Longitudinal Measurements of Blood Biomarkers in Patients with Crohn's Disease or Ulcerative Colitis Treated with Infliximab: Only the Latest Values in the Induction Period Predict Treatment Failure.

Background: Few studies have incorporated longitudinal assessments or used combinations of blood biomarkers as predictors of loss of response to biologic therapy for patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: This is a population-based cohort study comprising Danish patients with CD or UC from 2008 to 2018. We used logistic regression to analyze whether levels and changes in levels of C-reactive protein (CRP), serum albumin, and hemoglobin, routinely measured during a 14-week infliximab induction period, predicted a change to another biologic medication or cessation of biologic therapy. Results: During the induction period, 2883 (1626 CD, 1257 UC) patients had 12,730, 12,040, and 13,538 specimens with CRP, serum albumin, and hemoglobin, respectively. In all, 284 patients (9.9%) switched to another biologic medication, and 139 (4.8%) ceased biologic therapy in the follow-up period. Only the most recent CRP and hemoglobin levels predicted the efficacy of infliximab treatment at approximately 14 weeks, a time point when the clinician often determines whether to continue treatment. Conclusion: Measurement of blood biomarkers prior to the clinical assessment does not predict the effectiveness of infliximab.

Paternal preconception exposure to non-steroid anti-inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry-based cohort study.

BACKGROUND AND AIM: Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations). METHODS: We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals. RESULTS: We identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure. CONCLUSIONS: Overall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

Inflammatory Bowel Disease in Adults and Elderly: The Use of Selected Non-IBD Medication Examined in a Nationwide Cohort Study.

BACKGROUND: Real-world data on medications used for conditions other than inflammatory bowel disease (IBD) are sparse. We examined how the onset of IBD affects the prescription pattern of selected non-IBD medication and the risk of becoming an incident user. METHODS: This nationwide cohort study utilized data from Danish health registers. We included incident patients with young adult-onset IBD (18-39 years of age), adult-onset IBD (40-59 years of age), and elderly-onset IBD (60+ years of age), from 1998 to 2018 and followed all for 3 years. We examined redeemed prescriptions before and after the onset of IBD and estimated the risk of becoming a user of non-IBD medications using logistic regression models. RESULTS: We identified 36165 patients, 16 771 (46%) with young adult onset, 10615 (29%) with adult onset, and 8779 (24%) with elderly onset. The onset of IBD increased the use of antidepressants, antipsychotics, sedatives/hypnotics, opioids, nonopioid analgesics, antidiabetics, and proton pump inhibitors, even in patients with no other underlying comorbid diseases. The adjusted odds ratio for using antidepressants 1 year after the onset of IBD in elderly was 1.50 (95% confidence interval [CI], 1.14-1.82), in opioids 1.69 (95% CI, 1.45-1.95), in nonopioid analgesics 2.10 (95% CI, 1.77-2.48), in cardiovascular medication 2.20 (95% CI, 1.86-2.61), and in proton pump inhibitors 1.51 (95% CI, 1.31-1.74) compared with adults. CONCLUSIONS: In all 3 age groups, the proportions of patients with redeemed prescriptions for several groups of non-IBD medication were significantly increased after the IBD diagnosis compared with before. The risk of becoming an incident user for several groups of non-IBD medication was increased in elderly patients.

In patients with young adult onset, adult onset, and elderly onset of inflammatory bowel disease (IBD), the proportions of prescriptions for non-IBD medication was significantly increased after the IBD onset compared with before. The risk of new use of non-IBD medication was increased in elderly-onset IBD patients.

Physical activity measured by accelerometry in paediatric and young adult patients with inflammatory bowel disease.

