management of recurrent miscarriage.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

  • Women referred to early pregnancy assessment services are seen by the service at least within 24 hours of referral.
  • Women who are referred with suspected ectopic pregnancy or miscarriage are offered a transvaginal ultrasound scan to identify the location and viability of the pregnancy.
  • Women with a suspected miscarriage who have had an initial transvaginal ultrasound scan are offered a second assessment to confirm the diagnosis.

[NICE, 2014]

Background information

What is it?

  • Miscarriage is the spontaneous loss of pregnancy before the fetus reaches viability. The term includes all pregnancy losses from the time of conception until 24 weeks of gestation [Ghosh, 2021; Regan, 2023]. 
  • A miscarriage is described as [Jurkovic, 2013]:
    • Early — if it occurs before 13 weeks of gestation.
    • Late — if it occurs between 13 and 24 weeks of gestation.
  • The stages of miscarriage may include [Jurkovic, 2013] [WHO, 2017] [BMJ Best Practice, 2023a]:
    • Threatened miscarriage — when vaginal bleeding, with or without lower abdominal pain, occurs in the first 24 weeks of gestation. Pregnancy may continue.
    • Inevitable miscarriage — when specific clinical features indicate that a pregnancy is in the process of physiological expulsion from within the uterine cavity. Pregnancy will not continue and will proceed to incomplete or complete miscarriage.
    • Missed miscarriage (also known as delayed or silent miscarriage) — when a non-viable pregnancy is identified on an ultrasound scan without associated pain and bleeding.
    • Incomplete miscarriage — when products of conception are partially expelled from the uterus. Many incomplete miscarriages may be missed miscarriages.
    • Complete miscarriage — when all the products of conception have been expelled from the uterus, and bleeding has stopped.
  • Recurrent miscarriage is the loss of three or more pregnancies before 24 weeks of gestation [BMJ Best Practice, 2023a] [Regan, 2023].
    • In some European countries and the US, recurrent miscarriage is defined as two or more miscarriages, either consecutive or non-consecutive [Jurkovic, 2013; ESHRE, 2023].

How common is it?

What are the causes?

  • The most common cause of spontaneous pregnancy loss in the first trimester is fetal chromosomal abnormalities (detected in 50–85% of pregnancy tissue specimens after spontaneous miscarriage) [Jurkovic, 2013; Colley, 2019; ACOG, 2021; BMJ Best Practice, 2023b; Regan, 2023]. 
  • No causes or associations are found in about 50% of couples with recurrent miscarriage (unexplained or idiopathic recurrent miscarriage).
    • Up to 75% of these couples achieve a successful live birth in future pregnancies if given only supportive care and psychological support in a dedicated early pregnancy assessment unit (EPAU) [BMJ Best Practice, 2023b].

What are the risk factors?

