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EMMA BERTUCCI

Docente a contratto
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
Tutor di tirocinio
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico

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Pubblicazioni

2024 - Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome [Articolo su rivista]
Di Caprio, A.; Rossi, C.; Bertucci, E.; Bedetti, L.; Bertoncelli, N.; Miselli, F.; Corso, L.; Bondi, C.; Iughetti, L.; Berardi, A.; Lugli, L.
abstract

: Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (KAT6A) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of KAT6A syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach. In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift KAT6A pathogenic variant, displaying a severe phenotype with previously unreported clinical features.

2024 - Prenatal ultrasound signs of Aarskog‐Scott syndrome in a twin pregnancy: A case report [Articolo su rivista]
Bertucci, Emma; Giulini, Simone; Sighinolfi, Giovanna; Benuzzi, Martina; Lugli, Licia
abstract

2023 - De novo variants and recombination at 4q35: hints for preimplantation genetic testing in facioscapulohumeral muscular dystrophy [Articolo su rivista]
Pini, Sara; Napoli, Floriana Maria; Tagliafico, Enrico; Marca, Antonio La; Bertucci, Emma; Salsi, Valentina; Tupler, Rossella
abstract

2023 - Determinants of emergency delivery in pregnancies complicated by placenta previa or placenta accreta spectrum disorders: analysis of ADoPAD Cohort [Articolo su rivista]
Lucidi, A; Fratelli, N; Maggi, C; Cavalli, C; Sciarrone, A; Buca, D; Garofalo, A; Viora, E; Vergani, P; Ornaghi, S; Betti, M; Vaglio Tessitore, I; Cavaliere, A F; Buongiorno, S; Vidiri, A; Fabbri, E; Ferrazzi, E; Maggi, V; Cetin, I; Frusca, T; Ghi, T; Kaihura, C; Di Pasquo, E; Stampalija, T; Belcaro, C; Quadrifoglio, M; Veneziano, M; Mecacci, F; Simeone, S; Locatelli, A; Consonni, S; Chianchiano, N; Labate, F; Calcagno, G; Cromi, A; Bertucci, E; Facchinetti, F; Giuliani, G A; Fichera, A; Granata, D; Foti, F; Avagliano, L; Bulfamante, G P; Khalil, A; Flacco, M E; Manzoli, L; Prefumo, F; Calì, G; D'Antonio, F
abstract

Objectives: To report the rate and the outcomes of unplanned caesarean delivery (CD) delivery in women with placenta accreta spectrum disorders (PAS) and placenta previa without PAS, and to elucidate the diagnostic accuracy of ultrasound in predicting this outcome. Methods: Secondary analysis of a multicenter prospective study involving 14 referral hospital in Italy (ADoPAD Study). Inclusion criteria were women with a low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the os), aged ≥ 18 years, who underwent trans-abdominal and transvaginal ultrasound assessment at ≥ 26 + 0 weeks of gestation. The primary outcome was the occurrence of emergency CD, defined as the need of immediate surgical intervention performed for emergency maternal or fetal indications, including active labour, cumulative maternal bleeding >500 ml, severe and persistent vaginal bleeding such that maternal hemodynamic stability cannot be achieved or maintained or category III fetal heart rate tracing unresponsive to resuscitative measures in women with PAS and in those with placenta previa with no PAS. The primary outcome was reported in the population of women with placenta previa and with no PAS confirmed after birth and in those with PAS separately. The secondary aim was to report the strength of association and to test the diagnostic accuracy of ultrasound in predicting emergency delivery. Univariate, multivariate, and diagnostic accuracy analyses were used to analyse the data. Results: 450 women (97 with PAS and 353 with placenta previa but not PAS) were included in the analysis. In women with PAS disorders, emergency CD was required in 21% (95% CI 14-30%) and 60% women delivered before 34 weeks of gestation. Mean gestational age at delivery was 32.3±2.7 weeks in women undergoing emergency and 34.9±1.8 weeks (p<0.001) in those undergoing elective CD. Women undergoing emergency CD had a higher median estimated blood loss (2500 ml, IQR 1350-4500 vs 1100 ml, IQR 625-2500, p=0.012) and mean units of blood transfused (4.3±1.6 vs 0.8±2.2; p= 0.02) compared to those undergoing elective delivery. At univariate analysis, the presence of interrupted retroplacental space, bladder line and placental lacunae were more common in women not experiencing emergency CD. At multivariate analysis, only maternal BMI (OR: 0.83. 95% CI 0.69-0.99, p= 0.045) was independently associated with emergency delivery in women with PAS. However, ultrasound signs of PAS, including presence of interrupted retroplacental space, bladder line and placental lacunae, were not associated neither predictive of emergency CD. In women with placenta previa but not PAS, emergency CD was required in 31.1% (95% CI 26.6-36.2) and 32.8% delivered before 34 weeks of gestation. Mean gestational age at delivery was lower in women undergoing compared to those not undergoing emergency delivery (34.2±2.9 vs 36.7±1.6; p<0.001). Pregnancies complicated by emergency CD, had new-borns with a lower birthweight (2330±620 g vs 2800±620 g, p<0.001) and had a higher risk of receiving blood transfusions (22.7% vs 10.7%, p= 0.003) compared to those who underwent elective CD. At multivariate analysis, only placental thickness (p= 0.046) and a cervical length < 25 mm (OR: 3.89, 95% CI 3.89-11.33, p= 0.01) were associated with emergency CD. However, a short CL showed a low diagnostic accuracy for predicting emergency CD in these women. Conclusion: Emergency CD complicated about 20% of women with PAS disorders and 30% of those with placenta previa and not PAS and is associated with a worse maternal and perinatal outcome compared to elective intervention. Prenatal ultrasound cannot entirely predict the risk of emergency delivery in women with these disorders. This article is protected by copyright. All rights reserved.

2023 - Effect of the Enrichment in c-Kit Stem Cell Potential of Foetal Human Amniotic Fluid Cells: Characterization from Single Cell Analysis to the Secretome Content [Articolo su rivista]
Casciaro, Francesca; Beretti, Francesca; Gatti, Martina; Persico, Giuseppe; Bertucci, Emma; Giorgio, Marco; Maraldi, Tullia
abstract

Human amniotic fluid cells (hAFSCs) are a fascinating foetal cell-type that have important stem cell characteristics; however, they are a heterogeneous population that ranges from totally differentiated or progenitor cells to highly multipotent stem cells. There is no single approach to isolating the stem cell component, but the selection of a subpopulation of hAFSCs expressing c-Kit is widely employed, while a deep characterization of the two populations is still lacking. Here we performed single-cell and bulk RNAseq analysis to compare the gene expression profiles of adherent amniotic fluid cells and their subpopulation c-Kit . Information deriving from this high throughput technology on the transcriptome was then confirmed for specific targets with protein expression experiments and functional analysis. In particular, transcriptome profiling identified changes in cellular distribution among the different clusters that correlated with significant differential expression in pathways related to stemness, proliferation, and cell cycle checkpoints. These differences were validated by RT-PCR, immunofluorescence, WB, and cell cycle assays. Interestingly, the two populations produced secretomes with different immune-modulating and pro-regenerative potentials. Indeed, the presence of TGF, HGF, IDO was higher in EVs deriving from c-Kit+ cells, unlike IL- 6. These results suggest the existence of deep intra-population differences that can influence the stemness profile of hAFSCs. This study represents a proof-of-concept of the importance of selecting c-Kit positive fractions with higher potential in regenerative medicine applications.

2023 - Healthy preterm newborns: Altered innate immunity and impaired monocyte function [Articolo su rivista]
De Biasi, Sara; Neroni, Anita; Nasi, Milena; Lo Tartaro, Domenico; Borella, Rebecca; Gibellini, Lara; Lucaccioni, Laura; Bertucci, Emma; Lugli, Licia; Miselli, Francesca; Bedetti, Luca; Neri, Isabella; Ferrari, Fabrizio; Facchinetti, Fabio; Berardi, Alberto; Cossarizza, Andrea
abstract

: Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.