OBJECTIVES: Physical activity in paediatric and young adult patients suffering from inflammatory bowel disease (IBD) may play an important role in the overall health status. However, physical activity in these patients has not been reported using objective methods. We aimed to describe accelerometry-measured physical activity levels in paediatric and young adult IBD patients with either ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We recruited Danish patients with IBD aged 10-20 years in clinical remission and with a faecal calprotectin below 200 µg/mg. Physical activity was assessed using tri-axial wrist accelerometry over seven days and quantified using the activity-related acceleration derived as the conventional Euclidian Norm Minus One (ENMO) metric expressed in milli-gravity units (mg). Time spent in Moderate-to-Vigorous Physical Activity (MVPA) was classified as ENMO > 210 mg in 5 s epoch resolution (unbouted). RESULTS: We included 61 patients with a median age of 17 years [Inter Quartile Range, IQR 14-19]. The total volume of activity expressed as average acceleration (ENMO) per day was 31.5 mg (95% CI 29.1-33.9). Time spent in unbouted MVPA was 32 min per day (95% CI 26-37). There was no significant difference in activity volume between patients with UC to patients with CD, the adjusted linear regression coefficient was - 1.7 mg (95% CI -6.2-2.7). Activity volume was higher for males (36.2 mg, 95% CI 31.9-40.5) than for females (27.8 mg, 95% CI 25.6-30.0), and younger patients were more active than older patients; Activity volume in 10-13 year olds was 37.2 mg (95% CI 28.6-45.7), whereas it was 28.5 mg (95% CI 25.2-31.7) for those aged 18-20 years. CONCLUSIONS: We collected tri-axial accelerometry in young patients with IBD in clinical remission, and described their level of physical activity by the conventional ENMO measure. We found no statistically significant difference in patients with UC compared to patients with CD. The volume of physical activity was higher in males compared to females, and inversely associated with age.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

INTRODUCTION: Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. METHODS: In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. RESULTS: Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. DISCUSSION: Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.

Does Disease Activity After Induction Treatment With Biologics Predict Short-Term Outcome in Crohn's Disease and Ulcerative Colitis?

BACKGROUND: Secondary loss of response to biological therapy is a challenge when treating Crohn's disease (CD) and ulcerative colitis (UC). Currently, no single marker has been found to be valid as a prognostic indicator of response to biologic therapy in patients with CD and UC. In this study, we aimed to assess whether disease activity after 14 weeks of biologic therapy has a prognostic impact on surgery and steroid-free remission during 6 months following completion of induction therapy. METHODS: In an unselected cohort study based on data from 4 national Danish health registries, we identified 493 patients with UC and 620 patients with CD who completed induction therapy with biologics from 2016 to 2019. Following induction therapy with biologics, we defined disease activity based on C-reactive protein and clinical scores of disease activity. The composite endpoint, "not being well treated," included surgery or use of corticosteroid within 6 months following induction therapy. RESULTS: In patients with UC with disease activity following induction therapy, the adjusted odds ratio for surgery or steroid treatment during 6 months of follow-up was 3.9 (95% CI, 1.6-9.3) compared with patients without disease activity, and in patients with CD, the adjusted odds ratio was 3.6 (95% CI, 1.7-7.6). CONCLUSIONS: A positive treatment response to biologic treatment after induction therapy (measured by C-reactive protein and clinical scores) predicts a better short-term outcome in patients with CD and UC.

The impact of medical therapies and factors related to treatment procedures in women with rheumatoid arthritis and inflammatory bowel disease receiving assisted reproduction: a nationwide cohort study.

OBJECTIVE: To examine whether medications used to treat rheumatoid arthritis (RA)/chronic inflammatory bowel disease (IBD), or factors related to the assisted reproductive technology (ART) procedures, impact the success of ART. In women with RA/IBD, initial studies have shown a reduced chance of a live-born child after ART. DESIGN: Cohort study. SETTING: Nationwide Danish health registries. PATIENTS: All Danish women with a fresh embryo transfer from January 1, 2006, through 2018. The cohorts comprised 1,824 embryo transfers in women with RA/IBD and 97,191 embryo transfers in women without RA/IBD. INTERVENTIONS: Observational, noninterventional study. MAIN OUTCOME MEASURE: Live birth per fresh embryo transfer. RESULTS: The chance of a live birth in women with RA/IBD receiving ART, compared with other women receiving ART, had an adjusted odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.68-0.91). Prescribed corticosteroids before embryo transfer were positively associated with a live-born child (adjusted OR, 1.21; 95% CI, 1.12-1.31), while the use of antiinflammatory/immunosuppressive agents did not have significant importance. Intracytoplasmic sperm injection was associated with a reduced chance (adjusted OR, 0.94; 95% CI, 0.90-0.97). Type of hormone treatment protocol did not have significant importance, and transfer at the blastocyst stage was positively associated with a live-born child (adjusted OR, 1.54; 95% CI, 1.46-1.62). CONCLUSIONS: In women with RA and/or IBD, prescribed corticosteroid before embryo transfer and embryo transfer at the blastocyst stage were associated with successful ART. Intracytoplasmic sperm injection was associated with a slightly reduced chance. Antiinflammatory/immunosuppressive agents and type of hormone protocols did not have significant importance.

The Efficacy of Assisted Reproduction in Women with a Wide Spectrum of Chronic Diseases - A Review.

