Tubal Ectopic Pregnancy Management
/Here’s the RoshReview Question of the Week!
A 24-year-old G2P1 woman presents to the emergency department with right-sided pelvic pain and vaginal spotting. She has been trying to conceive and her last menstrual period was 8 weeks ago. The patient reports her left fallopian tube was removed 3 years ago due to hydrosalpinx. Her beta-human chorionic gonadotropin is 6,700 mIU/mL. On ultrasound, there is no intrauterine pregnancy identified. Fetal heart tones are detected in the right fallopian tube. There is a minimal amount of free fluid noted in the posterior cul-de-sac. What is the most indicated intervention at this time?
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While we have reviewed the workup of the early unlocated pregnancy and diagnosis of ectopic pregnancy previously with Dr. Cleary, and talked about the unusual problem of cesarean ectopic pregnancy before on the show, somehow we missed the management of the regular tubal ectopic!
ACOG PB 191 is a great resource for all things ectopic pregnancy and important companion reading for the podcast today.
Background Info
Ectopic pregnancy represents about 2% of reported pregnancies, but this is likely an undercall as not all ectopic pregnancies are reported.
Ruptured ectopic accounts for a significant cause of maternal morbidity and mortality - 2.7% of maternal deaths in 2011-2013 were attributable to ruptured ectopics.
Fallopian tube is the most common location for an ectopic (90%), but as we’ve talked about before, these can be anywhere – abdomen (1%), cervix (1%), ovary (1-3%), and cesarean scar (1-3%).
Can also co-occur with an intrauterine pregnancy – heterotopic pregnancy.
Naturally conceived: 1 in 4,000 to 1 in 30,000
IVF: as high as 1 in 100
Risk Factors for Ectopic Pregnancy
50% of those who receive a diagnosis don’t have any known risk factor.
Risk factors that can be present include:
Prior ectopic - recurrence risk is about 10% after 1 prior, 25% after 2 prior
Prior fallopian tube surgery / damage
History of PID or ascending pelvic infection
ART - tubal infertility, multiple embryo transfer, infertility in general
Cigarette smoking
AMA > 35yo
Contraception and ectopic risk:
Those using IUDs are at lower risk overall of ectopic because IUDs are highly effective at preventing pregnancy in general.
However, in those who do become pregnant with an IUD in place, up to 53% of these pregnancies are ectopic.
OCP use, emergency contraceptive failure, previous pregnancy termination, pregnancy loss, and cesarean delivery have not been associated with increased risk of ectopic pregnancy.
Confirming a Diagnosis of Ectopic Pregnancy
We covered this pretty extensively in our episode with Dr. Cleary - there we do a great job of talking you through the “pregnancy of unknown location” workup, especially when you see a patient in ED/triage with bleeding/pain and early pregnancy.
We won’t go through it all again today, as we want to focus primarily on management, but a few big points:
Trending bHCG every 48 hours helps to determine if the pregnancy is normal or abnormal.
If a bHCG is higher than the DZ and you don’t see anything - that’s a good indicator of an abnormal pregnancy, with 50-70% being ectopic.
Transvaginal ultrasound to assess the uterus and adnexae will help you identify any unusual mass that might be an ectopic.
So let’s start from the point of abnormally rising bHCG, so we know our suspicion is for an abnormal IUP versus ectopic. What options are available?
Expectant Management
We can continue to trend bHCG in a stable patient, particularly in the case of highly desired pregnancy or low bHCG values that may need more time to declare itself.
These patients should be counseled strongly about presenting for care should they experience significant bleeding, severe pain, or other symptoms worrisome for ectopic rupture.
Uterine Aspiration
If we are reasonably certain the pregnancy is abnormal, a uterine aspiration can be done to determine if the pregnancy is intrauterine or not.
The aspirate can be sent to pathology or floated to quickly identify chorionic villi – if found, then you know it was an IUP.
If villi are not found, then hCG should be measured again at 12-24 hours after aspiration.
If the hCG drops at least 10-15%, it was likely successful aspiration of a failed IUP; however, drops of 50% or greater are more indicative.
Serial hCG should be followed to zero in these patients since no pathology was identified.
If the hCG is plateaued or rising, then the pregnancy is ectopic, and the patient will need additional treatment.
Proceeding Directly to Treatment
The PB mentions there is debate whether aspiration is necessary before treating an abnormal pregnancy with methotrexate.
On one hand, confirmation of the diagnosis with the procedure helps avoid unnecessary exposure to MTX.
On the other hand though, the procedure adds at least 12-24 hours of additional time (and potential ectopic rupture) before giving treatment.
ACOG notes that the risk of rupture during this time period overall is low, and that presumptive treatment with MTX doesn’t confer cost savings
However, it reserves the choice for patients and their physicians after discussion of risks and benefits.
Medical Treatment of Ectopic Pregnancy
The standard, as we’ve mentioned, is methotrexate.
Folate antagonist binding to catalytic site of dihydrofolate reductase → inhibits synthesis of nucleotides and amino acids, thus inhibiting DNA synthesis, cell repair, and cell replication.
