| 1. |
- Abdalla, Maie, et al.
(författare)
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Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients
- 2020
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Ingår i: Digestive Diseases and Sciences. - : Springer-Verlag New York. - 0163-2116 .- 1573-2568. ; , s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.
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| 2. |
- Abdalla, Maie
(författare)
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Cancer and reconstructive surgery in Inflammatory bowel disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. According to the literature, some thirty percent of UC patients may require a subtotal colectomy and ileostomy due to failure of medical treatment, acute toxic colitis or dysplasia/cancer diagnosis. Some patients choose to get continence restored with either an ileorectal anastomosis (IRA) or an ileal pouch-anal anastomosis (IPAA). Worldwide most surgeons prefer an IPAA to an IRA, despite reports of pouchitis, impaired fertility and fecundity. Fear of recurring proctitis and fear of rectal cancer in the remaining rectum is contributing to the choice of an IPAA. Little is known regarding the outcomes of IRA compared with IPAA in UC patients. We aimed to investigate the anorectal function, quality of life (QoL), risk of failure and rectal cancer in patients with UC restored with IRA and IPAA respectively. Methods: Data about all Inflammatory bowel disease (IBD) patients was obtained from the Swedish National Patient Register (NPR) between 1964-2014 and in one study from the Linköping University Hospital medical records 2006-2012. Patients who developed cancer were identified from the Swedish National Cancer Register. We investigated the risk of cancer and inflammation, functional outcome and failure as well as the quality of life for IRA and IPAA patients. Investigation of risk for cancer in IRA and IPAA compared with the background population was performed using survival analytic techniques: uni-and multivariate regression, Kaplan Meier curves and standardized incidence ratio. Results: Twelve percent (7,889 /63,795) of UC patients required colectomy according to the NPR. The relative risk for rectal cancer among patients with an IRA was increased (SIR 8.7). However, the absolute risk was 1.8% after a mean follow up of 8.6 years and the cumulative risk 10- and 20-years after IRA was 1.6% and 5.6%, respectively. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio 6.12), and severe dysplasia or cancer of the colon prior to subtotal colectomy in patients with a diverted rectum in place (hazard ratio 3.67). Regarding IPAA, the relative risk to develop rectal cancer was (SIR 0.4) compared with the background population and the absolute risk was only 0.06% after a mean of 12.2 years of follow up. Among patients operated at the Linköping University Hospital: IRA patients reported better overall continence according to the Öresland score with in median3 (IQR 2–5) for IRA (n=38) and 10 (IQR 5–15) for IPAA (n=39, p<0.001). There were no major differences regarding the QoL. According to the NPR, after a median follow up of 12.4 years failure occurred in 265(32%) out of 1112 patients, of which 76 were secondarily reconstructed with an IPAA. Failure of the IPAA occurred in 103 (6%) patients with primary and in 6 (8%) patients after secondary IPAA (log-rank p=0.38). Conclusion: IRA is a safe restorative procedure for selected UC patients. Patients should be aware of the annual postoperative endoscopic evaluation with biopsies as well as the need to the use of local anti-inflammatory preparations. However, IRA should not be offered for UC patients with an associated primary sclerosing cholangitis diagnosis due to the increased risk to develop rectal cancer in their rectal mucosa. In such case, IPAA is probably the treatment of choice.
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| 3. |
- Abdalla, Maie, et al.
(författare)
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Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study
- 2017
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 15:7, s. 1055-1060
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND amp; AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy.METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis.RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67).CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.
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| 4. |
- Dimberg, Jan, et al.
(författare)
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Effects of diabetes type 2 and metformin treatment in Swedish patients with colorectal cancer
- 2022
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 28:19, s. 2148-2151
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients. The association between DM and the survival of patients with CRC is controversial. Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM. In our cohort, we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin. On the other hand, we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients. The dominance of the T bearing genotypes in patients with DM was statistically significant (P = 0.038), with an odds ratio of 1.66 (95% confidence interval: 1.03-2.69).
