Persistent Pregnancy of Unknown Location: Landmark Evidence to Guide Management

Andrew M. Kaunitz, MD


September 20, 2021

This transcript has been edited for clarity.

Today I'd like to discuss treatment of persistent pregnancies of unknown location (PUL). When women present with a positive pregnancy test, ultrasound may not identify the site of the gestation. In one third of PULs, serial serum hCG levels clarify that although the pregnancy is not viable, the rate of hCG decline does not indicate a resolving pregnancy loss. Such pregnancies are considered persistent PULs. What constitutes optimum management in this clinical setting has been unclear.

Researchers conducted an NIH-funded trial at 12 US academic centers comparing uterine aspiration followed by methotrexate (if indicated), primary methotrexate treatment, and expectant management. This study was recently published in JAMA.

Therapy was considered successful when the initial treatment, whether active (meaning uterine aspiration or primary methotrexate) or expectant, resulted in pregnancy resolution without deviating from the initial approach. Among women randomized to active treatment, almost half declined the therapy they were assigned to. Among those randomized to expectant management, approximately one quarter declined. Ultimately, 62 patients underwent uterine aspiration, 84 received primary methotrexate, and 107 received expectant management.

After analysis based on treatment as received, active treatments were almost 95% successful, whereas expectant management was only 56% successful. Success rates were similar for uterine aspiration and primary methotrexate.

With each of the treatments, the most common adverse event was vaginal bleeding, which occurred in approximately half of the women. Five women were found to have a ruptured ectopic pregnancy. All of these participants were successfully treated laparoscopically. Among women receiving methotrexate, one was hospitalized for pain and one for stomatitis.

One participant who had conceived with clomiphene citrate and intrauterine insemination was randomized to expectant management and subsequently noted to have a viable intrauterine pregnancy, and ultimately had an uncomplicated term delivery. This pregnancy indicates that even the conservative criteria used in this trial to label pregnancies as persistent PULs did not eliminate the possibility of a viable pregnancy.

In terms of patient satisfaction, almost three quarters of participants rated their treatment as acceptable, regardless of treatment.

In summary, although participants preferred expectant management, this trial clarifies that active management with uterine aspiration or primary methotrexate represents the most effective treatment for women with persistent PUL. When we diagnose PUL, we should use the results of this landmark study to help our patients make sound therapeutic choices. Thanks for the honor of your time. I'm Andrew Kaunitz.

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