Pregnancy of unknown location—meeting the challenge


Determining the location of very early pregnancies can be challenging.  A recent ACOG treatment bulletin reminded that “pregnancy of unknown location should not be considered a diagnosis, rather it should be treated as a transient state and efforts should be made to establish a definitive diagnosis when possible.”[1] That these pregnancies could be ectopic calls for a time-driven evaluation. In the new edition of Contraceptive Technology (in press), Maureen Baldwin and Alison Edelman write that serial measurements of hCG concentration can play a helpful role in determining a diagnosis and in guiding management.[2]

About half of women presenting with very early pregnancy of unknown location have an undesired pregnancy and it is acceptable to proceed with abortion (medical or surgical) prior to localization of the pregnancy in certain circum­stances. In stable patients with desired pregnancy, serial hCG should be ob­tained to determine if the pregnancy is abnormal prior to any intervention. A small proportion (estimated 2%) of these pregnancies of unknown location may be ectopic pregnancies, which are important to identify and monitor or treat.[3]

All patients with pregnancy of unknown location need follow-up to ensure resolution of the pregnancy, but the length of the follow-up may vary. First, write Baldwin and Edelman, determine whether the patient is stable and symptomatic (bleed­ing, pain, etc.). Determine if the pregnancy is desired or whether the pa­tient would like to proceed with an abortion.

Initial Evaluation of Pregnancy of Unknown Location

Symptomatic Patients. The following symptoms may require further evaluation or management: abdominal or pelvic pain, vaginal bleeding, and free fluid noted in the pelvis on ultrasound examination. Obtain a detailed medical and surgical history, including risk factors for ectopic pregnancy (assisted reproductive technologies, prior tubal occlusive sur­gery, intrauterine contraception, prior ectopic, history of pelvic infections, prior pelvic surgery, and smoking). Symptomatic patients can undergo initial triage evaluation in an outpatient clinic setting unless they demon­strate severe pain, unstable vital signs, ongoing heavy bleeding, or other symptoms concerning for ruptured ectopic pregnancy.

Asymptomatic Patients. Asymptomatic patients who have an unde­sired pregnancy can proceed with medical or surgical abortion regardless of pregnancy localization and without waiting. The probability of ectopic preg­nancy in this setting is estimated to be 0.4% if they are asymptomatic and have expected gestational dating based on menstrual age of less than 35 days.[4]

Asymptomatic patients who have a positive urine pregnancy test with a desired pregnancy, no risk factors for ectopic pregnancy, and normal exam findings can be scheduled for routine prenatal care. An ultrasound can be performed at the first prenatal visit to aid in accurate gestational dating as well as pregnancy localization. Waiting until after 6 weeks ges­tation to perform this visit is less likely to lead to additional testing or confusion and anxiety about the results. A clinical dilemma arises when a serum hCG level or an ultrasound is obtained in asymptomatic patient and is non-diagnostic, either for pregnancy viability or localization.

Uterine Aspiration for Pregnancy Localization. Uterine aspiration with serial hCG assessment can be used for pregnancy location and is par­ticularly helpful in the following scenarios:

  • A patient with undesired pregnancy who desires termination
  • A patient with a desired pregnancy and abnormal hCG rise (<40%), plateau, or decline

Gross pathologic or histologic examination of the uterine tissue should be performed either by the clinician and/or a pathologist. The sensitivity of visualization of chorionic villi is similar between clinicians and pa­thologists at around 60%.[5],[6],[7],[8] Since not seeing villi might result in an over-diagnosis of ectopic pregnancy, serial hCG should be obtained for correlation. Additionally, false-positive visualization of villi can occur re­sulting in over-reassurance.

Ongoing serum hCG monitoring should be performed after the uter­ine aspiration. A repeat serum hCG between the day of the procedure and 48 hours later, but as soon as 12 hours later, documenting decline of .50% demonstrates a completed pregnancy and suggests that the pregnancy was intrauterine. No further follow-up is necessary.[9],[10] If the serum hCG does not decline, either the uterine evacuation was not com­plete or the pregnancy may be ectopic. The next step in this scenario, advise Baldwin and Edelman, is to repeat an ultrasound.

Clinical steps for pregnancy of unknown location

  1. Perform urine pregnancy test.
  2. Document whether the patient plans to continue or terminate the pregnancy.
  3. Assess symptoms (bleeding, pain, etc.).
  4. Document the last menstrual period.
  5. Conduct pelvic exam with attention to adnexal exam and uterine size.
  6. Obtain a transvaginal ultrasound.
  7. Draw serum for hCG measurement if no visible intrauterine pregnancy.
  8. Determine Rh status (If bleeding/spotting, administer Rhogam if Rh negative and obtain CBC).


[1] American College of Obstetricians and Gynecologists. ACOG practice Bulletin no. 193. Obstet Gynecol 2018: Tubal ectopic pregnancy. Accessed Sept. 16, 2018 at

[2] Baldwin MK, Edelman AB. Pregnancy testing and assessment of early normal and abonormal pregnancy. In: Hatcher RA, Nelson AL, Trussell J, et al. Contraceptive technology, 21st edition. New York, NY: Ayer Company Publishers, in press.

[3] American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 94: medical management of ectopic pregnancy. Obstet Gynecol 2008;111:1479-85.

[4]  Li CL, Song LP, Tang SY, et al. Efficacy, safety, and acceptability of low-dose mifepristone and self-administered misoprostol for ultra-early medical abortion: a randomized controlled trial. Reprod Sci 2017;24:731-7.

[5] Edwards J, Carson SA. New technologies permit safe abortion at less than six weeks’ gestation and provide timely detection of ectopic gestation. Am J Obstet Gynecol 1997;176:1101-6.

[6] Lindahl B, Ahlgren M. Identification of chorion villi in abortion specimens. Obstet Gynecol 1986;67:79-81.

[7]Dean G. Accuracy of POC detection after early abortion with MVA vs EVA: a random­ized trial. The Forum; 2012 Oct 27, 2012; Denver, CO.

[8] Paul M, Lackie E, Mitchell C, Rogers A, Fox M. Is pathology examination useful after early surgical abortion? Obstet Gynecol 2002;99:567-71.

[9] Schaff EA, Fielding SL, Eisinger S, Stadalius L. Mifepristone and misoprostol for early abortion when no gestational sac is present. Contraception 2001;63:251-4.

[10] Pocius KD, Maurer R, Fortin J, Goldberg AB, Bartz D. Early serum human chorionic gonadotropin (hCG) trends after medication abortion. Contraception 2015;91:503-6.