2023 - How adenomyosis changes throughout pregnancy: A retrospective cohort study [Articolo su rivista]
Bertucci, Emma; Sileo, Filomena G; Diamanti, Marialaura; Alboni, Carlo; Facchinetti, Fabio; La Marca, Antonio
abstract

Objective To study how adenomyosis changes during pregnancy and to possibly correlate these changes to maternal and fetal outcomes. Methods Retrospective exploratory cohort study including 254 women with a pre-conceptional/first-trimester scan to document adenomyosis and known obstetric outcome. If visible, adenomyosis signs were documented in each trimester and postpartum. Mann-Whitney U tests or chi(2) tests were used for continuous and categorical variables, respectively. Results A globular uterus was reported in 79% (n = 52) of women with adenomyosis in the first trimester, in 38% (n = 20) and 2% (n = 1) of women in the second and third trimesters, respectively, and postpartum in 77% (n = 34) of women. Asymmetrical thickening (n = 20, 30%) and cysts (n = 15, 23%) were only visible in 1st trimester. Adenomyosis was associated with miscarriage (odds ratio [OR] 5.9, 95% confidence interval [CI] 2.4-14.9, P < 0.001) also in normal conception only (OR 5.1, 95% CI 1.8-14.2, P = 0.002) or adjusting for maternal age (adjusted OR 5.9, 95% CI 2.3-15.2, P < 0.001). Gestational age at delivery was lower in adenomyosis (P = 0.004); the cesarean section rate was higher than in controls (OR 2.5, 95% CI 1.3-4.8, P = 0.007) also adjusting for age (adjusted OR 2.07, 95% CI 1.06-4.08, P = 0.035). Conclusions Signs of adenomyosis were visible but progressively disappeared in pregnancy; adenomyosis was associated with an increased risk of early miscarriage. Prospective studies are needed to confirm our results.

2023 - Human Neuromuscular Junction on a Chip: Impact of Amniotic Fluid Stem Cell Extracellular Vesicles on Muscle Atrophy and NMJ Integrity [Articolo su rivista]
Gatti, Martina; Dittlau, Katarina Stoklund; Beretti, Francesca; Yedigaryan, Laura; Zavatti, Manuela; Cortelli, Pietro; Palumbo, Carla; Bertucci, Emma; Van Den Bosch, Ludo; Sampaolesi, Maurilio; Maraldi, Tullia
abstract

: Neuromuscular junctions (NMJs) are specialized synapses, crucial for the communication between spinal motor neurons (MNs) and skeletal muscle. NMJs become vulnerable in degenerative diseases, such as muscle atrophy, where the crosstalk between the different cell populations fails, and the regenerative ability of the entire tissue is hampered. How skeletal muscle sends retrograde signals to MNs through NMJs represents an intriguing field of research, and the role of oxidative stress and its sources remain poorly understood. Recent works demonstrate the myofiber regeneration potential of stem cells, including amniotic fluid stem cells (AFSC), and secreted extracellular vesicles (EVs) as cell-free therapy. To study NMJ perturbations during muscle atrophy, we generated an MN/myotube co-culture system through XonaTM microfluidic devices, and muscle atrophy was induced in vitro by Dexamethasone (Dexa). After atrophy induction, we treated muscle and MN compartments with AFSC-derived EVs (AFSC-EVs) to investigate their regenerative and anti-oxidative potential in counteracting NMJ alterations. We found that the presence of EVs reduced morphological and functional in vitro defects induced by Dexa. Interestingly, oxidative stress, occurring in atrophic myotubes and thus involving neurites as well, was prevented by EV treatment. Here, we provided and validated a fluidically isolated system represented by microfluidic devices for studying human MN and myotube interactions in healthy and Dexa-induced atrophic conditions-allowing the isolation of subcellular compartments for region-specific analyses-and demonstrated the efficacy of AFSC-EVs in counteracting NMJ perturbations.

2023 - Role of fetal magnetic resonance imaging in fetuses with congenital cytomegalovirus infection: multicenter study [Articolo su rivista]
Di Mascio, D.; Rizzo, G.; Khalil, A.; D'Antonio, F.; Di Mascio, D.; Rizzo, G.; Khalil, A.; Giancotti, A.; Manganaro, L.; Visentin, S.; Cosmi, E.; Prefumo, F.; Stampalija, T.; D'Ambrosio, V.; Brunelli, R.; Liberati, M.; Buca, D.; Matarrelli, B.; D'Amico, A.; Oronzii, L.; Tinari, S.; Caulo, M.; Gentile, L.; Fantasia, I.; Mappa, I.; Maruotti, G. M.; Saccone, G.; Carbone, L.; Sarno, L.; Bracalente, G.; Bertucci, E.; Sileo, F. G.; Pellegrino, M.; De Santis, M.; Lanzone, A.; Pinelli, L.; Murru, F.; Trincia, E.; Pajno, C.; Sorrenti, S.; Vasciaveo, L.; Nappi, L.; Greco, P.; D'Antonio, F.
abstract

Objective: To investigate the role of fetal brain magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses with congenital cytomegalovirus (CMV) infection and normal neurosonography. Methods: This was a multicenter, retrospective cohort study of patients examined between 2012 and 2021 in 11 referral fetal medicine centers in Italy. Inclusion criteria were fetuses with congenital CMV infection diagnosed by polymerase chain reaction analysis of amniotic fluid, pregnancies that underwent detailed multiplanar ultrasound assessment of the fetal brain as recommended by the International Society of Ultrasound in Obstetrics and Gynecology, maternal age ≥ 18 years, normal fetal karyotype and MRI performed within 3 weeks after the last ultrasound examination. The primary outcome was the rate of central nervous system (CNS) anomalies detected exclusively on MRI and confirmed after birth or autopsy in fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography at diagnosis. Additional CNS anomalies were classified into anomalies of the ventricular and the periventricular zone, intracranial calcifications in the basal ganglia or germinal matrix, destructive encephalopathy in the white matter, malformations of cortical development, midline anomalies, posterior fossa anomalies and complex brain anomalies. We evaluated the relationship between the incidence of structural CNS malformations diagnosed exclusively on fetal MRI and a number of maternal and gestational characteristics. Univariate and multivariate logistic regression analyses were used to identify and adjust for potential independent predictors of the MRI diagnosis of fetal anomalies. Results: The analysis included 95 fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography referred for prenatal MRI. The rate of structural anomalies detected exclusively at fetal MRI was 10.5% (10/95). When considering the type of anomaly, malformations of cortical development were detected on MRI in 40.0% (4/10) of fetuses, destructive encephalopathy in 20.0% (2/10), intracranial calcifications in the germinal matrix in 10.0% (1/10) and complex CNS anomalies in 30.0% (3/10). On multivariate logistic regression analysis, only CMV viral load in the amniotic fluid, expressed as a continuous variable (odds ratio (OR), 1.16 (95% CI, 1.02-1.21); P = 0.02) or categorical variable (> 100 000 copies/mL) (OR, 12.0 (95% CI, 1.2-124.7); P = 0.04), was independently associated with the likelihood of detecting fetal anomalies on MRI. Associated anomalies were detected exclusively at birth and missed by both prenatal neurosonography and fetal MRI in 3.8% (3/80) of fetuses with congenital CMV infection. Conclusions: Fetal brain MRI can detect additional anomalies in a significant proportion of fetuses with congenital CMV infection and negative neurosonography. Viral load in the amniotic fluid was an independent predictor of the risk of associated anomalies in these fetuses. The findings of this study support a longitudinal evaluation using fetal MRI in congenital CMV infection, even in cases with negative neurosonography at diagnosis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

2022 - Autosomal recessive cutis laxa type IIIA: Report of a patient with severe phenotype and review of the literature [Articolo su rivista]
Lugli, Licia; Cavalleri, Francesca; Bertucci, Emma; Fischer-Zirnsak, Björn; Cinelli, Giulia; Trevisani, Viola; Rossi, Cecilia; Riva, Marika; Iughetti, Lorenzo; Berardi, Alberto
abstract

Autosomal recessive cutis laxa type IIIA is a very rare genetic condition, caused by pathogenic variants in ALDH18A1, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS). This enzyme catalyzes the reduction of glutamic acid to delta1-pyrroline-5-carboxylate, playing a key role in the de novo biosynthesis of proline, ornithine, and arginine. Autosomal recessive cutis laxa type IIIA is characterized by abundant and wrinkled skin, skeletal anomalies, cataract or corneal clouding and neuro-developmental disorders of variable degree. We report on a patient with autosomal recessive cutis laxa type IIIA, due to a homozygous missense c.1273C > T; p. (Arg425Cys) pathogenic variant in ALDH18A1. The patient presented a severe phenotype with serious urological involvement, peculiar cerebro-vascular abnormalities and neurodevelopmental compromise. This description contributes to better characterize the phenotypic spectrum associated with ALDH18A1 pathogenic variants, confirming the systemic involvement as a typical feature of autosomal recessive cutis laxa type IIIA.

