Ectopic pregnancy and miscarriage: diagnosis and initial management

1Guideline Overview and Scope

• Early pregnancy is defined as up to 13 completed weeks of pregnancy (first trimester).
• • Key presenting complications include pain and bleeding.
• Adverse event reporting requirements:
  • All problems (adverse events) related to a medicine or medical device used for treatment or in a procedure must be reported.
  • Reports should be submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) using the Yellow Card Scheme.

2Early Pregnancy Assessment Services (EPAS)

Service configuration, availability, and referral criteria for regional early pregnancy assessment units.

• 2012Regional services must organize EPAS to be available 7 days a week for diagnostic scanning and management decisions.
• 2012EPAS minimum service requirements:
  • Dedicated service run by healthcare professionals competent in managing early pregnancy pain and bleeding.
  • Ability to perform ultrasound and assess serum human chorionic gonadotrophin (hCG) levels.
  • Staffed by professionals trained in sensitive communication and breaking bad news.
• 2012Self-referral criteria: EPAS must accept self-referrals from women with a history of:
  • Recurrent miscarriage.
  • Previous ectopic pregnancy.
  • Previous molar pregnancy.
• 2012Professional referral: All other women presenting with pain and/or bleeding must be assessed by a healthcare professional (GP, A&E doctor, midwife, or nurse) before referral to EPAS.
• 2012Referral timeline: Systems must enable referred women to attend EPAS within 24 hours if clinically indicated.
  • If EPAS is unavailable and clinical symptoms warrant urgent assessment, refer to the nearest facility with specialist clinical assessment and ultrasound (e.g., gynaecology ward or A&E with specialist gynaecology support).

3Symptoms, Signs, and Initial Assessment of Ectopic Pregnancy

• 2012Emergency Referral: Refer women who are haemodynamically unstable, or who have significant pain or bleeding, directly to A&E.
• 2012Atypical presentation: Ectopic pregnancy frequently presents atypically and can mimic gastrointestinal conditions or urinary tract infections (UTIs).
• 2012Risk factor caution: Always exclude ectopic pregnancy even if no risk factors are present; approximately one-third (33%) of women with an ectopic pregnancy have no known risk factors.
• 2012Pregnancy testing: All healthcare professionals caring for women of reproductive age must have access to pregnancy tests and consider testing even for non-specific symptoms.
• 2012Immediate EPAS or Out-of-Hours Gynaecology Referral: Required for women with a positive pregnancy test and any of the following on examination:
  • Pain and abdominal tenderness.
  • Pelvic tenderness.
  • Cervical motion tenderness.
• 2012Standard EPAS or Out-of-Hours Gynaecology Referral: Required for women with bleeding or other symptoms of early pregnancy complications who have:
  • Pain.
  • A pregnancy of 6 weeks' gestation or more.
  • A pregnancy of uncertain gestation.
  • Note: The urgency of this referral depends on the clinical situation.
• 2012, amended 2019Expectant Management for Low-Risk Presentations: Use for women with a pregnancy of < 6 weeks' gestation who are bleeding but have NO pain and NO risk factors (e.g., no previous ectopic pregnancy).
  • Advise the woman to return immediately if bleeding continues or pain develops.
  • Advise to repeat a urine pregnancy test after 7 to 10 days.
  • If the repeat test is positive, they must return for review; if negative, the pregnancy has miscarried.

4Using Ultrasound for Diagnosis of Viability and Location

• ModalityOffer a transvaginal ultrasound (TVS) as the primary scan to identify pregnancy location, fetal pole, and heartbeat.
  • Consider a transabdominal ultrasound (TAS) for women with an enlarged uterus or other pelvic pathology (e.g., fibroids, ovarian cysts).
  • If TVS is unacceptable to the woman, offer TAS and clearly explain its diagnostic limitations.
• ProtocolSystematic scanning sequence to determine viability of an intrauterine pregnancy:
  • First: Look to identify a fetal heartbeat.
  • Second: If no heartbeat is visible but a fetal pole is present, measure the Crown-Rump Length (CRL).
  • Third: Only measure the Mean Gestational Sac Diameter (MSD) if the fetal pole is NOT visible.
• CautionDo not use gestational age calculated from the last menstrual period (LMP) alone to determine if a fetal heartbeat should be visible.
  • LMP-based dating is often inaccurate due to menstrual cycle variability.
  • Reassure women that waiting for a repeat scan has no detrimental effects on the pregnancy outcome.
  • Provide a 24-hour contact telephone number.
• PUL WarningWhen diagnosing a complete miscarriage on ultrasound in the absence of a previous scan confirming an intrauterine pregnancy, always consider the possibility of a Pregnancy of Unknown Location (PUL).
  • Advise these women to return for active follow-up (e.g., serial hCG levels, repeat scans) until a definitive diagnosis is made.