  • Risk factors for miscarriage include: 
    • Advanced maternal age — advanced maternal age (usually defined as age 35 years or older) is strongly related to fetal chromosomal abnormalities [du Fossé, 2020; BMJ Best Practice, 2023b]. This is due to a decline in both the number and quality of the remaining oocytes, resulting in higher rates of aneuploidy in the fertilized embryos [Regan, 2023]. In a population-based register linkage study, the risk of spontaneous abortion was 8.9% in women aged 20–24 years and 74.7% in those aged 45 years or more. High maternal age was a significant risk factor for spontaneous abortion irrespective of the number of previous miscarriages, parity, or calendar period [Nybo Anderson, 2000].
    • Advanced paternal age — a systematic review and meta-analysis reported an increased miscarriage rate for men aged over 45 years and older. However, the effect of paternal age is less pronounced than that observed with advanced maternal age and residual confounding by maternal age cannot be excluded [du Fossé, 2020].
    • Congenital uterine anomalies — there is an increased risk of miscarriage in women with septate or bicornuate uteri [Regan, 2023].
    • Endocrine disorders — maternal endocrine disorders, such as polycystic ovary syndrome (PCOS), diabetes mellitus, and thyroid disease, have been associated with miscarriage [Zhang, 2017; Regan, 2023]. Poorly controlled diabetes with a high HbA1c in the first trimester may increase the risk of miscarriage and fetal malformation [BMJ Best Practice, 2023a]. 
    • Vitamin D deficiency — a systematic review and meta-analysis found that vitamin D deficiency and insufficiency are associated with miscarriage. However, it is unknown whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage [Tamblyn, 2022].
    • Previous miscarriage — the risk of a future miscarriage increases with increasing number of previous miscarriages. A systematic review reported miscarriage rates of 11.3%, 17%, 28%, 39.6%, 47.2%, and 63.9% for women with no, one, two or three, four, five, and six previous miscarriages, respectively [Coomarasamy, 2020].
    • Black ethnic background — a large observational study found that the odds of a sporadic miscarriage were increased in Black African and Black Caribbean women compared with white European women [Oliver-Williams, 2015].
    • Maternal lifestyle choices — there is some evidence for an association between sporadic miscarriage and smoking, alcohol consumption (approximately 10 units per week) [Sundermann, 2019], increased caffeine intake, and obesity. Exposure to environmental risk factors (such as air pollution and household chemicals) may increase the risk of sporadic miscarriage [Regan, 2023].
  • Risk factors for recurrent miscarriage may include:
    • Chromosomal abnormalities — chromosome abnormalities are the most common cause of explained recurrent miscarriage [Regan, 2023]. However, the frequency of fetal chromosomal abnormality significantly decreases with increasing number of previous miscarriages [BMJ Best Practice, 2023b].
    • Blood clotting factors — antiphospholipid syndrome is found in about 15% of people with recurrent miscarriage. Inherited thrombophilic defects (such as factor V Leiden mutation and hyperhomocysteinaemia) predispose people to thromboembolic events; this may partially explain the weak association of some of these defects with recurrent miscarriage [BMJ Best Practice, 2023b; Regan, 2023]. 
    • Parental chromosomal anomaly — these account for about 3–5% of cases of recurrent miscarriage and are most commonly balanced reciprocal or Robertsonian translocations [BMJ Best Practice, 2023b; BMJ Best Practice, 2023a].
    • PCOS — the risk of recurrent miscarriage is thought to be increased by hyperandrogenism, obesity, and insulin resistance. Women with PCOS with abnormal ovarian morphology on ultrasound scan, elevated luteinising hormone, and elevated testosterone have been found to have similar live birth rates to women without PCOS [BMJ Best Practice, 2023b].
    • Male factor — meta-analyses have found an association between increased sperm DNA fragmentation in male partners and unexplained recurrent miscarriage [McQueen, 2019; Yifu, 2020]. 
    • Subclinical hypothyroidism and thyroid autoantibodies — uncontrolled thyroid disorders are associated with miscarriages. The presence of thyroid antibodies is associated with a higher miscarriage rate; however, the presence of association does not mean causation and could be explained by mechanisms such as an underlying autoimmune state or mild thyroid failure [BMJ Best Practice, 2023b].
    • Prolactin imbalances — both increased and reduced levels of prolactin have been implicated in recurrent miscarriage. Overall, it appears that maintaining a normal level of prolactin may be beneficial in reducing the risk of recurrent miscarriage [Regan, 2023].
    • Body mass index (BMI) — evidence from a systematic review and meta-analysis of lifestyle factors and risk of recurrent pregnancy loss showed that women with a BMI below 19 kg/m2 and above 25 kg/m2 were at higher odds of recurrent miscarriage [Ng, 2021].

What are the complications of miscarriage?