2022 - Complete hydatidiform mole in higher-order multiple pregnancies [Articolo su rivista]
Sileo, F. G.; Giuliani, G. A.; Facchinetti, F.; Contu, G.; Chiossi, G.; Bertucci, E.
abstract

Molar degeneration of the trophoblast is a rare, yet possible, complication of pregnancies. Complete hydatidiform mole is the most common histological type among all trophoblastic tumors and it is the result of the fertilization of an empty oocyte from two sperms or by one sperm that then duplicates. Complete mole is characterized by hydropic degeneration of abnormal chorionic villi, diffused trophoblast hyperplasia and the absence of identifiable embryonic or fetal tissue; the hyperplastic trophoblast justifies the common finding of high serum beta HCG levels. Twin molar pregnancy is an uncommon obstetric event, and even less frequent are triplet/quadruplet molar pregnancies. We hereby report a case of a complete hydatidiform mole with two coexistent fetuses in a triplet pregnancy after in vitro fertilization procedure; the pregnancy ended with a therapeutic abortion. During the follow-up, the serum beta human chorionic gonadotropin concentration started to rise, and the diagnosis of post-molar gestational trophoblastic neoplasia was made and consequently methotrexate treatment was started. Due to the rarity of this condition, there are no specific guidelines for the management of multiple pregnancies complicated by complete hydatidiform mole. We therefore performed a review of the literature including all reported cases of triplets/quadruplets pregnancies complicated by complete mole of a fetus focusing on ultrasound diagnosis, treatment and outcomes of this rare and life-threatening condition.

2022 - Counseling and prenatal diagnosis in facioscapulohumeral muscular dystrophy: A retrospective study on a 13‐year multidisciplinary approach [Articolo su rivista]
Di Feo, Maria Francesca; Bettio, Cinzia; Salsi, Valentina; Bertucci, Emma; Tupler, Rossella
abstract

2022 - First-trimester prediction model for placental vascular disorders: an observational prospective study [Articolo su rivista]
Monari, Francesca; Spano' Bascio, Ludovica; Banchelli, Federico; Neri, Isabella; Bertucci, Emma; Ferrari, Francesca; Menichini, Daniela; D'Amico, Roberto; Facchinetti, Fabio
abstract

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications.

2022 - Implementation of guidelines about women with previous cesarean section through educational/motivational interventions [Articolo su rivista]
Monari, Francesca; Menichini, Daniela; Bertucci, Emma; Neri, Isabella; Perrone, Enrica; Facchinetti, Fabio
abstract

Objective: The study reports the effect of a quality improvement project with an educational/motivational intervention, in northern Italy on the implementation of the trial of labor after Caesarean Section (CS). Method: A pre-post study design was used. Every birth center (23) of the Emilia-Romagna region was included. Gynecologists' opinion leaders were first trained about CS Italian recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected in 2 periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes. Results: A total of 20,496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (p<0.001). The likelihood of VBAC, adjusted for age ≥40, Caucasian, BMI ≥30, previous vaginal delivery, and labor induction, was increased by the intervention of 42% (OR=1.42, 95% CI 1.31-1.54). Neonatal well-being was improved by intervention, indeed neonates requiring resuscitation decreased from 2.1% to 1.6% (p=0.001). Conclusion: Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being.

2022 - Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol [Articolo su rivista]
Bronacha, Mylrea-Foley; Jim G, Thornton; Edward, Mullins; Neil, Marlow; Kurt, Hecher; Christina, Ammari; Birgit, Arabin; Astrid, Berger; Eva, Bergman; Amarnath, Bhide; Caterina, Bilardo; Julia, Binder; Andrew, Breeze; Jana, Brodszki; Pavel, Calda; Rebecca, Cannings-John; Andrej, Černý; Elena, Cesari; Irene, Cetin; Andrea, Dall'Asta; Anke, Diemert; Cathrine, Ebbing; Torbjørn, Eggebø; Ilaria, Fantasia; Enrico, Ferrazzi; Tiziana, Frusca; Tullio, Ghi; Jenny, Goodier; Patrick, Greimel; Wilfried, Gyselaers; Wassim, Hassan; Constantin, Von Kaisenberg; Alexey, Kholin; Philipp, Klaritsch; Ladislav, Krofta; Peter, Lindgren; Silvia, Lobmaier; Karel, Marsal; Giuseppe M, Maruotti; Federico, Mecacci; Kirsti, Myklestad; Raffaele, Napolitano; Eva, Ostermayer; Aris, Papageorghiou; Claire, Potter; Federico, Prefumo; Luigi, Raio; Jute, Richter; Ragnar Kvie, Sande; Dietmar, Schlembach; Ekkehard, Schleußner; Tamara, Stampalija; Basky, Thilaganathan; Julia, Townson; Herbert, Valensise; Gerard Ha, Visser; Ling, Wee; Hans, Wolf; Lees, ; TRUFFLE 2 Collaborators List: Andrea Smith, Christoph C.; Sharp, Andrew; Simm, Andy; Ramoni, Angela; Lloyd, Barry; Masturzo, Bianca; Morfeld, Christine; Lloyd, Christopher; Seidig, Claudia; Thornton, Danielle; Mantovani, Elena; Taricco, Emanuela; Bertucci, Emma; Cosmi, Erich; Ostermayer, Eva; Macsali, Ferenc; Ferrari, Francesca; D'Antonio, Francesco; Picciotto, Francesco; Waring, Gareth; Rembouskos, Georgios; Cali, Giuseppe; Rizzo, Giuseppe; Maria Tiralongo, Grazia; Fantasia, Ilaria; Giuditta Ramezzana, Ilaria; Mappa, Ilenia; Kyvernitakis, Ioannis; Derwig, Iris; Dressler-Steinbach, Iris; Vojěch, Jiří; Linde, Jørgen; Binder, Julia; Melchiorre, Karen; Walker, Kate; Chalubinski, Kinga; Rull, Kristiina; Kernell, Kristina; Brodowski, Lars; Sarno, Laura; Jokibkiene, Ligita; Rajasalu, Liina; Fryszer, Lina-Ana; Jones, Louisa; Bednarek-Jędrzejek, Magdalena; Savvidou, Makrina; Stefopoulou, Maria; Rambaldi, Marianna; Kilby, Mark; Jones, Nia; Fratelli, Nicola; Deole, Nishigandh; Greimel, Patrick; Pateisky, Petra; Palmrich, Pilar; Schild, Ralf; Devlieger, Roland; Ondrová, Sabina; Gumpert, Sarah; Taylor, Sasha; Schmidt, Saskia; Kwiatkowski, Sebastian; Caterina, Serena; Ottanelli, Serena; Simeone, Serena; Ferrazzani, Sergio; Salvi, Silvia; Visentin, Silvia; Amylidi-Mohr, Sofia; Bakalis, Spyros; Verlohren, Stefan; Dargel, Susanne; Kehl, Sven; Groten, Tanja; Radaelli, Tatjana; Mesens, Tinne; Fanelli, Tiziana; Eggebø, Torbjørn; Ghi, Tullio; Haabpiht, Tuuli; Hassan, Wassim; Heiman, Yvonne; Khodzhaeva, Zulfiya; Thilaganathan, Baskaran; Brezinka, Christoph; Gordijn, Sanne; Ganzevoort, Wessel; Thomas Andrea Smith, Abin; Sharp, Andrew; Simm, Andy; Ramoni, Angela; Lloyd, Barry; Masturzo, Bianca; Morfeld, Christine; Lloyd, Christopher; Seidig, Claudia; Thornton, Danielle; Mantovani, Elena; Taricco, Emanuela; Bertucci, Emma; Cosmi, Erich; Ostermayer, Eva; Macsali, Ferenc; Ferrari, Francesca; D'Antonio, Francesco; Picciotto, Francesco; Waring, Gareth; Rembouskos, Georgios; Cali, Giuseppe; Rizzo, Giuseppe; Maria Tiralongo, Grazia; Fantasia, Ilaria; Giuditta Ramezzana, Ilaria; Mappa, Ilenia; Kyvernitakis, Ioannis; Derwig, Iris; Dressler-Steinbach, Iris; Vojěch, Jiří; Linde, Jørgen; Binder, Julia; Melchiorre, Karen; Walker, Kate; Chalubinski, Kinga; Rull, Kristiina; Kernell, Kristina; Brodowski, Lars; Sarno, Laura; Jokibkiene, Ligita; Rajasalu, Liina; Fryszer, Lina-Ana; Jones, Louisa; Bednarek-Jędrzejek, Magdalena; Savvidou, Makrina; Stefopoulou, Maria; Rambaldi, Marianna; Kilby, Mark; Jones, Nia; Fratelli, Nicola; Deole, Nishigandh; Greimel, Patrick; Pateisky, Petra; Palmrich, Pilar; Schild, Ralf; Devlieger, Roland; Ondrová, Sabina; Gumpert, Sarah; Taylor, Sasha; Schmidt, Saskia; Kwiatkowski, Sebastian; Caterina, Serena; Ottanelli, Serena; Simeone, Serena; Ferrazzani, Sergio; Salvi, Silvia; Visentin, Silvia; Amylidi-Mohr, Sofia; Bakalis, Spyros; Verlohren, Stefan; Dargel, Susanne; Kehl, Sven; Grot
abstract

