Ectopic pregnancy
An ectopic pregnancy is an extrauterine pregnancy – when a fertilized which implants outside the lining of the uterus
An ectopic pregnancy is an extrauterine pregnancy.
Almost all ectopic pregnancies occur in the fallopian tube (98 percent).
Ectopic pregnancy is a potentially lethal condition due to rupture and haemorrhage and so is an important diagnosis that needs to be considered in any woman of child bearing age who presents with abdominal pain and or vaginal bleeding.
Clinical history and examination cannot reliably make or rule out a diagnosis of ectopic pregnancy.
All suspected cases must therefore have a serum beta HCG performed and a pelvic ultrasound.
Treatment can be conservative, medical or surgical.
Pathophysiology
Ectopic pregnancy occurs when the developing blastocyst becomes implanted at a site other than the endometrium of the uterine cavity.
The most common extra-uterine location is the fallopian tube, which accounts for 98 percent of all ectopic gestations but other possible sites include: cervical, cornual; (also called interstitial – a pregnancy located in the proximal segment of the fallopian tube that is embedded within the muscular wall of the uterus), hysterotomy scar, ovarian, or intraabdominal.
Risk Factors:
Note that many women (over 50 %) do not have any identifiable risk factor for ectopic pregnancy.
Recognized risk factors include:
1. Previous tubal pathology, including:
● Previous ectopic pregnancy in general (including conservatively managed cases).
● Previous tubal surgery:
Including:
♥ Tubal reconstructive surgery
♥ Tubal sterilization
The estimated failure rate during the first year after tubal sterilization is < 1 % and approximately one third of these pregnancies are ectopic.
● PID:
♥ In particular; chlamydia/ gonorrhoea
● Endometriosis
● Congenital anomalies
2. Increased age, (> 35 years).
3. IUDs.
4. Assisted reproduction:
The incidence of ectopic pregnancy is higher in the infertility population, which could reflect:
● The increased incidence of tubal abnormality in this group of women.
● An association between fertility drugs and ectopic pregnancy, which may be related to altered tubal function secondary to hormonal fluctuation.
5. Smoking:
● Possibly related to impairment of normal tubal motility.
Heterotopic pregnancy:
The identification of an intrauterine pregnancy does not absolutely exclude the possibility of an ectopic pregnancy.
A twin ectopic pregnancy may rarely co-exist with an intrauterine pregnancy (heterotopic pregnancy).
The incidence of heterotopic pregnancies in the general population is uncommon, approximately 1:4000, however in patients who have undergone assisted reproduction this condition becomes relatively more important as the incidence rises to 1:100 to 1:500.
The Natural History of Ectopic Pregnancy:
If left untreated, an ectopic pregnancy in the fallopian tube can progress to a tubal rupture a tubal abortion, or spontaneous regression.
1. Tubal Rupture:
● Tubal rupture is usually associated with profound hemorrhage, which can be fatal if surgery is not performed expeditiously to remove the ectopic gestation.
Salpingectomy is the most common surgical approach when the tube has ruptured.
Ruptured ectopic pregnancy is the major cause of pregnancy-related maternal mortality in the first trimester .
Most of these deaths occur prior to hospitalization or proximate to the woman’s arrival in the emergency department.
2. Tubal Abortion:
● Tubal abortion refers to expulsion of the products of conception through the fimbria.
This can be followed by resorption of the tissue or by reimplantation of the trophoblasts in the abdominal cavity (i.e, abdominal pregnancy) or on the ovary (i.e, ovarian pregnancy).
Tubal abortion may be accompanied by severe intraabdominal bleeding, necessitating surgical intervention, or by minimal bleeding, not requiring further treatment.
3. Spontaneous resolution:
● The incidence of spontaneous resolution of an ectopic pregnancy is unknown.
It is difficult to predict which patients will experience uncomplicated spontaneous resolution.
Potential candidates are hemodynamically stable women with an initial hCG concentration less than 2000 IU/L that is declining.
Gestational products left in the fallopian tube may resorb completely or, less commonly, may cause tubal obstruction. Alternatively, a tubal abortion may occur.
