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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 1 - Tubal Ectopic Pregnancy

Updated: Jul 20, 2019

“A physician is not angry at the intemperance of a mad patient; nor does he take it ill to be railed at by a man in a fever. Just so should a wise man treat all mankind, as a physician does his patient; and looking upon them only as sick and extravagant.” ― Lucius Annaeus Seneca

2016 667 Pinot Noir from Noble Vines

PB#193 - Published March 2018

Epidemiology

- 2% of all pregnancies

- ~3% of all pregnancy-related deaths

- 90% in tube

- 1-3% cervical, ovarian, abdominal, cesarean scar

- These can be more dangerous due to delay in diagnosis

- Heterotopic are rare with prevalence anywhere from 1 in 4,000 - 1 in 30,000

- In IVF, risk is as high as 1 in 100


Initial presentation

- Prevalence of ectopic in women presenting to the ED w/ first-trimester bleeding and abd pain is 20%

- Every woman of reproductive age presenting with abdominal pain or vaginal bleeding should be screened for pregnancy

- if positive, get a serum Hcg and tvus

- if IUP, great. Done.

- if no definitive visible pregnancy, “pregnancy of unknown location”

- definitive diagnosis requires trophoblastic tissue to be removed from a location other than the uterus and confirmed by pathology

- do a thorough exam, check H/H, was this a spontaneous pregnancy?


Risk factors

- a thorough history can help identify risk factors

- 50% of women with ectopic have no risk factors

- Risk of repeat is 10%

- If 2+, risk of repeat is 25%

- Other risks factors: damage to fallopian tubes, PID, tubal factor infertility, multiple embryo transfer, smoking, and age >35.

- If IUD in place, overall pregnancy rate decreased, but if pregnancy with IUD in place, 50/50 ectopic


Interpretation of TVUS and serum hCG

- If GS + YS in adnexa anywhere other than the uterus, you’ve got an ectopic

- PPV of hypoechoic area separate from ovary seen on TVUS is only 80%

- Paratubal cyst, corpus luteum, hydrosalpinx, endometrioma, or bowel can produce false positives

- Intrauterine GS can be visualized as early as 5 wks gestation (GS+YS should be visible between 5 and 6 wks gestation)

- Beware of pseudo sac


Serial hCG

- Serial serum hCG is used to distinguish between normal and abnormal pregnancies

- After a single hCG, you should allow 2 days to pass before re-checking

- Subsequently, hCG levels should be drawn 2-7 days apart

- Early in pregnancy, HCG levels will rise until around 10 wks where you’ll expect to see a plateau around 100,000


- Rate of increase depends on initial hCG level:

If <1500 mIU/mL), expect a minimum increase of ~50% 2 days later

If 1500-3000 - 40%

If >3000 - 33%

- This is a general guideline, but if the increase is less than these values, you should at least be suspicious of an abnormal pregnancy (either ectopic or early pregnancy loss). 99% of pregnancies will have a rate of increase that’s faster than these minimal values

- Even if values are normal, still doesn’t completely rule out ectopic!

- When performing TVUS, keep discriminatory zone in mind (serum HCG threshold above which a GS should be visible on TVUS)

- Discriminatory zone should be sufficiently high (3500 mIU/mL) to avoid the potential for misdiagnosis and possible interruption of an IUP that a woman hopes to avoid.

- Remember that multi-gestation pregnancy will have higher HCG levels than singleton gestation, so traditional discriminatory zones don’t apply


Pregnancy of unknown location

- If pregnancy test is positive, but there is no evidence of a pregnancy - intrauterine or elsewhere we call this “pregnancy of unknown location”

- it’s not so much a diagnosis as a transient state until a definitive pregnancy location is identified

- if a pt walks into your ER, no IUP on TVUS, positive serum hCG, hemodynamically stable, and no abdominal pain: do they want the pregnancy?

- if yes: ACOG recommends repeating at least the hCG in 2 days and, if possible, repeat ultrasound depending on your level of suspicion for ectopic

- this is to avoid unnecessary exposure to methotrexate, which can lead to interruption or teratogenicity of a normal IUP


What if hCG decreases or is otherwise abnormal?

- 95% of woman with early pregnancy loss will have a decrease in hCG of 20-35% over 2 day period

- If ectopic is still suspected, even as levels are decreasing, continue to monitor hCG levels until undetectable, as ectopics can still rupture during a normal decline in level

- if hCG trend is abnormal, highly recommended to aspirate uterine cavity

- if chorionic villi noted, you are looking at a failed IUP

- if no chorionic villi noted, repeat hCG 12-24 hrs later

- nearly all women who have a drop in hCG of 50% or greater after aspiration of uterine cavity had failed IUP

- in that case, simply continue to monitor hCG

- if hCG increases or plateaus (ie drops by less than 10-15%), the aspiration was either incomplete or you’re looking at an ectopic, so further treatment may be warranted

- in studies looking at hCG trends after aspiration in patients who ultimately did have an ectopic, 55% had a hCG decrease of >10%, 25% had a decrease of >30, and 7% had a decrease of >50%

- for your practice, if you see a plateau (again, less than 10-15% 12-24 hrs after aspiration), consider treatment particularly if hCG plateau persists/increases, if patient develops symptoms, or if that patient has strong risk factors


To aspirate or not to aspirate?