5Ultrasound Diagnosis of Tubal Ectopic Pregnancy

• Definitive TVS SignsTVS signs diagnostic of a tubal ectopic pregnancy:
  • An adnexal mass, moving separate to the ovary ('sliding sign'), comprising a gestational sac containing a yolk sac.
  • An adnexal mass, moving separate to the ovary, comprising a gestational sac and a fetal pole (with or without a fetal heartbeat).
• High Probability TVS SignsTVS signs indicating a high probability of a tubal ectopic pregnancy:
  • An adnexal mass, moving separate to the ovary ('sliding sign'), with an empty gestational sac (often described as a 'tubal ring' or 'bagel sign').
  • A complex, inhomogeneous adnexal mass, moving separate to the ovary.
  • Action: Correlate these features with other scan findings, clinical presentation, and serum hCG levels before finalizing the diagnosis.
• Possible TVS SignsTVS signs indicating a possible ectopic pregnancy:
  • An empty uterus.
  • A collection of fluid within the uterine cavity (pseudo-sac).
  • Differentiate a pseudo-sac from an early intrauterine sac, which is identified by an eccentrically located hypoechoic structure with a double decidual sign (two concentric echogenic rings) in the endometrium.
• Free FluidLook for moderate to large amounts of free fluid in the peritoneal cavity or Pouch of Douglas on TVS or TAS.
  • This fluid may represent haemoperitoneum.
  • Correlate with other scan features, clinical presentation, and hCG levels.
• RuleAlways scan both the uterus and the adnexae to evaluate for the possibility of a heterotopic pregnancy.

6hCG Measurements in Pregnancy of Unknown Location (PUL)

• PUL Safety PrincipleAssume any woman with a PUL could have an ectopic pregnancy until the definitive location is determined.
• Clinical PriorityPlace greater importance on clinical symptoms than on serum hCG results. Review the patient immediately if symptoms change, regardless of previous hCG values.
• Role of hCGUse serum hCG measurements solely to assess trophoblastic proliferation to guide subsequent management. Do not use hCG to determine the physical location of the pregnancy.
• Progesterone RestrictionDo NOT use serum progesterone measurements as an adjunct to serial hCG when diagnosing viable IUP or ectopic pregnancy.
• Sampling ProtocolTake exactly 2 serum hCG measurements as close as possible to 48 hours apart (and no earlier). Any further hCG measurements require review and authorization by a senior healthcare professional.
• Safety NettingProvide all women with a PUL written instructions on emergency actions for new or worsening symptoms, including 24-hour emergency care access details.

7Management of Threatened Miscarriage and Progesterone Therapy

• Threatened miscarriage with NO history of previous miscarriage:
  • Applies to women with a confirmed IUP and visible fetal heartbeat.
  • Advise to return for further assessment if bleeding worsens or persists beyond 14 days.
  • Advise to continue or start routine antenatal care if bleeding stops.
• Progesterone therapy for threatened miscarriage with history of previous miscarriage:
  • Indication: Offer to women with a scan-confirmed intrauterine pregnancy, active vaginal bleeding, and a history of at least one previous miscarriage.
  • Regimen: Vaginal micronised progesterone 400 mg twice daily.
  • Initiation: Can be started before a fetal heartbeat is detected, provided IUP is confirmed on scan (to avoid accidental administration in ectopic pregnancy or PUL).
• Duration of progesterone therapy:
  • If a fetal heartbeat is confirmed, continue the progesterone regimen until 16 completed weeks of pregnancy.
• GPPClinical notes on progesterone prescribing:
  • There is no evidence of benefit for any other preparations or doses of progesterone.
  • No benefit is seen in women with bleeding but no previous miscarriage, or women with previous miscarriage but no bleeding in the current pregnancy.
  • Initial prescription is typically provided by the Early Pregnancy Unit (EPU), with continuation to 16 weeks managed via local GP shared care arrangements.
  • Progesterone recommendations are not applicable in other circumstances, such as after the use of mifepristone.