  • Complications of miscarriage include [Ghosh, 2021; NICE, 2023]:
    • Psychological distress — the loss of an early pregnancy can affect couples as significantly as a neonatal death [BMJ Best Practice, 2023a]. About 20% of women who experience a miscarriage develop symptoms of depression and/or anxiety. Symptoms may persist for up to 3 years, impacting quality of life and subsequent pregnancies [Nynas, 2015].
    • Infections and sepsis — these may occur before or after the miscarriage. 
    • Treatment complications, including [BMJ Best Practice, 2023a]: 
      • Bleeding — retained early pregnancy tissue within the uterine cavity could result in persistent vaginal bleeding and suprapubic pain. Brisk bleeding may occur after complete evacuation of the uterus.
      • Uterine or cervical perforation — may occur during surgical evacuation of the uterus and can result in severe blood loss and shock. 
      • Asherman's syndrome (rare) — may occur as a result of trauma to the endometrial lining during a curettage procedure. Scar tissue forms inside the uterus and/or the cervix and can result in infertility, recurrent miscarriage, and high-risk pregnancies.
    • Recurrent miscarriage — the risk of a future miscarriage increases with increasing number of previous miscarriages. A systematic review reported miscarriage rates of 11.3%, 17%, 28%, 39.6%, 47.2%, and 63.9% for women with no, one, two or three, four, five, and six previous miscarriages, respectively [Coomarasamy, 2020].

Assessment of miscarriage

How should I assess the woman?

  • Confirm pregnancy with a urine pregnancy test.
    • If the woman has had a recent home pregnancy test, consider repeating the test to reconfirm the diagnosis of pregnancy. 
  • Take a detailed history.
    • Ask about her presenting symptoms, including when they started, as well as the duration, severity, and nature.
      • Suspect a miscarriage if a woman who is pregnant, or has symptoms of pregnancy (such as amenorrhoea or breast tenderness), presents with vaginal bleeding, with or without pain, in the first 24 weeks of pregnancy.
      •  Bleeding is typically scanty, varying from a brownish discharge to bright red bleeding, and may recur over several days.
      •  Lower abdominal cramping pain or lower backache, when it occurs, usually develops after the onset of bleeding.
    • Ask about her:  
      • Gynaecological history, including menstrual cycle (last menstrual period [LMP], cycle length, and nature of bleeding), cervical smear history, and previous gynaecological diagnosis or surgery. 
      • Obstetric history, including previous live births, method of delivery, and previous miscarriage, ectopic pregnancy, or termination.
      • Medical history, including a history of endocrine disorders (such as diabetes, polycystic ovary syndrome, and thyroid disorder).
      • Social history, including smoking and alcohol status.
    • Ask about symptoms (or risk factors) of ectopic pregnancy.
      • Common symptoms include abdominal or pelvic pain, amenorrhoea or missed period, and vaginal bleeding with or without clots.
      • Other reported symptoms include breast tenderness; gastrointestinal symptoms; dizziness, fainting, or syncope; shoulder tip pain; urinary symptoms; passage of tissue; and rectal pressure or pain on defecation.
      • Exclude the possibility of ectopic pregnancy, even in the absence of risk factors (such as previous ectopic pregnancy).
      • Be aware that atypical presentations for ectopic pregnancy are common. See the CKS topic on Ectopic pregnancy for more information.
  • Examine the woman.
    • Assess for signs of haemodynamic instability, including pallor, tachycardia, tachypnoea, and hypotension.
    • Consider performing a speculum examination to assess the cervical os, rule out other sources of bleeding (such as an ectropion, a cervical polyp, or a genital tract laceration), quantify the bleeding, and assess for visible products of conception.
    • Examine for signs of an ectopic pregnancy.
      • Perform an abdominal examination to assess for signs of an acute abdomen (for example, rebound tenderness and guarding), which may be suggestive of an ectopic pregnancy. 
      • If there is no abdominal pain or tenderness, perform a gentle pelvic examination. Do not palpate for an adnexal or pelvic mass, as this may increase the risk of rupture of an ectopic pregnancy if present.
      • Common signs of an ectopic pregnancy include pelvic tenderness, adnexal tenderness, and abdominal tenderness.
      • Other reported signs include cervical motion tenderness, rebound tenderness or peritoneal signs, pallor, abdominal distension, enlarged uterus, tachycardia (more than 100 beats per minute), hypotension (less than 100/60 mmHg), shock or collapse, and orthostatic hypotension.
      • Be aware that the clinical features of ectopic pregnancy can resemble those of other conditions, such as gastrointestinal conditions or urinary tract infections. See the CKS topic on Ectopic pregnancy for more information.
  • Be alert for symptoms and signs of tubal rupture and intra-abdominal bleeding. For example:
    • Vomiting and diarrhoea may be the presenting symptoms of abdominal bleeding. 
    • Shoulder pain may be caused by irritation of the diaphragm due to leakage of blood from the implantation site.
    • Pallor, tachycardia, hypotension, and shock or collapse may indicate tubal rupture and severe bleeding.
  • Exclude other conditions that can cause bleeding or pain in pregnancy, such as haemorrhoids and adnexal torsion.