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

2022 - Ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from ADoPAD study [Articolo su rivista]
Fratelli, N; Prefumo, F; Maggi, C; Cavalli, C; Sciarrone, A; Garofalo, A; Viora, E; Vergani, P; Ornaghi, S; Betti, M; Tessitore, I Vaglio; Cavaliere, A F; Buongiorno, S; Vidiri, A; Fabbri, E; Ferrazzi, E; Maggi, V; Cetin, I; Frusca, T; Ghi, T; Kaihura, C; Di Pasquo, E; Stampalija, T; Belcaro, C; Quadrifoglio, M; Veneziano, M; Mecacci, F; Simeone, S; Locatelli, A; Consonni, S; Chianchiano, N; Labate, F; Cromi, A; Bertucci, E; Facchinetti, F; Fichera, A; Granata, D; Antonio, F D'; Foti, F; Avagliano, L; Bulfamante, G P; Calì, G
abstract

Objectives: To evaluate the diagnostic performance of third trimester ultrasound for the diagnosis of clinically significant Placenta accreta spectrum disorder (PAS) in women with a low-lying placenta (less than 20 mm from the internal cervical os) or placenta praevia (covering the os) METHODS: Pregnant women with a low-lying placenta or placenta praevia, age ≥ 18 years and gestational age at ultrasound ≥ 26+0/7 weeks of gestation were prospectively included in the study. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs: (1) obliteration of the hypoechoic space between the uterus and the placenta; (2) interruption of the hyperechoic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. In order to assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprehensive of both active management at delivery and histopathological confirmation of PAS was considered as the reference standard. PAS was considered of clinical significance if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation, uterine artery embolization. Results: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations. Of them, 95 delivered in local hospitals and placental pathology according to the study protocol was therefore not available. Among the 473 for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%). A normal hypoechoic space between the uterus and the placenta reduces post-test probability of PAS from 21% to 5% in women with a low-lying placenta or placenta previa in the third trimester of pregnancy, and from 62% to 9% in the subgroup of women with previous cesarean section and anterior placenta. The absence of lacunae reduces post-test probability of PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy, and from 62% to 36% in the subgroup with previous cesarean section and anterior placenta. On the other side, when lacunae are seen the post-test probability increases from 21% to 59% in the whole study population and from 62% to 78% in women with placenta previa, previous cesarean section and anterior placenta. Conclusions: Grey-scale ultrasound is a good test to identify pregnancies at low risk of PAS in this high risk population. Ultrasound can be safely used to guide management decisions, concentrating greater resources in patients with the higher risk of clinically significant PAS This article is protected by copyright. All rights reserved.

2022 - Ultrasound screening for fetal anomalies in a single center: diagnostic performances twenty years after the Eurofetus Study [Articolo su rivista]
Sileo, F. G.; Finarelli, A.; Contu, G.; Lugli, L.; Dipace, V.; Ballarini, M.; Guidi, C.; Facchinetti, F.; Bertucci, E.
abstract

Purpose: To establish the accuracy of ultrasound in detecting fetal anomalies looking at the concordance between prenatal and postnatal diagnosis. Materials and methods: Retrospective analysis of concordance between prenatal and postnatal/autoptic diagnosis of fetuses with congenital abnormalities. Data are from a single center (Policlinico di Modena); all fetuses included were born between 2017 and 2018 and with a follow-up of at least 6 months. We included all deliveries (including perinatal deaths) and termination of pregnancy (TOP) for fetal indication. We calculated sensibility, sensitivity, Positive and Negative Likelihood Ratio, positive and negative predictive value of ultrasound. Results: During the study period 5920 deliveries, including perinatal deaths, and 28 TOP for fetal indication were registered at our center. The prevalence of congenital malformations was 2.6% (153/5920). At least one ultrasound was performed in our center in 1250 women delivering in our unit. All 28 TOP had the anomaly scan performed in our center. Among the total 1278 women scanned in our unit, there were 128 (10%) suspicious scans. In 5/128 (3.9%) cases we diagnosed a false alarm; in 8/128 (6.2%) cases an evolutive malformation with in-utero regression. The prenatal diagnosis was confirmed in 77 (60.2%) cases at birth and in 28/128 (21.9%) at postmortem analysis while there were 10/128 false positive (7.8%). Among the 153 congenital malformations diagnosed at birth, the anomaly scan was performed in our Prenatal Medicine Unit in 92 (60.1%) fetuses. Among these, there were 15 false negatives (9.8%) while in 77/92 (83.7%) the malformation at birth agreed with the sonographic diagnosis. Sensitivity and specificity of ultrasound were 87.5% (IC95 80.2–92.8%) and 99.1% (IC95 98.4–99.6%) respectively with a Positive Likelihood Ratio and Negative Likelihood Ratio of 101.3 (IC95 54.5–188.5) and 0.13 (IC95 0.08–0.2); Positive Predictive Value and Negative Predictive Value were 91.3% (IC95 85–95.1%) and 98.7(IC95 98–99.2%). Conclusion: Anomaly scan in pregnancy allows the diagnosis of congenital malformations with a sensibility of 87.5% and specificity of 99.1%. The main limitations of this study are its retrospective design and that it was conducted in a single referral center.

2021 - Amniotic fluid stem cell-derived extracellular vesicles counteract steroid-induced osteoporosis in vitro [Articolo su rivista]
Gatti, M.; Beretti, F.; Zavatti, M.; Bertucci, E.; Luz, S. R.; Palumbo, C.; Maraldi, T.
abstract

Background—Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods—human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological as-says. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results—AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexa-methasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion— these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.

2021 - CD133 expression in placenta chorioangioma presenting as a giant asymptomatic mass [Articolo su rivista]
Massa, G. D.; Stabile, G.; Romano, F.; Balduit, A.; Mangogna, A.; Belmonte, B.; Canu, P.; Bertucci, E.; Ricci, G.; Salviato, T.
abstract

Background: Placental chorioangioma is the most common benign non-trophoblastic neoplasm of the placenta. Its clinical relevance lies in the size of the tumor since larger masses cause pregnancy complications, including an unfavorable neonatal outcome. Case presentation: We report the case of a 34-year-old second gravida and nullipara at the 35th week of gestation, admitted to the gynecological department for antibiotic-resistant fever. The cardiotocography performed during hospitalization showed an abnormal fetal pattern. A 2250 g newborn was delivered by cesarean section. No complications were observed during childbirth and postpartum was insignificant. On gross inspection a white fleshy intraparenchymal mass blooming on the maternal surface was noted; routinely stained sections revealed features consistent with chorioangioma with vascular channels lined by inconspicuous endothelial cells immunoreactive for CD31 and CD133. Focal expression of CD133 was also observed in placental villi. Discussion: CD133 expression indicated the presence of stem cells in chorioangioma, suggesting their possible role in the development of mesenchymal lesions including chorioangioma.

2021 - Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study [Articolo su rivista]
Di Mascio, Daniele; Herraiz, Ignacio; Villalain, Cecilia; Buca, Danilo; Morales-Rossello, Jose; Loscalzo, Gabriela; Sileo, Filomena; Finarelli, Alessandra; Bertucci, Emma; Facchinetti, Fabio; Rizzo, Giuseppe; Brunelli, Roberto; Giancotti, Antonella; Muzii, Ludovico; Maria Maruotti, Giuseppe; Carbone, Luigi; D’Amico, Alice; Tinari, Sara; Morelli, Roberta; Cerra, Chiara; Nappi, Luigi; Greco, Pantaleo; Liberati, Marco; Galindo, Alberto; D’Antonio, Francesco
abstract

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.

2021 - Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study [Articolo su rivista]
Villalain, C.; Galindo, A.; Di Mascio, D.; Buca, D.; Morales-Rossello, J.; Loscalzo, G.; Giulia Sileo, F.; Finarelli, A.; Bertucci, E.; Facchinetti, F.; Rizzo, G.; Brunelli, R.; Giancotti, A.; Muzii, L.; Maria Maruotti, G.; Carbone, L.; D'Amico, A.; Tinari, S.; Morelli, R.; Cerra, C.; Nappi, L.; Greco, P.; Liberati, M.; D'Antonio, F.; Herraiz, I.
abstract

Background: Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight. Objective: To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery. Study design: Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than −11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed. Results: 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46–3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39–0.51)] and late FGR fetuses [AUC: 0.56 (0.49–0.61)]. Conclusions: CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.