Assisted reproductive technology (ART) treatments in women with underlying chronic diseases have become increasingly frequent. The objective of this review is to provide an overview of the literature examining the chance of having a live born child after ART in women with chronic diseases, compared to other women receiving ART. We focused on some of the most prevalent chronic diseases in women during their reproductive years, ie ulcerative colitis, Crohn's disease, rheumatoid arthritis, multiple sclerosis, epilepsy, hyperthyroidism, hypothyroidism, and diabetes mellitus. Secondly, we studied the chance of successful implantation. The literature search was performed in the database Pubmed.gov. including all studies published before October 2020. Title and abstracts of 58 papers were reviewed, 37 papers were excluded and other 8 studies were excluded after full-text evaluation. Only 13 papers were eligible for review. Results indicate that women with ulcerative colitis, Crohn's disease, rheumatoid arthritis, hyperthyroidism, and diabetes mellitus type 2 might have problems with low implantation rate or early embryo development during ART. On the contrary, the few studies on women with hypothyroidism, diabetes mellitus type 1, and epilepsy suggest an equivalent chance of a live birth compared to other women undergoing ART. A possible explanation behind these differences could reside in the disease-specific dysregulation of the innate or adaptive immune system. To our knowledge, this is the first review on ART in women with chronic diseases, and it has disclosed that the evidence in this area is indeed sparse. We encourage others to examine live birth after ART in women with chronic diseases.

Outcome of COVID-19 in hospitalized patients with chronic inflammatory diseases. A population based national register study in Denmark.

OBJECTIVE: COVID-19 has substantial morbidity and mortality. We studied whether hospitalized patients with COVID-19 and chronic inflammatory diseases experienced worse outcomes compared to patients hospitalized with COVID-19 without chronic inflammatory diseases. METHODS: Danish nationwide registers were used to establish a cohort of hospitalized patients with COVID-19 and inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) (exposed), and a control cohort without these diseases (unexposed) between March 1, 2020, and October 31, 2020. We compared median length of hospital stay, used median regression models to estimate crude and adjusted differences. When estimating crude and adjusted odds ratio (OR) for continuous positive airway pressure (CPAP) and mechanical ventilation, in-hospital death, 14-day and 30-day mortality, we used logistic regression models. RESULTS: We identified 132 patients with COVID-19 and IBD, RA, SpA, or PsA, and 2811 unexposed admitted to hospital with COVID-19. There were no differences between exposed and unexposed regarding length of hospital stay (6.8 days vs. 5.5 days), need for mechanical ventilation (7.6% vs. 9.4%), or CPAP (11.4% vs. 8.8%). Adjusted OR for in-hospital death was 0.71 (95% CI 0.42-1.22), death after 14-days 0.70 (95% CI 0.42-1.16), and death after 30-days 0.68 (95% CI 0.41-1.13). CONCLUSION: Hospitalized patients with COVID-19 and chronic inflammatory diseases did not have statistically significant increased length of hospital stay, had same need for mechanical ventilation, and CPAP. Mortality was similar in hospitalized patients with COVID-19 and chronic inflammatory diseases, compared to patients hospitalized with COVID-19 and no chronic inflammatory diseases.

The Danish National Register of assisted reproductive technology: content and research potentials.

The Danish National Register of assisted reproductive technology (ART) was initially established in 1994. The register comprises complete information on all ART procedures in public and private clinics in Denmark from 2013 and onwards, including baseline information on the cause of infertility and a number of health-related patient characteristics. The register enables monitoring and research on infertility treatment and reproductive topics in single women or couples seeking assisted reproduction, and the register is thus a key component of the Danish health information system within human reproduction. We aimed to provide an updated description of the register including advantages and pitfalls when using the register for reproductive epidemiological research, and a description of the accessibility for researchers. The Danish ART register is a valuable tool for epidemiological research. However, the inherent strengths and limitations ought to be in perspective when designing studies and interpreting the study results. Reports with annually aggregated data on ART treatments, can be accessed on the Danish Health Data Authority web page and researchers may obtain access to individual pseudonomized data via secure servers at the Danish Health Data Authority and Statistics Denmark.

Body mass index influences the risk of reoperation after first-time surgery for pelvic organ prolapse. A Danish cohort study, 2010-2016.