Basis for recommendation

These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management [NICE, 2023] and the British Medical Journal (BMJ) Best Practice guides Assessment of recurrent miscarriage [BMJ Best Practice, 2023b] and Miscarriage [BMJ Best Practice, 2023a]. 

Being alert for the clinical features of tubal rupture and intra-abdominal bleeding

  • The clinical features of rupture and intra-abdominal bleeding are based on expert opinion in a narrative review Diagnosis and management of ectopic pregnancy [Jurkovic, 2011], a systematic review Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review [Crochet, 2013] and the British Medical Journal (BMJ) Best Practice guides Assessment of recurrent miscarriage [BMJ Best Practice, 2023b] and Miscarriage [BMJ Best Practice, 2023a]. 

What else might cause bleeding or pain in pregnancy?

  • Other possible causes of bleeding include:
    • Pregnancy-related conditions, such as:
      • Ectopic pregnancy. See the CKS topic on Ectopic pregnancy for more information.
      • Molar pregnancy — a rare condition of a slow-growing cystic tumour which develops from trophoblastic cells after fertilization. This is more likely if bleeding is heavy and prolonged, symptoms of pregnancy are exaggerated, the uterus is large for dates, and/or vesicles or cysts are passed.
    • Non-pregnancy-related conditions, such as:
      • Cervicitis, cervical ectropion, or cervical polyps.
      • Cancer of the cervix, vagina, or vulva. See the CKS topic on Cervical cancer and HPV for more information.
      • Haemorrhoids. See the CKS topic on Haemorrhoids for more information.
      • Trauma of the cervix, vagina, or vulva.
      • Urethral bleeding.
      • Vaginitis.
  • Other possible causes of abdominal pain include:
    • Pregnancy-related conditions, such as:
      • Ruptured ovarian corpus luteal cyst.
      • Adnexal torsion.
      • Pregnancy-related degeneration of a fibroid.
    • Non-pregnancy-related conditions, such as:

Basis for recommendation

The information on differential diagnoses of miscarriage is based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management [NICE, 2023], the British Medical Journal (BMJ) Best Practice guide Miscarriage [BMJ Best Practice, 2023a] and exert opinion in a chapter on Early Pregnancy Loss in Danforth's Obstetrics and Gynecology [Porter, 2008], a chapter on Female genital infections in Clinical Obstetrics and Gynaecology [Clutterbuck, 2009], a chapter on Pelvic pain and ectopic pregnancy in Clinical Obstetrics and Gynaecology [Latthe and Khan, 2009], a chapter on Miscarriage in Clinical Obstetrics and Gynaecology [Owen, 2009] and a chapter on Gestational trophoblastic disease in Clinical Obstetrics and Gynaecology [Savage, 2009].

Management

Scenario: Managing suspected first trimester miscarriage

From age 16 years onwards (Female).

