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%).

Cesarean Scar Ectopic Pregnancy

Here’s the RoshReview Question of the Week!

A 31-year-old G2P0102 woman at 6 weeks gestation by last menstrual period presents with vaginal spotting. Her history is significant for a previous twin pregnancy where the second twin was emergently delivered by cesarean. Her vital signs are normal, hCG level is 4,440 mIU/mL, and ultrasound findings are shown above. After reviewing the treatment options, the patient indicates she prefers medical management. You further counsel her that compared to medical therapy, most interventional options have a lower risk of which of the following?

Check out the answer at the links above and get 20% off the Rosh Review question bank!


More reading: SMFM Consult Series #49

What is a Cesarean Scar Ectopic? 

  • The implantation of an early gestation in the hysterotomy incision from a previous cesarean birth. Two main types:

    • Endogenic - implantation in the scar itself  

    • Exogenic - implantation in the defect or “niche” left behind by incomplete healing of the scar 

  • Why do we care?

    • Overall very rare → 1 in 2000 pregnancies and 6% of ectopic pregnancies in total among patient with history of cesarean delivery.

    • Doesn’t seem to be related to number of prior cesareans

    • Risk factors: 

      • Not very well studied, since it is so rare 

      • There may be some increased risk associated with smoking, higher parity

    • Unrecognized C-section scar ectopics can rupture and cause hemorrhage and death! 

How do we diagnose a cesarean scar ectopic? 

  • We may suspect ectopics when there is not an appropriate rise in beta HCG (if following)

  • Signs and symptoms:

    • Early on can be asymptomatic 

    • Later on, can result in vaginal bleeding 

    • If ruptured, will lead to hemoperitoneum and hypovolemic shock 

    • Usually patients present early in first trimester 

  • Diagnosis is usually with ultrasound

    • Can be suspected if hx of C-section 

    • Gestational sac center is low (<5cm from cervical os) and anterior on ultrasound 

    • Appears to be an enlarged hysterotomy scar with embedded mass which may bulge beyond anterior contour of the uterus and toward adjacent pelvic structures 

    • Other findings that support:

      • Empty uterine cavity and endocervix  

      • Triangular gestational sac and < 8 weeks or rounded or oval sac > 8 weeks that fills the scar area 

      • Thin or absent myometrial layer between GS and bladder (1-3 mm) 

      • Prominent vascular pattern on Doppler suggestive of blood flow at the area 

  • Can also be diagnosed with surgery, where it is directly visualized 

Treatment and Management 

  • Termination of pregnancy due to risk of maternal morbidity and mortality 

  • If hemodynamically unstable

    • To OR 

    • Wedge resection or gravid hysterectomy 

      • If profusely bleeding, usually will require hysterectomy  

  • If hemodynamically stable 

    • Can consider medical or surgical treatment 

    • Medical 

      • Usually methotrexate injection 

      • Options include intrasac injection of MTX or systemic injection of MTX 1mg/kg of maternal weight up to 50 mg

        • One lit review showed that 74% of the time, no other treatment is needed.

        • Also, an additional IM or intrasac injection of MTX led to resolution up to 89% of cases 

        • However, numbers vary widely. Another review said the intrasac injection was effective 65% of the time, and UAE made it 69% effective  

    • Other surgical options 

      • Can consider UAE in addition to MTX, which seems to increase efficacy 

    • Expectant management 

      • Not recommended due to likelihood of maternal morbidity/mortality without fetal benefit 

      • May be reasonable if there is already embryonic/fetal demise and lowering bHCGs 

Follow up

  • Should have weekly HCGs drawn (like after MTX injection after other ectopics 

  • Periodic ultrasound evaluation 

  • More likely to have favorable outcome with ectopics that are diagnosed earlier vs later 

  • There have been reports of pregnancy after treatment of C-section scar ectopic, but risks include recurrence (reported at rate of 5-40%), rupture, and PAS  

Management of an Early Unlocated Pregnancy

Today we’re bringing back Dr. Erin Cleary one more time before she transitions to her new role as an MFM fellow at the Ohio State University! Dr. Cleary today talks with us on early pregnancy of unknown location - a common problem in the office or the emergency department/triage.