Clinical Features
Although always important, the clinical history and examination cannot make a definitive diagnosis of ectopic pregnancy.
Beta HCG levels and ultrasound examination will be required to do this.
Important points of history:
1. Pelvic pain:
● This is seen in 90% of cases (usually localized to one side).
● Tubal rupture may be associated with an abrupt onset of severe pain, but rupture may also present with mild or intermittent pain.
● Over 50 percent of women are asymptomatic before tubal rupture occurs.
2. Short period of amenorrhoea:
● Most commonly this will be at around 6-8 weeks after the last normal menstrual period
Symptoms can occur later however, especially if the pregnancy is in an extrauterine site other than the fallopian tube.
3. Vaginal bleeding:
● Vaginal bleeding is seen in approximately 70% of cases, however, this is usually of minor degree only.
● Generally speaking ectopic pregnancies typically produce pain first followed by a small bleed compared to spontaneous abortions which tend to present with bleeding first followed by pain.
● The vaginal bleeding associated with ectopic pregnancy is typically preceded by a period of amenorrhea.
Note that some women may misinterpret bleeding as normal menses, and may not realize they are pregnant prior to developing symptoms associated with ectopic pregnancy. This is particularly true in women who have irregular menses or who do not keep track of menstrual cycles.
4. Enquire about the recognized risk factors for ectopic pregnancy, (see above).
Important points of examination:
1. Assess the stability of the patient with respect to hemodynamic status.
● This will be the most urgent consideration.
An ectopic pregnancy may be unruptured or ruptured at the time of presentation to medical care.
Tubal rupture (or rupture of other structures in which an ectopic pregnancy is implanted) can result in life-threatening hemorrhage.
2. Adnexal tenderness/ abdominal peritonism:
● Pelvic pain/ tenderness is typically localized to one side, however this may not always be present, and may not always be unilateral.
● Significant diffuse abdominal pain/tenderness/ peritonism suggests rupture and bleeding.
3. Detection of an adnexal mass:
● This may be found in some women, but it is a subjective and unreliable sign.
Care should be taken as excessive pressure may rupture an ectopic pregnancy.
Investigations
Blood tests:
1. FBE:
● Hemoglobin and/or hematocrit.
2. U&Ss/ glucose
3. Serum beta HCG:
● Serum beta HCG is far more reliable than urinary tests for beta HCG.
● A quantitative test is done, giving a beta HCG level, (see beta HCG guidelines). This is useful in enabling serial estimations to monitor pregnancy viability.
● In urgent cases, a quick qualitative test (i.e positive or negative) may be done rather than a quantitative test.
● In very urgent cases, a urinary beta HCG, may be quicker however it must be kept in mind that this is less reliable than a serum result.
4. Blood group and cross matching:
● Blood is grouped and held or cross matched according to clinical necessity.
● The blood group is also required in order to determine the need for anti D.
Ultrasound:
If the beta HCG is >1500 IU / L:
Transvaginal ultrasound should be able to detect an intrauterine pregnancy at these beta HCG levels.
The ectopic pregnancy itself may be seen within the fallopian tube.
If the uterine cavity is empty, the diagnosis must remain “ectopic pregnancy till proven otherwise”, even if the adnexal structures appear normal.
If the beta HCG is < 1500 IU / L
Transvaginal ultrasonic diagnosis of ectopic pregnancy is more problematic with beta HCG levels that are below 1500 IU / L.
At these levels a gestational sac cannot be reliably detected even on transvaginal scans.
An empty uterine cavity or clear adnexa therefore cannot rule out the possibility of an early normal pregnancy or an early ectopic pregnancy.
A finding of echogenic fluid (consistent with blood) in the pelvic cul-de-sac and/or abdomen is consistent with rupture
In these cases, the clinical state of the patient will be important in determining the disposition of the patient, (see below).
FAST Scan
Unstable patients should never leave the ED for ultrasound examination.
A FAST scan done in the ED may detect intraperitoneal blood, especially in cases of patients who are hemodynamically unstable.
