Guideline sources The following summarized guidelines for the evaluation and management of ectopic pregnancy are prepared by our editorial team based on guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC 2021), the Royal College of Obstetricians and Gynaecologists (RCOG 2021; 2016), and the American College of Obstetricians and Gynecologists (ACOG 2018; 2017). 1 2 3 4 5 Guidelines 1. Classification and risk stratification Risk stratification: use risk models (such as M6 model) to stratify pregnancy of unknown location as either high or low risk for ectopic pregnancy to guide treatment decisions. B 2. Diagnostic investigations https://web.pathway.md/diseases/recGWlD9mm9btrJfc 1/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway Serum hCG levels: As per ACOG 2018 guidelines: Do not use serum hCG values alone for the diagnosis of ectopic pregnancy, rather correlate it with the patient's history, symptoms, and ultrasound findings. D Use the conservatively high value (such as high as 3,500 mIU/mL), if the hCG discriminatory level is being used as a diagnostic aid in patients at risk of ectopic pregnancy, to avoid the potential for misdiagnosis and possible interruption of an intrauterine pregnancy that the patient hopes to continue. B As per RCOG 2016 guidelines, consider obtaining serum -human chorionic gonadotrophin measurement for planning the management of an ultrasound visualized tubal pregnancy. C Show 4 more Serum progesterone: do not obtain a measurement of serum progesterone level to predict ectopic pregnancy. D Other laboratory tests: do not obtain routine biochemical investigations for the diagnosis of Cesarean scar pregnancy. D Transvaginal ultrasound, general principles: As per ACOG 2018 guidelines: Obtain transvaginal ultrasound evaluation and confirmation of pregnancy as the minimum diagnostic evaluation in patients with a suspected ectopic pregnancy. Obtain serial evaluation with transvaginal ultrasound or hCG level measurement, or both, to confirm the diagnosis. B Obtain repeated transvaginal ultrasound and serial measurement of hCG, or both, to confirm the diagnosis and guide management in clinically stable patients with a pregnancy of unknown location desiring to continue pregnancy, if intrauterine. B As per RCOG 2016 guidelines, obtain ultrasound as the primary diagnostic modality, using a transvaginal approach supplemented by transabdominal imaging if required. B Show 3 more Transvaginal ultrasound (tubal pregnancy): Obtain transvaginal ultrasound as the diagnostic tool of choice for tubal ectopic pregnancy. B Confirm tubal ectopic pregnancy, if possible, by visualizing an adnexal mass moving separate to the ovary. B Transvaginal ultrasound (cervical pregnancy): Consider using the following ultrasound criteria for the diagnosis of cervical ectopic pregnancy: empty uterus barrel-shaped cervix gestational sac present below the level of the internal cervical os absence of the 'sliding sign' blood flow around the gestational sac using on colort Doppler. C Transvaginal ultrasound (interstitial pregnancy): Consider using the following ultrasound criteria for the diagnosis of interstitial pregnancy: empty uterine cavity https://web.pathway.md/diseases/recGWlD9mm9btrJfc 2/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway products of conception/gestational sac located laterally in the interstitial (intramural) part of the tube and surrounded by < 5 mm of myometrium in all imaging planes presence of the 'interstitial line sign'. C Transvaginal ultrasound (cornual pregnancy): Consider using the following ultrasound criteria for the diagnosis of cornual pregnancy: visualization of a single interstitial portion of the fallopian tube in the main uterine body gestational sac/products of conception seen mobile and separate from the uterus and completely surrounded by myometrium vascular pedicle adjoining the gestational sac to the unicornuate uterus. C Transvaginal ultrasound (ovarian pregnancy): insufficient evidence to recommend specific ultrasound criteria for the diagnosis of ovarian ectopic pregnancy. I Transvaginal ultrasound (abdominal pregnancy): Consider using the following ultrasound criteria for the diagnosis of abdominal pregnancy: absence of an intrauterine gestational sac absence of both an