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Ectopic Pregnancy (1 of 6)

No

Yes

Salpingectomy

Salpingostomy

No

Yes

1Patient presents w/ signs &

symptoms suggestive of ectopic pregnancy

2DIAGNOSIS

Inventory of risk factors, physical exam, β-hCG tests

& ultrasound confirm diagnosis of ectopic

pregnancy?

3CLINICAL DECISION

Should patient be treated medically or expectantly?

EVALUATIONIs the patient

hemodynamically unstable or presenting w/ severe

symptoms?

Was salpingostomy

or salpingectomy performed?

ALTERNATIVE DIAGNOSIS

A Patient educationB Surgery

• Laparoscopy• Laparotomy

TREATMENTSee next page

FOLLOWUP• Monitor patient

appropriately

FOLLOWUP• Serial

measurements of β-hCG serum concentrations© M

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TREATMENT OF CONFIRMED ECTOPIC PREGNANCY

Medical ManagementA Patient educationC Methotrexate

FOLLOWUP• Serial

measurements of β-hCG serum concentrations

D Expectant managementWarrants careful patient selection• Patient education• Serial monitoring of

hCG levels

1 ECTOPIC PREGNANCY

• Any pregnancy in which the blastocyst implants outside the endometrial lining of the uterine cavity - 90% are located in the fallopian tube while the rest are extratubal (eg abdominal, cervical, heterotopic, interstitial, ovarian, cornual or cesarean scar pregnancies)

Accurate early diagnosis is life-saving, reduces invasive diagnostic procedures & allows conservative treatment that can preserve fertility• Ectopic pregnancy must be excluded in women of reproductive age w/ a positive pregnancy test, abdominal

pain &vaginal bleeding• Ruptured ectopic pregnancy remains to be the leading cause of maternal mortality in the 1st trimesterRisk FactorsLow to Moderate Risk• Cigarette smoking• Vaginal douching• First intercourse <18 years old• Infertility or infertility treatments• History of chlamydial or gonococcal cervicitis• Multiple sexual partners• Salpingitis isthmica nodosa

High Risk• History of pelvic infl ammatory disease (PID)• Previous tubal or pelvic surgery• Tubal ligation• Previous ectopic pregnancy• In utero diethylstilbestrol (DES) exposure • Current intrauterine device (IUD) use • Documented tubal abnormality• Assisted reproduction

Clinical Presentation• Abdominal pain & irregular bleeding are the most common presenting symptoms

- Bleeding is usually referred to as “spotting”, dark brown & may be intermittent or continuous• Symptoms usually manifest 6-8 weeks after the last normal menstrual period• Patient may also present w/ vertigo or syncope• Other presentations will depend on the location of the ectopic pregnancy

- Eg pleuritic pain may result from irritation of the diaphragm by a large hemoperitoneum• Clinical manifestations depend on whether the ectopic pregnancy has ruptured

- A ruptured ectopic pregnancy commonly presents w/ sudden onset of severe lower abdominal pain charac-terized as sharp, stabbing, or tearing

- Symptoms suggestive of intra-abdominal hemorrhage include syncope, hypotension, tender abdomen w/ guarding or rebound, & tenderness of adnexal mass on pelvic exam

Not all products are available or approved for above use in all countries.Specifi c prescribing information may be found in the latest MIMS.

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2 DIAGNOSIS

History• Heightened index of suspicion is imperative to facilitate prompt diagnosis prior to catastrophic events • � orough review of history can identify risk factors & raise the index of suspicionPhysical Exam• Tenderness on abdominal palpation & cervical motion on pelvic exam; guarding & rebound tenderness suggest rupture• Absence of pain or failure to elicit tenderness does not rule out ectopic pregnancy; pelvic exam may be normal

in 10% of patientsDiagnostic StudiesStandard Urine Pregnancy Test• Used as the initial step in diagnosis• Identifi es the presence of hCG in concentrations as low as 25 mIU/mLSerum Progesterone• Viable intrauterine pregnancies (IUP) are associated w/ serum progesterone level of ≥79.5 nmol/L (25 ng/mL)

& at this level, ectopic pregnancy can be excluded (97.5% sensitivity) & no further testing is required • Nonviable pregnancies, both intrauterine & ectopic, are associated w/ serum progesterone level of ≤15.9 nmol/L

(5 ng/mL) - Diagnostic uterine curettage can be performed to check for chorionic villi from incomplete abortion

