S765 Paternal Biologic and Thiopurine Exposure in Inflammatory Bowel Disease and Association With Adverse Pregnancy Outcomes and Semen Parameters: A Systematic Review and Meta-Analysis
Bibliographic record
Abstract
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. Conclusion: 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.Figure 1.: Baseline variables associated with (A) live birth, (B) pregnancy loss, (C) preterm birth and (D) low birth weight from multivariate logistic regression analysis. The following baseline variables were evaluated in the multivariate logistic regression analyses if they included ≥10% of the population and there were patients both with and without the pregnancy outcome in question: maternal age (≤35 years/>35 years); indication for CZP treatment (rheumatoid arthritis, axial spondyloarthritis, Crohn’s disease); concomitant medications (systemic corticosteroids, NSAIDs, methotrexate/leflunomide); and maternal infections. Only variables identified as being significantly associated with the pregnancy outcome of interest are shown (p<0.05 for entry into the multivariate model and p≥0.1 for elimination). [a] Includes spontaneous miscarriages, and elective and medically indicated abortions. CI: confidence interval; CZP: certolizumab pegol; NSAID: non-steroidal anti-inflammatory drug; OR: odds ratio.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.029 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.029 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".