Benefits, Harms, and Costs
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).
- 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).
- 9In appropriately selected cervical pregnancies, clinicians should offer medical management over surgical management with dilatation and curettage (conditional, low).
- 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).
- 12Clinicians may choose either laparotomy or laparoscopy to excise an abdominal pregnancy (conditional, low).
- 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).
- 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).
Abbreviations:β-hCG (β-human chorionic gonadotropin), IUP (Intrauterine pregnancy), MA (Medical abortion), PUL (Pregnancy of unknown location)
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- Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases.Hum Reprod. 2002; 17: 3224-3230
- Demographic, lifestyle, and reproductive risk factors for ectopic pregnancy.Fertil Steril. 2018; 110: 1328-1337
- Significant adverse events and outcomes after medical abortion.Obstet Gynecol. 2013; 121: 166-171
- No. 375-clinical practice guideline on the use of first trimester ultrasound.J Obstet Gynaecol Can. 2019; 41: 388-395
- Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location.Hum Reprod Update. 2014; 20: 250-261
- Introduction of a single visit protocol in the management of selected patients with pregnancy of unknown location: a prospective study.BJOG. 2011; 118: 693-697
- Is there a need to definitively diagnose the location of a pregnancy of unknown location? The case for “no”.Fertil Steril. 2012; 98: 1085-1090
- Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome.Fertil Steril. 2011; 95: 857-866
- The clinical performance of the M4 decision support model to triage women with a pregnancy of unknown location as at low or high risk of complications.Hum Reprod. 2016; 31: 1425-1435
- Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis.BJOG. 2019; 126: 190-198
- Triaging women with a pregnancy of unknown location using a two-step triage protocol including the M6 model: a clinical implementation study.Ultrasound Obstet Gynecol. 2020; 55: 105-114
- Expectant management of tubal ectopic pregnancy: prediction of successful outcome using decision tree analysis.Ultrasound Obstet Gynecol. 2004; 23: 552-556
- Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.Ultrasound Obstet Gynecol. 2017; 49: 171-176
- Efficacy and safety of a clinical protocol for expectant management of selected women diagnosed with a tubal ectopic pregnancy.Ultrasound Obstet Gynecol. 2013; 42: 102-107
- Spontaneous resolution of ectopic tubal pregnancy: natural history.Fertil Steril. 1995; 63: 15-19
- Prognostic factors for successful expectant management of ectopic pregnancy.Fertil Steril. 1995; 63: 469-472
- Randomised trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy.Lancet. 1997; 350: 774-779
- Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: a randomized trial.Acta Obstet Gynecol Scand. 2009; 88: 1331-1337
- Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy.Obstet Gynecol. 1998; 92: 989-994
- Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility.Hum Reprod. 1998; 13: 3239-3243
- Outpatient chemotherapy of unruptured ectopic pregnancy.Fertil Steril. 1989; 51: 435-438
- Single-dose methotrexate: an expanded clinical trial.Am J Obstet Gynecol. 1993; 168 (discussion 1762–5): 1759-1762
- Single-dose methotrexate for treatment of ectopic pregnancy.Obstet Gynecol. 1991; 77: 754-757
- Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases.Obstet Gynecol. 1991; 77: 749-753
- The medical treatment of unruptured ectopic pregnancy with methotrexate and citrovorum rescue: preliminary experience.Fertil Steril. 1986; 46: 811-813
- Nonsurgical management of unruptured ectopic pregnancy: an extended clinical trial.Fertil Steril. 1987; 48: 752-755
- Single injection of methotrexate for treatment of ectopic pregnancies.Am J Obstet Gynecol. 1994; 171: 1584-1587
- The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens.Obstet Gynecol. 2003; 101: 778-784
- Comparison of single and multiple dose methotrexate therapy for unruptured tubal ectopic pregnancy: a prospective randomized study.Acta Obstet Gynecol Scand. 2010; 89: 889-895
- Comparison of two different protocols of methotrexate therapy in medical management of ectopic pregnancy.Iran Red Crescent Med J. 2015; 17: e20147
- Comparison of single-dose and two-dose methotrexate protocols for the treatment of unruptured ectopic pregnancy.J Obstet Gynaecol. 2011; 31: 330-334
- Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy.Int J Gynaecol Obstet. 2012; 116: 67-71
- A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy.BJOG. 2001; 108: 192-203
- Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies.N Engl J Med. 1999; 341: 1974-1978
- Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review.Fertil Steril. 2007; 87: 481-484
- Yolk sac on transvaginal ultrasound as a prognostic indicator in the treatment of ectopic pregnancy with single-dose methotrexate.Am J Obstet Gynecol. 2009; 200 (338 e331–4)
- Predictors of methotrexate treatment failure in ectopic pregnancy.J Reprod Med. 2006; 51: 87-93
- Factors predicting the success rate of a single dose of systemic methotrexate for the treatment of ectopic pregnancy.J Minim Invasive Gynecol. 2015; 22: S89-S90
- Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate.Am J Obstet Gynecol. 1998; 178: 1354-1358
- The importance of gestational sac size of ectopic pregnancy in response to single-dose methotrexate.ISRN Obstet Gynecol. 2013; 2013269425
- Predictive value of hemoperitoneum for outcome of methotrexate treatment in ectopic pregnancy: an observational comparative study.Ultrasound Obstet Gynecol. 2014; 43: 698-701
- Multiple-dose and double-dose versus single-dose administration of methotrexate for the treatment of ectopic pregnancy: a systematic review and meta-analysis.Reprod Biomed Online. 2017; 34: 383-391
- Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial.Human Reprod. 2016; 31: 332-338
- Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis.Am J Obstet Gynecol. 2019; 221 (95–108.e2)
- Methotrexate exposure prior to and during pregnancy.Teratology. 1994; 49: 79-81
- Effect of methotrexate treatment of ectopic pregnancy on subsequent pregnancy.Can Fam Physician. 2011; 57: 37-39
- Unexplained elevated maternal serum alpha-fetoprotein levels and perinatal outcome in an urban clinic population.Am J Obstet Gynecol. 1994; 171: 1030-1035
- Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy.Int J Gynaecol Obstet. 2017; 139: 170-173
- The safety of conception occurring shortly after methotrexate treatment of an ectopic pregnancy.Reprod Toxicol. 2009; 27: 85-87
- Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial.Lancet. 2014; 383: 1483-1489
- Comparison of the fertility outcome of salpingotomy and salpingectomy in women with tubal pregnancy: a systematic review and meta-analysis.PloS One. 2016; 11e0152343
- Fertility after ectopic pregnancy: the DEMETER randomized trial.Hum Reprod. 2013; 28: 1247-1253
- Optimal treatment for patients with ectopic pregnancies and a history of fertility-reducing factors.Arch Gynecol Obstet. 2011; 283: 41-45
- Pregnancy in a cesarean scar.Ultrasound Obstet Gynecol. 2000; 16: 592-593
- Outcome of Cesarean scar pregnancy managed expectantly: systematic review and meta-analysis.Ultrasound Obstet Gynecol. 2018; 51: 169-175
- Cesarean scar pregnancy is a precursor of morbidly adherent placenta.Ultrasound Obstet Gynecol. 2014; 44: 346-353
- The efficacy of the systemic methotrexate treatment in caesarean scar ectopic pregnancy: a quantitative review of English literature.J Obstet Gynaecol. 2015; 35: 290-296
- Surgical management algorithm for caesarean scar pregnancy.J Obstet Gynaecol Can. 2017; 39: 619-626
- Transvaginal ultrasound-guided local methotrexate administration as the first-line treatment for cesarean scar pregnancy: follow-up of 18 cases.J Obstet Gynaecol Res. 2015; 41: 803-808
- Uterine artery embolization followed by dilation and curettage within 24 hours compared with systemic methotrexate for cesarean scar pregnancy.Int J Gynaecol Obstet. 2014; 127: 147-151
- Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review.Hum Reprod. 1998; 13: 2636-2642
- Transvaginal ultrasound-guided treatment of cervical pregnancy.Obstet Gynecol. 2007; 109: 1076-1082
- Outcomes of bilateral uterine artery chemoembolization in combination with surgical evacuation or systemic methotrexate for cervical pregnancy.J Minim Invasive Gynecol. 2015; 22: 1029-1035
- Management of interstitial ectopic pregnancy with intravenous methotrexate: an extended study of a standardised regimen.Aust N Z J Obstet Gynaecol. 2015; 55: 176-180
- Successful rescue of an early interstitial pregnancy after failed systemic methotrexate treatment: a case report.J Reprod Med. 2007; 52: 332-334
- Three conservative approaches to treatment of interstitial pregnancy.J Am Assoc Gynecol Laparosc. 2001; 8: 154-158
- Hysteroscopic methotrexate injection under ultrasonographic guidance for interstitial pregnancy.J Minim Invasive Gynecol. 2016; 23: 1195-1199
- Conservative management of nontubal ectopic pregnancies.Fertil Steril. 2011; 96 (1391–5.e1391)
- Minimally invasive treatment of live ectopic pregnancy.Clin Exp Obstet Gynecol. 1997; 24: 92
- Therapeutic outcomes of methotrexate injection in unruptured interstitial pregnancy.Obstet Gynecol Sci. 2017; 60: 571-578