8Expectant Management of Miscarriage

• First-line management strategy: Use expectant management for 7 to 14 days as the first-line strategy for women with a confirmed diagnosis of miscarriage.
• Indications to explore other management options (medical or surgical) instead of expectant management:
  • Increased risk of haemorrhage (e.g., woman is in the late first trimester).
  • Previous adverse and/or traumatic experience associated with pregnancy (e.g., stillbirth, miscarriage, or antepartum haemorrhage).
  • Increased risk from the effects of haemorrhage (e.g., coagulopathies or inability to receive a blood transfusion).
  • Evidence of infection.
• Medical management alternative: Offer medical management if expectant management is not acceptable to the woman.
• Information and safety netting during expectant management:
  • Explain that most women will need no further treatment.
  • Provide advice on pain relief and clear instructions on where and when to seek help in an emergency.
• Follow-up after completed expectant management:
  • If bleeding and pain resolve within 7 to 14 days (indicating completion), provide a home urine pregnancy test to carry out 3 weeks after the miscarriage.
  • Advise the woman to return for individualised care if the 3-week pregnancy test is positive.
• Indications for a repeat scan after the expectant management period:
  • Bleeding and pain have not started (suggesting the miscarriage process has not begun).
  • Bleeding and pain are persisting and/or increasing (suggesting an incomplete miscarriage).
  • If a repeat scan is indicated, discuss all treatment options (continued expectant, medical, or surgical management) to allow an informed choice.
• Review for continued expectant management: If the woman chooses to continue expectant management, review her condition at a minimum of 14 days after the first follow-up appointment.

9Medical and Surgical Management of Miscarriage

• Off-label NoteThe use of mifepristone and misoprostol for medical management of miscarriage was off-label in the UK as of August 2023.
• Missed MiscarriageOffer a combination regimen of mifepristone and misoprostol to reduce the failure of gestational sac passage and minimize the need for surgical intervention.
  • Step 1: Administer 200 mg oral mifepristone.
  • Step 2: Administer 800 micrograms misoprostol (vaginal, oral, or sublingual) 48 hours later, unless the gestational sac has already passed.
• Incomplete MiscarriageOffer misoprostol alone; do not offer mifepristone for incomplete miscarriage as there is no evidence to support its use.
  • Standard regimen: Single dose of misoprostol 600 micrograms (vaginal, oral, or sublingual).
  • Alternative regimen: Misoprostol 800 micrograms may be used to align treatment protocols with missed miscarriage.
• Bleeding ExpectationsAdvise patients that bleeding typically begins 2 to 3 days after misoprostol treatment.
  • If bleeding has not started within 48 hours of misoprostol, the patient must contact their healthcare provider to determine individualized care.
  • Proactive follow-up: Early pregnancy services should proactively contact patients who may have difficulty initiating contact to check if bleeding has begun.
• Supportive Care
  • Offer pain relief and anti-emetics as needed.
  • Counsel patients on what to expect, including the length and extent of bleeding, and potential side effects (pain, diarrhoea, vomiting).
• Follow-up & TestingProvide all patients undergoing medical (and expectant) management with a urine pregnancy test to perform at home 3 weeks later.
  • Worsening symptoms: Advise patients to return immediately to the responsible healthcare professional if symptoms worsen before the 3-week mark.
  • Positive test at 3 weeks: Patient must return for review to rule out retained products of conception, molar pregnancy, or ectopic pregnancy.
  • Negative test but symptomatic at 3 weeks: If the test is negative but the patient is still bleeding heavily or has other symptoms (e.g., pelvic pain, fever), assess the need for further investigations or treatment.
• Surgical OptionsWhere clinically appropriate, offer a choice of surgical management:
  • Manual vacuum aspiration (MVA) under local anaesthetic in an outpatient or clinic setting.
  • Surgical management in a theatre under general anaesthetic.

