Ellen L. Brock
History of present illness
A 32-year-old gravida 4, para 3 woman presented with right lower quadrant pain. Her last menstrual period was six weeks, five days ago, and she had a positive home pregnancy test six days ago. She describes the pain as cramping, with intermittent episodes of sharper pain of moderate severity. She reports nausea but no vomiting, and has a decreased appetite. She denies fever. She has no pain with urination or defecation, and bowel function has been normal.
Her only surgery was a Cesarean delivery for active phase arrest. She has no medical problems. She is a Jehovah’s Witness. Her only medication is a prenatal vitamin.
Physical examination
General appearance:Woman is alert and oriented, appears uncomfortable but is in no acute distress
Vital signs:
Temperature: 36.8°C Pulse: 72 beats/min
Blood pressure: 100/60 mmHg Respiratory rate: 18 breaths/min
Abdomen:Soft, tenderness to palpation in right lower quadrant without rebound
Vulva:Normal
Vagina:Normal, no blood in vault Cervix:Normal appearing, closed
Uterus:Upper normal size, slightly tender, more on the right side than left
Ovaries:Without palpable masses, right exquisitely tender to palpation
Laboratory studies:
Beta-hCG: 5622 mIU/L WBCs: 10 200/μL Hb: 12.6 g/dL
Imaging:An ultrasound image taken from the right cornual area is displayed inFig. 34.1. The uterus measured normal size with a 15 mm endometrial stripe. There was a
1.2 × 1.5 × 1.0 cm pocket of cul-de-sacfluid. The left adnexa imaged normally
How would you manage this patient?
The patient has an advanced apparently unruptured ectopic pregnancy. The findings are concerning for a cornual
pregnancy, but tubal or ovarian pregnancy are also possibil- ities. This patient has a high human chorionic gonadotropin (hCG) level, fetal cardiac motion, and a refusal to accept blood transfusions. Medical management is not appropriate for this patient. Our patient underwent laparoscopic salpingectomy and cornual resection. Findings at laparoscopy (Fig. 34.2) were
Fig. 34.1 Ultrasound image of an interstitial pregnancy. The endometrial stripe was seen entirely separate from the gestational sac and adjacent to the ovary. Note the thin rim of myometrium surrounding the gestational sac.
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
Fig. 34.2 Image of an interstitial pregnancy at surgery. The pregnancy appears as a bulge in the cornual region. The myometrium surrounding the pregnancy is obviously thinner than the remainder of the uterus.
consistent with interstitial pregnancy, and cornual resection was performed. The cornual defect was sutured in two layers, and the final result is shown in Fig. 34.3. The patient was discharged home in good condition on the day of surgery.
Unruptured ectopic pregnancy
Advanced unruptured ectopic pregnancy can be found in the fallopian tube, uterine cornu, Cesarean scars, cervix, or ovary, and location has some bearing on the management. Taken as a group, advanced ectopic pregnancies have a higher failure rate with medical management than small ectopic pregnancies [1].
Factors which are associated with higher failure rates are increased level of hCG (with 5000 mIU/mL proposed as a cutoff point by several authors of case reviews), presence of embryonic cardiac activity and higher serum progesterone level. While methotrexate therapy has been effective in extra- tubal ectopic pregnancies, these pregnancies are associated with greater morbidity; and careful selection and counseling is required before medical therapy should be considered [2].
If this patient’s pregnancy had been tubal, and if blood transfusions were an option should rupture occur, then we could reasonably offer her medical therapy to her. Methotrex- ate management is successful in approximately 90% of suitably selected patients. Failure rates for single dose methotrexate from 13 to 65% have been reported in patients with initial serum hCG levels above 5000 mIU/mL. While this range is too broad to be useful in counseling, it is clear that failure risk with single dose therapy is increased when initial hCG level exceeds 5000 mIU/mL [3], and that the presence of fetal cardiac activ- ity roughly doubles the risk of failure [4]. Multidose therapy should be considered for patients with these findings where medical therapy is still being considered.
Multidose therapy for ectopic pregnancy consists of administration of methotrexate at a 1 mg/kg dose in alternat- ing daily doses with leucovorin 0.1 mg/kg. Dosing is continued
up to four doses each or until the hCG level falls by 15% from the prior value (checked on days 1, 3, 5, and 7). Approximately half of women will require fewer than four doses, and a rapidly rising hCG level following the second dose is considered treat- ment failure. The only randomized trial comparing multidose to single-dose therapy found them equally effective but excluded pregnancies with fetal cardiac motion and included patients with low hCG levels [4]. Larger retrospective reviews have concluded that multidose therapy is more effective in advanced pregnancies [5].