- of course the decision to aspirate is a shared-decision with your patient

- fortunately, risk of rupture is low

- in large studies looking at patients with “pregnancy of unknown location”, risk of rupture during surveillance was 0.03% among all-comers and only 1.7% when ectopic pregnancies have actually been diagnosed

- takeaway: close follow-up is critical


Medical management of ectopic

- candidates for medical management (ie methotrexate, or MTX) are hemodynamically stable, unruptured mass, and who have no absolute contraindications

- MTX is a chemotherapeutic medication, so it carries its own risks, dates back to 1956, used for ectopics since 1982

- it binds to dihydrofolate reductase in competition w/ folate, which inhibits DNA synthesis

- it affects actively proliferating tissues like BM, linings of the GI and respiratory tracts, cancer, and trophoblastic tissue

- Don’t give MTX to a patient if they have a sick liver, kidneys, or BM

- There are also several relative contraindications

- less an issue of danger so much as carrying a higher risk of treatment failure

- these include high hCG levels (>5000 mIU/mL has a failure rate of 15% compared to 4% failure rate if <5000 mIU/mL)

- other predictors of failure include rapidly increasing hCG (>50% increase in 48 hrs), presence of cardiac activity, and 4cm mass on sono

- lastly, as ruptured ectopic pregnancies can lead to rapid blood loss, not performing surgery exposes the patient to a risk of hemorrhage, and patient’s refusal to accept blood products should play a role in your counseling


MTX treatment protocols

- there are three treatment protocols: 1 dose, 2 dose, and multi-dose

- instead of remembering the protocols, just remember these principles:

1-dose

- dosing is the same for single dose and 2-dose protocols: IM injection of 50 mg/m^2 on day 1

- hCG levels measured on days 4 and 7, if <15% decrease, repeat dose on day 7, recheck day 11

- if still insufficient drop, recommend surgery

2-dose

- the 2-dose protocol differs in that it includes a 2nd injection on day 4

- same principles as 1-dose thereafter


Multi-dose

- 1mg/kg IM MTX injections on days 1,3,5,7 w/ folinic acid rescue injections on days 2,4,6,8

- check hCG on all MTX days,

- stop injections and monitor serial hCG weekly once you see a drop of at least 15% on consecutive levels

- after 4 injections, if still insufficient drop, recommend surgery


Efficacy of MTX

- Successful treatment is defined as resolution of the ectopic without the need for surgery

- overall, success through medical management is 70-95%

- compare single and 2-dose: single-dose is the easiest, though a 2nd dose may be required for up to 25% of patients for successful treatment

- in general, single-dose most appropriate if initial hCG is low; two-dose regimen better if initial hCG is higher (3600-5500 mIU/mL)

- multi-dose has been found to be equally effective compared to single dose but with increased risk of adverse effects


Follow-up after MTX

- after MTX, hCG levels may initially increase but should then progressively decrease

- failure of hCG to decrease at least 15% between days 4 and 7 is associated with high risk of failure

- options are two either give additional dose or to proceed with surgical management

- if uterus wasn’t aspirated prior to MTX, aspirate before repeating the dose, as MTX failure is higher in the event that you were actually looking at an abnormal IUP, UNLESS you see an adnexal GS+YS on TVUS

- surveillance going forward should include hCG; resolution to non-detectable levels usually occurs in 2-4 weeks but can take up to 8 weeks (faster w/ 2-dose regimen)

- routine serial TVUS is not recommended as it has not been found to be predictive of rupture

- after MTX, abdominal pain and vaginal spotting are common 2-3 days after administration

- if no clinical signs of rupture, abdominal pain can be monitored

- serial H/H and increasing free fluids in pelvis can be helpful

- other rare side effects: elevated LFTs, alopecia, and pneumonitis

- after MTX, recommend that they avoid bright sunlight for a few days,

- stop taking their prenatal vitamins and folic acid supplements, and avoid folic acid-rich foods as they can decrease efficacy

- MTX is cleared from serum before the 4-12 weeks necessary for full resolution of ectopic, though some studies have found MTX in hepatocytes up to 116 days past exposure

- recommend waiting until 3 months post-MTX and resumption of normal ovulatory cycles before attempting conception again

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