MTX affects all rapidly-proliferating cells because of it – marrow, mucosa, cancers, and trophoblasts.
This is helpful to keep in mind to thinking about side effects of MTX:
Nausea, vomiting
Stomatitis
Abdominal pain
Alopecia (rare)
Pneumonitis (rare)
There are no recommended alternatives to MTX for medical therapy.
Contraindications to MTX:
Absolute:
Intrauterine pregnancy
Chronic liver or kidney disease
Bone marrow dysfunction (anemia, blood dyscrasia, thrombocytopenia, leukopenia).
Active GI disease (i.e., PUD) or respiratory disease.
Breastfeeding
Hemodynamically unstable patient.
Inability to participate in follow up.
Relative:
Cardiac activity in the ectopic pregnancy
High hCG concentration (>5000 mIU/mL)
Reviews demonstrate a failure rate of 14.3% or higher at this concentration (vs 3.7% when under 5000 mIU/mL)
Ectopic size greater than 4cm on TVUS
Refusal to accept blood transfusion
MTX Regimens:
ACOG in the PB 191 mentions three primary regimens: single-dose, two-dose, and fixed multi-dose.
Single-dose is the simplest but may require additional dose in up to 25% of patients.
Two-dose has high success rate with similar monitoring to single-dose regimen.
A recent review article suggested the two-dose protocol was more successful while also exposing patients to only minimal, transient side effects versus single dose, and has higher success rates with higher hCG levels.
Multi-dose fixed regimen requires up to 8 days of treatment with alternating MTX and folinic acid for rescue and minimization of MTX side effects.
What about surveillance / labs for MTX?
Before administration (day 1), you should obtain:
bHCG
CBC
CMP
Patients should be counseled about side effects of MTX, and should avoid medications, foods, and supplements that may worsen efficacy
Have them stop prenatal vitamins at this time, so the folate doesn’t counteract the MTX!
Folate-rich foods and NSAIDs may also decrease the efficacy of MTX.
Narcotics, alcohol, and gas-producing foods should also be avoided so as not to mask or be confused with signs of rupture.
Patients should also avoid vigorous activity and sex until confirmation of resolution so as not to induce ectopic rupture.
With single and two-dose protocols, you’ll evaluate bHCG again on days 4 and day 7.
Success in these protocols is noted with a 15% or more decline between days 4 and 7.
If the decline is less than that, or bHCG increases, then an additional dose of MTX should be administered on day 7.
With repeat doses of MTX, it’s reasonable to consider repeat laboratories to evaluate for any toxicity.
bHCG should continue to decline to zero, and should be followed at least weekly once the initial 15% decline is noted.
Resolution can take up to 8 weeks, though average:
Two dose: 25.7 +/- 13.6 days
One dose: 31.9 +/- 14.1 days
Finally, patients should consider avoiding pregnancy for at least 3 months after the last dose of MTX.
Studies have found MTX still detectable in cells up to 116 days past exposure.
However, limited evidence also suggests that anomalies and pregnancy loss is not elevated in those who become pregnant shortly after MTX exposure.
MTX does not have a measurable effect on fertility.
Surgical Therapy
For patients who do not desire MTX or are not candidates, surgical therapy is the other option. Surgical therapy is also needed for the patient with hemodynamic instability or symptoms of rupture/intraperitoneal bleeding.
Can also be reasonably considered in stable patients with an indication for another procedure, like salpingectomy for sterilization or hydrosalpinx removal.
Surgeries available include salpingectomy (removal of the tube) or salpingostomy (opening the tube).
These are generally accomplished laparoscopically – laparotomy is reserved for unstable patients or patients with large bleeding and compromised laparoscopic visualization.
Surgery may be more effective than medical therapy and requires less follow up, but does expose patient to surgical risk.
Salpingectomy is technically easier to perform, and that’s likely how most of us have trained.
Salpingostomy can be considered in patients with desired fertility and damage to the contralateral fallopian tube, and would require ART for future pregnancy.
To perform, typically you make an incision along the long axis of the tube over the ectopic, and resect the pregnancy tissue.
Achieving hemostasis is rather tricky in these cases, and may additionally cause damage to the tube. The tube is usually left to heal on its own and not sutured as this may crimp the tube and cause further damage.
Because you may not resect all of the pregnancy tissue at salpingostomy, bHCG monitoring after salpingostomy is needed to ensure complete resolution.
MTX may also be given prophylactically if incomplete resection is considered.
Expectant Management
We bet you weren’t expecting this one… but ACOG does mention there may be a role for expectant management of ectopic.
They note that candidates for EM should be:
Asymptomatic
Objective evidence of resolution (i.e., plateau or decreasing bHCG)
Accepting of potential risks after counseling, including tubal rupture, hemorrhage, emergent surgery.
EM should be abandoned if hCG insufficiently decreases or begins to rise or with any suspicion for tubal rupture.
If initial hCG is under 200 mIU/mL, 88% of patients will have spontaneous resolution.
In a single small RCT of patients with hCG < 2000 mIU/mL, EM was not associated with lower treatment success than single dose MTX (59% vs 76%).