10Management of Ectopic Pregnancy

• 2019Expectant Management Eligibility Criteria (Tubal Ectopic):
  • Clinically stable and pain-free.
  • Tubal ectopic measures < 35 mm with no visible heartbeat on transvaginal ultrasound (TVUS).
  • Serum hCG levels are 1,000 IU/L or less (offer) or between 1,000 IU/L and 1,500 IU/L (consider).
  • Patient is able and willing to return for follow-up.
• 2019Expectant Management Monitoring Protocol:
  • Measure serum hCG on days 2, 4, and 7 after the initial test.
  • If hCG drops by 15% or more from the previous value on days 2, 4, and 7: Repeat hCG weekly until a negative result (< 20 IU/L) is achieved.
  • If hCG drops by < 15%, plateaus, or rises: Review clinical condition and seek senior advice to determine further management.
• 2019Expectant Management Counselling:
  • Advise that there is no significant difference in the rate of ectopic pregnancies ending naturally, risk of tubal rupture, overall health status, time to resolution, or future fertility compared to medical management.
  • Warn patients that they must seek urgent medical attention if their clinical condition deteriorates.
• 2012Systemic Methotrexate (Medical Management) Criteria:
  • Note: Methotrexate use for this indication was off-label in April 2019.
  • Offer as first-line if: No significant pain AND unruptured tubal ectopic with adnexal mass < 35 mm AND no visible heartbeat AND serum hCG < 1,500 IU/L AND no intrauterine pregnancy (IUP) on ultrasound AND patient is able to return for follow-up.
  • Only offer methotrexate on the first visit if there is a definitive diagnosis of ectopic pregnancy and a viable IUP has been completely excluded.
  • Offer surgery if methotrexate is unacceptable to the patient.
• 2012Primary Surgical Management Criteria:
  • Offer surgery as first-line treatment if the patient is unable to return for follow-up after methotrexate, or has any of the following:
  • Significant pain.
  • Adnexal mass size of 35 mm or larger.
  • Fetal heartbeat visible on ultrasound.
  • Serum hCG level of 5,000 IU/L or more.
• 2012Choice of Methotrexate or Surgery (hCG 1,500 to 5,000 IU/L):
  • Offer a choice of either treatment if serum hCG is >= 1,500 IU/L and < 5,000 IU/L, the patient can return for follow-up, and they meet all of the following: no significant pain, unruptured ectopic with adnexal mass < 35 mm, no visible heartbeat, and no IUP on ultrasound.
  • Advise women choosing methotrexate that they have an increased risk of needing further intervention and may require urgent admission if they deteriorate.
• 2012Post-Methotrexate Monitoring Protocol:
  • Take 2 serum hCG measurements in the first week (on days 4 and 7) post-treatment.
  • Thereafter, measure serum hCG once per week until a negative result is obtained.
  • If hCG levels plateau or rise, reassess clinical condition for further intervention.
• 2012Surgical Techniques (Salpingectomy vs. Salpingotomy):
  • Surgical Approach: Perform surgically indicated treatments laparoscopically whenever possible, accounting for patient stability and surgical complexity.
  • Offer salpingectomy as standard unless the patient has other risk factors for infertility.
  • Consider salpingotomy as an alternative if risk factors for infertility (e.g., contralateral tube damage) are present.
  • Counselling for salpingotomy: Inform patients that up to 1 in 5 (20%) may require further treatment (methotrexate and/or salpingectomy) due to persistent trophoblastic tissue.
  • Salpingotomy follow-up: Measure serum hCG at day 7 post-surgery, then weekly until a negative result is obtained.
  • Salpingectomy follow-up: Advise the patient to take a urine pregnancy test 3 weeks post-surgery. If positive, they must return for further assessment.

11Anti-D Immunoglobulin Prophylaxis

• 2026Gestation up to and including 11+6 weeks:
  • Do NOT offer anti-D immunoglobulin prophylaxis to women experiencing ectopic pregnancy, miscarriage, or threatened miscarriage.
  • This restriction applies regardless of whether management is expectant, medical, or surgical.
  • If there is a discrepancy between ultrasound and LMP gestation, use ultrasound measurements to guide management.
• 2026Gestation 12+0 to 12+6 weeks:
  • Offer anti-D prophylaxis (minimum dose 250 IU / 50 micrograms) to RhD-negative individuals undergoing medical or surgical management for ectopic pregnancy or miscarriage.
  • Consider anti-D prophylaxis (minimum dose 250 IU / 50 micrograms) for RhD-negative individuals experiencing threatened miscarriage with heavy or recurrent bleeding (based on clinical judgement).
  • Note: 250 IU is the minimum dose; larger doses can be administered if 250 IU is unavailable in local NHS settings.
• 2026Patient Discussion Points:
  • Anti-D is a protein obtained from human blood plasma.
  • It is a filtered blood product and does not contain blood cells.
  • This discussion is critical as some individuals may decline blood products for personal, ethical, or religious reasons.
• 2012Diagnostic Restriction:
  • Do NOT use a Kleihauer test to quantify feto-maternal haemorrhage in these early pregnancy settings.

12Terms Used in this Guideline

• Early pregnancy: Defined as pregnancy in the first trimester, up to 13 completed weeks of pregnancy.
• Expectant management: A 'wait and watch' approach where no medical or surgical treatment is given, allowing the condition to resolve naturally.
• Pregnancy of unknown location (PUL): Defined as a positive pregnancy test where no intrauterine or extrauterine pregnancy is visible on a transvaginal ultrasound scan.