INTRODUCTION AND HYPOTHESIS: The aims of this study were to evaluate the impact of body mass index (BMI) on the risk of reoperation for pelvic organ prolapse (POP) up to 5 years after first-time surgery. MATERIALS AND METHODS: This nationwide register-based study includes first-time POP surgery in 2010 through 2016. The cumulative incidence proportions of reoperation were analyzed in a Cox regression model and described using Kaplan-Meier plots stratified in BMI categories. RESULTS: A total of 28,533 first-time procedures were performed in 22,624 women; 76.6% had single-compartment repair. The 1- and 5-year reoperation rate within the same compartment was 2.6% and 6.1% respectively for women with BMI < 25, and for women with BMI > 35 it was 3.7% and 11.2 respectively. In the anterior compartment there was a significantly increased adjusted hazard ratio for reoperation in the same compartment with increasing BMI (reference group BMI < 25), BMI 30-34.9 with an aHR = 1.34 (CI 95% 1.04-1.71) and BMI ≥ 35 aHR = 1.77 (CI 95% 1.17-2.67). The 1- and 5-year reoperation rate in an adjacent compartment was 0.6% and 1.6% respectively for women with BMI < 25, and for women with BMI > 35 it was 1.0% and 4.4 respectively. For reoperation in an adjacent compartment the adjusted results were BMI 30-34.9 aHR = 1.64 (95% CI 1.05-2.56) and BMI > 35 aHR = 2.64 (95% CI 1.36-5.14) when the first-time operation was in the anterior compartment. CONCLUSIONS: If the woman had BMI > 35 and first-time surgery was in the anterior compartment, she had an almost doubled risk of reoperation within 5 years both in the same compartment and in an adjacent compartment compared to women with BMI < 35. In the apical and posterior compartment there was a trend towards increasing risk of reoperation with increasing BMI, although with a broad confidence interval.

Surgical repair of vaginal vault prolapse; a comparison between ipsilateral uterosacral ligament suspension and sacrospinous ligament fixation-a nationwide cohort study.

INTRODUCTION AND HYPOTHESIS: Hysterectomy is frequently performed and associated with increased risk of subsequent genital prolapse including vaginal vault prolapse. Ipsilateral uterosacral ligament suspension (IUSLS) and sacrospinous ligament fixation (SSLF) are two commonly performed surgical techniques to treat vaginal vault prolapse. There is no consensus on the ideal operation technique. The aim of this study was to compare IUSLS and SSLF to treat vaginal vault prolapse based on the number of repeat surgeries. METHODS: Previously hysterectomized patients operated on with IUSLS or SSLF in Denmark in 2010-2016 were included in this nationwide register-based cohort study and followed until June 2017. Data were obtained from Danish National Databases, to which reporting is mandatory by law, entailing high validity and completeness of data. Data were analyzed using Cox proportional hazard regression analysis adjusted for age, preoperative prolapse stage, smoking, BMI, and previous prolapse surgery. RESULTS: In total, 744 patients were included; 384 underwent IUSLS while 360 underwent SSLF. After 5 years, 6.5% of patients operated on with IUSLS and 21.8% operated on with SSLF had a repeat surgery in the apical compartment and 12.4% and 30.6% in any compartment, respectively. The risk of repeat surgery was 4.8 times higher after SSLF compared to IUSLS [confidence interval (CI): 2.7-8.4] in the apical compartment and 2.4 times higher (CI: 1.2-5.1) in the anterior compartment. No difference was seen in the posterior compartment. CONCLUSIONS: This study finds significantly higher numbers of repeat surgeries after SSLF compared to after IUSLS in a Danish nationwide cohort.

Infliximab, Immunomodulators and Treatment Failures in Paediatric and Adolescent Patients with Crohn's Disease: a Nationwide Cohort Study.

BACKGROUND AND AIMS: In paediatric patients with Crohn's disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months. DESIGN: Using Danish registries, we identified patients with Crohn's disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015. RESULTS: We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32-0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45-0.97] in patients receiving combination therapy. CONCLUSIONS: The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.

Hospitalization for COVID-19 in patients treated with selected immunosuppressant and immunomodulating agents, compared to the general population: A Danish cohort study.