A hybrid two-dose regimen has been proposed in which methotrexate is administered in a 50 mg/m2dose on day 1, and repeated on day 7 and day 11 if there is a less than 15%
decrease in hCG level between days 4 and 7. The two multidose regimens have not been compared in a randomized controlled trial.
Standard precautions and follow-up apply for patients with advanced unruptured ectopic pregnancy treated with methotrexate. RhoGam should be administered to Rh-negative women. Adequate compliance should be assured. Patients should avoid intercourse, should not take folic acid supple- ments, should not take aspirin or NSAIDs, and should not use alcohol. Stomatitis is a potential complication of multidose regimens and chlorhexidine mouthwashes are helpful. It is also recommended that patients delay conception for three months following medical therapy because of the potential teratogeni- city of residual methotrexate.
Desire for future pregnancy need not alter choice of treat- ment. Success rates for future pregnancy do not differ between the two methods. The outcomes of tubal preservation, tubal patency, and subsequent intrauterine pregnancy are not sig- nificantly different when systemic methotrexate therapy is compared with salpingostomy [6].
Cost of therapy is a consideration. Published data are old, and may include practices such as a dilatation and curettage in patients planning to undergo medical therapy that are not always performed now. A cost–benefit analysis that takes into account pregnancy location, hCG level, single- versus multi- dose medical treatment regimens, and salpingostomy or sal- pingectomy would be useful but does not exist.
For our patient, medical therapy is not a reasonable option given her elevated risk of failure. This would be particularly risky in this patient, given her refusal of transfu- sion and inability to safely respond if her pregnancy ruptures.
Surgery can be performed via laparoscopy or laparotomy, depending largely on operator expertise and experience.
The techniques for surgical resection are similar regardless of approach, with cornual resection with or without salpin- gectomy being the most commonly used [7]. Regardless of approach, methods to minimize blood loss should be employed. These include injection of the myometrium just proximal to the pregnancy with a dilute vasopressin solution (10 U in 100 cc saline), placing sutures into the uterus and mesosalpinx just below the resection line, and careful use of energy sources to maximize coagulation during excision.
Fig. 34.3 Image of the cornual region following laparoscopic salpingectomy and cornual resection of the pregnancy shown inFig. 34.2.
Care must be taken with the use of ultrasonic or electrical energy so that damage to the remaining myometrium is minimized.
Key teaching points
Advanced ectopic pregnancy has a higher likelihood of failure with single-dose medical therapy, and multidose regimens should be considered in those patients opting for medical management.
Medical management of extratubal ectopic pregnancies has been successfully undertaken, but decisions for medical management of these pregnancies should be considered in light of risk and morbidity of rupture, as well as other contraindications to medical management.
Women with advanced tubal pregnancies who desire future fertility can be offered either medical or surgical
management.
References
1. Medical Treatment of Ectopic Pregnancy: A Committee Opinion.
American Society for Reproductive Medicine.Fertil Steril2013;100:
638–44.
2. American College of Obstetricians and Gynecologists. Medical Management of Ectopic Pregnancy. ACOG Practice Bulletin No. 94.Obset Gynecol2008;
111: 1479–85.
3. Menon S, Colins J, Barnhart K.
Establishing a human chorionic gonadotropin cutoffto guide
methotrexate treatment of ectopic pregnancy: a systematic review.Fertil Steril2007; 87(3): 481–4.
4. Lipscomb G, McCord M, Stovall T, HuffG, Portera S, Ling F. Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies.N Engl J Med1999; 341:
1974–8.
5. Alleyassin A, Khandemi A, Aghahosseini M, Safdarian L,
Badenoosh B, Hamed EA. Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose
administration of methotrexate: a prospective randomized clinical trial.
Fertil Steril2006; 85(6): 1661–6.
6. Hajenius PJ, Mol F, Mol BWJ, Bossuyt PMM, Ankum WM, Van der Veen F.
Interventions for tubal ectopic pregnancy.Cochrane Database of Systematic Reviews2007, Issue 1. Art.
No.: CD000324. DOI 10.1002/
14651858.CD000324.pub2.
7. Moawad N, Mahajan S, Moniz M, Taylor S, Hurd W. Current diagnosis and treatment of interstitial pregnancy.
Am J Obstet Gynecol2010; 202(1):
15–29.
Case 34: Unruptured advanced ectopic pregnancy