2021 - Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG [Articolo su rivista]
Lugli, L.; Bariola, M. C.; Ferri, L.; Lucaccioni, L.; Bertucci, E.; Cattini, U.; Torcetta, F.; Morrone, A.; Iughetti, L.; Berardi, A.
abstract

Congenital disorders of glycosylation (CDG) are an expanding group of metabolic disorders that result from abnormal protein glycosylation. A special subgroup of CDG type II comprises defects in the Conserved Oligomeric Golgi Complex (COG). In order to further delineate the genotypic and phenotypic spectrum of COG complex defect, we describe a novel variant of COG6 gene found in homozygosity in a Moroccan patient with severe presentation of COG6-CDG (OMIM #614576). We compared the phenotype of our patient with other previously reported COG6-CDG cases. Common features in COG6-CDG are facial dysmorphism, growth retardation, microcephaly, developmental disability, liver or gastrointestinal disease, recurrent infections, hypohidrosis/hyperthermia. In addition to these phenotypic features, our patient exhibited a disorder of sexual differentiation, which has rarely been reported in COG6-CDG. We hypothesize that the severe COG6 gene mutation interferes with glycosylation of a disintegrin and metalloprotease family members, inhibiting the correct gonadal distal tip cells migration, fundamental for the genitalia morphogenesis. This report broadens the genetic and phenotypic spectrum of COG6-CDG and provides further supportive evidence that COG6-CDG can present as a disorder of sexual differentiation.

2021 - Homozygous n.64C>T mutation in mitochondrial RNA-processing endoribonuclease gene causes cartilage hair hypoplasia syndrome in two siblings [Articolo su rivista]
Lugli, L.; Ciancia, S.; Bertucci, E.; Lucaccioni, L.; Calabrese, O.; Madeo, S.; Berardi, A.; Iughetti, L.
abstract

Cartilage hair hypoplasia syndrome (OMIM # 250250) is a rare autosomal recessive metaphyseal dysplasia, characterized by disproportionate short stature, hair hypoplasia and variable extra-skeletal manifestations, including immunodeficiency, anemia, intestinal diseases and predisposition to cancers. Cartilage hair hypoplasia syndrome has a broad phenotype and it is caused by homozygous or compound heterozygous mutation in the mitochondrial RNA-processing endoribonuclease on chromosome 9p13. Although it is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. To add further details to the knowledge of the phenotypic spectrum of the disease, we report on two siblings with cartilage hair hypoplasia syndrome, presenting n.64C > T homozygous mutation in the mitochondrial RNA-processing endoribonuclease gene. We describe the prenatal and postnatal growth pattern of the two affected patients, showing severe pre- and post-natal growth deficiency.

2021 - Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study [Articolo su rivista]
Di Mascio, D.; Villalain, C.; Rizzo, G.; Morales-Rossello, J.; Sileo, F. G.; Maruotti, G. M.; Prefumo, F.; Galindo, A.; D'Antonio F, induction of labor in late fetal growth restriction COLLEGE study Group: Di Mascio D.; Villalain, C.; Buca, D.; Herraiz, I.; Rizzo, G.; Morales-Rossello, J.; Loscalzo, G.; Sileo, Fg.; Finarelli, A.; Bertucci, E.; Facchinetti, F.; Brunelli, R.; Giancotti, A.; Muzii, L.; Maruotti, Gm.; Carbone, L.; Saccone, G.; D'Amico, A.; Tinari, S.; Cerra, C.; Prefumo, F.; Nappi, L.; Greco, P.; Monaci, R.; Fichera, A.; Fratelli, N.; Liberati, M.; Galindo, A.; D'Antonio, F.
abstract

Introduction: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. Material and methods: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. Results: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001). Conclusions: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.

2021 - Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder [Articolo su rivista]
Sileo, Fg; Tramontano, Al; Leone, C; Meacci, M; Gennari, W; Ternelli, G; La Marca, A; Lugli, L; Berardi, A; Facchinetti, F; Bertucci, E
abstract

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35 t5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.

2021 - Role of prenatal magnetic resonance imaging in fetuses with isolated agenesis of corpus callosum in the era of fetal neurosonography: A systematic review and meta-analysis [Articolo su rivista]
Sileo, F. G.; Di Mascio, D.; Rizzo, G.; Caulo, M.; Manganaro, L.; Bertucci, E.; Masmejan, S.; Liberati, M.; D'Amico, A.; Nappi, L.; Buca, D.; Van Mieghem, T.; Khalil, A.; D'Antonio, F.
abstract

Introduction: Corpus callosum agenesis (ACC) is frequently diagnosed during fetal life; its prognosis depends also on additional anomalies. The additional value of fetal magnetic resonance imaging (MRI) in fetuses with “isolated” complete (cACC) and partial (pACC) agenesis of the corpus callosum on ultrasound is still debated. Material and methods: We performed a systematic literature review and meta-analysis including fetuses with a prenatal diagnosis of cACC and pACC without associated structural anomalies on ultrasound, undergoing fetal MRI. The primary outcome was the rate of additional anomalies detected at fetal MRI. Further analyses assessed the effect of type of ultrasound assessment (neurosonography vs standard axial assessment), gestational age at fetal MRI and rate of postnatally detected brain anomalies. Random-effect meta-analyses of proportions were used to analyze the data. Results: Fourteen studies (798 fetuses) were included. In cases with isolated cACC, 10.9% (95% CI 4.1-20.6) and 4.3% (95% CI 1.4-8.8) additional anomalies were detected by fetal MRI and postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 5.7% (95% CI 0.5-16.0) with dedicated neurosonography and 18.5% (95% CI 7.8-32.4) with a standard axial assessment. In fetuses with isolated pACC, 13.4% (95% CI 4.0-27.0) and 16.2% (95% CI 5.9-30.3) additional anomalies were detected by fetal MRI or postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 11.4% (95% CI 2.7-25.0) when dedicated neurosonography was performed. Cortical and posterior fossa anomalies represented the most common anomalies missed at ultrasound with both cACC and pACC. Due to the very small number of included cases, stratification according to early (<24 weeks of gestation) and late (>24 weeks) fetal MRI could not be done for either cACC or pACC. Conclusions: The rate of associated anomalies detected exclusively at fetal MRI in isolated ACC undergoing neurosonography is lower than previously reported. Cortical and posterior fossa anomalies are among the most common anomalies detected exclusively at MRI, thus confirming the crucial role of fetal MRI in determining the prognosis of these fetuses. However, some anomalies still go undetected prenatally and this should be stressed during parental counseling.

2021 - Role of prenatal magnetic resonance imaging in fetuses with isolated anomalies of corpus callosum: multinational study [Articolo su rivista]
Sileo, Filomena Giulia; Pilu, Gianluigi; Prayer, Daniela; Rizzo, Giuseppe; Khalil, Asma; Managanaro, Lucia; Volpe, Paolo; Van Mieghem, Tim; Bertucci, Emma; Morales Roselló, José; Facchinetti, Fabio; Di Mascio, Daniele; Stampalija, Tamara; Buca, Danilo; Tinari, Sara; Oronzi, Ludovica; Ercolani, Giada; D’Amico, Alice; Matarrelli, Barbara; Cerra, Chiara; Fantasia, Ilaria; Pasquini, Lucia; Masini, Giulia; Olivieri, Claudiana; Ghi, Tullio; Frusca, Tiziana; Dall’Asta, Andrea; Visentin, Silvia; Cosmi, Erich; D’Errico, Ignazio; Villalain, Cecilia; Quintero, Olivia Mendez; Giancotti, Antonella; D’Ambrosio, Valentina; Antonelli, Amanda; Caulo, Massimo; Panar, Valentina; De Santis, Marco; Mappa, Ilenia; Prefumo, Federico; Pinelli, Lorenzo; Loscalzo, Gabriela; Bracalente, Gabriella; Liberati, Marco; Filippi, Elisa; Trincia, Elena; Pateisky, Petra; Kiss, Herbert; Curado, Joana; Almeida, Marta; Santos, Antonia; Galindo, Alberto; D’Antonio, Francesco
abstract

To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography).

