1. MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY
Cary L. Clarke, MD

2. Definition Pregnancy located outside the uterus
Most common site is in the fallopian tube
Tubal pregnancy may be the most dangerous
Abdominal pregnancy may be carried to term in some patients

3. Incidence and Impact Occurs in 1 in 50 pregnancies
Is becoming increasingly more common
Is the second leading cause of maternal mortality overall, and primary mortality factor in first trimester pregnancies
May lead to impairment or loss of fertility

4. Risk Factors Previous ectopic pregnancy
Tubal damage from infection or surgery
Increased age (more common after 35)
Smoking (?)
Use of an Intrauterine Device

5. Assisted reproduction (GIFT, IVF, ovulation induction)
Tubal ligation
History of infertility (implying underlying damage)
History of PID (C.Trachomatis especially) is a predictor of ectopic pregnancy risk

6. Symptoms (early) Amenorrhea for an average of 7 weeks
Abdominal pain (usually lateral)
Caveat: some women have no pain, and about one-third of women will not have adnexal tenderness.
Vaginal bleeding after an interval of amenorrhea
may include uterine cast, the pregnancy endometrium which is sloughed with loss of progesterone from corpus luteum failure

7. Symptoms (later) Hemodynamic instability
Peritoneal signs/acute abdomen
Distended, silent, “doughy” abdomen
Shoulder pain

8. Pathophysiology Conceptus lodges and implants in tube
Positive beta-HCG and symptoms of pregnancy
Overdistension of the tube eroding the blood vessels supplying the corpus luteum
Failure of the pregnancy
Bleeding into the abdominal cavity

9. Natural history May regress spontaneously
Abortion out the end of the tube
Chronic hematoma formation
Reimplantation elsewhere (abdominal pregnancy)

10. Diagnosis History and physical
any woman presenting with pain and vaginal bleeding should be considered to have an ectopic pregnancy until otherwise ruled out

11. Laboratory markers
Beta-HCG(measured in mIU/mL) --lack of doubling signals only impending failure, not indicative of location;absolute value only helpful in correlation with ultrasound
Progesterone--also only indicates impending loss, not location

12. Ultrasound--transvaginal is most sensitive at this stage of pregnancy.
Correlation with the quantitative serum hormone levels is suggested to increase your sensitivity
if intrauterine gestational sac is seen and b-HCG is 1,000-2,000, normal pregnancy is virtually certain.
If b-HCG is <1,000 and there is an empty uterus, ectopic pregnancy is very likely

13. if b-HCG is is less than 1,000 and definite intrauterine ring of pregnancy is seen, SAB is imminent. Serum progesterone may be helpful (if less than 5ng/mL, pregnancy is nonviable).

14. Finding Ectopic risk No mass or free fluid Any free fluid
Echogenic mass
Moderate to large amount fluid
Echogenic mass and fluid
20%
71%
85%
95%
100%

15. Treatment Options Surgery Expectant mangagment
Tube sparing salpingotomy--used when gestational sac is <2cm and in distal tube; lateral incision made and gestational sac removed
Tube sacrificing salpingectomy
Expectant mangagment
b-HCG is <1000 and falling, there is minimal pain and bleeding, and patient is reliable for follow-up

16. Methotrexate Requires proper patient selection
Spares patient from surgery and its risks
Does not require hospitalization
May help preserve future fertility

17. Patient Selection Hemodynamically stable
No medical contraindications (normal LFTs, renal function, CBC and Plt)
Unruptured ectopic pregnancy
Absence of embryonic cardiac activity
Ectopic mass 4cm or less
Starting b-HCG <5,000mIU/mL
Reliable for follow up

18. Mechanism of Action
Methotrexate is an antimetabolite which inhibits the reduction of folic acid to tetrahydrofolate. This interferes with DNA synthesis and cell multiplication. Ideal for disrupting trophoblastic tissue proliferation.

19. Success Rate Defined as resolution of pregnancy without surgery
Systemic administration carries a rate between 85% and 95%, with preservation of fertility
Single dose regimens are essentially as effective, with fewer side effects
If a second dose is required, success rate is around 98%

20. Method of administration
May inject into the gestational sac under ultrasound guidance
Single dose systemic treatment
Methotrexate 50mg/M2 body surface area
Usual dose range is mg, average dose is 80-90mg
Injected IM

21. Follow up b-HCG is measured on days 1,4 and 7
If hormone levels fail to decline at least 15% between days 4 and 7, or at least 15% each week thereafter, repeat methotrexate dosing.
Average time to resolution
for single administration, 26days
two dose patients, 48 days

22. Failure to resolve
if the serial quantitative analysis fails to reach near zero levels, patient needs further ultrasonographic evaluation and possible exploratory surgery.

23. Surgical Consultation
Cervical pregnancy
Tubal rupture
Broad ligament pregnancy
Interstitial/Cornuate pregnancy (implantation at the segment of tube penetrating uterine wall)
Heterotypic ectopic (concurrent ectopic and intrauterine pregnancies)