P0569 - Paternal Biologic and Thiopurine Exposure in Inflammatory Bowel Disease and Association With Adverse Pregnancy Outcomes and Semen Parameters: A Systematic Review and Meta-Analysis

John Gubatan, MD¹, Grant Barber, MD², Ole Haagen Nielsen, MD, DMSc³, Cartsen Juhl, PT, MPH, PhD⁴, Cynthia Maxwell, MD⁵, Michael Eisenberg, MD², Sarah Streett, MD^2
1Stanford University, Stanford, CA; ²Stanford University School of Medicine, Stanford, CA; ³University of Copenhagen, Herlev, Hovedstaden, Denmark; ⁴University of Southern Denmark, Odense, Syddanmark, Denmark; ⁵University of Toronto, Toronto, ON, Canada

Introduction: Studies evaluating reproductive outcomes in males with inflammatory bowel disease (IBD) are limited. We explored the association between biologic therapy and thiopurines in male patients with IBD and adverse pregnancy outcomes and semen parameters.

Methods: We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to March 2021 for studies reporting adverse pregnancy outcomes and semen parameters in male IBD patients exposed to biologics. We also compared adverse pregnancy outcomes and semen parameters in biologic versus thiopurine users. Prevalence, standardized mean difference (SMD), and odds ratios (OR) of outcomes were pooled and analysed using a random effects model.

Results: Eight studies reporting adverse pregnancy outcomes (735 IBD patients) and four studies with semen parameters (68 patients) with biologics (5 anti-TNF, 2 vedolizumab, 1 mixed exposure) were included. In patients exposed to biologics, the prevalence of adverse pregnancy outcomes was 4% for early pregnancy loss, 5% for preterm birth and 3% for congenital malformations. Biologic use did not result in impaired sperm count (SMD 0.21, I2=33.0%, P=0.15), morphology (SMD 0.62, I2=83.0%, P=0.08), motility (SMD 0.62, I2=84.0%, P=0.09), or increased early pregnancy loss (OR 1.26, 95% 0.61-2.61, I2=0%), preterm birth (OR 1.10, 95% 0.96-1.26, I2=0%), or congenital malformations (OR 1.03, 95% 0.89-1.19, I2=0%). Five studies reporting adverse pregnancy outcomes (905 IBD patients) and three studies with semen parameters (95 male patients) with thiopurines were included. Thiopurine use was associated with increased sperm count (SMD 0.53, I2=0.0%, P< 0.001) but was not associated with impaired sperm motility (SMD 0.25, I2=83.0%, P=0.08) or sperm morphology (SMD 0.30, I2=97%, P=0.33). Thiopurine use in male patients with IBD was not associated with increased risk of early pregnancy loss (OR 1.13, 95% 0.89-1.94, I2=19%), preterm birth (OR 1.05, 95% 0.94-1.18, I2=0%), or congenital malformations (OR 1.07, 95% 0.93-1.23, I2=7%). Semen parameters and risk of adverse pregnancy outcomes did not differ between biologic versus thiopurine users.

Discussion: Biologic therapy (mostly anti-TNF) or thiopurine use in male patients with IBD is not associated with more prevalent adverse pregnancy outcomes or impairment in semen parameters. The safety profile of biologics appears to be comparable to thiopurines based on available evidence. Larger studies with vedolizumab and ustekinumab are needed.



Disclosures:


John Gubatan, MD¹, Grant Barber, MD², Ole Haagen Nielsen, MD, DMSc³, Cartsen Juhl, PT, MPH, PhD⁴, Cynthia Maxwell, MD⁵, Michael Eisenberg, MD², Sarah Streett, MD². P0569 - Paternal Biologic and Thiopurine Exposure in Inflammatory Bowel Disease and Association With Adverse Pregnancy Outcomes and Semen Parameters: A Systematic Review and Meta-Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.