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Definition: Pregnancy outside of endometrial cavity.

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Location:

1. Fallopian tube (including interstitial pregnancy)

2. Ovary

3. Broad ligament

4. Abdominal cavity

5. Cervix 

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Incidence:1.4% of pregnancy, increased with parity and age, highest in 35-44y/o. 

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Part I: Tubal Pregnancy

I. General considerations:

A 95% of ectopic pregnancy, 80% in ampulla. 

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B. Risk factors:

1. Laparoscopically proved PID:

2. Previous tubal pregnancy:

a. Subsequent ectopic pregnancy: 10-25%(7-13X).

b. Subsequent IUP: 50-80%.

3. Current use of IUD: 6-10X risk for tubal pregnancy.

4. Previous tubal surgery for infertility:

a. Sterilization: 5-16% for tubal pregnancy, the greatest risk is in the first 2 years.

b. Tubal repair or reconstruction:4-5X.

5. Abdominal surgery:Removal for ruptured appendix: increased.

6. Others:

a. Abortion

b. Infertility

c. Salpingitis Isthmica Nodosa(SIN)

d. Endometriosis and Leiomyomata: not consistently associated.

e. DES

f. Smoking: >2X

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 II. Diagnosis:

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A. History:

1. Past history:

a. Systemic disease.

b. Operation, esp. for infertility or ruptured appendicitis.

2. Gyn history:

a. Two recent menstrual periods, interval/duration, amount of menses.

b. Infertility, ectopic pregnancy, abortion.

c. PID, laparoscopically-proved.

d. Contraceptives use, IUD(copper or progesterone-containing).

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 B. Symptom/sign:

1. Missed period: pregnancy test should be performed.

2. Abdominal or pelvic pain: >95%, The pain may be localized unilaterally.

3. Abnormal vaginal bleeding: 60-80%, due to tubal myometrial invasion by trophoblasts.

4. Others: nausea/vomiting, shoulder soreness, faintness, shock.

5. Pelvic exam:

a. Cervix: lifting pain.

b. Uterus: soft, slightly enlarged but tender.

c. Adnexae: palpable, tender mass or not(may be due to guarding).

d. CDS: may be bulging.

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 C. hCG: serial hCG

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1. Discriminatory zone:

2. Doubling time:

a. In the first 6 weeks of amenorrhea: 48hr, regardless of the initial level..

b. 85% of normal IUP, hCG will rise >66%, only 15% of the ectopics > 66%.

c. 85% of the ectopics, hCG rises < 66%. 

d. After 6th week, rise of hCG is not consistent.

e. If hCG become plateau or half ³ 7days: ectopics are most likely.

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3. Half life:

a. < 1.4 days: rarely ectopic pregnancy.

b. ³ 7days or plateau: mostly ectopic pregnancy.

c. drop of hCG < 50% over 48hr: ectopic pregnancy is most likely.

d. drop of hCG > 50% over 48 hr: complete abortion is likely.

4. "20-day window":

a. hCG can be detected on the 8th day after fertilization, and gestational sac is visible on the 28th day after fertilization. During this period, if no IUP is detected by vaginal sonography, recheck GS on the day when hCG is expected to be > 2,000mIUI/mL.

5. Other markers:

Progesterone: 1.5% of ectopic pregnancies with progesterone > 25ng/ml, whereas only <1/1500 of viable IUP with progesterone < 5ng/ml.  Useful in "20-day window" or hCG not available.

D. Ultrasound:

1. Diagnostic triad: (1).empty uterus, (2).adnexal mass clearly separated from ovary, (3)hCG>2,000mIU/mL.

2. CDS fluid: suggestive of hemoperitoneum if adnexal mass is also seen.

3. GS may be seen at 4.5-5 weeks gestation by vaginal sonar and 6-7weeks by abdominal sonography.

4. Doppler: high-velocity, low-resistance peritrophoblast flow.

E. Culdocentesis: 18-20 gauge needle with syringe.

1. Positive: unclotting blood(liquefied old blood clot), source uncertain.

2. Negative: clear fluid.

3. Nondiagnostic: nothing is withdrawn.

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F. D&C: for villi. If no villi can be found, check hCG.

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G. Laparoscopy: old standard for diagnosis of ectopic pregnancy.

III.Treatment:

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A. Principles: on vaginal sonography:

1. If no IUP and hCG > 2,000mIU/mL: treat without further testing.

2. Adnexal fetal cardiac activity: treat without further testing.

3. A tubal mass as small as 1 cm can be identified and characterized.  Masses > 3.5-4.0 cm should not be treated medically.

4. Suction D&C is used to differentiate nonviable IUP from ectopic pregnancies: < 50% rise in hCG/48hr, hCG < 2,000mIU/mL and an indeterminate sonography.