2021 - The appropriate counseling on prenatal screening test for foreign women in Emilia-Romagna [Articolo su rivista]
Menichini, Daniela; Sciutti, Giovanna; Miano, Maria Vittoria; Ricchi, Alba; Infante, Ramona; Molinazzi, Maria Teresa; Bertucci, Emma; Facchinetti, Fabio; Neri, Isabella
abstract

Objective: The increase in the migratory phenomenon entails the need to adapt obstetric care to the population which includes foreign pregnant women. In this context, it emerged a little adherence to the prenatal screening test among foreign women compared to Italian women, which is assumed to be attributable to an inadequate counseling. This study aims to evaluate midwife's perception of the  counseling effectiveness in foreign women for the combined test and subsequently assess its adequacy through an external evaluation. Methods: this is a cross-sectional study conducted from September to November 2019. An ad hoc questionnaire was administered to midwives working in the territorial district of the Emilia-Romagna Region, investigating their counseling skills. Then an external evaluation of the counseling was conducted by observing the interview between the midwives and the patients (N = 10), to analyze its appropriateness. Results: Seventy-five midwives completed the questionnaire with a positive response rate of 57.2%. In general, 69.3% of midwives are satisfied with the training received from the regional course, but 85% found many difficulties in counseling foreign women. The 14% of midwives state that they always have the cultural and linguistic mediator available and 44% of them state that they use brochures translated into several foreign languages. In the interviews observed, the counseling to foreign women was found to be shorter and more limited than that provided to Italian women. Conclusions: Most of the consulting midwives declare that they feel prepared to perform a correct prenatal counseling also for foreign women, but the external evaluation of the interviews, and the regional data on adherence to the antenatal screening of foreign women, show many critical points. It becomes necessary to carry out further studies that investigate not only the counseling skills of midwives, but also the needs of assisted women about prenatal diagnosis.

2021 - Unravelling Heterogeneity of Amplified Human Amniotic Fluid Stem Cells Sub-Populations [Articolo su rivista]
Casciaro, Francesca; Zia, Silvia; Forcato, Mattia; Zavatti, Manuela; Beretti, Francesca; Bertucci, Emma; Zattoni, Andrea; Reschiglian, Pierluigi; Alviano, Francesco; Bonsi, Laura; Follo, Matilde Yung; Demaria, Marco; Roda, Barbara; Maraldi, Tullia
abstract

Human amniotic fluid stem cells (hAFSCs) are broadly multipotent immature progenitor cells with high self-renewal and no tumorigenic properties. These cells, even amplified, present very variable morphology, density, intracellular composition and stemness potential, and this heterogeneity can hinder their characterization and potential use in regenerative medicine. Celector® (Stem Sel ltd.) is a new technology that exploits the Non-Equilibrium Earth Gravity Assisted Field Flow Fractionation principles to characterize and label-free sort stem cells based on their solely physical characteristics without any manipulation. Viable cells are collected and used for further studies or direct applications. In order to understand the intrapopulation heterogeneity, various fractions of hAFSCs were isolated using the Celector® profile and live imaging feature. The gene expression profile of each fraction was analysed using whole-transcriptome sequencing (RNAseq). Gene Set Enrichment Analysis identified significant differential expression in pathways related to Stemness, DNA repair, E2F targets, G2M checkpoint, hypoxia, EM transition, mTORC1 signalling, Unfold Protein Response and p53 signalling. These differences were validated by RT-PCR, immunofluorescence and differentiation assays. Interestingly, the different fractions showed distinct and unique stemness properties. These results suggest the existence of deep intra-population differences that can influence the stemness profile of hAFSCs. This study represents a proof-of-concept of the importance of selecting certain cellular fractions with the highest potential to use in regenerative medicine.

2020 - Case of Fetal Cardiomyopathy Diagnosis and Brugada Syndrome [Articolo su rivista]
Bertucci, Emma; Lugli, Licia; Guidi, Cristina; Dipace, Vincenza; Rossi, Katia; Vincenzo Livio, Malavasi; Facchinetti, Fabio
abstract

2020 - Comparison of the therapeutic effect of amniotic fluid stem cells and their exosomes on monoiodoacetate-induced animal model of osteoarthritis [Articolo su rivista]
Zavatti, M.; Beretti, F.; Casciaro, F.; Bertucci, E.; Maraldi, T.
abstract

The cartilage tissue engineering associated with stem cell-related therapies is becoming very interesting since adult articular cartilage has limited intrinsic capacity for regeneration upon injury. Amniotic fluid stem cells (AFSC) have been shown to produce exosomes with growth factors and immunomodulating molecules that could stop tissue degradation and induce cartilage repair. Based on this state of the art, the main aim of this study was to explore the efficacy of the secreted exosomes, compared to their AFSC source, in MIA-induced animal model of osteoarthritis mimicking a chronic and degenerative process, where inflammation is also involved and lead to irreversible joint damage. Exosomes, obtained by the use of a commercial kit, prior to the injection in animal knee joints, were characterized for the presence of typical markers and HGF, TGFβ, and IDO. Then, analyses were performed by histology, immunohistochemistry, and behavioral scoring up to 3 weeks after the treatment. Exosome-treated defects showed enhanced pain tolerance level and improved histological scores than the AFSC-treated defects. Indeed by 3 weeks, TGFβ-rich exosome samples induced an almost complete restoration of cartilage with good surface regularity and with the characteristic of hyaline cartilage. Moreover, cells positive for resolving macrophage marker were more easily detectable into exosome-treated joints. Therefore, a modulating role for exosomes on macrophage polarization is conceivable, as demonstrated also by experiments performed on THP1 macrophages. In conclusion, this study demonstrates for the first time the efficacy of human AFSC exosomes in counteract cartilage damage, showing a positive correlation with their TGFβ content.

2020 - Core outcome set for studies investigating management of selective fetal growth restriction in twins [Articolo su rivista]
Townsend, R.; Duffy, J. M. N.; Sileo, F.; Perry, H.; Ganzevoort, W.; Reed, K.; Baschat, A. A.; Deprest, J.; Gratacos, E.; Hecher, K.; Lewi, L.; Lopriore, E.; Oepkes, D.; Papageorghiou, A.; Gordijn, S. J.; Khalil, A.; Perales-Marin, A.; Johnson, A.; Silvana, A.; Papageorghious, A.; Khurana, A.; Trinder, B.; Combs, C. A.; Bailie, C.; Huddy, C.; Bolch, C.; Coutinho, C. M.; Skupski, D.; Hake, D.; Schlembach, D.; Lindahl, E.; Carreras, E.; Mantovani, E.; Giallongo, E.; Marler, E.; Bertucci, E.; Prefumo, F.; Guy, G.; Rizzo, G.; King, H.; Valensise, H.; Samarage, H.; Duffy, J.; Denton, J.; Curado, J.; Marsden, J.; Tolosa, J. E.; Toms, J.; Copel, J.; Richards, J.; Ishii, K.; Palmer, K.; Watkins, K.; McGrath, L.; Canolini, L.; Dhuri, M. V.; Kyriakidou, M.; Lanna, M.; Treadwell, M.; Watson, M.; Rankin, M.; Fenwick, N.; Moore, P.; O'Brien, P.; Cincotta, R.; Linton, S.; Robinson, S.; McSorley, T.; Fuchs, T.; Ghi, T.; Omosebi, W.; Acheampong, Y.
abstract

Objective: Selective fetal growth restriction (sFGR) occurs in monochorionic twin pregnancies when unequal placental sharing leads to restriction in the growth of just one twin. Management options include laser separation of the fetal circulations, selective reduction or expectant management, but what constitutes the best treatment is not yet known. New trials in this area are urgently needed but, in this rare and complex group, maximizing the relevance and utility of clinical research design and outputs is paramount. A core outcome set ensures standardized outcome collection and reporting in future research. The objective of this study was to develop a core outcome set for studies evaluating treatments for sFGR in monochorionic twins. Methods: An international steering group of clinicians, researchers and patients with experience of sFGR was established to oversee the process of development of a core outcome set for studies investigating the management of sFGR. Outcomes reported in the literature were identified through a systematic review and informed the design of a three-round Delphi survey. Clinicians, researchers, and patients and family representatives participated in the survey. Outcomes were scored on a Likert scale from 1 (limited importance for making a decision) to 9 (critical for making a decision). Consensus was defined a priori as a Likert score of ≥ 8 in the third round of the Delphi survey. Participants were then invited to take part in an international meeting of stakeholders in which the modified nominal group technique was used to consider the consensus outcomes and agree on a final core outcome set. Results: Ninety-six outcomes were identified from 39 studies in the systematic review. One hundred and three participants from 23 countries completed the first round of the Delphi survey, of whom 88 completed all three rounds. Twenty-nine outcomes met the a priori criteria for consensus and, along with six additional outcomes, were prioritized in a consensus development meeting, using the modified nominal group technique. Twenty-five stakeholders participated in this meeting, including researchers (n = 3), fetal medicine specialists (n = 3), obstetricians (n = 2), neonatologists (n = 3), midwives (n = 4), parents and family members (n = 6), patient group representatives (n = 3), and a sonographer. Eleven core outcomes were agreed upon. These were live birth, gestational age at birth, birth weight, intertwin birth-weight discordance, death of surviving twin after death of cotwin, loss during pregnancy or before final hospital discharge, parental stress, procedure-related adverse maternal outcome, length of neonatal stay in hospital, neurological abnormality on postnatal imaging and childhood disability. Conclusions: This core outcome set for studies investigating the management of sFGR represents the consensus of a large and diverse group of international collaborators. Use of these outcomes in future trials should help to increase the clinical relevance of research on this condition. Consensus agreement on core outcome definitions and measures is now required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

2020 - MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women [Articolo su rivista]
Fiocchi, Federica; Monelli, Filippo; Besutti, Giulia; Casari, Federico; Petrella, Elisabetta; Pecchi, Annarita; Caporali, Cristian; Bertucci, Emma; Busani, Stefano; Botticelli, Laura; Facchinetti, Fabio; Torricelli, Pietro
abstract

To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI.

