Fetal methotrexate and misoprostol exposure: the past revisited
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Updated: Sep 29, 2026

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
Marsha Wheeler1, Patrick O'Meara, Michelle Stanford
1Denver Health Medical Center, Department of Obstetrics and Gynecology, Department of Pediatrics, Denver, Colorado 80204, USA. Mwheeler@dhha.org
Background:
Fetal aminopterin/methotrexate syndrome was described nearly 50 years ago when these agents were first used as abortifacients. Physicians essentially stopped using these agents when the associated anomalies were recognized. Over the last several years the use of methotrexate with or without misoprostol for management of ectopic pregnancy and medical terminations of pregnancy has increased.
Methods:
A 23-year-old female sought a termination at eight weeks gestation. She was given methotrexate followed by misoprostol.
Results:
The medical termination was unsuccessful. The patient elected to continue the pregnancy secondary to financial considerations. She presented at 39 weeks without intervening prenatal care. She was diagnosed with severe preeclampsia. At delivery the infant was hypotonic and growth restricted with multiple anomalies.
Conclusions:
Physicians are increasingly using methotrexate with or without misoprostol for treatment of ectopic pregnancies and medical terminations. Clinicians need to be aware of the characteristic teratologic effects of these two agents.