Safety and efficacy of in vitro fertilisation in patients with chronic liver disease and liver transplantation recipients.

BACKGROUND & AIMS: Chronic liver disease and liver transplantation (LT) can delay both timing and ability of women to conceive. With increased awareness and availability of in vitro fertilisation (IVF), the need for accurate counselling is paramount. To date, minimal data exist on outcomes of IVF in patients with chronic liver disease, cirrhosis, or post-LT. We report the largest experience of IVF in women with liver-related subfertility (LRSF). METHODS: A retrospective analysis was performed on 42 women with LRSF who had undergone 57 IVF cycles between 1990 and 2019. RESULTS: Forty-two women with LRSF received IVF; 9 cycles in 6 women with cirrhosis, 14 cycles in 11 women post-LT, and 34 cycles in 25 women without cirrhosis. The main aetiologies of liver disease included HBV, HCV, and autoimmune hepatitis (AIH). Of 57 IVF cycles evaluated, 43 (75%) resulted in successful implantation. Eight (2 post-LT, 3 with cirrhosis, 4 without cirrhosis) resulted in miscarriage. The live birth rate (LBR) was 74% (32/43). Two of 9 (22%) patients with cirrhosis, 4/14 (29%) patients who were post-LT, and 6/34 (18%) patients without cirrhosis had unsuccessful IVF attempts. Nine of 57 (16%) IVF cycles resulted in new liver enzyme derangement during therapy, which improved after treatment completion. Six pregnancies (2 in patients who were post-LT, 4 without cirrhosis) were complicated by obstetric cholestasis (OC). Ovarian hyperstimulation syndrome (OHSS) was rare (n = 3, 7%). One patient with AIH-related cirrhosis decompensated after initiating IVF, warranting discontinuation of therapy. There were no maternal deaths. Three women developed a hypertensive disorder of pregnancy. Half the pregnancies resulted in premature deliveries (range 27-36 weeks). CONCLUSIONS: In selected cases, IVF in women with LRSF can be successful. However, patients should be counselled on the potential increased risks of OHSS, OC, and prematurity. LAY SUMMARY: Women with liver disease or those who have had a liver transplant can experience difficulties getting pregnant. In this study, we look at whether alternative approaches to achieve pregnancy are harmful in these women. Overall, there were no significant issues with the use of in vitro fertilisation in women with liver disease, but they need to be aware of potential risks, such as early delivery of the baby.

Collaborative care model versus usual care for the management of musculoskeletal and co-existing mental health conditions: a randomised feasibility mixed-methods study.

OBJECTIVE: This study aimed to assess the feasibility of a future trial comparing the collaborative care model with usual care for patients with musculoskeletal conditions and co-existing symptoms of anxiety and depression. DESIGN: A single-centre, parallel-arm, one-to-one, randomised controlled trial design using a mixed-methods approach was used. semistructured interviews and focus groups were conducted post intervention with all participants and staff respectively to explore acceptability towards the model and identify recommendations for improvements. SETTING: An orthopaedic rehabilitation outpatient tertiary hospital. PARTICIPANTS: Adult patients with musculoskeletal conditions and co-existing moderate or severe symptoms of anxiety and depression attending outpatient therapy appointments. INTERVENTION: The collaborative care model consisted of a tailored management programme to facilitate the integration of care provided by physical and mental healthcare professionals. A case manager screened and coordinated targeted mental health support for participants. Participants allocated to usual care had no support from the case manager. MAIN OUTCOMES MEASURE: Feasibility indicators (rates of recruitment, randomisation and retention), acceptability of clinical outcome measures, usage of additional resources and cost of intervention implementation. RESULTS: Of the 89 patients who provided consent to take part, 40 participants who matched the eligibility criteria were randomised to either the intervention (n=20) or usual care arm (n=20). Overall adherence to the intervention was 58.82%, while the withdrawal rate was 37.5% at 6 months. All of the 27 participants who were retained completed self-reported outcomes. Qualitative data highlighted that integrated mental health support was favourably perceived. In addition to prenegotiating protected psychology time, the need for operationalised communication between the case manager and clinicians was identified as a recommendation for a future trial. CONCLUSIONS: The trial and intervention were acceptable to patients and healthcare professionals. While the findings demonstrate the feasibility of trial recruitment, a future trial will require optimised retention strategies to improve adherence and withdrawal rates. TRIAL REGISTRATION NUMBER: NCT05018039.

Collaborative care model versus usual care for people with musculoskeletal conditions and co-existing anxiety and depression: protocol for a feasibility mixed-methods randomised controlled trial.

BACKGROUND: In the UK 17.8 million people have musculoskeletal pathophysiology, which becomes universal with age. Levels of discomfort and incapability correlate with symptoms of anxiety and depression. People with sufficient symptoms who seek care can benefit from collaborative diagnosis and treatment of mental and physical health organised by a case manager. This paper presents the protocol for a feasibility trial of collaborative care in an orthopaedic setting. AIMS: To determine the feasibility and acceptability of providing collaborative care for patients with musculoskeletal conditions and co-existing symptoms of anxiety and depression identified on a screening tool in a physical and occupational therapy out-patient setting. METHOD: A two-arm parallel-group randomised controlled trial will recruit 40 adult out-patients with at least moderate anxiety and depression, who have been referred for physiotherapy and occupational therapy. Participants will be allocated on a 1:1 ratio to collaborative care or to usual care. Co-primary outcomes will be key feasibility indicators collected at baseline and at 6 months. A qualitative study will be conducted post-intervention to explore the acceptability and potential improvements to the collaborative care model. RESULTS: This study will investigate the use of the collaborative care model for patients with musculoskeletal and co-existing moderate or severe levels of anxiety or depression. CONCLUSIONS: The results will provide important evidence to determine a future trial.

Quantitative magnetic resonance imaging to aid clinical decision making in autoimmune hepatitis.

Background: In autoimmune hepatitis (AIH), clinical practice and treatment guidelines frequently diverge as a reflection of disease heterogeneity and challenges in achieving standardised care. We sought to explore the utility of multiparametric (mp) MR in patients with AIH, and the impact of this technology on physicians' decision making and intended patient management. Methods: 82 AIH patients, recruited from two sites between June and November 2019 as part of an observational cohort study, underwent non-contrast MRI alongside their standard clinical investigations. Correlations between iron-corrected T1 (cT1) and other markers of disease were investigated alongside the utility of imaging markers to risk stratify patients in biochemical remission. The impact of mpMR on clinical decision making was evaluated using pairwise t-tests. The discriminatory ability of the imaging markers was assessed using area under the receiver operating characteristic curves (AUCs). Findings: cT1 had a significant impact on clinician intended patient management (p<0.0001). cT1 correlated with ALT (p = 0.0005), AST (p<0.001), IgG (p = 0.0005), and liver stiffness (p<0.0001). Patients in deep biochemical remission (N = 11; AST/ALT <50% upper limit of normal [ULN] and IgG <12 g/L) had low cT1, while 7/34 in normal biochemical remission (AST/ALT between 50 and 100% of ULN) had high cT1 and were at risk of disease flare. cT1 measures of disease heterogeneity, ALP and bilirubin made the best predictor of those not in biochemical remission (AUC:0.85). Interpretation: This study investigates the impact of mpMR results on intended clinical management in a real world setting. Findings showed that mpMR demonstrated a significant impact on clinical management of AIH and has the potential to inform patient risk stratification. Funding: This paper presents independent research supported by the Innovate UK grant (104,915).