A systematic review of the effectiveness, safety, and acceptability of medical management of intrauterine fetal death at 14-28 weeks of gestation

Background: Optimal dose, interval, and administration route of misoprostol with added benefit of mifepristone for management of second trimester intrauterine fetal death (IUFD) are not established.

Objectives: To assess effectiveness, safety, and acceptability of medical management of second trimester IUFD.

Search strategy: Research databases from January 2006 to October 2018.

Selection criteria: Randomized controlled trials with IUFD cases at 14-28 weeks of gestation.

Data collection and analysis: We screened and extracted data, assessed risk of bias, conducted analyses, and assessed overall certainty of the evidence.

Main results: Sixteen trials from 1695 citations. When misoprostol is used alone, 400 μg is more effective than 200 μg (RR 0.78; 95% CI, 0.66-0.92, moderate certainty evidence); the sublingual route is more effective than the oral route (RR 0.88; 95% CI, 0.70-1.11, low certainty evidence). There may be little to no difference between the sublingual and vaginal route (RR 0.93; 95% CI, 0.85-1.03, low certainty evidence). Certainty of evidence related to mifepristone-misoprostol regimens and safety and acceptability is very low.

Conclusions: Misoprostol 400 μg every 4 hours, sublingually or vaginally, may be effective. We cannot draw conclusions about safety and acceptability, or about the added benefits of mifepristone.