• Serum progesterone as a diagnostic procedure is limited by the fact that most patients have levels in the gray zone between 15.9-79.5 nmol/L (5-25 ng/mL) - � ere is too much overlap between IUP & ectopic pregnancy in this range

• A meta-analysis demonstrated that a single progesterone level cannot be used to predict an ectopic pregnancy • Usually, progesterone testing is not a rapid procedure & results are not readily available for use in the emergency

departmentSerial β-hCG Measurements• In normal pregnancy, the rise in β-hCG level is gestational age-specifi c; concentration usually increases 66-67%

over a 48-hour interval in the fi rst 6 weeks• A rate of rise <53-66% over a 48-hour period suggests an abnormally growing IUP or an ectopic pregnancy • Serum β-hCG level can be used in the planning of expectant & medical management of ultrasound-confi rmed

ectopic pregnancy - When β-hCG level is falling or failed to increase by at least 53-66% in 48 hours & nonviable IUP is suspected, uterine curettage may be performed

• Ectopic pregnancy is suspected when β-hCG fails to decline by at least 15% in 48 hours or no chorionic villi was evacuated via uterine curettage

Ultrasound (US)• β-hCG testing is usually combined w/ US• Tubal ectopic pregnancy is best diagnosed w/ a transvaginal ultrasound • Suspect ectopic pregnancy when

- Tubal ring is present, which appears as a thick-walled cystic structure in the adnexa independent of the ovary & uterus, or a complex adnexal mass

- An adnexal mass that moved separate to the ovary identifi es a tubal ectopic pregnancy - IUP is not detected by abdominal US at serum level above the threshold of 6500 IU/L (6500 mIU/mL) - Discriminatory zone level (serum hCG level at which it is assumed that all viable IUP will be visualized by transvaginal US, >1500-2500 IU/L) is dependent upon the experience of the sonographer, quality of the US equipment, prior knowledge of the woman’s symptoms & risks, & the presence of physical factors (eg multiple pregnancy, uterine fi broids)

• Sonographic absence of IUP, positive pregnancy test, fl uid in the cul-de-sac, & an abnormal pelvic mass, ectopic pregnancy is almost certain

Culdocentesis• � is technique is considered only in emergent situations when US is unavailable• Non-clotting bloody fl uid aspirated from the cul-de-sac is compatible w/ the diagnosis of hemoperitoneum

resulting from an ectopic pregnancy• Nondiagnostic since blood in the cul-de-sac may be due to other causes (eg ruptured ovarian cyst)• May be unsatisfactory in patients w/ obliterated cul-de-sac from previous salpingitis & pelvic peritonitis; thus,

failure to aspirate blood does not rule out ectopic pregnancyLaparoscopy• An invasive procedure for defi nitive diagnosis by complete visualization of the pelvis• As a diagnostic tool, availability of sensitive non-invasive tests reduced the need for this procedure in ruling

out ectopic pregnancy in women w/ a positive result of pregnancy test

3 CLINICAL DECISION

• Treatment decision should be made on an individual basis • For heterotopic pregnancy, the IUP must be considered when planning management Surgical Management• Surgical treatment remains the preferred approach for most ectopic pregnancies Surgical management is indicated if:• � e patient’s condition deteriorates• β-hCG levels are rising or plateaued & ectopic mass >3-4 cm • Unreliable patient who may not be available for close follow-up

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3 CLINICAL DECISION (CONT’D)

Medical Management• Success is greatest if gestation <6 weeks & tubal mass <3.5 cm in diameter • Serial measurements of β-hCG are necessary in patients being managed medicallyMedical management may be an option if:• Patient is hemodynamically stable w/ normal hemogram & normal liver & renal function• Ectopic pregnancy has been confi rmed by US• Ectopic mass has not ruptured & is <3-4 cm in diameter by US• Absence of active bleeding or signs of hemoperitoneum• Patients w/ β-hCG levels <5000 IU/L (5000 mIU/mL) are more likely to respond to therapy• Patient is willing to comply w/ close follow-upMedical management is contraindicated if:• Breastfeeding• Presence of fetal cardiac activity • Presence of fl uid in the cul-de-sac• Immunodefi ciency • β-hCG levels >5000 IU/L (5000 mIU/mL) • Presence of contraindications related to Methotrexate use • Ruptured ectopic pregnancy • Active pulmonary or peptic ulcer disease Expectant Management• May be considered if the patient remains stable, is reliable & is willing to accept the potential risk of tubal rupture• Evidence of resolution eg declining β-hCG levels• 68-77% of ectopic pregnancies resolve without intervention but clinical markers to identify these patients have

not been defi ned• Spontaneous resolution is more likely in patients w/ β-hCG levels <1000 IU/L (1000 mIU/mL)• Risk of rupture will remain until pregnancy is completely resolved • Serial measurements of β-hCG are necessary in patients being managed expectantlyExpectant management may be an option if:• β-hCG levels are <1000 IU/L (1000 mIU/mL) & are declining• Vaginal sonography shows no evidence of intra-abdominal rupture or bleeding• Patient is willing to comply w/ close follow-up