AIMS: In the Danish population, we examined whether patients treated with thiopurines, methotrexate, systemic corticosteroids, anti-tumour necrosis factor (TNF)-α agents, anti-interleukin therapeutic agents, selective immunosuppressive agents and cyclosporine/tacrolimus had an increased risk of hospitalization for COVID- 19, compared to the background population. METHODS: A nationwide cohort study including all people alive in Denmark on 1 March 2020. Exposed patients constituted those exposed to thiopurines (n = 5484), methotrexate (n = 17 977), systemic corticosteroids (n = 55 868), anti-TNF-α agents (n = 17 857), anti-interleukin therapeutic agents (n = 3744), selective immunosuppressive agents (n = 3026) and cyclosporine/tacrolimus (n = 1143) in a period of 12 months prior to 1 March 2020 (estimated time of outbreak in Denmark). We estimated the adjusted risk of hospitalization for COVID-19 for patients treated with the above-mentioned categories of medications, compared to the rest of the population. RESULTS: The adjusted odds ratios of hospitalization in patients treated with corticosteroids and cyclosporine/tacrolimus were 1.64 (95% confidence interval [CI] 1.35 to 2.00) and 4.75 (95% CI 1.96 to 11.49), respectively. The risks of hospitalization in patients treated with thiopurines, methotrexate, and anti-TNF-α agents, were 1.93 (95% CI 0.91 to 4.08), 0.74 (95% CI 0.43 to 1.28), 1.00 (95% CI 0.52 to 1.94), respectively. The number of outcomes in patients treated with anti-interleukin therapeutic agents and selective immunosuppressive agents was too small for analysis. CONCLUSION: Patients treated with systemic corticosteroids and cyclosporine/tacrolimus had a significantly increased risk of being hospitalized for COVID-19. Our study does not uncover whether the increased risk is related to the drug itself, the underlying condition for which the patient is treated or other factors.

The efficacy of assisted reproductive treatment in women with epilepsy.

RESEARCH QUESTION: The question of interest for this study was to examine the chance of a live birth following assisted reproductive technology (ART) treatment in women with epilepsy compared with women without epilepsy. In sub-analyses, the chance of biochemical and clinical pregnancies, and the impact of antiepileptic drugs (AED) treatment prior to embryo transfer, was analysed. DESIGN: This register-based cohort study was based on the Danish ART register comprising all women who underwent embryo transfer during 2006 to 2017, which included 730 ART treatments in 264 women with a history of epilepsy, and 128,387 ART treatments in 42,938 women without epilepsy. Adjustments were made for comorbidity, women's age, calendar year, type of infertility treatment and cause of infertility. A possible impact of AED use at the time of embryo transfer was studied in a sub-analysis. The primary outcome was live birth within a period of 140-308 days after the date of embryo transfer. RESULTS: The adjusted odds ratio for a live birth per embryo transfer in women with epilepsy, relative to women without epilepsy, was 1.06 (95% confidence interval [CI] 0.88-1.28). The adjusted odds ratio for a live birth among users of an AED was 1.22 (95% CI 0.77-1.92) relative to women who had stopped the use of AED prior to embryo transfer. CONCLUSIONS: The chances of a live birth per embryo transfer were similar in women with and without epilepsy. These are novel and reassuring findings on the efficacy of infertility treatment in women with epilepsy.

Live-born children after assisted reproduction in women with type 1 diabetes and type 2 diabetes: a nationwide cohort study.

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes are among the most prevalent chronic diseases in women in the fertile years and women with diabetes may experience several reproductive issues. We aimed to examine the chance of biochemical pregnancy, clinical pregnancy and live birth after assisted reproductive technology (ART) treatment in women with type 1 and type 2 diabetes and whether obesity per se influenced the results. METHODS: This nationwide register-based cohort study is based on the Danish ART Registry comprising 594 women with either type 1 diabetes or type 2 diabetes from 2006 to 2017. RESULTS: Relative to women without diabetes, the adjusted OR (95% CI) of a live birth per embryo transfer was 0.50 (0.36, 0.71) in women with type 2 diabetes and 1.10 (0.86, 1.41) in women with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our data on the efficacy of ART treatment in women with type 1 and type 2 diabetes is the first in this field. When compared with women without diabetes, women with type 1 diabetes had an equivalent chance of a live birth per embryo transfer whereas women with type 2 diabetes had a reduced chance. The findings in women with type 2 diabetes did not seem to be driven by obesity per se as the same pattern was seen in both normal-weight and obese women. Graphical abstract.

Live birth in women with multiple sclerosis receiving assisted reproduction.