A formal ultrasound may also be organised to be done in the resuscitation cube.
If the beta HCG level is <1500 IU / L then ultrasound confirmation of ectopic pregnancy may be problematic. If the patient is hemodynamically unstable (or has significant adnexal pain or tenderness), then ectopic pregnancy is not ruled out and these patients must be assessed by the obstetric unit.
Ultrasound need not be performed at all when the patient is particularly unstable. A decision may be made by the obstetric unit to proceed directly to the operating theatre.
Laparoscopy:
Occasionally when beta HCG is elevated but ultrasound is non-diagnostic laparoscopic examination may be considered, when clinical suspicion of ectopic pregnancy remains particularly if the patient is unstable.
See also diagnostic flow chart in appendix 1 below.
Management
The guiding principle of treatment is now a conservative approach that attempts to save the tube, rather than salpingectomy.
However, it is important to remember that hemorrhage from ectopic pregnancy is still the leading cause of pregnancy related maternal death in the first trimester, and saving the tube must always be balanced against saving the patient.
There are 3 approaches to treatment:
1. Expectant management:
2. Medical management:
3. Surgical management
Expectant management:
Ectopic pregnancy is usually a gynaecologic emergency, requiring expeditious surgical or medical treatment.
However, in a small number of cases of presumed or possible ectopic pregnancy, in which the risk of tubal rupture is minimal, expectant management can be appropriate.
Criteria that must be met before expectant treatment is considered include:
1. Cases where the pregnancy is of unknown location, i.e no pregnancy has been visualized on transvaginal scan, (in the uterus or the tube).
Patients with no extrauterine mass on TVUS can be described as a pregnancy of unknown location since imaging and laboratory assessment do not clearly distinguish between a failed intrauterine pregnancy and a resolving ectopic pregnancy at this low level of beta HCG.
2. An asymptomatic patient.
3. The patient is understanding, motivated and reliable and has ready access to the hospital.
4. The beta HCG is < 200 IU/ml (and declining).1
These cases should be closely monitored by the Obstetric unit.
Quantitative beta HCG levels are performed at 48-72 hour intervals.
Women should be followed until the beta HCG level is < 5
There should be active intervention if:
● Symptoms of ectopic pregnancy occur.
● Beta HCG levels rise.
Medical management:
Methotrexate (often abbreviated as MTX) therapy is a noninvasive medical option in carefully selected patients, that has comparable efficacy, safety, and fertility outcomes with surgery.
The advantages of surgical treatment are less time for resolution of the ectopic pregnancy and avoidance of the need for prolonged monitoring.
Surgery is required when urgent treatment is indicated or methotrexate therapy is unlikely to be successful.
Criteria for methotrexate therapy include:
1. Hemodynamically stable.
2. Pain free
3. Willing and able and motivated to comply with post-treatment follow-up
● Including the capability of timely access to a medical institution (for management of tubal rupture should this occur).
4. Willing to use reliable contraception for 3 months post treatment.
5. Smaller pregnancies:
● Beta HCG concentration ≤ 3,500 IU/L.
♥ A high serum beta HCG concentration is the most important factor associated with treatment failure. Women with a high baseline beta HCG concentration (greater than 5000 mIU/mL) are more likely to require multiple courses of medical therapy or experience treatment failure.
● No fetal cardiac activity.
● Ectopic mass size less than 3.5 cm is also commonly used as a patient selection criterion. However, this has not been confirmed as a predictor of successful treatment.
6. There is no free fluid on ultrasound (cases with minimal free fluid may be considered with caution).
7. There are no medical contraindications:
● To methotrexate itself, e.g. allergies, hepatic/ renal impairment/ immunosuppression.
● Should have normal baseline blood tests – FBE/ U&S/LFTs.
Methotrexate procedure:
Methotrexate dosing is complex, and is based on the total body surface area .
A high degree of patient education is required.
Patients are therefore admitted under the Obstetric Unit to have this treatment initiated.
Methotrexate is usually given as an IM stat dose, (though some centers use different protocols with IV or oral dosing).
Occasionally further doses are required.
