TY - JOUR
T1 - The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome after Paternal Exposure
AU - Grosen, Anne
AU - Kelsen, Jens
AU - Hvas, Christian Lodberg
AU - Bellaguarda, Emanuelle
AU - Hanauer, Stephen B.
N1 - Publisher Copyright:
Copyright © 2017 Crohn's & Colitis Foundation of America, Inc.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background: Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. Methods: A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. Results: In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. Conclusions: This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.
AB - Background: Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. Methods: A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. Results: In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. Conclusions: This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.
KW - IBD
KW - male fertility
KW - methotrexate
KW - paternal exposure
KW - pregnancy outcome
UR - http://www.scopus.com/inward/record.url?scp=85016185102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016185102&partnerID=8YFLogxK
U2 - 10.1097/MIB.0000000000001064
DO - 10.1097/MIB.0000000000001064
M3 - Review article
C2 - 28267049
AN - SCOPUS:85016185102
SN - 1078-0998
VL - 23
SP - 561
EP - 569
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 4
ER -