[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Embryology](https://durgical.com/en/embryology/) › [Teratology and prenatal diagnosis](https://durgical.com/en/embryology/#a-teratology) › Methotrexate and misoprostol [Embryology](https://durgical.com/en/embryology/) · [Teratology and prenatal diagnosis](https://durgical.com/en/embryology/#a-teratology) # 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)](https://durgical.com/en/anatomy/facial-nerve/) · [Abducens nerve (VI)](https://durgical.com/en/anatomy/abducens-nerve/) · [Radius](https://durgical.com/en/anatomy/radius/) ## Key points - Methotrexate: folate antagonist; craniosynostosis or poor skull ossification, limb defects and heart defects. - The risk is best documented with the regimens used for ectopic pregnancy or termination rather than rheumatological ones. - Misoprostol: uterine contractions reduce fetal blood flow and cause vascular disruption. - Möbius sequence (cranial nerve VI and VII palsy), terminal transverse limb defects, clubfoot and arthrogryposis. - Both carry the most risk with first-trimester exposure. ## 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. ## Memory aid Methotrexate 'steals folate' from the skull; misoprostol 'squeezes' the uterus and starves the face and hands of blood. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/embryology/methotrexate-and-misoprostol/) ## See it in 3D The structures of Durgical's 3D anatomy where it is found. - [Facial nerve (VII)](https://durgical.com/en/anatomy/facial-nerve/) - [Abducens nerve (VI)](https://durgical.com/en/anatomy/abducens-nerve/) - [Radius](https://durgical.com/en/anatomy/radius/) ## Related - [Limb defects: amelia, meromelia, polydactyly and syndactyly](https://durgical.com/en/embryology/limb-defects-amelia-meromelia-polydactyly-and-syndactyly/) - [Craniosynostosis](https://durgical.com/en/embryology/craniosynostosis/) - [Clubfoot (talipes equinovarus)](https://durgical.com/en/embryology/clubfoot/) - [Folic acid and neural tube defect prevention](https://durgical.com/en/embryology/folic-acid-and-neural-tube-defect-prevention/) - [Malformation, disruption, deformation, sequence, syndrome, association](https://durgical.com/en/embryology/malformation-disruption-deformation-sequence-syndrome-association/) - [Neural tube defects: anencephaly, spina bifida and encephalocele](https://durgical.com/en/embryology/neural-tube-defects-anencephaly-spina-bifida-and-encephalocele/) - [Congenital hydrocephalus: aqueductal stenosis](https://durgical.com/en/embryology/congenital-hydrocephalus-aqueductal-stenosis/) ## Related conditions - [Ectopic pregnancy](https://durgical.com/en/conditions/ectopic-pregnancy/) - [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/) - [Psoriasis](https://durgical.com/en/conditions/psoriasis/) - [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/) - [Clubfoot (talipes equinovarus)](https://durgical.com/en/conditions/clubfoot/) - [Miscarriage (early pregnancy loss)](https://durgical.com/en/conditions/miscarriage/) ## In Pharmacology - [Methotrexate](https://durgical.com/en/pharmacology/methotrexate/) - [Misoprostol](https://durgical.com/en/pharmacology/misoprostol/) [← All of embryology](https://durgical.com/en/embryology/) 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](https://pmc.ncbi.nlm.nih.gov/articles/PMC10030667/) (RMD Open (PubMed Central), 2023); [Misoprostol](https://www.ncbi.nlm.nih.gov/books/NBK539873/) (StatPearls Publishing (NCBI Bookshelf), 2024). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/embryology/methotrexate-and-misoprostol/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/embryology/methotrexate-and-misoprostol/