Advanced Therapy and Non-Pelvic Surgery Do Not Affect Time to Pregnancy in Women With Inflammatory Bowel Disease

Abstract BACKGROUND Data on the impact of inflammatory bowel disease (IBD) and pelvic surgery on fertility are largely derived from retrospective studies. While advanced therapies (AT), including biologics and small molecules, are not thought to impact fertility, objective evidence is limited. In the prospective Women with Inflammatory Bowel Disease and Motherhood (WIsDoM) study, we assessed the effect of AT exposure within three months of conception and history of IBD surgery on time to pregnancy (TTP, months) in women with IBD. METHODS Women aged 18–45 with IBD planning pregnancy within 15 months were enrolled in WIsDoM (2021–present). Baseline surveys collected medical, treatment, surgical, reproductive, social, and family history, supplemented by medical record review. Monthly questionnaires captured pregnancy status, reproductive and sexual health, IBD activity, and treatment. Active disease was defined by patient-reported IBD symptoms, active perianal disease, and/or interim treatment escalation, corticosteroid use, IBD-related surgery, or hospitalization. Primary outcomes were TTP in women exposed vs unexposed to AT within three months of conception and in those with prior IBD-related surgery. Secondary outcome was TTP in women with active disease within three months of conception. Descriptive statistics summarized the data using percentages and medians with interquartile ranges IQR. Associations were evaluated using univariate and Cox proportional hazards models adjusted for age, parity, pelvic surgery, and disease activity within three months of conception. RESULTS Of 444 women enrolled, 115 became pregnant (56.5% CD, 43.5% UC/IBD-U), median age 32.61 years 30.42, 34.53, 86 (74.7%) with AT exposure (Table 1). AT exposure within three months of conception was not associated with longer TTP (median months TTP AT exposed= 2 1, 4 vs unexposed= 2 1,5, p = 0.295). Survival analyses showed no significant difference between groups (log rank p = 0.23, Figure 1); results were consistent across AT classes (log rank p = 0.45). Neither AT exposure (HR 1.93, 95% CI 0.76-1.88, p = 0.446) nor active disease within three months of conception (HR 1.5, 95% CI 0.98-2.3, p = 0.06) was independently associated with increased TTP, though active disease trended toward significance. History of any IBD surgery was linked to increased TTP (HR 0.47, 95% CI 0.29-0.74, p = 0.002), driven by pelvic surgical history (median months TTP pelvic surgery=6 2, 13.75 vs no pelvic surgery=2 1, 4, p = 0.03). In CD patients, history of non-pelvic IBD surgery was not associated with increased TTP (p = 0.20). CONCLUSION This is the first prospective study showing that preconception AT exposure does not affect TTP in women with IBD and reaffirms that pelvic IBD surgery impairs fertility. Continuation of AT before conception is safe and can improve fertility by maintaining remission.