A PATIENT EDUCATION• Advise the patient on the advantages & disadvantages of each treatment option • Women may grieve at the loss of pregnancy & may need appropriate support • Explain that fertility rates after either medical or surgical management are similar in patients w/ no history of

subfertility or tubal pathology - In patients w/ a history of subfertility, improved reproductive outcomes are observed w/ medical or expectant management than w/ surgery

• Women undergoing medical management should avoid alcoholic beverages, NSAIDs, vitamins containing folic acid, sexual intercourse, sun exposure due to risk of Methotrexate dermatitis, & ultrasound & pelvic examinations during Methotrexate therapy surveillance

• Patient w/ confi rmed ectopic pregnancy should avoid using intrauterine device as contraception since this can increase the chance of ectopic pregnancy

• Describe the side eff ects of medical therapy & symptoms to monitor (eg severe abdominal pain, lightheadedness)• Patients should be advised regarding their risk of future ectopic pregnancy

- In patients w/ no history of subfertility or tubal pathology, no diff erence in the risk of future tubal ectopic pregnancy or tubal patency rates is seen between the diff erent management approaches

B SURGERY• Besides preventing death, the current focus in the surgical management of ectopic pregnancies includes

preservation of fertility, rapid recovery & reduction of costs• Laparoscopic salpingostomy & partial salpingectomy are gaining ground over laparotomy• 90% of women w/ ectopic pregnancy & serum β-hCG levels of >200 IU/L require operative intervention owing

to increasing symptoms or tubal ruptureLaparoscopy• Preferred approach & is superior to laparotomy when considering recovery time, rate of subsequent IUP, & recurrent

ectopic pregnancy Laparotomy• Surgery of choice for patients w/ compromised hemodynamic status or cornual ectopic pregnancy when

laparoscopic approach is too diffi cult or if the surgeon is not trained in operative laparoscopy


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B SURGERY (CONT’D)Salpingostomy• Standard laparoscopic procedure for unruptured ectopic mass of <4 cm in length by US• Over the bulging anti-mesenteric border of the implantation site, a longitudinal incision is made & left unsutured• Salpingostomy is reasonable if there is only one tube but it carries a risk of 20% of repeated ectopic pregnancy• It may also be considered in women w/ a contralateral tubal damage or previous ectopic pregnancy, abdominal

surgery or pelvic infl ammatory disease • � ere is a 5-11% risk of persistent trophoblast (detected by decrease of β-hCG levels of <20% every 72 hours)

- β-hCG level should be followed up until it becomes undetectable or decreases to <5 IU/L (5 mIU/mL)Salpingectomy• Indicated in patients w/ uncontrolled bleeding, extensive tubal damage, recurrent ectopic pregnancy in the same

fallopian tube, severely damaged fallopian tube (eg isthmic ectopic pregnancies), ectopic gestation >5 cm, or as a sterilization procedure

• Salpingectomy is preferred if the contralateral tube is healthy because there is a lower rate of persisting trophoblast

C METHOTREXATE• Action: Methotrexate is a folic acid antagonist that interferes w/ DNA synthesis in rapidly dividing cells like

the trophoblastic tissue• Eff ects: Reported success rates are between 65-95%

- Treatment success rates following Methotrexate therapy are comparable to surgery - Failure rates are higher w/ larger ectopic pregnancies, evidence of fetal cardiac activity & higher β-hCG levels - Studies have shown that a single-dose protocol may have similar effi cacy to a multidose protocol

- Failure rate is lower w/ multidose Methotrexate• Patients for Methotrexate therapy must be hemodynamically stable w/ serum β-hCG level of <5000 IU/L, has

no demonstrated US evidence of fetal cardiac activity or IUP, & no abdominal pain that is severe or persistent • Methotrexate treatment of tubal ectopic pregnancy has no eff ect on ovarian reserve • Muscle relaxation training may be of help to patients on Methotrexate therapy • Patients treated w/ Methotrexate may experience self-limiting abdominal pain which may mimic acute ectopic

rupture, a transient rise in β-hCG levels, & vaginal spotting or bleeding• Side eff ects are infrequent w/ short regimen but can also be mitigated by co-administration of Leucovorin• Patient must be willing & available for close follow-up which may take as long as 7 weeks

