MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY

Cary L. Clarke, MD

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

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

Risk Factors

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

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

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

Symptoms (later)

Hemodynamic instability Peritoneal signs/acute abdomen Distended, silent, “doughy” abdomen Shoulder pain

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

Natural history

May regress spontaneously Abortion out the end of the tube Chronic hematoma formation Reimplantation elsewhere (abdominal

pregnancy)

Diagnosis

History and physical – any woman presenting with pain and

vaginal bleeding should be considered to have an ectopic pregnancy until otherwise ruled out

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

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

– 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).

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%

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

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

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

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.

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%

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

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

Failure to resolve– if the serial quantitative analysis fails to

reach near zero levels, patient needs further ultrasonographic evaluation and possible exploratory surgery.

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)