RESEARCH QUESTION: Multiple sclerosis is predominant in women during the childbearing years and, in case of problems with conceiving naturally, assisted reproductive technology (ART) becomes relevant. The efficacy of ART treatment in women with multiple sclerosis has not previously been studied. Our aim was to examine the chance of a liveborn infant after an embryo transfer in women with multiple sclerosis and to examine whether corticosteroids before embryo transfer had a beneficial effect. DESIGN: This cohort study is based on nationwide Danish health registries, including all women who underwent embryo transfers between 1 January 1995 to 31 December 2017. The exposed cohort comprised 2267 embryo transfers in women with multiple sclerosis and the unexposed cohort comprised 200,684 in women without multiple sclerosis. Multilevel logistic regression analysis was used to compute the crude and the adjusted risk estimates. RESULTS: A total of 21.97% of the embryo transfers in women with multiple sclerosis resulted in a liveborn infant compared with 24.17% in women without multiple sclerosis, and the adjusted odds ratio was 0.91 (95% CI 0.81 to 1.02). The adjusted odds ratio of live birth in women with multiple sclerosis using corticosteroids before embryo transfer was 0.90 (95% CI 0.49 to 1.68), compared with women with multiple sclerosis receiving no corticosteroids. CONCLUSION: The chance of a live birth was not decreased in women with multiple sclerosis undergoing ART compared with women without multiple sclerosis. The use of corticosteroids had no effect on the result. These novel results on ART treatment are useful when counselling women with multiple sclerosis undergoing assisted reproduction.

Corticosteroids Prior to Embryo Transfer in Assisted Reproduction in Women with Crohn's Disease and Ulcerative Colitis - A Nationwide Cohort Study.

PURPOSE: Former studies have suggested that women with Crohn's disease (CD) and ulcerative colitis (UC) have a decreased chance of a live born child after assisted reproductive technology (ART) treatment. It is debated whether corticosteroids before ART may improve outcomes, either by decreasing inflammatory bowel disease-related inflammation or increasing endometrial receptivity. We examined the efficacy of corticosteroids before embryo transfer in women with CD and UC. PATIENTS AND METHODS: Our cohort study is based on nationwide Danish health registries, comprising women with CD and UC receiving an embryo transfer (1 January 2006 through 2017). Exposed cohorts constituted women with CD and UC who had received corticosteroids within three months before embryo transfer, and the unexposed cohorts women with CD and UC who did not receive corticosteroids. Our primary outcome was live birth. We controlled for multiple covariates in the analyses. RESULTS: We examined 2408 embryo transfers. In patients with CD, 114 embryo transfers were preceded by a corticosteroid prescription, and 964 were not. The corresponding numbers in UC were 122 and 1208, respectively. The adjusted odds ratio (aOR) for live birth in women with CD receiving corticosteroids before embryo transfer, relative to women with CD not receiving corticosteroids, was 0.89 (95% CI 0.49-1.63). The corresponding aOR in UC was 0.98 (95% CI 0.55-1.74). CONCLUSION: Corticosteroids prior to ART in women with CD and UC did not increase the chance of a live born child. The exact impact of corticosteroids prior to embryo transfer in patients with CD and UC still remains to be determined.

The impact of anti-TNFα therapy on colectomy rates and corticosteroid treatment among 3001 paediatric and adolescent patients with ulcerative colitis-a nationwide study from 1995 to 2015.

BACKGROUND: The long-term effects of anti-TNFα therapy in ulcerative colitis are debatable. AIM: To examine whether anti-TNFα therapy changed the colectomy proportion and reduced the use of corticosteroids. METHODS: A nationwide cohort study among patients (age 0-20) diagnosed with ulcerative colitis through 1995-2015 from Danish health registries. We calculated the cumulative 5-year risk of colectomy after diagnosis and used a Cox regression model for comparison between a historical pre-anti-TNFα cohort 1 (1995-2003) and a cohort 2 for the era of anti-TNFα (2004-2015). Based on anti-TNFα users, defined as patients who had at least four anti-TNFα treatments within 4 months, we examined the subsequent need for corticosteroids. RESULTS: We identified 3001 patients from 1995 to 2015. The 5-year cumulative proportion of colectomy in cohort 2 was 9.7% (95% confidence interval [CI] 8.4-11.1) and 12.3% (95% CI 10.4-14.6) in cohort 1. The adjusted 5-year hazard ratio (HR) was 0.76 (95% CI 0.60-0.96) for colectomy in cohort 2 compared to cohort 1. A total of 334 patients received anti-TNFα treatments, and 16.8% (56/334) were prescribed corticosteroids in the subsequent 3-month period. Corticosteroid treatment declined with follow-up after 6 and 12 months, 5.4% and 1.2%, respectively. CONCLUSION: In patient's ≤20 years, the HR for colectomy within a period of 5 years from the time of diagnosis was reduced in the era of anti-TNFα compared to a historical cohort. In patients treated with anti-TNFα, prescriptions of corticosteroids were virtually ceased after 12 months.