Pocket ObGyn – Ectopic Pregnancy
See Abbreviations
Definitions & Epidemiology (Obstet Gynecol 2008;111:1479; NEJM 2009;361:379)
- Preg outside of the endometrial 2% of 1st trimester pregnancies.
- 6% of all pregnancy-related deaths (leading cause of death in the 1st trimester).
- Ectopic Preg increasing (4.5/1000 pregnancies in 1970 ® 7/1000 in 1992).
- Rate of rupture w/ ectopic Preg is 20–35%.
Etiology
- Blastocyst implants & invades improperly at nonendometrial 97% in fallopian tubes, most frequently in the ampullary region. Other implantation sites include the isthmic portion of the tube, fimbria, uterine cornua, cervix, ovary, prior C/S scar, or abd.
- Heterotopic Preg ® 2 or more implantation sites (ie, an IUP & ectopic Preg). Rare, only 1:8000–1:30000 nml pregnancies. Increased to 1.5/1000 after assisted reproductive
- Risk factors: Prior ectopic Preg, prior tubal Surg, tobacco smoking, prior PID, Chlamydia trachomatis infxn, 3 or more prior spont miscarriages, age >40 y, prior medical or surgical abortion, infertility >1 y, lifelong sexual partners >5, current IUD use, IVF/ART.
Clinical Manifestations and Physical Exam
- Lower abdominal pain on the affected side.Vaginal
- Clinical findings are often unremarkable w/ unruptured ectopic Preg. Only 75% develop marked abdominal May p/w shoulder pain, dizziness, syncope. Hx & risk factors are useful to assess risk/suspicion.
- VS & clinical assessment to look for signs of hemodynamic
- Pelvic exam: Adnexal mass (20%). Abdominal exam: Tenderness to Evaluate for surgical abd: Rebound, guarding, rigidity.
Diagnostic Workup and Studies
- Labs: CBC (sometimes serial Hgb), bld type (RhoGAM if Rh-negative), CMP for BUN/Cr, & AST/ALT (if considering MTX).
• Serum (quantitative) hCG:
If hCG above “discriminatory zone” of 1500–2000 mIU/mL, nml IUP seen on TVUS. If hCG >1500–2000 mIU/mL & no IUP on TVUS ® likely abn Preg (eg, ectopic
Preg, incomplete AB, resolving completed AB)
If hCG <1500 mIU/mL & no IUP ® rpt hCG in 48 h (at SAME lab). In 85% of women w/ a nml IUP, the hCG will ³63% in 48 h.
In 99% of women w/ a nml IUP, the hCG will ³53% in 48 h. An in serum hCG of <~60% in 48 h ® abn Preg
- TVUS: 91% accuracy of TVUS for dx of ectopic Extrauterine GS or embryo seen in only 15–30% of cases. Most common US finding is a solid mass btw the ovary & uterus.
Adnexal mass (other than a simple ovarian cyst) is 84% sensitive & 99% specific for ectopic Preg.
Trilaminar endometrial stripe (only) is 38% sensitive & 94% specific for an ectopic Preg.
Pseudosac (intrauterine midline fluid collection) is neither sensitive nor specific for the dx of ectopic Preg. Do not confuse pseudosac for IUP.
- Serum progesterone: Often not Levels from 5–20 ng/mL are equivocal. Serum progesterone <5 ng/mL sugg abn Preg (100% specific, 60% sensitive). Serum progesterone >20 ng/mL sugg nml IUP (40% specific, 95% sensitive)
- Endometrial curettage: For “Preg of unk location,” D&C can evaluate POCs (float the villi), & assist in decision for diagnostic laparoscopy dx of abn Preg (eg, missed AB).