evident dilated tube and a complex adnexal mass gestational cavity surrounded by loops of bowel and separated from them by peritoneum wide mobility similar to the fluctuation of the sac, particularly evident with the pressure of the transvaginal probe toward the posterior cul-de-sac. C Transvaginal ultrasound (heterotopic pregnancy): diagnose heterotopic pregnancy if ultrasound findings demonstrate an intrauterine pregnancy and a coexisting ectopic pregnancy. B Magnetic resonance imaging: consider obtaining MRI as a second-line investigation if the diagnosis is equivocal and there is local expertise in the MRI diagnosis of Cesarean scar pregnancies. C Show 2 more 3. Medical management General principles: As per ACOG 2018 guidelines, decide on the choice of management (methotrexate versus surgery) of ectopic pregnancy guided by the initial clinical, laboratory, and radiologic data as well as patient-informed choice based on a discussion of the benefits and risks of each approach. A As per RCOG 2016 guidelines, take into account the possibility of an intrauterine pregnancy in the management plan of patients with ectopic pregnancy. B Expectant management: As per SOGC 2021 guidelines, consider offering expectant management and very close follow-up in carefully selected patients with early, asymptomatic tubal pregnancy. C As per ACOG 2018 guidelines, consider offering expectant management in patients with ectopic pregnancy in specific circumstances. C https://web.pathway.md/diseases/recGWlD9mm9btrJfc 3/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway As per RCOG 2016 guidelines, consider offering expectant management as an option in clinically stable patients with an ultrasound diagnosis of ectopic pregnancy and decreasing - human chorionic gonadotrophin initially < 1,500 IU/L. C Show 2 more Methotrexate: As per SOGC 2021 guidelines, consider administering single- or double-dose methotrexate in patients with tubal pregnancy meeting criteria for medical management. C Show 5 more As per ACOG 2018 guidelines, recognize that both laparoscopic surgery and IM methotrexate are safe and effective treatment options in clinically stable patients with non- ruptured ectopic pregnancy. Decide between surgical and medical management based on the initial clinical, laboratory, and radiologic data as well as patient-informed choice based on a discussion of the benefits and risks of each approach. A Show 3 more As per RCOG 2016 guidelines, consider administering systemic methotrexate in suitable patients with tubal pregnancy. Do not use methotrexate at the first visit unless the diagnosis of ectopic pregnancy is absolutely clear and a viable intrauterine pregnancy has been excluded. C Show 6 more Anti-D immunoglobulin: As per ACOG 2017 guidelines, administer RhD immune globulin in RhD-negative patients with ectopic pregnancy. B As per RCOG 2016 guidelines, offer anti-D prophylaxis in all RhD-negative patients undergoing surgical removal of an ectopic pregnancy or if bleeding is repeated, heavy or associated with abdominal pain. B 4. Therapeutic procedures Transvaginal targeted injection and aspiration: consider administering a local injection of potassium chloride or hyperosmolar glucose with the aspiration of the sac contents as an option in clinically stable patients with heterotopic pregnancy. C 5. Surgical interventions Surgical management (general indications): Recognize that both laparoscopic surgery and IM methotrexate are safe and effective treatment options in clinically stable patients with non-ruptured ectopic pregnancy. Decide between surgical and medical management based on the initial clinical, laboratory, and radiologic data as well as patient-informed choice based on a discussion of the benefits and risks of each approach. A Perform surgery in patients with ectopic surgery exhibiting any of the following: hemodynamic instability symptoms of an ongoing ruptured ectopic mass (such as pelvic pain) https://web.pathway.md/diseases/recGWlD9mm9btrJfc 4/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway signs of intraperitoneal bleeding. A Surgical management, tubal pregnancy: As per SOGC 2021 guidelines, use a minimally invasive approach, if feasible, for surgical management of patients with tubal pregnancy. A Show 2 more