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| 5. |
- Dimberg, Jan, et al.
(författare)
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Emerging role and clinical implication of mRNA scavenger decapping enzyme in colorectal cancer
- 2023
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Ingår i: Pathology, Research and Practice. - : Elsevier. - 0344-0338 .- 1618-0631. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Turnover of RNA is a regulated process that in part controls gene expression. This process is partly controlled by the scavenger decapping enzyme (DcpS). This study aimed to investigate the expression of DcpS in colorectal cancer (CRC) tissue, to evaluate its prognostic significance in patients with CRC and to investigate potentially targeted genes by DcpS.METHODS: Immunohistochemical analysis was used to determine localization of DcpS in normal and CRC tissue, western blot analysis for quantification of protein expression and qPCR for mRNA expression in normal and CRC tissue and expression in cell lines after silencing using siRNA. Gene array analysis was used to study regulation of genes after silencing of DcpS. Proliferation was studied using BRDU.RESULTS: DcpS expression was localized to the epithelial cells of both control and cancer tissue. Tumor and paired control tissue samples from 100 patients who underwent surgical resection for primary colorectal adenocarcinomas were utilized. mRNA and protein of DcpS was significantly up-regulated in the patients with CRC and the mRNA level was higher in rectal cancer tissue compared to colon cancer tissue (p < 0.05). Lowest tertile levels of DcpS mRNA in cancer tissue was associated with a decreased cancer-specific survival rate with a hazard ratio (HR) of 4.7 (95% CI=1.02-12.3), independent of disease stage. The low level of DcpS mRNA was a predictor of poorer survival in patients with rectal and disseminated cancer and in patients receiving adjuvant treatment (p < 0.05). After silencing DcpS in Caco-2 cancer cells, altered expression of several genes associated with RNA, cell cycle regulation, alternative splicing and microRNA was observed and resulted in 23% increase in proliferation.CONCLUSIONS: These results indicate that DcpS has potential as a prognostic factor for CRC but further studies in a broader cohort are warranted to evaluate the significance of the findings in the clinic.
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| 6. |
- Dimberg, Jan, et al.
(författare)
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Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:9, s. 4933-4940
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.
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| 7. |
- Druvefors, Emma, 1985-, et al.
(författare)
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Female and Male Fertility after Colectomy and Reconstructive Surgery in Inflammatory Bowel Diesase : A National Cohort Study from Sweden.
- 2023
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Ingår i: Journal of Crohn's & Colitis. - 1873-9946 .- 1876-4479. ; 17:10, s. 1631-1638
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Colectomy and reconstruction in patients with inflammatory bowel disease (IBD) may adversely affect fertility, but few population-based studies are available.METHODS: Fertility was assessed in 2,989 women and 3,771 men with IBD and prior colectomy 1964-2014, identified from the Swedish National Patient Register, and 35,092 matched individuals.RESULTS: Reconstruction with ileoanal pouch anastomosis (IPAA) was as common as ileorectal anastomosis (IRA) in ulcerative colitis (UC) and IBD-unclassified (IBD-U) while rare in Crohn's disease (CD). Compared with the matched reference cohort, women with IBD had lower fertility overall after colectomy (HR 0.65, CI 0.61-0.69), with least impact leaving the rectum intact (HR 0.79, CI 0.70-0.90). Compared with colectomy only, fertility in female patients remained unaffected after IRA (HR 0.86, CI 0.63-1.17 for UC, 0.86, CI 0.68-1.08 for IBD-U and 1.07, CI 0.70-1.63 for CD), but was impaired after IPAA, especially in UC (HR 0.67CI 0.50-0.88), and after completion proctectomy (HR 0.65, CI 0.49-0.85 for UC, 0.68, CI 0.55-0.85 for IBD-U and 0.61, CI 0.38-0.96 for CD). In men, fertility was marginally reduced post colectomy (HR 0.89, CI 0.85-0.94), regardless of reconstruction.CONCLUSIONS: Fertility was reduced in women after colectomy for IBD. The least impact was seen when a deviated rectum was left intact. IRA was associated with no further reduction in fertility, whereas proctectomy and IPAA were associated with the strongest impairment. IRA therefore seems to be the preferred reconstruction to preserve fertility in selected female patients. Fertility in men was only moderately reduced after colectomy.