Treatment and Medications
- Expectant mgmt: 68% ® successful resolution (Lancet 1998;351:1115)
If initial hCG is <200 mIU/mL, 88% resolve w/o rx
Recheck hCG 48 h after initial lab tests to ensure declining serum hCG
- Medical mgmt: MTX inhibits dihydrofolate reductase ® decreased tetrahydrofolate
® ¯ purine nucleotide synthesis ® ¯ DNA/RNA in S-phase of cell cycle® prevent proliferation (in active tissues like trophoblast, bone marrow, buccal/intestinal mucosa). 2 protocols (see below). Multidose regimen more effective for advanced GA & +ve fetal cardiac activity.
Side effects: Usually self-limited. Most common are nausea, vomiting, stomatitis, conjunctivitis, worsening abdominal pain 2–3 d after MTX dose due to expan- sion of the affected gestational tissue, transient liver dysfxn, & uncommonly myelosuppression, alopecia, pulmonary damage, anaphylaxis.
Pt instructions: Stop taking prenatal vitamins & folate supplements, avoid sun exposure, refrain from EtOH consump, intercourse, & vigorous physical activity.
Strong contraindications to MTX: Tubal rupture or hemodynamic instability, breast-feeding, alcoholism, alcoholic liver dz, or chronic liver dz, immunodeficiency, pre-existing bld dyscrasias (bone marrow hypoplasia, leukopenia, thrombocyto- penia, signif anemia), active pulmonary dz, peptic ulcer dz, hepatic, renal, or hematologic dysfxn, Cr >1.3 mg/dL, AST or ALT >50 IU/L.
Relative contraindications to MTX:
GS >3.5 cm. Single-dose MTX 93% effective when the GS is <3.5 cm. Decreases to 87–90% efficacy when >3.5 cm. Large GS ® ¯ success.
Embryonic cardiac activity. Single-dose MTX is 87% effective if +ve fetal heart motion.
Serum hCG level >5000 mIU/mL. Failure w/ single-dose MTX is 14.3% if hCG
>5000 mIU/mL (compared to 3.7% failure if hCG <5000 mIU/mL). Consider multidose therapy or surgical mgmt.
| Single-dose MTX regimen |
| 89% success rate, MTX dose: 50 mg/m2
Day 1: Check hCG (& other labs above), administer MTX Day 4 & day 7: Check beta hCG ¯ in hCG of 15% from day 4–day 7 ® continue to monit weekly serum hCG levels until undetectable (Note: hCG may from day 1–day 4) If hCG does not fall appropriately from day 4–day 7 ® consider rpt US, then rpt MTX dose or perform laparoscopy |
| Multidose MTX regimen |
| 93% success rate
MTX dose: 1 mg/kg + Leucovorin (folinic acid) dose: 0.1 mg/kg Day 1: Check hCG, administer MTX Day 2: Administer Leucovorin Day 3: Check hCG. If hCG has NOT decreased by 15% from day 1, then administer MTX Day 4: Administer Leucovorin Day 5: Check hCG. If hCG has NOT decreased by 15% from day 3, then administer MTX Day 6: Administer Leucovorin Day 7: Check hCG. If hCG has NOT decreased by 15% from day 5, then administer MTX Day 8: Administer Leucovorin If 4 doses of MTX are given w/o a 15% decline in hCG over 48 h ® proceed w/ laparoscopy If there is a 15% decline in hCG over 48 h ® follow weekly serum hCG levels until undetectable |
- Surgical mgmt: Laparoscopy preferred if the pt is hemodynamically stable ® shorter operative times, less bld loss, less analgesic requirements, shorter hospital stay, no difference in tubal patency rates, similar rates of subseq Salpingostomy: Gold std Surg for ectopic. Open affected tube & evacuate ecto-
pic POCs. Esp useful for pt w/ abn contralateral tube who desires future fertility. Persistent ectopic Preg in 4–15% of cases. Follow weekly serum hCG levels until they are undetectable. Check pathology to confirm POCs.
Salpingectomy: Removal of entire affected fallopian tube. Appropriate for pts w/ a nml appearing contralateral tube who desire future fertility, or pts who do not desire future fertility. Eliminates risk of persistent ectopic Preg, or recurrent, ipsilateral ectopic Preg. If confident that all trophoblast removed, no need for serial hCGs.