- β-hCG level should be followed up until it becomes undetectable or decreases to <15 IU/L - If hCG level increases or plateaus, patient may be given another dose of Methotrexate

- Patient should also be made aware that medical therapy fails in approximately 5-10% of patients & will lead to surgery• Patients who underwent Methotrexate therapy must wait for at least 3 months before attempting to become

pregnant again

D EXPECTANT MANAGEMENT• Expectant management w/ close observation may be undertaken in an attempt to increase possible future

tubal patency in carefully selected patients• � is option should be off ered only when transvaginal US fails to locate the gestational sac & the serum levels

of β-hCG & progesterone are low & declining - Candidates must be asymptomatic & clinically stable w/ declining β-hCG levels, initially <1500 IU/L

• Serum β-hCG should be monitored on weekly basis while transvaginal US is done on weekly interval to confi rm reduction in hCG level & decrease in the adnexal mass size in 7 days - � ereafter, serum β-hCG & transvaginal US monitoring are done on a weekly basis until serum hCG concentration is no longer detectable since there are reports of tubal rupture at low levels of β-hCG

• � is method of treatment tends to be discouraged due to persistence of the risk of rupture until the pregnancy has been completely resolved

ANTI-D IMMUNOGLOBULIN• Based on expert opinion, anti-D immunoglobulin is recommended in nonsensitized patients who are rhesus

negative & who have ectopic pregnancy• Anti-D prophylaxis may be off ered to women who had surgical removal of an ectopic pregnancy or if bleeding

is heavy, repeated or w/ abdominal pain • Suggested dose is 250 IU (50 mcg)


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Please see the end of this section for the reference list.

All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated.Not all products are available or approved for above use in all countries.

Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information.

Specifi c prescribing information may be found in the latest MIMS.

Dosage Guidelines

CYTOTOXIC CHEMOTHERAPY

Drug Dosage Remarks

Folic Acid Analog Methotrexate Single dose regimen:

Day 1: 50 mg/m2 BSA IM based on actual body wt as a single dose Monitor β-hCG levels at days 1, 4 & 7, then wkly until hCG levels are undetectableIf the β-hCG declines <15% between days 4-7, then the procedure is repeatedIf β-hCG level declines ≥15% between days 4-7, then β-hCG is measured wkly until the level is undetectableIf the level declines <15% in any wk of follow-up, the procedure is repeatedMultiple dose: 1 mg/kg of body wt IM every other day for 4 doses or until β−hCG drops >15% in 48 hrAdminister w/ Leucovorin: 0.1 mg/kg IM every other day alternating w/ MethotrexateMonitor β-hCG on days 1, 2, 5 then every 5 days after that until β-hCG is undetectable

Adverse Reactions • Can cause bone marrow suppression, acute

& chronic hepatotoxicity, stomatitis, pulmonary fi brosis, alopecia, hematosalpinx, pneumonitis, & photosensitivity; toxic eff ects are rare in single inj & may be mitigated w/ Leucovorin administration in multiple-dose regimens

Special Instructions• Patient should immediately report any signs

or symptoms of tubal rupture (eg vag bleeding, abdominal & pleuritic pain, syncope or dizziness)

• Patients should be counseled that abdominal pain may increase after therapy & is usually self-limiting & can be treated w/ NSAIDs - If NSAIDs do not relieve pain, re-evaluation is indicated

• Recommend initial blood count, platelet count & liver enzymes

VACCINES, ANTISERA & IMMUNOLOGICALS

Drug Dosage Remarks

Immunoglobulin, Anti-D [ Rho (D) immunoglobulin; Human anti-D Ig]

Before 12th week of pregnancy: 600-750 IU slow IMAfter 12th week of pregnancy:1250-1500 IU slow IMDoses are to be given w/in 72 hr of event

Adverse Reactions• Local pain & tenderness at inj site;

occasionally fever, chills, malaise, headache, cutaneous reaction

Special Instructions• Use w/ caution in patients w/ IgA

defi ciency, active immunization• Avoid in Rh(D) positive patients• Discontinue if allergic or anaphylactic-type

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