- Factors influencing the success of conservative treatment of interstitial pregnancy.Ultrasound Obstet Gynecol. 2005; 26: 279-282
- Comparison of laparoscopic cornual resection and cornuotomy for interstitial pregnancy.J Minim Invasive Gynecol. 2017; 24: 397-401
- Abdominal pregnancy in the United States: frequency and maternal mortality.Obstet Gynecol. 1987; 69: 333-337
- Ectopic pregnancy in the liver. Report of a case and angiographic findings.Acta Chir Scand. 1983; 149: 633-635
- A hepatic ectopic pregnancy treated with direct methotrexate injection.Aust N Z J Obstet Gynaecol. 1995; 35: 221-223
- Ectopic pregnancy causing hemothorax managed by thoracoscopy and actinomycin D.Obstet Gynecol. 1998; 91: 837-838
- Primary abdominal pregnancy implanted on the sigmoid colon.J Obstet Gynaecol. 2003; 23: 667
- Management of primary abdominal pregnancy: twelve years of experience in a medical centre.Acta Obstet Gynecol Scand. 2007; 86: 1058-1062
- Minimally invasive management of an advanced abdominal pregnancy.Obstet Gynecol. 2004; 103: 1064-1068
- Laparoscopic treatment of early retroperitoneal abdominal pregnancy implanted on inferior vena cava.Surg Laparosc Endosc Percutan Tech. 2009; 19: e156-e158
- Minimally invasive management of 14.5-week abdominal pregnancy without laparotomy: a novel approach using percutaneous sonographically guided feticide and systemic methotrexate.J Ultrasound Med. 2003; 22: 709-714
- Abdominal pregnancy following total hysterectomy.Int Surg. 1983; 68: 253-255
- Successful outcome of advanced abdominal pregnancy with exclusive omental insertion.Ultrasound Obstet Gynecol. 2003; 21: 192-194
- Early abdominal ectopic pregnancies: a systematic review of the literature.Gynecol Obstet Invest. 2012; 74: 249-260
- Failed treatment of abdominal pregnancy with methotrexate. A case report.J Reprod Med. 2001; 46: 392-394
- Advanced abdominal pregnancy: still an occurrence in modern medicine.Aust N Z J Obstet Gynaecol. 2005; 45: 518-521
- Term abdominal pregnancy with healthy newborn: a case report.Ghana Med J. 2011; 45
- Full-term viable abdominalpregnancy: a case report and review.Arch Gynecol Obstet. 2003; 268: 340-342
- Fetal survival in abdominal pregnancy: a review of 11 cases.J Clin Ultrasound. 1996; 24: 513-517
- Early ultrasonographic diagnosis and laparoscopic treatment of abdominal pregnancy.Eur J Obstet Gynecol Reprod Biol. 2004; 113: 103-105
- Super-selective arterial embolization for uncontrolled bleeding in abdominal pregnancy.Obstet Gynecol. 2008; 112: 427-429
- Successful operative management of an intact second trimester abdominal pregnancy with additional preoperative selective catheter embolization and postoperative methotrexate therapy.Med Sci Monit. 2011; 17: CS53
- Ovarian pregnancy—a 12-year experience of 19 cases in one institution.Eur J Obstet Gynecol Reprod Biol. 2004; 114: 92-96
- Diagnosis and laparoscopic management of 12 consecutive cases of ovarian pregnancy and review of literature.J Minim Invasive Gynecol. 2009; 16: 354-359
- Is ovarian pregnancy a medical illness? Methotrexate treatment failure and rescue by laparoscopic removal.Taiwan J Obstet Gynecol. 2008; 47: 471-473
- Combined intrauterine and extrauterine gestations: a review.Am J Obstet Gynecol. 1983; 146: 323-330
- Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001–2011.Obstet Gynecol. 2015; 125: 70
- Laparoscopic management of ruptured heterotopic pregnancy after intrauterine insemination.CMAJ. 2016; 188: E525-E527
- The risk factors of miscarriage and obstetrical outcomes of intrauterine normal pregnancy following heterotopic pregnancy management.Medicine. 2018; 97
- Heterotopic pregnancy: two cases and a comparative review.Fertil Steril. 2007; 87 (417.e9–15)
- Surgical management of a heterotopic cesarean scar pregnancy with preservation of an intrauterine pregnancy.Obstet Gynecol. 2016; 128: 613-616
- A successfully managed spontaneous heterotopic pregnancy diagnosed in the second trimester of pregnancy.Niger Postgrad Med J. 2016; 23: 101
- Non-surgical management of live ectopic pregnancy with ultrasound-guided local injection: a case series.Ultrasound Obstet Gynecol. 2005; 25: 282-288
- A comparison of heterotopic and intrauterine-only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002.Fertil Steril. 2007; 87: 303-309
- Heterotopic pregnancy.J Obstet Gynaecol. 2011; 31: 7-12
- Casuistry in ovarian pregnancy.Arch Gynecol Surv. 1978; 13: 73-79
- Sonographic evolution of cornual pregnancies treated without surgery.Obstet Gynecol. 1992; 79: 1044-1049
- Diagnosis and management of cervical ectopic pregnancy.J Hum Reprod Sci. 2013; 6: 273-276
- Diagnosis and treatment of early cervical pregnancy: a review and a report of two cases treated conservatively.Ultrasound Obstet Gynecol. 1996; 8: 373-380
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