Clin Gastroenterol Hepatol. 2023 Aug;21(9):2222-2238.doi: 10.1016/j.cgh.2022.07.008. Epub 2022 Jul 20.

John Gubatan ¹, Grant E Barber ², Ole Haagen Nielsen ³, Carsten Bogh Juhl ⁴, Cynthia Maxwell ⁵, Michael L Eisenberg ⁶, Sarah E Streett ²

Author information

¹Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California. Electronic address: jgubatan@stanford.edu.

²Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.

³Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.

⁴Department of Sports Science and Biomechanics, University of Southern Denmark, Odense, Denmark; Department of Physiotherapy and Occupational Therapy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

⁵Department of Obstetrics & Gynaecology, Mount Sinai Hospital, Toronto, Ontario, Canada.

⁶Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California; Department of Urology, Stanford University School of Medicine, Stanford, California.

Abstract

Background & aims: Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]).

Methods: We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model.

Results: Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I² = 0%; P = .12), PB (OR, 1.10; I² = 0%; P = .17), or CM (OR, 1.03; I² = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I² = 19%; P = .17), PB (OR, 1.05; I² = 0%; P = .20), or CM (OR, 1.07; I² = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I² = 0%; P = .62) or CM (OR, 1.03; I² = 0%; P = .81).

Conclusions: Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.