As per ACOG 2018 guidelines, decide on performing a salpingostomy or salpingectomy for the management of patients with tubal pregnancy guided by the patient's clinical status, desire for future fertility and the extent of fallopian tube damage. B As per RCOG 2016 guidelines, prefer laparoscopic approach over open surgery in patients with tubal pregnancy. A Show 2 more Surgical management (cervical pregnancy): reserve surgical methods of management for cervical pregnancy only for patients with life-threatening bleeding, because of the associated high failure rate. B Surgical management (interstitial pregnancy): Consider performing laparoscopic cornual resection or salpingotomy as an effective option in patients with interstitial pregnancy. C Consider performing hysteroscopic resection under laparoscopic or ultrasound guidance as alternative surgical techniques in patients with interstitial pregnancy. C Surgical management, cornual pregnancy: As per SOGC 2021 guidelines, consider performing either laparoscopic cornuotomy or cornual wedge resection if surgery is required for the treatment of patients with interstitial or cornual pregnancy, as both procedures have comparable results. C As per RCOG 2016 guidelines, perform excision of the rudimentary horn via laparoscopy or laparotomy for the management of patients with cornual pregnancy. B Surgical management, Cesarean scar pregnancy: As per SOGC 2021 guidelines: Consider performing hysteroscopy for surgical management of patients with type I Cesarean scar pregnancy. C Consider performing laparoscopy for surgical management of patients with type II Cesarean scar pregnancy. C As per RCOG 2016 guidelines, consider preferring surgical over medical management in patients with Cesarean scar pregnancy, recognizing that insufficient evidence to recommend any one specific intervention over another. C Surgical management, ovarian pregnancy: As per SOGC 2021 guidelines, consider performing laparoscopic ovarian wedge resection rather than oophorectomy in patients with ovarian ectopic pregnancy, if clinically appropriate. C As per RCOG 2016 guidelines, perform definitive surgical treatment if laparoscopy is required to make the diagnosis of ovarian ectopic pregnancy. B Surgical management, abdominal pregnancy: https://web.pathway.md/diseases/recGWlD9mm9btrJfc 5/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway As per SOGC 2021 guidelines, consider performing either laparotomy or laparoscopy to excise an abdominal pregnancy. C As per RCOG 2016 guidelines: Consider performing laparoscopic removal as an option of treatment in patients with early abdominal pregnancy. C Perform laparotomy for the management of patients with advanced abdominal pregnancy. B Surgical management, heterotopic pregnancy: As per SOGC 2021 guidelines: Consider performing surgical excision of the ectopic pregnancy in patients with heterotopic pregnancy. C Consider adding dilatation and curettage to the surgical procedure to evacuate the uterine cavity if the intrauterine pregnancy is not desired. C As per RCOG 2016 guidelines, consider performing surgical removal of ectopic pregnancy as the method of choice in hemodynamically unstable patients with heterotopic pregnancy and as an option in hemodynamically stable patients with heterotopic pregnancy. C 6. Specific circumstances Patients with molar pregnancy: Manage patients with ectopic pregnancy suspected to be molar in nature as any other case of ectopic pregnancy. E Send a tissue specimen to a center with appropriate expertise for pathological review, if there is a local tissue diagnosis of ectopic molar pregnancy. E 7. Patient education General counseling: inform patients with tubal pregnancy undergoing salpingotomy about the risk of persistent trophoblast with the need for serum -human chorionic gonadotrophin level follow-up and that there is a small risk that they may need further treatment in the form of systemic methotrexate or salpingectomy. E Show 3 more Fertility counseling: as per RCOG 2016 guidelines, counsel patients without a history of subfertility or tubal pathology that there is no difference in the rate of fertility, the risk of future tubal ectopic pregnancy or tubal patency rates between the different management methods. B Show 4 more Counseling