Do we trust scientific evidence? A multicentre retrospective analysis of first IVF/ICSI cycles before and after the OPTIMIST trial.

STUDY QUESTION: Has the practice of individualizing the recombinant-FSH starting dose been superseded after the largest randomized controlled trial (RCT) in assisted reproduction technology (ART), the OPTIMIST trial? SUMMARY ANSWER: The OPTIMIST trial has influenced our ART daily practice to a limited degree, but adherence is still generally poor. WHAT IS KNOWN ALREADY: Although the 'one size fits all' approach has been discouraged for decades by most authors, the OPTIMIST study group demonstrated in a large prospective RCT that, in general, dosage individualization does not improve the prospects for live birth, although it may decrease ovarian hyperstimulation syndrome (OHSS) risk in expected high responders. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of all first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles from 1st January 2017 to 31st December 2018, before and after the OPTIMIST publication on November 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two thousand six hundred and seventy-seven patients, between 18 and 42 years old, undergoing their first IVF-ICSI cycle in seven Italian fertility centres, were included. Patients were allocated to three groups according to their ovarian reserve markers: predicted poor ovarian responders (POR), predicted normo-responders (NR) and expected hyper-responders (HRs). MAIN RESULTS AND THE ROLE OF CHANCE: Between 2017 and 2018, there was an overall increase in prescription of the standard 150 IU dose proposed by the OPTIMIST trial and a reduction in the use of a starting dose >300 IU. After subgroup analysis, the decrease in doses >300 IU remained significant in the POR and NR sub-groups. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study. Physicians need time to adapt to new scientific evidence and a comparison between 2017 and 2019 may have found a greater impact of the Optimist trial, although other changes over the longer time span might have increased confounding. We cannot be sure that the observed changes can be attributed to knowledge of the OPTIMIST trial. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians may be slow to adopt recommendations based on RCTs; more attention should be given to how these are disseminated and promoted. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. E.P. reports grants and personal fees from MSD, grants from Ferring, from IBSA, grants and personal fees from Merck, grants from TEVA, grants from Gedeon Richter, outside the submitted work. E.S. reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, outside the submitted work. All other authors do not have conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Conversion from twice-daily to once-daily Tacrolimus administration in liver transplant patient: results of long term follow-up.

OBJECTIVES: The aim of this study was to assess the long term effects of once-daily tacrolimus (OD-TAC) in a cohort of stable liver recipients converted from the twice daily tacrolimus (TD TAC), with a particular attention on the possible effects on renal function. PATIENTS AND METHODS: Between September 2008 and September 2010 conversion from TD-TAC to OD-TAC was proposed in adult stable liver transplant recipients who were followed as outpatients in our Transplant centre. Conversion from TC-TAC to OD-TAC was based on a 1 mg: 1 mg proportion. Tacrolimus through levels, laboratory parameters, metabolic disorders and any adverse events were evaluated at 1, 3, 6, 12 and 24 months after conversion. Renal function was evaluated using creatinine plasma levels and estimated glomerular filtration rate (GFR) derived from the Modification of Diet in Renal Disease (MDRD). Analysis of variance and t test for paired data were utilised for the comparison of the results obtained at the scheduled controls. RESULTS: Sixty-five patients were enrolled in the study (50 males, 15 females, mean age 59±8 years). Median time since liver transplant (LT) was 39 months (range: 6 to 83 months). All patients were followed for a minimum of 12 months. Ninety per cent of patients stabilized their blood levels within 45 days. Liver function, glucose and plasma lipids concentration and arterial blood pressure remained stable during the study. Renal function improved during the 24 months of follow-up. No adverse events or acute rejection episodes were recorded during the study. CONCLUSIONS: Considering the advantage on patient compliance, the equivalent efficacy and the adequate safety of OD-TAC formulation may represent a useful option in liver transplant patients, with a possible advantage on renal function.

The influence of high dietary protein, energy and mineral intake on deficient young camel (Camelus dromedarius)--I. Changes in metabolic profiles and growth performance.

1. The main forage for camels in northern Djibouti (mangrove with Avicennia marina) is very poor in nitrogen and energy. In a trial, 32 young camels (less than 2 years old) were used in four groups of eight each. 2. All the camels received mangrove as basal diet ad lib. 3. After 1 month, the camels received mineral supplementation in copper and zinc (groups 1 and 3) or/and a concentrate rich in protein and energy (groups 2 and 3) or continued with the basal diet (controls). 4. Any supplementation was stopped after 2 months for 1 month. 5. Growth performance was 550 g/day (concentrate-supplemented camels) and 570 g/day (concentrate+mineral-supplemented camels). 6. The growth was negative for the two others groups (-260 g/day). 7. Food intake of mangrove was slightly more important with mineral supplementation only and with mineral+concentrate supplementation. 8. The changes in metabolic profiles have shown an important catabolism in non-supplemented animals, an increase of urea and free fatty acid concentrations in plasma and a decrease of glucose concentrations. 9. Three camels died in the control group with symptoms of starvation and signs of liver damage (increase of liver enzymes glutamate dehydrogenase and gamma-glutamyl transferase).

The influence of high dietary protein, energy and mineral intake on deficient young camel (Camelus dromedarius)--II. Changes in mineral status.

1. Mangrove Avicennia marina is poor in some trace elements such as copper, zinc and manganese. In a trial we used 32 young camels divided into four groups. 2. Groups 1 and 3 were supplemented with copper and zinc in drinking water after 1 month of mangrove feeding. 3. Groups 2 and 3 received concentrate rich in protein and energy. The supplementation was stopped after 2 months. 4. All the camels were deficient in trace elements at the beginning of mineral supplementation. 5. The plasma concentration of copper increased significantly up to normal levels (less than 70 micrograms/100 ml) in energy protein supplemented groups, but the quantity supplied (100 mg of copper sulphate/day) was not sufficient to maintain this level after the end of supplementation. 6. The original zinc deficiency was too severe to observe a significant effect of the mineral supplementation. 7. Calcium, magnesium and phosphorus levels were improved during the supplementation period in protein-energy supplemented groups. 8. A high interaction between mineral absorption and quality of the diet was observed. A well-balanced diet seems essential to avoid deficient mineral status.