Anti-D is given as per protocol for any rhesus negative woman.
Quantitative beta HCG should then be repeated weekly until there are two consecutive negative measurements, (even if this takes longer than 6 weeks).
A written action plan should be given to the patient.
Surgical management
Surgery may be done via laparoscopy or laparotomy.
Choice of laparoscopy or laparotomy will depend on the clinical situation. Laparoscopy is preferred in the haemodynamically stable patient. Many surgeons prefer laparotomy in haemodynamically unstable patients.
Surgical treatment consists of:
● Salpingostomy:
♥ Incising the tube to remove the tubal gestation but leaving the remainder of the tube intact
Or
● Salpingectomy:
♥ Removal of the fallopian tube.
Choice of salpingostomy or salpingectomy will depend on the surgeon and clinical situation.
Salpingectomy is more commonly performed.
Salpingostomy may be attempted in women who desire future fertility in the presence of contralateral tubal disease. It should be noted that the availability and high intrauterine pregnancy rate of in vitro fertilization (IVF) have decreased the need to preserve diseased fallopian tubes, including tubes with an ectopic pregnancy. However, many women do not have access to IVF for financial, geographic, or ethical reasons.
Salpingectomy is the standard procedure if:
● The condition of the tube is compromised (ruptured or otherwise disrupted)
● Bleeding is uncontrolled
● The gestation appears too large to remove with salpingostomy.
The patient should be informed of the risk of irreversible tubal damage by the presence of an ectopic pregnancy and that ongoing follow-up will be required.
Surgery is indicated in:
1. Ruptured (or suspected ruptured) tube:
● Clinical signs of symptoms of impending or ongoing rupture of ectopic mass (e.g., pelvic or abdominal pain or evidence of intraperitoneal bleeding suggestive of rupture
● Ruptured mass on ultrasound or moderate to large free peritoneal fluid on ultrasound.
Intervention is urgent in hemodynamically unstable patients.
2. Larger ectopic pregnancies:
● Beta HCG > 3,500 IU/L
● Adnexal mass > 3.5 cm on ultrasound
3. Situations where a concurrent surgical procedure is planned, (e.g. tubal ligation)
4. Cases where there is a relative or absolute contraindication to MTX therapy:
● Including inability/ unsuitability to comply with the follow-up required for MTX therapy.
5. Failed medical therapy
6. Patient preference
● Surgical treatment is a reasonable option for women who value treatment that is of shorter duration and involves less follow-up and are willing to take the operative risks and recovery that are involved in surgery.
In hemodynamically unstable patients ED priorities will include:
1. Initial fluid resuscitation:
● Establish two large bore catheter IV access and use giving sets with “hand pumps”.
2. Blood/ blood products as clinically required/ including O negative blood if necessary.
3. Titrated IV opioid analgesia, as required.
4. Urgent qualitative urine/ serum beta HCG (if pregnancy not already known)
5. Urgent notification of the:
● Obstetric unit
● Anaesthetics
6. Though not an urgent priority, anti-D prophylaxis should be given for all Rhesus negative women according to usual guidelines.
In hemodynamically stable patients:
1. Women should participate in the selection of the most appropriate treatment, and be given time to make the decision.
2. Management may take into account future fertility requirements.
● For example a patient undergoing IVF may opt for surgical treatment despite being suitable for medical treatment as the 3-month wait after this treatment may be inappropriate and a fallopian tube is no longer required.
Investigation pathway
References
FOAMed
- Nickson C. Ectopic Pregnancy. CCC
- Rippey J. Ultrasound case 013. LITFL
- Rippey J. Ultrasound case 013. LITFL
- Rippey J. Ultrasound case 029. LITFL
- Cadogan M. Cullen sign. LITFL
Publications
Fellowship Notes
Doctor at Sir Charles Gairdner Hospital in Western Australia. Graduated from Curtin University in 2023 with a Bachelor of Medicine, Bachelor of Surgery. I am passionate about Obstetrics and Gynaecology, with a special interest in rural health care.
Physician in training. German translator and lover of medical history.