BACKGROUND Several interventions and techniques are suggested to improve the outcome of embryo transfer (ET) in assisted conception. However, there remains no consensus on the optimal practice, with high variations among fertility specialists. OBJECTIVE AND RATIONALE We conducted a comprehensive systematic review and meta-analyses of randomized controlled trials (RCTs) aiming to identify effective interventions that could be introduced around the time of ET to improve reproductive outcomes. SEARCH METHODS We searched the electronic databases (MEDLINE, EMBASE and Cochrane CENTRAL) from inception until March 2021 using a multi-stage search strategy of MeSH terms and keywords, and included all RCTs that evaluated an intervention in the 24-h period before/after ET in women undergoing IVF/ICSI. Our primary outcome was clinical pregnancy rate post-ET confirmed as viable pregnancy on ultrasound scan. We assessed the risk of bias in included trials and extracted data in duplicate. We pooled data using a random-effect meta-analysis and reported using risk ratio (RR) with 95% CI. We explored publication bias and effect modifiers using subgroup analyses. OUTCOMES Our search yielded 3685 citations of which we included 188 RCTs (38 interventions, 59 530 participants) with a median sample size of 200 (range 26–1761). The quality of included RCTs was moderate with most showing a low risk of bias for randomization (118/188, 62.8%) and attrition (105/188, 55.8%) but there was a significant risk of publication bias (Egger’s test P = 0.001). Performing ET with ultrasound guidance versus clinical touch (n = 24, RR 1.265, 95% CI 1.151–1.391, I2 = 38.53%), hyaluronic acid versus routine care (n = 9, RR 1.457, 95% CI 1.197–1.261, I2 = 46.48%) and the use of a soft versus hard catheter (n = 27, RR 1.122, 95% CI 1.028–1.224, I2 = 57.66%) led to higher clinical pregnancy rates. Other pharmacological add-ons also showed a beneficial effect including granulocyte colony-stimulating factor (G-CSF: n = 4, RR 1.774, 95% CI 1.252–2.512, I2 = 0), Atosiban (n = 7, RR 1.493, 95% CI 1.184–1.882, I2 = 68.27%) and hCG (n = 17, RR 1.232, 95% CI 1.099–1.382, I2 = 57.76%). Bed rest following ET was associated with a reduction in clinical pregnancy (n = 6, RR 0.857, 95% CI 0.741–0.991, I2 = 0.01%). Other commonly used interventions, such as non-steroidal anti-inflammatory drugs, prophylactic antibiotics, acupuncture and cervical mucus removal, did not show a significant benefit on reproductive outcomes. Our effect estimates for other important outcomes, including miscarriage and live birth, were limited by the varied reporting across included RCTs. WIDER IMPLICATIONS Using ultrasound guidance, soft catheters and hyaluronic acid at the time of ET appears to increase clinical pregnancy rates. The use of Atosiban, G-CSF and hCG showed a trend towards increased clinical pregnancy rate, but larger trials are required before adopting these interventions in clinical practice. Bed rest post-ET was associated with a reduction in clinical pregnancy and should not be recommended.

Background Smoking tobacco and drinking alcohol are associated with increased arterial stiffness, a critical intermediate endpoint for cardiovascular disease, in adults and in teenagers. The relationship between these risky behaviours and changes in arterial stiffness from late adolescence to early adulthood is not known. Purpose To investigate associations between smoking and drinking habits and the change in arterial stiffness between ages 17 and 24 using a large population-based cohort. Methods Participants underwent repeated measurements of arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)), anthropometrics, resting blood pressure and blood biomarkers, at ages 17 and 24 years. Participants were grouped and scored by alcohol (never, medium intensity (MI): ≤4 drinks on a typical day of drinking, high intensity (HI): >5) and smoking (never, past, MI, <10 cigarettes a day HI, ≥10) exposure at both clinics. Average scores between clinics were taken (scores 0–5) and composite alcohol (never, MI, HI) and smoking (never, past, MI, HI) groups were created. Multivariable regression analysis was performed to investigate associations between smoking/drinking habits and change in cfPWV from 17 to 24 years (ΔPWV). Associations were adjusted for age, gender, and socioeconomic status (model 1). Model 2 was additionally adjusted for body mass index, systolic blood pressure, LDL cholesterol, glucose, and C-reactive protein at age 24. Data are presented as means (95% confidence intervals). Results 1,655 participants (1,013 females and 642 males) had cfPWV recorded at both ages. cfPWV increased from 17 to 24 years in both women (ΔPWV 0.56m/s (0.50, 0.62), p<0.001) and men (0.65m/s (0.56, 0.74), p<0.001). There was a 0.05m/s (0.00, 0.10) increase in ΔPWV per 1 unit increase in average alcohol score (p=0.039). Compared to never drinkers, ΔPWV increased by 0.18m/s (−0.03, 0.38) in MI (p=0.09), and 0.21m/s (−0.01, 0.41) in HI drinkers (p=0.055). There was no association between ΔPWV and average smoking score (β=0.03m/s (−0.03, 0.08), p=0.4). Compared to never smokers, HI smokers had a slightly greater ΔPWV (0.17m/s (−0.08, 0.42), p=0.18). After stratifying by sex, this difference was evident in women (0.32m/s (0.04, 0.60), p=0.028) while no association was seen in men (−0.12m/s (−0.59, 0.35), p=0.6). No differences were found between never-smokers and ex-smokers (difference = 0.04m/s (−0.08, 0.16), p=0.5). Adjustment for potential confounders (model 2) did not attenuate these associations. Figure shows estimated marginal means for ΔPWV between (a) alcohol and (b) smoking groups from model 1. Error bars represent 95% confidence intervals. Conclusion Smoking and alcohol use in young adulthood is associated with an accelerated increase in arterial stiffness, with evidence of a graded adverse association for alcohol. Our findings also suggest that adverse effects of smoking in youth may be reversible with smoking cessation. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

ObjectivesThe faecal immunochemical test (FIT) was introduced to triage patients with lower-risk symptoms of colorectal cancer (CRC) in English primary care in 2018. While there is growing evidence on its utility to triage patients in this setting, evidence is still limited on how official FIT guidance is being used, for which patients and for what symptoms. We aimed to investigate the use of FIT in primary care practice for lower-risk patients who did not immediately meet criteria for urgent referral.DesignA prospective, descriptive study of symptomatic patients offered a FIT in primary care between January and June 2020.SettingEast of England general practices.ParticipantsConsenting patients (aged ≥40 years) who were seen by their general practitioners (GPs) with symptoms of possible CRC for whom a FIT was requested. We excluded patients receiving a FIT for asymptomatic screening purposes, or patients deemed by GPs as lacking capacity for informed consent. Data were obtained via patient questionnaire, medical and laboratory records.Primary and secondary outcome measuresFIT results (10 µg Hb/g faeces defined a positive result); patient sociodemographic and clinical characteristics; patient-reported and GP-recorded symptoms, symptom severity and symptom agreement between patient and GP (% and kappa statistics).ResultsComplete data were available for 310 patients, median age 70 (IQR 61–77) years, 53% female and 23% FIT positive. Patients most commonly reported change in bowel habit (69%) and fatigue (57%), while GPs most commonly recorded abdominal pain (25%) and change in bowel habit (24%). Symptom agreement ranged from 44% (fatigue) to 80% (unexplained weight loss). Kappa agreement was universally low across symptoms.ConclusionAlmost a quarter of this primary care cohort of symptomatic patients with FIT testing were found to be positive. However, there was low agreement between patient-reported and GP-recorded symptoms. This may impact cancer risk assessment and optimal patient management in primary care.