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| 8. |
- Druvefors, Emma, 1985-
(författare)
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Fertility in Inflammatory Bowel Disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel diseases (IBD) often present in adolescence or early adulthood and is thus frequently diagnosed in men and women in their reproductive age. Previous population-based studies of fertility in patients with IBD are scarce.From the Swedish National Patient Register (NPR) all patients diagnosed with IBD of fertile age between 1964–2014 were identified. Statistics Sweden identified a matched reference cohort (ratio 1:5) from the general population matched for sex, age and place of birth. Children born were identified through the Medical Birth Register and the Swedish Multigeneration Register. For subgroup analyses information about medication was collected through Medical Drug Register and information about socioeconomic status from Longitudinal Integrated Database for Health Insurance and Labour Market Studies. From the SWedish Inflammatory Bowel disease quality REGister (SWIBREG) a cohort of women with UC who underwent colectomy 2000–2020 was identified. Demographic data from SWIBREG and information from a study specific questionnaire regarding reproductive history and voluntary childlessness were analysed.From the NPR 27,331 women and 29,104 men with IBD were identified, corresponding to 272,793 matched individuals.The fertility rate in women with IBD was 1.52 (standard deviation [SD] 1.22) births per 1000 person-years, compared with 1.62 (SD 1.28) (p <0.001) in the matched reference cohort. Fertility was negatively affected mainly in women with Crohn's disease (CD) and IBD-unclassified (IBD-U) and to a lesser extent in ulcerative colitis (UC). Disease activity, bowel resections and, in the case of CD, also perianal disease further adversely affected fertility. For women with UC and IBD-U, but not for women with CD, fertility improved throughout the study period. Contraceptive use was higher in female IBD patients, both before and after the diagnosis.In total 2,989 women underwent colectomy during the study period. Reconstruction with ileal pouch anal anastomosis (IPAA) and ileorectal anastomosis (IRA) was used to about the same extent in UC and IBD-U, although this was rare in CD. Compared with the matched reference cohort, women with IBD had lower fertility overall after colectomy (HR 0.65, CI 0.61–0.69), with least impact for operations that left the rectum intact (HR 0.79, CI 0.70–0.90). When the comparison was made within the group of patients undergoing colectomy, fertility in female patients remained nearly unaffected after IRA in all subtypes of IBD, but was impaired after IPAA, especially in UC (HR 0.67 CI 0.50–0.88), and after completion proctectomy in all subtypes of IBD (CD 0.61 CI 0.38–0.96), UC HR 0.65, CI 0.49–0.85 and IBD-U0.68, 0.55–0.85).The survey regarding reproductive behavior after colectomy was completed by 214 (73%) out of 294 eligible women identified in SWIBREG. The desire to have children was negatively affected by disease onset in 59% of the women, colectomy in 44% and by reconstruction in 37%. Altogether, 39% women with UC estimated that they chose to have fewer children in the end because of the disease, but only 10% expressed that the disease made them completely restrain from having children. On the contrary 37% of the women reported that they had experienced difficulties to conceive and 19% expressed that they could not conceive at all. Of the women undergoing reconstruction post colectomy, 37% reported that the choice of reconstruction method was influenced by their desire to have children. Difficulty conceiving was more commonly reported after reconstruction with IPAA (odds ratio [OR] 5.54) than IRA (OR 2.57).Men with IBD also had lower fertility rate compared with the matched reference population, although the impact on parity was limited; 1.28 (SD 1.27) versus 1.35 (SD 1.31) (p < 0.001). Fertility in men was nevertheless impaired in all IBD subtypes. The disease severity measured as order of hospital admissions (UC and IBD-U), intensity of medical treatment (CD), and bowel surgery (IBD-U) were further associated with impaired fertility in men. In the 3,771 men undergoing colectomy during the study period, fertility was only marginally (HR 0.89, CI 0.85–0.94) impaired, regardless of reconstruction.In conclusion, women with IBD have only slightly reduced fertility rates compared with the matched reference population with some exceptions. In non-surgically treated patients, the impact was most pronounced in female patients with CD. Women post colectomy have a particularly marked impact on fertility independent of IBD subtype. Bowel reconstruction with IPAA and proctectomy had a pronounced negative impact on fertility, while fertility was not further affected after IRA. More than half of the women with UC post colectomy reported that developing UC has affected their desire to have children, but difficulty to conceiving is also commonly reported. The impact of IBD in men was only minor.