How should I manage a woman with a suspected first-trimester miscarriage?

  • Arrange immediate hospital admission if: 
    • The woman has signs of haemodynamic instability, including pallor, tachycardia, tachypnoea, hypotension, shock, and collapse. Resuscitate with intravenous fluids if available. 
    • There is significant concern about the degree of bleeding or pain.
  • Arrange immediate admission to an early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service for:
    • Women with a positive pregnancy test and one or more of the following on examination: 
      • Abdominal pain and tenderness.
      • Pelvic tenderness.
      • Cervical motion tenderness.
  • Refer to EPAU or out-of-hours gynaecology service (with urgency dependent on the clinical situation):
    • Women with bleeding or other symptoms and signs of early pregnancy complications who have one or more of the following:
      • Pain.
      • A pregnancy of 6 weeks gestation or more.
      • A pregnancy of uncertain gestation.
  • Use expectant management for women with pregnancy of less than 6 weeks gestation who are bleeding but not in pain and who have no risk factors, such as previous ectopic pregnancy.
    • Advise these women:
      • To repeat a urine pregnancy test after 7–10 days and return if it is positive.
      • That a negative pregnancy test means that the pregnancy has miscarried. 
      • To return if bleeding continues or pain develops.
    • Refer to EPAU or out-of-hours gynaecology service: 
      • Women who return with worsening symptoms. The decision on whether she should be seen immediately or within 24 hours will depend on the clinical situation.
      • If there is doubt about the viability of a pregnancy.
  • Offer appropriate information, advice, and support to all women with early pregnancy complications.
    • For all women referred to an EPAU or out-of-hours gynaecology service, explain the reasons for the referral and what she can expect when she arrives there.
    • After a miscarriage, offer women the option of a follow-up appointment. 
    • Throughout the woman's care, provide appropriate information to the woman and (with her consent) her partner. This should include (as appropriate) information on:
      • The causes and risk factors of miscarriage. 
      • Secondary care management options.
      • When and how to seek help if existing symptoms worsen or new symptoms develop, including a 24-hour contact telephone number.
      • What to expect during the course of her care (including expectant management), such as the potential length and extent of pain and/or bleeding, and possible adverse effects.
    • Provide patient information on miscarriage. 

Diagnosis and management in secondary care

Diagnosis

  • Ultrasonography is used to assess the location and viability of the pregnancy.
    • A transvaginal ultrasound scan is preferred because, compared with a transabdominal scan, it provides good-quality imaging and can offer clearer pictures of the womb, ovaries, and surrounding areas. 
    • A transabdominal ultrasound scan may be considered:
      • For women with an enlarged uterus or other pelvic pathology, such as fibroids or an ovarian cyst.  
      • If a transvaginal ultrasound scan is unacceptable to the woman.
  • A single transvaginal ultrasound scan may not always accurately diagnose miscarriage. Therefore, women with a suspected miscarriage are usually offered a second assessment to confirm the diagnosis. 

 Expectant management

  • Expectant management is the first-line management option for women with a confirmed diagnosis of miscarriage.
  • Other management options (medical or surgical management) may be considered if:
    • The woman is at increased risk of haemorrhage (for example, she is in the late first trimester).
    • The woman has previous adverse and/or traumatic experiences associated with pregnancy (for example, stillbirth, miscarriage or antepartum haemorrhage).
    • The woman is at increased risk from the effects of haemorrhage (for example, if she has coagulopathies or is unable to have a blood transfusion).
    • There is evidence of infection.
    • Expectant management is not acceptable to the woman. 
  • The National Institute for Health and Care Excellence (NICE) recommends that: 
    • If the resolution of bleeding and pain indicates that the miscarriage has completed during 7–14 days of expectant management, the woman should be advised to do a pregnancy test after 3 weeks and return if it is positive.
    • A repeat scan should be offered if, after the period of expectant management, the bleeding and pain:
      • Has not started (suggesting that the process of miscarriage has not begun).
      • Are persisting and/or increasing (suggesting incomplete miscarriage). 

