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STUDY QUESTION: Has the practice of individualizing the recombinant-FSH starting dose been superseded after the largest randomized controlled trial (RCT) in assisted reproduction technology (ART), the OPTIMIST trial?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.

Comparison of pelvic masses score (PMS) and Risk of Malignancy Index (RMI 3) in the evaluation of pelvic masses.

PURPOSE: Ovarian cancer is the fourth cause of death from cancer in women worldwide and the majority of its diagnoses is made in an advanced stage of the disease. Several sonographic scoring systems have been created for a better preoperative discrimination between benign and malignant pelvic masses. The aim of this study was to evaluate the performances of the Risk of the Malignancy Index 3 (RMI 3) and the Pelvic Masses Score (PMS). MATERIALS AND METHODS: This retrospective study was performed in 55 women admitted to the department of Obstetrics and Gynecology of University of Udine for surgical exploration of pelvic masses between 2009 and 2012. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both the scores. RESULTS: PMS showed a sensitivity of 100%, a specificity of 93.8%, a PPV of 70%, and a NPV of 100%, while RMI 3 yielded a sensitivity of 85%, a specificity of 91%, a PPV of 60%, and a NPV of 97.8%. CONCLUSION: The authors found that, in discriminating between benign and malignant pelvic disease, the PMS method was more reliable than RMI3. PMS is a simple scoring system which can be used in clinical practice.

Prediction of large-for-gestation neonates with first-trimester maternal serum PAPP-A.

AIM: The aim of this paper was to identify maternal/pregnancy characteristics, first trimester ultrasound parameters and biochemical indices which are significant independent predictors of large-for-gestational age (LGA) neonates. METHODS: An Observational cross-sectional study was conducted at the Fetal Medicine Unit, Department of Obstetrics and Gynecology of the University of Udine (Italy). Seventy-two singleton pregnancies presenting for screening for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry at 11-14 weeks. Linear regression was applied to develop first trimester prediction models for LGA. RESULTS: Maternal height, parity, smoking, assisted conception and pregnancy-associated plasma protein-A were significant independent predictors of LGA. PAPP-A cut-off value expressed in MoM of 1.25 used for the study was chosen to obtain good sensitivity and specificity values. CONCLUSION: Prediction for birthweight deviations (LGA) is feasible using data available at the routine 11-14 weeks' examination.

Evaluation of fetal cerebral blood flow perfusion using power Doppler ultrasound angiography (3D-PDA) in growth-restricted fetuses.

OBJECTIVE: to explore the potential of 3D Power Doppler Angiography (3D PDA) to evaluate the cerebral circulation in normal and growth restricted fetuses (IUGR). STUDY DESIGN: in a pilot study, we enrolled 51 appropriate for gestational age (AGA) pregnancies and 17 singleton pregnancies presenting IUGR, all between 22 and 38 weeks of gestation. Using 3D power Doppler ultrasound, a -volume acquisition of the fetal brain was performed. Two regions of interest (ROI) were defined within the fetal brain. Zone 1 is anterior to the cavum septi pellucidi (CSP). Zone 2 is defined by a rectangle obtained tracing a contour -between the temporal bones as wide as the CSP, corresponding to the area of the middle cerebral artery. The Flow Index (FI), the Vascularization Index (VI), the Vascularization and Flow Index (VFI) were determined in both areas in both IUGR and AGA fetuses by a single operator. IUGR fetuses were divided into three groups: Group 1, with normal pulsatility index (PI) of umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV); Group 2, IUGR fetuses with abnormal UA PI, normal MCA PI, normal DV PI; in Group 3, IUGR fetuses with abnormal UA PI, MCA PI and DV PI. RESULTS: FI and VFI values of zone 1 were increased in Group 1.Values of VFI in zone 2 were increased in Group 2. CONCLUSIONS: Our findings are in line with recent studies in growth-restricted fetuses suggesting that the anterior -cerebral artery shows Doppler signs of vasodilatation before these are observed in the MCA, demonstrating the "frontal brain sparing effect".