ECTOPIC PREGNANCYECTOPIC PREGNANCY

Rukset Attar, MD, PhDRukset Attar, MD, PhD

Obstetrics and Gynecology Obstetrics and Gynecology DeparDeparttmentment

is a is a complication of pregnancy in which the pregnancy in which the pregnancy implants outside the implants outside the uterine cavity

1.4-2 %1.4-2 % With With rare exceptions, ectopic pregnancies are not viable. rare exceptions, ectopic pregnancies are not viable. About About 1%1% of pregnancies are in an ectopic location with of pregnancies are in an ectopic location with

implantation not occurring inside of the womb, and of implantation not occurring inside of the womb, and of these these 98% occur in the Fallopian tubes98% occur in the Fallopian tubes

The classic symptoms of ectopic pregnancy include:The classic symptoms of ectopic pregnancy include: abdominal pain,abdominal pain, the absence of menstrual periods (amenorrhea),the absence of menstrual periods (amenorrhea), vaginal bleedingvaginal bleeding..

The pain is caused by The pain is caused by prostaglandins released at the implantation site, and released at the implantation site, and free bloodfree blood in the peritoneal cavity, which is a local irritant. in the peritoneal cavity, which is a local irritant.

If left untreated, about If left untreated, about half of ectopichalf of ectopic pregnancies will pregnancies will

resolve without treatmentresolve without treatment

An intrauterine sac should be visible by An intrauterine sac should be visible by transvaginaltransvaginal ultrasound when the β-hCG is ultrasound when the β-hCG is approximately approximately 10001000 mIU/mLmIU/mL, and by , and by transabdominal ultrasound approximatelytransabdominal ultrasound approximately 1 1 week later, when the β-hCG is week later, when the β-hCG is 1800–36001800–3600 mIU/mL. mIU/mL.

ClassificationClassification

Tubal pregnancy Pregnancies can grow in

the fimbrial end (5% of all ectopics), the ampullary section (80%), the isthmus (12%), and the cornual and interstitial part of the tube (2%).

Isthmic pregnancies Isthmic pregnancies rupture rupture earliest,earliest, at at 6 to 8 weeks6 to 8 weeks’’- - duedue to the to the small diameter of this portion of the tube. small diameter of this portion of the tube.

AmpullaryAmpullary pregnancies pregnancies rupture later, generally at rupture later, generally at 8–128–12 weeks. weeks. Interstitial pregnancies Interstitial pregnancies are the are the lastlast to rupture, to rupture, usually at usually at 12–16 12–16

weeks, as the myometrium allowsweeks, as the myometrium allows mormore e room to grow than the room to grow than the tubal walltubal wall

Nontubal ectopic pregnancy Two percent of ectopic pregnancies occur in the

ovary, cervix, or are intraabdominal

Heterotopic pregnancy The survival rate of the uterine fetus of an ectopic

pregnancy is around 70%

Persistent ectopic pregnancy refers to the continuation of trophoplastic growth refers to the continuation of trophoplastic growth

after a surgical intervention to remove an ectopic after a surgical intervention to remove an ectopic pregnancy. pregnancy.

After a conservative procedure such as a After a conservative procedure such as a salpingotomy some trophoblastic tissue perhaps some trophoblastic tissue perhaps deeply embedded deeply embedded maymay escape removal and escape removal and continues to growth, generating a new rise in hCG continues to growth, generating a new rise in hCG levels.levels.

The most effective way to identify persistent ectopic The most effective way to identify persistent ectopic pregnancies is to monitor serum b-hCG levels during the pregnancies is to monitor serum b-hCG levels during the postoperative period.postoperative period.

Recommendations have varied from every 3 days to 2 weeksRecommendations have varied from every 3 days to 2 weeks Women in whom the serum b-hCG concentration falls less Women in whom the serum b-hCG concentration falls less

than than 50%50% are more than 3 times as likely to have a persistent are more than 3 times as likely to have a persistent ectopic pregnancy ectopic pregnancy

serum b-hCG on postoperative day serum b-hCG on postoperative day 1 and every 3–7 days 1 and every 3–7 days thereafter, depending on the rate of decline, until levels are thereafter, depending on the rate of decline, until levels are undetectable. undetectable.