2020 - Oxidative stress in Alzheimer's disease: In vitro therapeutic effect of amniotic fluid stem cells extracellular vesicles [Articolo su rivista]
Gatti, M.; Zavatti, M.; Beretti, F.; Giuliani, D.; Vandini, E.; Ottani, A.; Bertucci, E.; Maraldi, T.
abstract

Alzheimer's disease (AD) is characterized by abnormal protein aggregation, deposition of extracellular β-amyloid proteins (Aβ), besides an increase of oxidative stress. Amniotic fluid stem cells (AFSCs) should have a therapeutic potential for neurodegenerative disorders, mainly through a paracrine effect mediated by extracellular vesicles (EV). Here, we examined the effect of EV derived from human AFSCs (AFSC-EV) on the disease phenotypes in an AD neuron primary culture. We observed a positive effect of AFSC-EV on neuron morphology, viability, and Aβ and phospho-Tau levels. This could be due to the apoptotic and autophagic pathway modulation derived from the decrease in oxidative stress. Indeed, reactive oxygen species (ROS) were reduced, while GSH levels were enhanced. This modulation could be ascribed to the presence of ROS regulating enzymes, such as SOD1 present into the AFSC-EV themselves. This study describes the ROS-modulating effects of extracellular vesicles alone, apart from their deriving stem cell, in an AD in vitro model, proposing AFSC-EV as a therapeutic tool to stop the progression of AD.

2020 - Prolonged hypoxia delays aging and preserves functionality of human amniotic fluid stem cells [Articolo su rivista]
Casciaro, F.; Borghesan, M.; Beretti, F.; Zavatti, M.; Bertucci, E.; Follo, M. Y.; Maraldi, T.; Demaria, M.
abstract

Human amniotic fluid stem cells (hAFSCs) are an emerging tool in regenerative medicine because they have the ability to differentiate into various lineages and efficiently improve tissue regeneration with no risk of tumorigenesis. Although hAFSCs are easily isolated from the amniotic fluid, their expansion ex vivo is limited by a quick exhaustion which impairs replicative potential and differentiation capacity. In this study, we evaluate various aging features of hAFSCs cultured at different oxygen concentrations. We show that low oxygen (1% O2) extends stemness and proliferative features, and delays induction of senescence-associated markers. Hypoxic hAFSCs activate a metabolic shift and increase resistance to pro-apoptotic stimuli. Moreover, we observe that cells at low oxygen remain capable of osteogenesis for prolonged periods of time, suggesting a more youthful phenotype. Together, these data demonstrate that low oxygen concentrations might improve the generation of functional hAFSCs for therapeutic use by delaying the onset of cellular aging.

2020 - Role of prenatal magnetic resonance imaging in fetuses with isolated mild or moderate ventriculomegaly in the era of neurosonography: international multicenter study [Articolo su rivista]
Di Mascio, D.; Khalil, A.; Thilaganathan, B.; Rizzo, G.; Buca, D.; Liberati, M.; Celentano, C.; Melchiorre, K.; Caulo, M.; Pilu, G.; Salsi, G.; Toni, F.; Stampalija, T.; Fantasia, I.; Luise, G.; Gregori, M.; Volpe, P.; Olivieri, C.; Giancotti, A.; D'Ambrosio, V.; Brunelli, R.; Panici, P. B.; Manganaro, L.; Antonelli, A.; Ercolani, G.; Pasquini, L.; Masini, G.; Di Maurizio, M.; Lees, C.; Bracalente, G.; Morales-Rosello, J.; Loscalzo, G.; Saccone, G.; Carbone, L.; Sarno, L.; Maruotti, G. M.; Zullo, F.; Ghi, T.; Frusca, T.; Dall'Asta, A.; Volpe, N.; Ormitti, F.; Buongiorno, S.; De Santis, M.; D'Oria, L.; Lanzone, A.; Prefumo, F.; Pinelli, L.; Bertucci, E.; Sileo, F. G.; Flacco, M. E.; Manzoli, L.; Giangiordano, I.; Mastricci, L.; Meccariello, G.; Vasciaveo, L.; Nappi, L.; Familiari, A.; Scambia, G.; Berghella, V.; D'Antonio, F.
abstract

Objectives: To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. Methods: This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0–11.9 mm) or moderate (ventricular atrial diameter, 12.0–14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Results: Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8–7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7–0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6–13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1–15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. Conclusions: The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

2019 - Hormonal contraception in women with endometriosis: a systematic review [Articolo su rivista]
Grandi, G.; Barra, F.; Ferrero, S.; Sileo, F. G.; Bertucci, E.; Napolitano, A.; Facchinetti, F.
abstract

Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence. Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment. Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence. Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.

2017 - The Jellyfish Sign: A New Sonographic Cervical Marker to Predict Maternal Morbidity in Abnormally Invasive Placenta Previa [Articolo su rivista]
Bertucci, E.; Sileo, F. G.; Grandi, G.; Fenu, V.; Cani, C.; Mancini, L.; Mataca, E.; Facchinetti, F.
abstract

Purpose -To investigate the value of a new cervical sonographic sign, called the jellyfish sign (JS), for predicting the risk of maternal morbidity in cases of abnormally invasive placenta (AIP) previa totalis. Materials and Methods -Retrospective evaluation of transvaginal (TV) and transabdominal (TA) scans performed in all singleton pregnancies with placenta previa totalis. JS, i.e. the absence of the normal linear demarcation between the placenta previa and the cervix, was evaluated by TV scans. The presence/severity of AIP and outcomes of maternal morbidity were related to this sign. Results -JS was noted in 8/39 (20.5%) patients. The two analyzed groups, i.e. with and without JS, were similar. The specificity of JS in AIP diagnosis, histological findings of accreta/increta/percreta, need for caesarean hysterectomy or blood loss >2000ml ranges between 92% and 96.2%, with the PPV and NPV ranging between 71.4% and 85.7% and 61.3% and 80.6%, respectively. The JS group had a significant increase in blood loss (ml) (p=0.003), transfusions (%) (p=0.016), red blood cells (p=0.002) and plasma (p=0.002), admission to an postoperative intensive care unit (ICU) (%) (p=0.002), hospitalization length (p<0.001) and the need of cesarean hysterectomy (%) (p<0.001). JS was independently correlated to cesarean hysterectomy (OR 25.6; 95% CI 2.0:322.3, p=0.012) and blood loss >2000ml (OR 16.6; 95% CI 1.5:180.1, p=0.021) also in a logistic regression model. Conclusion -JS is useful in predicting the increase in maternal morbidity: massive transfusion, admission to the ICU and cesarean hysterectomy related to intraoperative bleeding in patients with a previa AIP.