Women presenting to the ED with first trimester bleeding, pain, or both, have had a demonstrated prevalence rate of ectopic pregnancy up to 18% in some studies. Ruptured ectopic is a leading cause of pregnancy-related mortality in the first trimester, accounting for 2.7% of pregnancy-related deaths overall in 2011-2013. Proper identification and management of early, unlocated pregnancy is life-saving!

Dr. Cleary was kind enough to put together her high points from this episode for our blog post today:

H&P:

  • Any patient with an unlocated pregnancy should be considered to have a potential ectopic pregnancy.

    • Women with prior ectopic, regardless of method of treatment, are at risk for ectopic in a subsequent pregnancy (three- to eightfold higher compared with other pregnant women).

    • If pregnancy is present while IUD is in place, risk of ectopic is 1 in 2 pregnancies for the levonorgestrel IUD and 1 in 16 pregnancies for the copper IUD.

    • Women with a history of PID have an approximately threefold increased risk of ectopic pregnancy

  • Pelvic exam. THIS MUST BE DONE.

Beta-HCG

  • The threshold for a positive qualitative β-hcg test is 20-50 milli-int units, depending on test. For quantitative serum tests, the threshold is 5-10 milli-int units, and 1-2 milli-int units, for ultrasensitive tests.

  • The β-hcg concentration doubles every 29 to 53 hours during the first 30 days after implantation of a viable, intrauterine pregnancy.

  • When ectopic pregnancy is on the differential, a qualitative test is not sufficient. A serum quantitative value is essential to:

    • 1. Interpret imaging (“discriminatory zone”)

    • 2. Have a baseline in the event the β-hcg must be trended

The Discriminatory Zone

  • Definition: A concept that there is a quantitative β-hcg level above which the landmarks of a normal intrauterine pregnancy (yolk sac and embryo) should be visible on ultrasound.

    • Therefore, the absence of a gestational sac when β-hcg level is above the DZ is strongly suggestive of nonviable pregnancy, with 50-70% being ectopic.

  • Pelvic ultrasound is the gold standard first line imaging modality in early pregnancy and for evaluation of suspected ectopic pregnancy

  • Imaging results will fall into 1 of 5 main categories

    • IUP with normal adnexa. Normal pregnancy!

    • IUP with abnormal adnexa. Although rare, must evaluate for heterotopic pregnancy, or presence of both an intra and extra-uterine pregnancy.

    • No IUP, extra-uterine mass with YS/FP. Confirms ectopic pregnancy.

    • No IUP, adnexal mass without YS/FP. Suspicious for ectopic pregnancy

    • No IUP, normal adnexa. Differential includes normal but early IUP, failed IUP, or unidentified ectopic.

  • A patient with a confirmed ectopic requires evaluation and counseling by an OBGYN to evaluate candidacy for medical or surgical evaluation.

Management:

  • Expectant management: serial quantitative β-hcg level assessment ~q 48 hours, only for stable patients.

    • Scenario A: The β-hcg level rises appropriately (doubles approximately every 2 days).

    • Scenario B: The β-hcg level falls precipitously.

    • Scenario C: The β-hcg level neither rises appropriately nor drops precipitously. Now we should be MORE concerned about ectopic pregnancy, but abnormal IUP is also on the differential.

  • Repeat pelvic imaging is very helpful

  • Every patient who is stable and an appropriate candidate to trend β-hcg levels will eventually declare herself, with either a located IUP, a failed IUP/SAB, or a confirmed or presumed ectopic pregnancy.

We will cover ectopics for surgical and medical management in a future episode, so stay tuned!