For those who exhibit evidence of persistent ectopic For those who exhibit evidence of persistent ectopic pregnancy (rising or slowly falling postoperative b-hCG pregnancy (rising or slowly falling postoperative b-hCG concentrations), the single-dose methotrexate treatment concentrations), the single-dose methotrexate treatment regimen (50 mg/m2 i.m.) is highly effective.regimen (50 mg/m2 i.m.) is highly effective.

Causes

one third to one half of ectopic pregnancies, no risk factors can be identified.

Risk factors include: pelvic inflammatory disease, infertility, use of an intrauterine device (IUD), those who have been exposed to DES, tubal surgery, smoking, previous ectopic pregnancy, and tubal ligation

Symptoms

Early signs include:Early signs include: PainPain Vaginal bleedingVaginal bleeding

Diagnosis

An ectopic pregnancy should be considered in any An ectopic pregnancy should be considered in any woman with abdominal pain or vaginal bleeding who has woman with abdominal pain or vaginal bleeding who has a positive a positive pregnancy test

ultrasound β-hCGβ-hCG Serum progesteron levelsSerum progesteron levels laparoscopy or or laparotomy CuldocentesisCuldocentesis Cullen's signCullen's sign

Treatment

Expectant managementExpectant management MedicalMedical

methotrexatemethotrexate SurgicalSurgical

laparoscopy laparoscopy or or laparotomylaparotomy salpingostomy salpingostomy salpingectomysalpingectomy

Expectant managementExpectant management Tubal ectopic pregnancies onlyTubal ectopic pregnancies only Decreasing serial -hCG levelsDecreasing serial -hCG levels Diameter of the ectopic mass not >3.5 cmDiameter of the ectopic mass not >3.5 cm No evidence of intra-abdominal bleeding or No evidence of intra-abdominal bleeding or

rupture by transvaginal sonographyrupture by transvaginal sonography

Medical treatment Medical treatment hCG < 5,000hCG < 5,000 No cardiac activityNo cardiac activity Mass < 4cmMass < 4cm

Absolute RequirementsAbsolute Requirements Hemodynamic stability Hemodynamic stability No evidence of acute intra-abdominal bleedingNo evidence of acute intra-abdominal bleeding Reliable commitment to comply with required Reliable commitment to comply with required

follow-up care follow-up care No contraindications to methotrexate treatment No contraindications to methotrexate treatment

Contraindications to Methotrexate TreatmentContraindications to Methotrexate Treatment Breastfeeding Breastfeeding Immunodeficiency states Immunodeficiency states Hematologic abnormalities (severe anemia, Hematologic abnormalities (severe anemia,

leukopenia, thrombocytopenia) leukopenia, thrombocytopenia) Known sensitivity to methotrexate Known sensitivity to methotrexate Active pulmonary disease Active pulmonary disease Active peptic ulcer disease Active peptic ulcer disease Alcoholism Alcoholism Clinically important hepatic or renal dysfunctionClinically important hepatic or renal dysfunction

Preferred CharacteristicsPreferred Characteristics Absent or mild symptoms (pain) Absent or mild symptoms (pain) Serum concentration less than 5,000Serum concentration less than 5,000 IU/LIU/L Absent embryonic heart activity Absent embryonic heart activity Ectopic mass measuring less than 4 cm in Ectopic mass measuring less than 4 cm in

diameterdiameter

PPre-treatment evaluation:re-treatment evaluation: Complete blood count Complete blood count Blood type and Rh(D)Blood type and Rh(D) Serum creatinine Serum creatinine Liver function tests Liver function tests Transvaginal ultrasonographyTransvaginal ultrasonography

ppatients should be advised to atients should be advised to discontinue any folic acid supplements they may be discontinue any folic acid supplements they may be

taking taking to avoid to avoid

sun exposure (to decrease risk of methotrexate dermatitis),sun exposure (to decrease risk of methotrexate dermatitis), use of non-steroidal antiinfl ammatory drugs (interaction with use of non-steroidal antiinfl ammatory drugs (interaction with

methotrexate may cause bone mar-row suppression or methotrexate may cause bone mar-row suppression or gastrointestinal toxicity), and gastrointestinal toxicity), and

intercourse or strenuous physical activity (to decrease the intercourse or strenuous physical activity (to decrease the risk of tubal rupture).risk of tubal rupture).