on methotrexate treatment: As per ACOG 2018 guidelines: Consider counseling patients that methotrexate treatment of ectopic pregnancy does not have an adverse effect on subsequent fertility or on ovarian reserve. C Counsel patients treated with methotrexate about the following: https://web.pathway.md/diseases/recGWlD9mm9btrJfc 6/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway risk of ectopic pregnancy rupture avoidance of certain foods, supplements, or drugs that can decrease efficacy importance of not becoming pregnant again until resolution has been confirmed. B As per RCOG 2016 guidelines: Consider offering muscle relaxation training in patients undergoing treatment for ectopic pregnancy with methotrexate. C Advise patients treated with methotrexate to wait at least 3 months before trying to conceive again. B 8. Follow-up and surveillance Serial hCG monitoring: obtain serial monitoring of hCG levels after administration of methotrexate treatment until a nonpregnancy level (based upon the reference laboratory assay) is reached. B 9. Quality improvement Healthcare professional training: ensure that clinicians undertaking ultrasound for the diagnosis of ectopic pregnancy have received appropriate training. E Show 4 more Equipment and care availability: ensure that providers of early pregnancy care provide a 7- day early pregnancy assessment service with direct access for patients referred by general practitioners and accident and emergency departments. E Show 2 more Clinical findings Symptoms Past medical history Abdominal cramps Chlamydia trachomatis infection Abdominal pain Pelvic inflammatory disease LLQ pain Use of intrauterine device Missed period Social history Pelvic pain RLQ pain Tobacco use Suprapubic pain Abdominal exam Vaginal bleeding Abdominal tenderness Past surgical history Cullen's sign Tubal ligation Grey Turner's sign Tubal surgery Peritoneal findings Rebound tenderness Vital signs https://web.pathway.md/diseases/recGWlD9mm9btrJfc 7/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway Signs of shock Lab findings Gynecologic exam urine pregnancy test Adnexal mass Adnexal tenderness Cervical motion tenderness Imaging findings Absence of intrauterine pregnancy Adnexal mass in the absence of an intrauterine pregnancy Likelihood Ratios Pertinent positives The following findings increase the probability of ectopic pregnancy in adults. 5 6 Finding LR+ Value Presence of adnexal mass in the absence of an intrauterine pregnancy 111 (12-1028) Presence of cervical motion tenderness 4.9 (1.7-14) Presence of peritoneal findings 4.2-4.5 Presence of adnexal mass 2.4 (1.6-3.7) Show 1 more Pertinent negatives The following findings decrease the probability of ectopic pregnancy in adults. 5 6 Finding LR- Value Absence of adnexal mass in the absence of an intrauterine pregnancy 0.12 (0.03-0.55) Absence of adnexal tenderness 0.57 (0.48-0.67) Absence of cervical motion tenderness 0.62 (0.47-0.83) Absence of peritoneal findings 0.78-0.81 Show 1 more References 1. Committee on Practice Bulletins Gynecology. ACOG Practice Bulletin No. 191 Tubal Ectopic Pregnancy. Obstet Gynecol. 2018 Feb;131 2):e65-e77. Open 2. https://obgyn.onlinelibrary.wiley.com/doi/./-. Diagnosis and Management of Ectopic Pregnancy: Green-top Guideline No. 21. BJOG. 2016 Dec;123 13):e15-e55. Open 3. Leslie Po, Jacqueline Thomas, Kelsey Mills et al. Guideline No. 414 Management of Pregnancy of Unknown Location and Tubal and Nontubal Ectopic Pregnancies. J Obstet Gynaecol Can. 2021 https://web.pathway.md/diseases/recGWlD9mm9btrJfc 8/9 6/29/23, 4:15 AM Ectopic pregnancy Pathway May;43 5 614 630.e1. Open 4. American College of Obstetricians and Gynecologists. Practice Bulletin No. 181 Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017 Aug;130 2):e57-e70. Open 5. No authors listed. Management of Gestational Trophoblastic Disease: Green-top Guideline No. 38 June 2020. BJOG. 2021 Feb;128 3):e1-e27. Open 6. Simel D, Rennie D. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. Mayo Clin Proc. 2009 Nov; 84 11 1045. Open 7. Crochet JR, Bastian LA, Chireau MV. Does this woman have an ectopic pregnancy? the rational clinical examination systematic review. JAMA. 2013 Apr 24;309 16 1722 9. Open https://web.pathway.md/diseases/recGWlD9mm9btrJfc 9/9