Pregnancy of Unknown Location (PUL) is the classification used to describe clinical scenarios in which it is unclear where a pregnancy is occurring.  Early pregnancies are often managed by serial bHCG values. A bhCG increase of less than 53% or a decrease of less than 12%–32% (depending on initial bhCG level) in 2 days is concerning for ectopic pregnancy (EP).  Using transvaginal ultrasound, a gestational sac is expected to be seen at five weeks and/or when the bHCG rises above the discriminatory zone (~1500-2000 IU/ml).  This can vary from facility to facility and is important to know within your respective center what is considered the discriminatory zone. Clinical practice of using methotrexate for “presumptive ectopic pregnancies” has come under increased scrutiny due in part to litigation involving incidental use of methotrexate for an intrauterine gestation.

PUL is a descriptive term for a woman with a positive pregnancy test but unable to identify a clear intrauterine pregnancy (IUP) or ectopic pregnancy (EP) on transvaginal ultrasound.  Clinically, these patients remain asymptomatic and are reliable for follow up. It is recommended to repeat a quantitative bHCG to assess for a particular trend. In cases of spontaneous resolution of bHCG; this is termed “spontaneous resolving PUL”. Within the US it is generally accepted that the pregnancy was intrauterine although in Europe that is not the case.  In cases where the bHCG increases and an eventual diagnosis is able to be made on ultrasound between EP and IUP then management occurs accordingly.  The challenge occurs in cases of abnormally rising bHCG and persistent inability to identify the pregnancy by US, or “persisting PUL”. Again, abnormal rise of bHCG is generally defined as < 53% increase in 2 days.  Many groups advocate the use of uterine sampling often by dilation and curettage to assess for abnormal intrauterine pregnancy. If an intrauterine pregnancy is not identified by the pathology specimen then methotrexate is “given in the recovery room”.

Approximately 30% of PUL will have an ongoing IUP, the remainder will be eventually diagnosed with an abnormal pregnancy either intrauterine or ectopic. The ability to differentiate between an abnormal intrauterine and abnormal extrauterine may require a D and C.  The drawbacks of this approach include: need for a surgicenter, anesthesia, time in the physician and patient’s schedule. Recently, Brady et al demonstrated the use of a Karman suction cannula to obtain a specimen in the office for clinical management of PUL.  Of note, their study was limited to IVF pregnancies where accurate dating exists.  45 patients were included in the study, following the suction cannula procedure 31 (68.9%) were diagnosed with abnormal intrauterine pregnancy and 14 (31.1%) were diagnosed as presumed EP and methotrexate was provided.  The authors noted that a decline in serum bHCG was more predictive than the pathologic specimen results.

The management of PUL has evolved and we hope this background will further enhance the understanding of our approach to early pregnancy. As is clear throughout the infertility process, but particularly with early pregnancy, we strive to clearly communicate and work with our obstetrical partners in providing the best care for our patients.

Suggested readings

1.     Barnhart et al.   Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. 2010. 2011;95:857–66.

2.     Barnhart et al. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. 2004;104:50–5.

3.     Kadar et al. The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study. 1994;61:1016–20.

4.     Kirk et al. Pregnancies of unknown location. Best Pract Res Clin Obstet Gynaecol 2009;23:493–9.

5.     Brady et al. Pregnancies of unknown location after in vitro fertilization: minimally invasive management with Karman cannula aspiration2014;101:420–6.