Inflammatory Bowel Disease Medication in Men Not Linked to Adverse Pregnancy Outcomes

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Researchers examined reproductive outcomes among men taking inflammatory bowel disease medication.

Biologic, thiopurine, or methotrexate use among men with inflammatory bowel disease (IBD) is not associated with impairment in fertility or increased odds of adverse pregnancy outcomes, according to a study in Clinical Gastroenterology and Hepatology.

Researchers conducted a systematic review and meta-analysis to evaluate the association of paternal exposure to biologics, thiopurines, and methotrexate with semen parameters and adverse pregnancy outcomes.

Researchers searched for relevant studies in the Medline (PubMed), EMBASE, Scopus, and Web of Science databases from inception to April 2022. Of 29 studies identified, researchers included 26 (10 studies regarding sperm parameters [n=268] and 16 studies regarding adverse pregnancy outcomes [n=>25,000]).

Sperm parameters were compared in men with IBD who were exposed to biologics (5 studies), thiopurines (3 studies), and methotrexate (2 studies) vs those with no exposure.

Compared with biologic nonexposure in men with IBD, biologic use was not associated with a change in sperm count (standardized mean difference [SMD], 0.14; 95% CI, -0.02 to 0.30; I2=0%), sperm motility (SMD, 0.47; 95% CI, -0.02 to 0.95; I2=85%), or change in abnormal sperm morphology (SMD, 0.42; 95% CI, -0.01 to 0.86; I2=81%).

Thiopurine use compared with thiopurine nonexposure in men with IBD was associated with an increased sperm count (SMD, 0.53; 95% CI, 0.40 to 0.66; I2=0%), but it was not associated with sperm motility change (SMD, 0.25; 95% CI, -0.03 to 0.53; I2=60%) or change in abnormal sperm morphology (SMD, 0.30; 95% CI, -0.29 to 0.88; I2=97%).

Methotrexate use compared with methotrexate nonexposure in men with IBD was not associated with change in sperm count (SMD, 0.16; 95% CI, -0.09 to 0.41; I2=0%) or sperm motility (SMD, 0.14; 95% CI, -0.11 to 0.39; I2=0%).

The pooled prevalence of all adverse pregnancy outcomes (composite of early pregnancy loss [EPL], preterm birth, and congenital malformations) was 5% (95% CI, 2%-7%; I2=82%) with paternal biologic exposure. Among thiopurine users, the pooled prevalence of all adverse pregnancy outcomes was 6% (95% CI, 4%-7%; I2=53%), and the pooled prevalence of all adverse pregnancy outcomes for methotrexate users was 6% (95% CI, 0%-11%; I2=0%). For men without biologic, thiopurine, or methotrexate exposure, the pooled prevalence of all adverse pregnancy outcomes was 5% (95% CI, 4%-6%; I2=100%).

Paternal use of biologics was not associated with increased odds of early pregnancy loss (odds ratio [OR], 1.26; 95% CI, 0.61-2.61; I2=0%), preterm birth (OR, 1.10; 95% CI, 0.96-1.26; I2=0%), or congenital malformations (OR, 1.03; 95% CI, 0.89-1.19; I2=0%) compared with no biologic use.

Paternal thiopurine use was not associated with increased odds of early pregnancy loss (OR, 1.31; 95% CI, 0.89-1.94; I2=19%), preterm birth (OR, 1.05; 95% CI, 0.97-1.14; I2=0%), or congenital malformations (OR, 1.06; 95% CI, 0.94-1.20; I2=0%).

Paternal methotrexate use was not associated with preterm birth (OR, 1.06; 95% CI, 0.85-1.32; I2=0%) or congenital malformations (OR, 1.03; 95% CI, 0.82-1.29; I2=0%) compared with no methotrexate exposure.

Study limitations include the use of observational studies in the meta-analysis. Researchers were unable to conduct further sensitivity analyses to adjust for potential confounders, such as paternal disease activity and maternal age. Also, the results primarily reflect the association of anti-tumor necrosis factor agents.

“Taken together, our data support the safety of continuing biologics, thiopurines, or methotrexate across the reproductive spectrum from preconception (semen health/male fertility) to the postconception (pregnancy and fetal outcomes) period in male patients with IBD wishing to conceive,” the study authors wrote.

Reference

Gubatan J, Barber GE, Nielsen OH, et al. Paternal medications in inflammatory bowel disease and male fertility and reproductive outcomes: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. Published online July 19, 2022. doi:10.1016/j.cgh.2022.07.008