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Questo documento definisce due elementi fondamentali per il Progetto 3DLab-Sicilia sui quali si costruiscono le numerose applicazioni e i casi d’uso applicativi che sono stati discussi con ampio dettaglio nel deliverable “D4.1 – Analisi dettagliata dei requisiti dei casi d’uso“. Tali elementi sono rappresentati da: l’infrastruttura del progetto, comprensiva dei relativi elementi hardware e software; il “liquid lab”. Un ulteriore punto di contatto tra il presente rapporto e il deliverable D4.1 è rappresentato dall’adozione condivisa trasversalmente della tassonomia dell’hardware e del software relativi al progetto 3DLab-Sicilia. Per la descrizione dettagliata della tassonomia in oggetto si rimanda alla Sezione 2.1 e all’Appendice 1 del deliverable D4.1. Il presente documento è organizzato come segue. La Sezione 2 tratta, insieme ad una introduzione ai contenuti e alle finalità del presente deliverable, la descrizione dello stato dell’arte delle soluzioni oggetto di analisi in queste pagine. La Sezione 3 dettaglia ad alto livello l’architettura dell’infrastruttura del progetto per la Realtà Virtuale nelle 3 sedi selezionate in 3DLab-Sicilia: Catania, presso SWING:IT; Palermo, presso lo IEMEST; e Troina (EN), presso l’IRCCS-OASI. Nella Sezione 4 la descrizione e l’analisi tecnica dell’infrastruttura sono illustrate approfonditamente, ponendo il fuoco sui diversi elementi compresi al suo interno. Sono state analizzate le caratteristiche tecniche delle VR CAVE e dei Visori per Realtà Virtuale (VR) nonché dei dispositivi per la Realtà Aumentata (AR), i laser scanner 3D per i rilievi, i droni, il videocapillaroscopio e l’archivio digitale. La Sezione 5 dettaglia, infine, gli obiettivi, l’architettura e le caratteristiche del “liquid lab” che sarà realizzato nell’ambito del progetto.

BACKGROUND Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment–covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17–1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23–1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38–2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01–1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00–1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00–1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87–1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01–1.06). WIDER IMPLICATIONS In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.