Effectiveness of different methods of feticide: systematic review and meta-analysis

To determine the efficacy and safety of different pharmacological and non-pharmacological methods of feticide to induce fetal asystole prior to termination of pregnancy (TOP).

MEDLINE, EMBASE, CINAHL, SCOPUS, PubMed and Cochrane Library databases were searched electronically from January 1991 to June 2025. Observational and randomized studies of feticides using pharmacological or non-pharmacological methods prior to TOP in the second or third trimester were included. The primary outcome was failure to achieve fetal asystole prior to TOP. Secondary outcomes included the total dose of feticidal agent, maternal complications and influence of feticide method on feasibility and quality of postmortem evaluation. Quality assessment of the included studies was performed using the Risk Of Bias In Non-randomized Studies of Interventions tool, Revised Cochrane Risk-of-Bias-2 tool and National Institutes of Health Quality Assessment Tools. A meta-analysis of the proportions of failed procedures was conducted using random-effects models.

Twenty-five studies with a total of 10 683 cases were included in the systematic review. Pooled proportions of failed procedures were 0.4% (95% CI, 0.1-2.4%) (I² = 0%) for intracardiac potassium chloride (KCl), 3.2% (95% CI, 1.2-8.2%) (I² = 0%) for intrafunic KCl, 4.8% (95% CI, 3.9-5.9%) (I² = 19.0%) for intrafetal digoxin and 10.6% (95% CI, 6.4-17.1%) (I² = 0%) for intra-amniotic digoxin. A range of doses were reported for KCl, lidocaine and digoxin by all routes of injection. There were four cases of postprocedure chorioamnionitis across all studies, but no other significant adverse events related directly to feticidal procedures. There was limited assessment of the impact of feticidal agent on postmortem examinations, but fetal intravascular lidocaine and KCl were associated consistently with cell lysis.

Feticide is an important procedure to induce asystole prior to TOP. Point estimates from the meta-analysis indicate that the most effective feticidal method is intracardiac KCl. Effectiveness should be considered alongside safety and feasibility when deciding on appropriate methods for different settings. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.