An initial active management strategy, rather than an expectant management strategy, for a nonviable pregnancy of unknown location resolves the condition more rapidly than treating symptoms as they arise, according to a new multicenter NIH study. However, the risks of adverse events (vaginal bleeding or fallopian tube rupture if ectopic pregnancy) were found to be similar in both the groups

The ACT-or-NOT randomized clinical trial published August 3, 2021 in the Journal of the American Medical Association evaluated 255 women diagnosed with persisting pregnancy of unknown location. These women were hemodynamically stable and were randomised to expectant management (close observation with no treatment unless symptoms develop), active management with uterine evacuation followed by methotrexate if needed, or active management with two doses of empirical methotrexate alone. The primary outcome was successful resolution of the pregnancy without change from initial strategy. 

Women who received methotrexate, with or without uterine evacuation (active management) recovered faster with successful resolution of pregnancy without requiring any additional treatment vs women randomized to receive expectant management; 51.5% vs 36.0%, respectively.

Women randomized to receive only two doses of methotrexate had better chances of achieving the primary outcome of successful pregnancy resolution of the pregnancy without additional treatment when compared to women actively managed with uterine evacuation; 54.9% vs 48.3%; respectively suggesting that empirical methotrexate was comparable in efficacy to uterine evacuation.

The study authors, however, emphasize that before going ahead with the treatment plan, it is first crucial to ensure that the pregnancy of unknown location is nonviable. To draw attention to this fact, they have narrated the case of a woman assigned to receive expectant management, who was later found to have a growing pregnancy in the uterus despite low hCG levels initially. She had conceived after infertility treatment and delivered at term without any complications.

Pregnancy of unknown location is the term used to describe a situation in which a positive pregnancy test occurs, but a transvaginal ultrasound (TVUS) does not show intrauterine or ectopic gestation, nor does it show the retention of conception products (Clinics (Sao Paulo). 2019; 74: e1111). Ectopic pregnancy is a likely complication in such women with its attendant morbidity and mortality. Hence, time is of the essence and successful resolution of pregnancy is of paramount importance. These patients need regular follow ups with serial serum hCG measurement. Consistently low hCG levels are an indication for treatment.

(Source: NIH News release & JAMA. 2021;326(5):390-400, August 3, 2021)

Dr Veena Aggarwal

Consultant Womens’ Health

CMD and Editor-in-Chief, IJCP Group & Medtalks

Trustee, Dr KK’s Heart Care Foundation of India