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 B. Surgery:

1. Indications:

a. Indeterminate pregnancy: suction D&C first.

b. Adnexal mass > 3.5cm.

c. Ruptured ectopic pregnancy.

d. Unstable hemodynamics: laparotomy.

e. Ectopics in other sites of abdominal cavity or pelvis than fallopian tubes.

f. Complications or failure of medical treatrment.

2. Linear salpingosotomy v.s salpingectomy:

Salpingostomy: unruptured ecotopics, desiring future fertility.

Salpingectomy: history of infertility.

3. Outcome:

a. Pregnancy rate is similar between L copy and laparotomy.

b. L copy salpingostomy: 60% of subsequent pregnancy is IUP.  L copy salpingectomy: 54%

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 C. Medical treatment:

1. Agnets: Methotrexate(MTX), KCl, hyperosmolar glucose, prostaglandin, RU486.

2. Systemic therapy--MTX:

a. Inhibiting dehydrofolate reductase and then inhibiting DNA synthesis.

b. Candidates for MTX:

(1) An hCG is present after salpingostomy or salpingectomy.

(2) A rising or plateaued hCG is present at least 12-24 hours after suction D&C.

(3) No intrauterine gestational sac or fluid collection is detected by TVUS, hCG level is < 2,000mIU/mL and an ectopic pregnancy mass < 3.5cm.

c. Initiating MTX:

(1) Obtain hCG level.

(2) Perform TVUS within 48hr.

(3) Suction D&C if hCG < 2,000mIU/mL.

(4) CBC, D/C (WBC > 2,000/mL, Platelet > 100,000), GOT, BUN, Cr.

(5) Adminster Rhgam if Rh(-).

(6) Identify unruptured ectopic pregnancy < 3.5cm.

(7) Prescribe FeSO4 if Hct < 30%.

(8) F/U hCG on Days 4, 6, 7.

(9) Well explain to the patient and avoid alcohol, multiple vitamins containing folic acid and intercourse untill hCG is negative.

(10) Call doctor if prolonged or severe vaginal bleeding or abdominal pain.  * Lower abdominal or pelvic pain is normal during the first 10-14 days of treatment.

(11) Use oral contraceptives or barrier methods for contracption.

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d. Regimens:

(1) Multiple MTX with citrovorum factor:

(a) Multiple MTX(1mg/kg/day), im injection on days 1, 3 , 5, 7, and citrovorum factor(0.1mg/kg/day) im on days 2, 4, 6, 8, until at least >15% decline between 2 consecutive daily hCG levels (maybe 2 or more courses are required) , then DC MTX and follow hCG level weekly until negative.

(b) Success rate: 96%. In case of FHB(+), success rate is 80%(4/5).

(2) Single dose of MTX(50mg/m2) without citroverum factor:

(a) Day 0 D&C, hCG

1 CBC, GOT, BUN, Cr, blood type and Rh

4 MTX 50mg/m2 i.m.

7 hCG

(b) If < 15% decline in hCG level between days 4 & 7, give 2nd dose of MTX If > 15% decline in hCG level between days 4 & 7, F/U hCG weekly untill hCG < 10 mIU/mL.

(c) Combine days 0 and1 in patients not requiring D&C.( hCG>2,000 and no IUP)

(d) Success rate: 96.7%.

(e) Surgical intervention if rupture of ectopics, precipitous drop of Hct or unstable hemodynamics occur.

(f) Avoid pregnancy within 2 months after completeness of therapy.

(g) Outcome: similar to outcome L‘scopically-treated.

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3. Local injection of agents into the amniotic sac with transvaginal ultrasound, tubal cannel or Laparoscopy, including MTX, PGF2a, KCl or hyperosmolar glucose.

4. Side-effects of MTX: < 1%.

a. Bone marrow inhibition: leukopenia, thrombocytopenia, bone marrow aplasia.

b. Mucosa damage: ulcerative stomatitis, diarrhea, hemorrhagic enteritis, and less commonly, alopecia, dermatitis, elevated liver enzyme and pneumonitis

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Part II: Nontubal ectopic pregnancy:

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I. Cervical pregnancy: 1/2,400-50,000 of pregnancies.

A. Risk factors:

1. Previous therapeutic abortion.

2. Asherman‘s syndrome.

3. Previous C/S.

4. Leiomyoma.

5. IVF.

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 B. Diagnosis:

1. Clinical criteria:

a. The uterus surrounding the distended cervix is smaller.

b. The internal os is closed.

c. Curettage of the endometrial cavity is nonproductive of placental tissue.

d. The external os opens earlier than in spontaneous abortion.

2. Ultrasound criteria:

a. Echo-free uterine cavity or the presence of a false gestational sac only.

b. Decidual transformation of the endometrium with dense echo structure.

c. Diffuse uterine wall structure.

d. Hourglass uterine shape.

e. Ballooned cervical canal.

f. Gestational sac in the endocervix.

g. Placental tissue in the cervical canal (or peritrophoblast flow on Doppler).

h. Closed internal os.

