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Date of issue: September 2015
Version: 2

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.


Methotrexate is a folic acid antagonist used in the treatment of a number of neoplastic conditions, rheumatoid arthritis and severe psoriasis.

Concerns often exist, particularly with antimetabolite medications such as methotrexate, that paternal exposure around the time of conception may induce genotoxic effects in sperm DNA such as de novo point mutations or chromosomal rearrangements that may lead to fetal malformation and/or genetic conditions.

The available data concerning paternal periconceptual methotrexate exposure are limited and consist mainly of case reports/series and two cohort studies detailing the outcomes of less than 250 exposed pregnancies. These data do not identify any increased risks of spontaneous abortion, congenital malformation, intrauterine death, preterm delivery or growth restriction following paternal methotrexate use. No studies or case reports concerning neonatal problems, cancer risk or neurodevelopmental effects of periconceptual paternal methotrexate exposure have been located.

There is insufficient evidence to state that paternal exposure to methotrexate around the time of conception is without risk for any of the above outcomes. Guidelines from the various manufacturers of methotrexate vary with respect to the recommended interval between medication discontinuation and attempting conception. Due to the lack of any solid evidence base it is generally advised that delaying conception for two sperm cycles (~six months) from medication discontinuation should be sufficient to allow regeneration of sperm in an environment free from exposure.

For pregnancies fathered within six months of last medication use, detailed ultrasound scans are recommended. Paternal methotrexate exposure would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from or to be sure you are using the most up-to-date version.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from or to ensure you are using the most up-to-date version.