Medical management

  • Medical management is offered if expectant management is not clinically appropriate or a woman has ongoing symptoms after 14 days of expectant management.
  • For the medical management of missed miscarriage, the woman is offered 200 mg oral mifepristone and, 48 hours later, 800 micrograms of misoprostol (vaginal, oral, or sublingual) unless the gestational sac has already been passed. 
  • For the medical management of incomplete miscarriage, the woman is offered a single dose of misoprostol 600 micrograms (vaginal, oral, or sublingual). Misoprostol 800 micrograms can be used as an alternative to allow alignment of treatment protocols for both missed and incomplete miscarriages.
  • The woman is advised to do a pregnancy test after 3 weeks and return if it is positive.

Surgical management

  • Surgical intervention may be required if products of conception are retained despite medical treatment or offered if the woman has ongoing symptoms after 14 days of expectant management.
  • The women are offered a choice of manual vacuum aspiration under local anaesthetic or surgical management under general anaesthetic.

Anti-D immunoglobulin 

  • Anti-D immunoglobulin prophylaxis is offered to all rhesus-negative women who have had a surgical procedure to manage a miscarriage.
  • It should not be given to women who:
    • Receive solely medical management for an ectopic pregnancy or miscarriage.
    • Have a threatened miscarriage.
    • Have had a complete miscarriage.
    • Have a pregnancy of unknown location.

[NICE, 2014; NICE, 2023]

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management [NICE, 2023].

Scenario: Follow up after a miscarriage

From age 16 years onwards (Female).

How should I follow up a woman after a miscarriage?

  • After a miscarriage:
    • Ensure that arrangements for routine antenatal care are cancelled (if they have been started).
    • Assess the woman's psychological well-being. Offer counselling if appropriate.
    • Ensure that all rhesus-negative women who have had a surgical procedure to manage miscarriage have received anti-D immunoglobulin prophylaxis. 
  • Discuss any questions the woman has about her miscarriage, including:
    • The causes and risk factors of miscarriage.
    • When to resume sexual activity.
      • Advise avoidance of sexual intercourse until miscarriage symptoms have completely settled.
    • When to try for another baby.
      • Explain that menstruation can be expected to resume within 4–8 weeks of the miscarriage, and ovulation will occur before this.
      • For women who wish to become pregnant, advise that they can do so as soon as they feel psychologically and physically ready, and offer pre-conception advice. See the CKS topic on Pre-conception - advice and management for more information.
      • For women who do not wish to become pregnant, advise the use of contraception immediately after the miscarriage. See the CKS topic on Contraception - assessment for information on how to assess women for the different methods of contraception.  
    • Provide additional patient information on miscarriage. 

Basis for recommendation

These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management [NICE, 2023].

Scenario: Managing recurrent miscarriage

From age 16 years onwards (Female).

How should I manage a woman with recurrent miscarriage?

For women with recurrent miscarriage (three or more first-trimester miscarriages):

  • Offer referral for investigation and management. 
    • Advise that it may not be possible to determine the cause of recurrent miscarriage.
      • If no cause is found, the prognosis for a successful future pregnancy with supportive care alone is about 75%. However, the prognosis worsens with increasing maternal age and the number of previous miscarriages.
  • Following referral, the woman may be offered:
    • Testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, before pregnancy. If antiphospholipid antibodies are found, treatment with aspirin plus heparin until at least 34 weeks of gestation will be considered in future pregnancies.
    • Cytogenetic analysis on pregnancy tissue of the third and subsequent first-trimester miscarriage(s).
    • Parental peripheral blood karyotyping (if testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality or there is unsuccessful or no pregnancy tissue available for testing). 
    • Assessment for congenital uterine anomalies.
    • Thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies.
      • Thyroxine supplementation may be considered for women with moderate subclinical hypothyroidism (thyroid-stimulating hormone [TSH] more than 4 mIU/l) but is not routinely recommended for women with mild subclinical hypothyroidism (TSH more than 2.5 mIU/l) irrespective of TPO status.
      • Regular TSH measurement from 7–9 weeks of gestation is recommended in cases with TPO and/or SCH.
    • Lifestyle advice, including (as appropriate) maintaining a body mass index (BMI) between 19 kg/m2 and 25 kg/m2, smoking cessation, limiting alcohol consumption, and limiting caffeine to less than 200 mg/day.
  • Provide patient information on recurrent miscarriage. 
  • If a woman experiences further miscarriage(s) following referral, ensure that the couple are offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic.