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 C. Treatment:

1. Nonsurgical: intra-amniotic or systemic injection of MTX.

2. If bleeding due to suction D&C, hemostasis may be tried by one of the following:

a. uterine packing,

b. lateral cervical suture to ligate lateral cervical vessels,

c. placement of cerclage,

d. insetion of 30-ml Foley for tamponade,

e. angiographic embolization.

3. Hysterectomy if massive bleeding or the above methods fail to stop bleeding. 

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II. Ovarian pregnancy: 0.5-1.0% of ectopic pregnancies.

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A. Risk factor: IUD.

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B. Diagnosis criteria(for primary ovarian pregnancy):

1. The fallopian tube on the affected side is intact.

2. The fetal sac must occupy the position of the ovary.

3. The ovary must be connected to the uterus by the ovarian ligment.

4. Ovarian tissue must be located in the sac wall.

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 C. Treatment:

1. Ovarian cystectomy via laparotomy or L‘scopy.

2. MTX or PG injection. 

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III. Abdominal pregngncy: 1/372-9714 live births.

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A. Primary or secondary:

1. Studdiford‘s criteria for diagnosis of primary abdominal pregnancy:

a. Presence of normal tubes and ovaries with no evidence of recent or past pregnancy.

b. No evidence of uteroplacental fistula.

c. The presence of a pregnancy related exclusively to the peritoneal surface and early enough to eliminate the possibility of secondary implantation after tubal nidation.

2. Secondary: subsequent implantation due to tubal rupture or abortion, or less commonly, uterine rupture. 

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B. Diagnosis:

1. Clinical manifestation:

a. Symptoms: painful fetal movement, fetal movement high in abdomen, sudden n cessation of fetal movement.

b. P.E: persisitent fetal lie, abdominal tenderness, displaced cervix, easy palpation of fetal parts, palpation of uterus separating from the gestation.

c. Diagnosis:

(1) No uterine contraction after oxytocin infusion.

(2) Image: MRI, X-ray, ultrasound, angiography for feeding vessels. 

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C. Treatment: surgery only

1. If feeding vessels of the placenta can be identified and ligated, remove the placenta and leave packing in the abdomen for 24-48 hours.

2. If feeding vessels of the placenta can not be identified and ligated, ligate the cord near the placenta and leave the placenta in the abdominal cavity, with serial follow-up of the hCG and, sonography. Watch for complications.

3. Complications: bowel obstruction, fistula formation, sepsis.

4. MTX is contraindication because of high rate of complications. 

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D. Pregnancy outcome:

1. Term pregnancy is possible but with high rate of complications and congenital anomalies.

2. Congenital anomaly: pulmonary hypoplasia, pressure deformity, facial and limb asymmetry. 

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IV. Others:

A. Ligmentous pregnancy: 1/3,000 of ectopic pregnancies.

Secondary implantation of the gestation through tubal serosa or uterine fistula.

B. Interstitial pregnancy: 1% of ectopic pregnancies.

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C. Heterotropic:1/30,000 of pregnancies.

Intraamniotic injection of KCl through TVUS or Laparoscopy or remove the ectopic, and the normal intrauterine gestation can continue. 

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D. Pregnancy after hysterectomy: secondary to

1. supracervical hysterectomy: perioperative period.

2. total hysterectomy: defect of vaginal cuff. 

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E. Spontaneous resolution:

1. by resoption or tubal abortion. 

2. hCG is falling but watch for the tubal rupture.

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F. Persistent ectopic pregnancy:

1. After a conservative surgery(salpingostomy, fimbrial expression), trophoblastic tissue remains.

2. Trophoblast tissue may be confined to the muscularis medial to the incision, or implanted in the peritoneum.

3. If postoperative hCG or progesterone levels on days 0, 3, 6, remain plateaued, the the diagnosis of persistent ectopic pregnancy should be made.

4. Risk factors: based on

a. types of surgical procedure: L copy salpingostomy: 3-20%.  laparotomy salpingtomy: 2%.  * the incidence is increased with the use of conservative surgery.

b. the initial hCG level:

(1) preoperative: <3,000--23%,  >3,000--1/67.

(2) postoperative D2 >1,000--36%,  D7 > 1,000--64%.

c. the duration of amenorrhea: < 7 weeks, increased risk.

d. the size of the ectopic: < 2cm, increased risk.

5. Treatment:

a. Salpingectomy or repeat salpingostomy.

b. MTX: preferable because the trophoblast tissue may be elsewhere out of tubes.

G. Chronic ectopic pregnancy:

1. Pregnancy did not resolve during the expectant management

2. Duration of amenorrhea: 90% ranging from 5-16 weeks.

3. S/S: pain--86%,  vaginal bleeding--68%,  both--58%, pelvic mass: most are asymptomatic.

4. Diagnosis:

a. Ultrasound: helpful if there are pelvic masses.

b. hCG: low or absent, may be mistaken as resolution.

5. Treatment: surgical removal of gestational tissue.