““single-dose” treatment regimensingle-dose” treatment regimen methotrexate is administered in a single dose methotrexate is administered in a single dose

(50 mg/m2, day 1) (50 mg/m2, day 1) if the serum b-hCG declines 15% or more if the serum b-hCG declines 15% or more

between days 4 and 7, treatment is deemed between days 4 and 7, treatment is deemed successful and b-hCG concentrations are successful and b-hCG concentrations are monitored weekly thereafter until undetectable. monitored weekly thereafter until undetectable.

In the majority of women (85%), serum b-hCG In the majority of women (85%), serum b-hCG concentrations rise somewhat between days 1 concentrations rise somewhat between days 1 and 4and 4- normal- normal

AAny subsequent further increase in b-hCG levels, or a ny subsequent further increase in b-hCG levels, or a decrease of less than 15% between days 4 and 7, is decrease of less than 15% between days 4 and 7, is indication for a second dose (on day 7), using the same indication for a second dose (on day 7), using the same criteria for judging response (on day 11). criteria for judging response (on day 11).

If required, a third dose can be administered on day 11 If required, a third dose can be administered on day 11 and the response evaluated by measuring b-hCG again and the response evaluated by measuring b-hCG again on day 14. on day 14.

Although a fourth dose can be administered (on day 14), Although a fourth dose can be administered (on day 14), surgical treatment generally is recommended after 2 surgical treatment generally is recommended after 2 weeks of failed medical treatment.weeks of failed medical treatment.

2-dose treatment regimen2-dose treatment regimen MMethotrexate is administered on days 1 and 4 (50 mg/m2) ethotrexate is administered on days 1 and 4 (50 mg/m2) If the serum b-hCG declines 15% or more between days 4 If the serum b-hCG declines 15% or more between days 4

and 7, levels are monitored weekly until levels become and 7, levels are monitored weekly until levels become undetectableundetectable

If If b-hCG concentrations decreases by less than 15% b-hCG concentrations decreases by less than 15% between days 4 and 7, a third dose of methotrexate is between days 4 and 7, a third dose of methotrexate is administered (on day 7) and the same criterion is applied administered (on day 7) and the same criterion is applied in judging the response to treatment on day 11.in judging the response to treatment on day 11.

If necessary, a fourth dose is administered (on day 11) If necessary, a fourth dose is administered (on day 11) and the serum b-hCG concentration is assessed again on and the serum b-hCG concentration is assessed again on day 14.day 14.

MMulti-dose treatment regimenulti-dose treatment regimen MMethotrexate (1 mg/kg i.m.) and leukovorin (0.1 ethotrexate (1 mg/kg i.m.) and leukovorin (0.1

mg/kg i.m.) are administered on alternate days, mg/kg i.m.) are administered on alternate days, up to a maximum of four doses, until the serum up to a maximum of four doses, until the serum b-hCG level declines by 15% from the previous b-hCG level declines by 15% from the previous value. value.

Thereafter, b-hCG concentrations are monitored Thereafter, b-hCG concentrations are monitored on a weekly basis until levels become on a weekly basis until levels become undetectable.undetectable.

IIndications for surgical treatmentndications for surgical treatment

Hemodynamic instability Hemodynamic instability Rupture of an ectopic mass Rupture of an ectopic mass Coexisting viable intrauterine pregnancyCoexisting viable intrauterine pregnancy Unwillingness or inability to comply with required follow-Unwillingness or inability to comply with required follow-

up after medical treatment up after medical treatment Lack of ready access to a hospital for management of Lack of ready access to a hospital for management of

tubal rupture tubal rupture Desire for permanent sterilization Desire for permanent sterilization Contraindications to medical treatment Contraindications to medical treatment Failed medical treatmentFailed medical treatment