Basis for recommendation

These recommendations are based largely on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Recurrent Miscarriage: Green-top Guideline No.17 [Regan, 2023]. 

Supporting evidence

The recommendations in this CKS topic are based largely on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management [NICE, 2023]. The recommendations for managing women with recurrent miscarriage are based largely on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Recurrent Miscarriage: Green-top Guideline No.17 [Regan, 2023]. 

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A full literature search was not requested/required as this CKS topic is primarily based on the National Institute for Health and Clinical Excellence (NICE) guideline Ectopic pregnancy and miscarriage:Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage.

Search dates

May 2018 - October 2023

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

  • exp Abortion, Spontaneous/, pregnancy ADJ loss.tw., miscarr$.tw., spontaneous ADJ abortion.tw.

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
  • Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
    • Guideline development groups where the topic is an implementation of a guideline.
    • The British National Formulary team.
    • The editorial team that develop MeReC Publications.
  • Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

  • ACOG (2021) ACOG Practice bulletin number 200. Early pregnancy loss. Obstetrics and Gynecology 132(5), e197-e207. [Free Full-text]
  • BMJ Best Practice (2023a) Miscarriage. BMJ Publishing Group Ltd. https://bestpractice.bmj.com
  • BMJ Best Practice (2023b) Assessment of recurrent miscarriage. BMJ Publishing Group Ltd. https://bestpractice.bmj.com
  • Clutterbuck, D. (2009) Female genital infections. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical Obstetrics and Gynaecology. 2nd edn. Edinburgh: Saunders Elsevier, 121-134.
  • Colley, E., Hamilton, S., Smith, P., et al. (2019) Potential genetic causes of miscarriage in euploid pregnancies: a systematic review. Human Reproduction Update 25(4), 452-472. [Abstract]
  • Coomarasamy, A., Devall, A. J., Brosens, J. J., et al. (2020) Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence. American Journal of Obstetrics and Gynecology 223(2), 167-176. [Abstract] [Free Full-text]
  • Crochet, J.R.,  Bastian, L.A. and Chireau, M.V. (2013) Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review. JAMA 309(16), 1722-1729. [Abstract]
  • du Fossé, N. A., van der Hoorn, M. P., van Lith, J. M. M., et al. (2020) Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Human Reproduction Update 26(5), 650-669. [Abstract]
  • ESHRE (2023) Guideline on the management of recurrent pregnancy loss. European Society of Human Reproduction and Embryology. http://www.eshre.eu [Free Full-text]
  • Ghosh, J., Papadopoulou, A., Devall, A. J., et al. (2021) Methods for managing miscarriage: a network meta-analysis (Cochrane Review/Cochrane Intervention Protocol). Issue 6. John Wiley & Sons, Ltd. http://www.cochranelibrary.com [Free Full-text]
  • Jurkovic, D. and Wilkinson, H. (2011) Diagnosis and management of ectopic pregnancy. British Medical Journal 342(d3397). [Abstract] [Free Full-text]
  • Jurkovic, D.,  Overton, C.,  Bender-Atik, R. (2013) Diagnosis and management of first trimester miscarriage. British Medical Journal 346(f3676). [Abstract]
