MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY

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

15. Treatment Options • Surgery • 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 50-120 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)