Embryology · Teratology and prenatal diagnosis
Methotrexate and misoprostol !
- Teratogen
Two medicines used to end pregnancies or treat other diseases; if the pregnancy continues, they can leave skull, face and limb defects.
Updated 2026-11-01
See it in 3D: Facial nerve (VII) · Abducens nerve (VI) · Radius
What it is
Methotrexate is a folate antagonist that slows DNA synthesis; it is used for ectopic pregnancy, termination of pregnancy, rheumatic disease and cancer. Misoprostol is a prostaglandin E1 analogue that contracts the uterus. When a pregnancy continues after exposure, defects can follow: methotrexate affects the skull, limbs and heart; misoprostol causes vascular disruptions such as Möbius sequence.
Key facts
- A misdiagnosed ectopic pregnancy treated with methotrexate can result in an exposed intrauterine pregnancy.
- Methotrexate also raises the risk of miscarriage.
- Hydrocephalus and posterior encephalocele have been described with misoprostol.
- Misoprostol is also used to prevent anti-inflammatory–induced ulcers, but not for that purpose in pregnancy.
- Misoprostol defects are disruptions: they damage structures that were forming normally.
Critical period and mechanism
- Critical period: first trimester, during organogenesis.
- Methotrexate: inhibits folate metabolism, slowing DNA synthesis and embryonic tissue proliferation.
- Misoprostol: contractions cut the embryo's blood supply; ischaemia damages the brainstem (nuclei of nerves VI and VII) and the growing limbs.
- The length of exposure influences the type of defect.
Prevention
- Confirming the location of the pregnancy before treating an ectopic.
- For women on methotrexate for chronic disease, a contraception and preconception plan with the treating professional.
- Medicines in pregnancy are decided with the treating professional.
What it does to the embryo and fetus
- Methotrexate: growth restriction, poorly ossified skull or craniosynostosis, unusual facial features, limb defects, heart defects.
- Misoprostol: expressionless face and eyes that cannot look outward (Möbius).
- Misoprostol: transverse amputations of digits or limbs, syndactyly, clubfoot.
- Miscarriage, preterm birth.
Test yourself
Think of the answer, then tap the question to see it.
What is Möbius sequence, and which drug is it linked to?
Congenital palsy of the abducens and facial nerves, often with limb defects; it is linked to first-trimester misoprostol.
Why does misoprostol cause disruptions rather than classic malformations?
Uterine contractions reduce fetal blood flow, and ischaemia destroys tissues that were forming normally.
What is methotrexate's teratogenic mechanism?
It is a folate antagonist that slows DNA synthesis and the proliferation of embryonic tissues.
See it in 3D
The structures of Durgical's 3D anatomy where it is found.
Related
- Limb defects: amelia, meromelia, polydactyly and syndactyly
- Craniosynostosis
- Clubfoot (talipes equinovarus)
- Folic acid and neural tube defect prevention
- Malformation, disruption, deformation, sequence, syndrome, association
- Neural tube defects: anencephaly, spina bifida and encephalocele
- Congenital hydrocephalus: aqueductal stenosis
Related conditions
- Ectopic pregnancy
- Rheumatoid arthritis
- Psoriasis
- Peptic ulcer disease
- Clubfoot (talipes equinovarus)
- Miscarriage (early pregnancy loss)
In Pharmacology
Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.
Sources: Methotrexate in pregnancy: still many unanswered questions (RMD Open (PubMed Central), 2023); Misoprostol (StatPearls Publishing (NCBI Bookshelf), 2024).
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Representative model, for educational purposes only.