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| 9. |
- Druvefors, Emma, 1985-, et al.
(författare)
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Impaired Fertility in Women With Inflammatory Bowel Disease : A National Cohort Study From Sweden
- 2021
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 15:3, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Inflammatory bowel disease [IBD] has been associated with reduced female fertility. We analyse fertility in a national cohort of women with IBD.Methods: Fertility was assessed in women with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register and a matched cohort [ratio 1:5]. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified [IBD-U].Results: The cohorts included 27 331 women with IBD and 131 892 matched individuals. The fertility rate in IBD was 1.52 (standard deviation [SD] 1.22) births per 1000 person-years and 1.62 [SD 1.28] [p<0.001] in matched individuals. Fertility was impaired in all IBD subtypes compared with the matched cohort (hazard ratio Crohn's disease [CD] 0.88, 95% confidence interval [CI] 0.85-0.91; IBD-U 0.86, 95% CI 0.83-0.89; and ulcerative colitis [UC] 0.96, 95% CI 0.93-0.98). Fertility improved during the study period for the IBD cohort except for CD. Parity progression ratio, the proportion of IBD women progressing from one parity to the next compared with the matched cohort, was decreased at all parity levels for CD and IBD-U, but only for multiparous women in UC. Contraceptive usage was higher in IBD, both before and after the diagnosis. Disease severity, bowel resections, and perianal disease in CD affected fertility negatively.Conclusions: Fertility was impaired mainly in women with CD and IBD-U, and less so in UC. During the study period, fertility improved in women with UC or IBD-U. Some results suggest a role of voluntarily reduced fertility.
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| 10. |
- Druvefors, Emma, et al.
(författare)
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Minor impact on fertility in men with inflammatory bowel disease : A National Cohort Study from Sweden
- 2022
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 56:2, s. 292-300
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Onset of inflammatory bowel disease (IBD) in men is most common during childbearing age, but little is known about the impact on fertility. Previous studies of fertility in men were small, which justifies this large nation-based registry study.Methods Fertility was assessed in a national cohort of men with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register, and in a reference cohort matched for age and place of residence (ratio 1:5). Information about childbirths was found in the Swedish Multi-Generation Register. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified (IBD-U).Results The cohorts included 29,104 men with IBD and 140,901 matched individuals. IBD patients had a lower fertility rate (number of births per 1000 person years) compared with the matched individuals; 1.28 (SD 1.27) versus 1.35 (SD 1.31; p < 0.001). Fertility was somewhat impaired in all IBD subtypes compared with the matched cohort; ulcerative colitis (UC) (hazard ratio [HR] 0.93, 95% CI 0.91-0.96), Crohn's disease (CD) (HR 0.95, 95% CI 0.92-0.98) and IBD-U 0.92, 95% CI 0.89-0.95. The cumulated total parity and the parity progression were also decreased for all IBD subtypes. Within the IBD cohort disease severity, intensity of medical treatment (CD) and bowel surgery (IBD-U) were further associated with impaired fertility.Conclusions This nationwide cohort study shows only slightly impaired fertility in men with IBD.
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