  • Latthe, P. and Khan, K.S. (2009) Pelvic pain and ectopic pregnancy. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical Obstetrics and Gynaecology. 2nd edn. Edinburgh: Saunders Elsevier, 143-149.
  • Linnakaari, R., Helle, N., Mentula, M., et al. (2019) Trends in the incidence, rate and treatment of miscarriage-nationwide register-study in Finland, 1998-2016. Human Reproduction (Oxford, England) 34(11), 2120-2128. [Abstract]
  • McQueen, D. B., Zhang, J. and Robins, J. C. (2019) Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis. Fertility and sterility, 112(1), 54–60.e3. 112(1), 54-60.e3. [Abstract]
  • Ng, K. Y. B., Cherian, G., Kermack, A. J., et al. (2021) Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss. Scientific Reports 11(1), 7081. [Abstract] [Free Full-text]
  • NICE (2014) Ectopic pregnancy and miscarriage (Quality standard). http://www.nice.org.uk [Free Full-text]
  • NICE (2023) Ectopic pregnancy and miscarriage: diagnosis and initial management. National Institute for Health and Care Excellence. http://www.nice.org.uk [Free Full-text]
  • Nybo Anderson, AM., Wohlfahrt, J., Christens, P., et al. (2000) Maternal age and fetal loss:population based register linkage study. British Medical Journal 192(7251), 1708-1712. [Abstract]
  • Nynas, J., Narang, P., Kolikonda, M. and Lippmann, S. (2015) Depression and anxiety following early pregnancy loss: recommendations for primary care providers. Primary Care Companion For CNS Disorders 17(1). [Free Full-text]
  • Oliver-Williams, C.T. and Steer, P.J. (2015) Racial variation in the number of spontaneous abortions before a first successful pregnancy, and effects on subsequent pregnancies. International Journal of Gynaecology and Obstetrics 129(3), 207-212. [Abstract] [Free Full-text]
  • Owen, P. (2009) Miscarriage. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical obstetrics and gynaecology. 2nd edn. Edinburgh: Saunders Elsevier, 97-102.
  • Porter, T.F., Branch, D.W. and Scott, J.R. (2008) Early pregnancy loss. In: Gibbs, R.S., Karlan, B.Y., Haney, A.F. and Nygaard, I. (Eds.) Danforth's Obstetrics and Gynecology. 10th edn. Philadelphia: Lippincott Williams & Wilkins, 60-70.
  • Regan, L., Rai, R., Saravelos, S., et al. (2023) Recurrent Miscarriage: Green-top Guideline No. 17. BJOG 130(12), e9-e39. [Free Full-text]
  • Savage, P. (2009) Gestational trophoblastic disease. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical Obstetrics and Gynaecology. 2nd edn. Edinburgh: Saunders Elsevier, 212-216.
  • Sundermann, A. C., Zhao, S., Young, C. L., et al. (2019) Alcohol Use in Pregnancy and Miscarriage: A Systematic Review and Meta-Analysis. Alcoholism, Clinical and Experimental Research 43(8), 1606-1616. [Abstract] [Free Full-text]
  • Tamblyn, J. A., Pilarski, N.S.P., Markland, A.D., et al. (2022) Vitamin D and miscarriage: a systematic review and meta-analysis. Fertility and Sterility 118(1), 111-122. [Abstract] [Free Full-text]
  • WHO (Eds.) (2017) Managing complications in pregnancy and childbirth: A guide for midwives and doctors - Second Edition. Geneva: World Health Organization.
  • Yifu, P., Lei, Y., Shaoming, L. and Yujin, G, Xingwang, Z. (2020) Sperm DNA fragmentation index with unexplained recurrent spontaneous abortion: A systematic review and meta-analysis. Journal of Gynecology Obstetrics and Human Reproduction 101740. Advance online publication. [Abstract]
  • Zhang, Y., Wang, H., Pan, X., et al. (2017) Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PloS One 12(4), e0175708. [Abstract] [Free Full-text]
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