Guideline No. 414: Management of Pregnancy of Unknown Location and Tubal and Nontubal Ectopic Pregnancies

ABSTRACT Objective To provide an evidence-based algorithm to guide the diagnosis and management of pregnancy of unknown location and tubal and nontubal ectopic pregnancy. Target Population All patients of reproductive age. Benefits, Harms, and Costs The implementation of this guideline aims to benefit patients with positive β-human chorionic gonadotropin results and provide physicians with a standard algorithm for expectant, medical, and surgical treatment of pregnancy of unknown location and tubal pregnancy and nontubal ectopic pregnancies. Evidence The following search terms were entered into PubMed/Medline and Cochrane in 2018: cesarean section, chorionic gonadotropin, beta subunit, human/blood, fallopian tubes/surgery, female, fertility, humans, infertility, laparoscopy, methotrexate, methotrexate/administration & dosage, methotrexate/therapeutic use, pregnancy (abdominal, angular, cervix, cornual, ectopic, ectopic/diagnosis, ectopic/diagnostic imaging, ectopic/drug therapy, ectopic/epidemiology, ectopic/mortality, ectopic/surgery, heterotopic, interstitial, isthmo-cervical, ovarian, tubal, unknown location), recurrence, risk factors, salpingectomy, salpingostomy, tubal pregnancy, ultrasonography, doppler ultrasonography, and prenatal. Articles included were randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Additional publications were identified from the bibliographies of these articles. Only English-language articles were reviewed. Validation Methods The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Intended Audience Obstetrician–gynaecologists, family physicians, emergency physicians, midwives, registered nurses, nurse practitioners, medical students, and residents and fellows. SUMMARY STATEMENTS (GRADE ratings in parentheses) 1Ectopic pregnancies account for the majority of first-trimester maternal deaths (high). 2Tubal pregnancies account for the majority of ectopic pregnancies (high). 3Pregnancy of unknown location is a transient state in the diagnostic process, leading to a final diagnosis of viable or nonviable intrauterine pregnancy, ectopic pregnancy, or persistent pregnancy of unknown location (high). 4Management protocols for pregnancy of unknown location are predictive and not diagnostic. They are formulated to risk stratify pregnancy of unknown location as either high or low risk for ectopic pregnancy (high). 5Methotrexate is a safe and effective treatment for carefully selected tubal and nontubal ectopic pregnancies (high). 6Expectant management of a tubal pregnancy can eliminate medication-related and surgical risks in carefully selected patients. However, expectant management can result in serious morbidity if it fails (low). 7There is no evidence to recommend conservative, tube-sparing salpingotomy over salpingectomy in the surgical management of the majority of tubal pregnancies (moderate). 8Ultrasound diagnosis of nontubal ectopic pregnancy requires experienced sonographers and radiologists (moderate). 9Providers should have a high index of suspicion for cervical ectopic pregnancy because severe outcomes often occur with delayed diagnosis and management (low). 10Women who will be undergoing treatment for a cervical pregnancy should be counselled about the risk of hemorrhage and the possible need for hysterectomy (low). 11The terms interstitial and cornual pregnancy are used interchangeably in the literature (low). 12Abdominal pregnancies are associated with high rates of maternal mortality owing to the high risk of catastrophic hemorrhage (low). 13Laparoscopy is often required for definitive diagnosis of ovarian pregnancy (very low). 14Spontaneous heterotopic pregnancies are rare (low). RECOMMENDATIONS (GRADE ratings in parentheses) 1We recommend the use of risk models (e.g., the M6 model) to stratify pregnancy of unknown location as either high or low risk for ectopic pregnancy to guide treatment decisions (strong, moderate). Tubal Pregnancies 2Clinicians can consider expectant management and very close follow-up in carefully selected patients with early, asymptomatic tubal pregnancies (conditional, low). 3If a patient meets the criteria for medical management of a tubal pregnancy, we suggest the single- or double-dose methotrexate protocol (conditional, moderate). 4If feasible, clinicians should use a minimally invasive approach in the surgical management of tubal pregnancy (strong, high). 5Consider both patient and surgeon factors when deciding between salpingectomy and salpingotomy; there is no evidence to recommend conservative, tube-sparing salpingotomy over salpingectomy when the contralateral fallopian tube is normal (conditional, low). Cesarean Scar Pregnancies 6Clinicians should consider medical management with multidose and/or local methotrexate as a safe and effective treatment in appropriately selected women with a cesarean scar pregnancy (conditional, moderate). 7Clinicians should consider treating type I cesarean scar pregnancies surgically with hysteroscopy (conditional, low). 8Clinicians should consider treating type II cesarean scar pregnancies surgically with laparoscopy (conditional, low). Cervical Pregnancies 9In appropriately selected cervical pregnancies, clinicians should offer medical management over surgical management with dilatation and curettage (conditional, low). Interstitial/Cornual Pregnancies 10Clinicians should offer conservative medical management with multidose and/or local methotrexate for interstitial or cornual pregnancies in appropriately selected patients (conditional, moderate). 11If surgery is required, clinicians may perform either laparoscopic cornuotomy or cornual wedge resection because both procedures have comparable results (conditional, low). Abdominal Pregnancies 12Clinicians may choose either laparotomy or laparoscopy to excise an abdominal pregnancy (conditional, low). Ovarian Pregnancies 13Clinicians may offer conservative medical management of ovarian pregnancies with methotrexate in appropriately selected patients (conditional, low). 14Clinicians can perform laparoscopic ovarian wedge resection rather than oophorectomy for ovarian ectopic pregnancies, if clinically appropriate (conditional, low). Heterotopic Pregnancies 15Clinicians should not offer systemic methotrexate in the presence of a desired intrauterine pregnancy (conditional, moderate). 16We suggest surgical excision of the ectopic pregnancy in cases of heterotopic pregnancy. If the intrauterine pregnancy is not desired, we conditionally recommend adding dilatation and curettage to the surgical procedure to evacuate the uterine cavity (conditional, moderate).