2016 - Development of the Fetal Vermis: New Biometry Reference Data and Comparison of 3 Diagnostic Modalities-3D Ultrasound, 2D Ultrasound, and MR Imaging [Articolo su rivista]
Katorza, E; Bertucci, Emma; Perlman, S; Taschini, Stefania; Ber, R; Gilboa, Y; Mazza, V; Achiron, Reuven
abstract

Normal biometry of the fetal posterior fossa rules out most major anomalies of the cerebellum and vermis. Our aim was to provide new reference data of the fetal vermis in 4 biometric parameters by using 3 imaging modalities, 2D ultrasound, 3D ultrasound, and MR imaging, and to assess the relation among these modalities. A retrospective study was conducted between June 2011 and June 2013. Three different imaging modalities were used to measure vermis biometry: 2D ultrasound, 3D ultrasound, and MR imaging. The vermian parameters evaluated were the maximum superoinferior diameter, maximum anteroposterior diameter, the perimeter, and the surface area. Statistical analysis was performed to calculate centiles for gestational age and to assess the agreement among the 3 imaging modalities. The number of fetuses in the study group was 193, 172, and 151 for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. The mean and median gestational ages were 29.1 weeks, 29.5 weeks (range, 21-35 weeks); 28.2 weeks, 29.05 weeks (range, 21-35 weeks); and 32.1 weeks, 32.6 weeks (range, 27-35 weeks) for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. In all 3 modalities, the biometric measurements of the vermis have shown a linear growth with gestational age. For all 4 biometric parameters, the lowest results were those measured by MR imaging, while the highest results were measured by 3D ultrasound. The inter- and intraobserver agreement was excellent for all measures and all imaging modalities. Limits of agreement were considered acceptable for clinical purposes for all parameters, with excellent or substantial agreement defined by the intraclass correlation coefficient. Imaging technique-specific reference data should be used for the assessment of the fetal vermis in pregnancy

2016 - Pre- and post-natal growth in two sisters with 3-M syndrome [Articolo su rivista]
Lugli, Licia; Bertucci, Emma; Mazza, Vincenzo; Elmakky, Amira; Ferrari, Fabrizio; Neuhaus, Christine; Percesepe, Antonio
abstract

3-M syndrome (OMIM #273750) is a rare autosomal recessive growth disorder characterized by severe pre- and post-natal growth restriction, associated with minor skeletal abnormalities and dysmorphisms. Although the 3-M syndrome is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. We report a family with variable phenotypic features of 3-M syndrome and we describe the prenatal and postnatal growth pattern of two affected sisters with a novel homozygous CUL7 mutation (c.3173-1G>C), showing a pre- and post-natal growth deficiency and a normal cranial circumference.

2015 - Fetal thymus volume estimation by virtual organ computer-aided analysis in normal pregnancies [Articolo su rivista]
Re, Claudia; Bertucci, Emma; Weissmann Brenner, Alina; Achiron, Reuven; Mazza, Vincenzo; Gindes, Liat
abstract

The thymus has a pyramidal shape, which is best shown in coronal planes. The aim of this study was to evaluate the potential of virtual organ computer-aided analysis to estimate fetal thymus volume in normal pregnancies. Three-dimensional volume data sets from the axial upper mediastinal section were acquired from 37 normal pregnancies between 12 and 35 weeks' gestation. Thymus volume was calculated by virtual organ computer-aided analysis by 2 separate examiners. In 12 cases, volumes were also acquired with 4-dimensional sonography and spatiotemporal image correlation software to assess the variability in thymus size between the systolic and diastolic periods of fetal heart motion. Linear regression analysis was used to assess the relationship between the fetal thymus volume and gestational age. Paired Student t tests were used to evaluate both the level of agreement for interobserver and intraobserver variability and the difference between diastolic and systolic thymus volumes. Identification of the borders of the thymus and calculation of its volume were successful in 28 patients (77.7%). Statistically significant linear growth of the thymus during pregnancy, from 12 to 35 weeks, was found. The growth coefficient for each gestational age was 0.43 (95% confidence interval, 0.355 to 0.504; P < .001). The difference in thymus size between systole and diastole was minor (0.0798 cm(3); 95% confidence interval, -0.044 to 0.203 cm(3)). Interobserver and intraobserver variability was not statistically significant. Although the thymus has a complex shape, it was possible to determine its borders and to calculate its volume by virtual organ computer-aided analysis in 77.7% of cases. Linear growth during pregnancy was found, and the minor changes during systole and diastole could be explained by condensation of the soft tissue of the thymus secondary to cardiac activity.

2015 - Prenatal diagnosis and follow-up of a case of branchio-oto-renal syndrome displays renal growth impairment after the second trimester [Articolo su rivista]
Bertucci, Emma; Mazza, Vincenzo; Lugli, Licia; Ferrari, Fabrizio; Stanghellini, Ilaria; Percesepe, Antonio
abstract

Branchio-oto-renal syndrome combines branchial arch defects, hearing impairment and renal malformations or hypoplasia. Due to the high phenotypic variability, prenatal diagnosis has a limited prognostic value in mutation-positive cases. We report the first branchio-oto-renal syndrome molecular prenatal diagnosis and ultrasonographic follow-up, showing a normal renal growth until the 24th week of pregnancy, a growth deceleration during the third trimester and a renal volume recovery during the first months of life.

2013 - Surface rendering of external genitalia of a fetus at the 32nd week of gestation affected by partial androgen insensitivity syndrome. [Articolo su rivista]
Mazza, V; Bertucci, Emma; Latella, S; Cani, C; Ceccarelli, P; Iughetti, Lorenzo; Baldinotti, F; Percesepe, Antonio
abstract

Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound. Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5α-reductase 2 gene (SRD5A2). Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications. Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.

2012 - Early visualization and measurement of the pericallosal artery: an indirect sign of corpus callosum development [Articolo su rivista]
M., Pati; C., Cani; Bertucci, Emma; C., Re; S., Latella; D'Amico, Roberto; V., Mazza
abstract

OBJECTIVES:The purpose of this study was to evaluate the feasibility of visualization and measurement of the pericallosal artery during early stages of gestation.METHODS:The study group comprised 80 pregnant women between 12 and 21 weeks' gestation who attended our ultrasound unit. Transabdominal or transvaginal sonography was performed to obtain the optimal angle of a midsagittal section. High-definition flow power Doppler imaging was used to visualize the pericallosal artery. In a sagittal plane, the lengths of the pericallosal artery were measured using a straight line to connect the most anterior and posterior points. All patients were reexamined at a later stage of pregnancy to verify the existence of the corpus callosum and pericallosal artery.RESULTS:Visualization of the pericallosal artery was evident in 71 fetuses, in all of whom the biparietal diameter was greater than 20 mm. We were able to verify normal anatomy and the existence of the pericallosal artery in these fetuses between 30 and 32 weeks' gestation. A positive linear association was found between the length of the pericallosal artery and the gestational age (R(2) = 0.95) and the biparietal diameter at each gestational age (R(2) = 0.99).CONCLUSIONS:Our data show that it is feasible to visualize and measure the pericallosal artery from an early stage of gestation, and this measurement could be an indirect indication of normal corpus callosum development.

2011 - First-trimester ultrasonographic diagnosis of Langer mesomelic dysplasia in a previously affected family. [Articolo su rivista]
Mazza, V; Latella, S; Pati, M; Re, C; Bertucci, Emma; Cani, C; Percesepe, Antonio
abstract

No abstract available

2011 - Second trimester amniocentesis is not a risk factor for very low birth weight and extremely low birth weight. [Articolo su rivista]
V., Mazza; M., Pati; Bertucci, Emma; C., Cani; S., Latella; G., Gargano; Percesepe, Antonio; Volpe, Annibale
abstract

Objectives. To assess the risk of very low birth weight (VLBW) and extremely low birth weight (ELBW) attributable to second trimester amniocentesis. Methods. Records of 4,877 consecutive amniocentesis, performed between 1997 and 2003, were analyzed. Only VLBW and ELBW in the study population (exposed) and in the control group (unexposed) were evaluated. Comparisons were made between the amniocentesis group versus nonexposed. Odds ratios (OR) and 95\% confidence intervals (95\% CI) were calculated for VLBW and ELBW classes. Results. In the study population, the VLBW were 35 (0.71\%) and the ELBW were 20 (0.41\%). In the control group, the VLBW were 220 (0.67\%) and the ELBW were 112 (0.34\%). The Odds ratios of the VLBW between the study and the control group did not show any statistical significant risk (OR = 1.07, 95\% CI = 0.72-1.54). Also in ELBW odds ratios between study and control group were not statistically significant (OR = 1.20, 95\% CI = 0.7-1.95). Conclusions. No effect of the second trimester amniocentesis was noted on VLBW and ELBW.

2011 - The transvaginal probe as a uterine manipulator: a new technique to simplify transabdominal chorionic villus sampling in cases with difficult access to the trophoblast. [Articolo su rivista]
Bertucci, Emma; M., Pati; C., Cani; Volpe, Annibale; V., Mazza
abstract

OBJECTIVES: To evaluate the efficacy of using the transvaginal probe to manipulate the uterus and change the position of the trophoblast, and to simplify access to the chorionic villus under difficult conditions. METHODS: One thousand five hundred and thirty-nine procedures were performed in our centre in 1524 pregnant women from September 2006 to September 2009. In 90 of these, a difficult access to the trophoblast was observed and uterine manipulation under continuous ultrasound guidance with a double needle technique, was applied to obtain the sample. Of these, 86 samples were taken from singleton pregnancies and 4 from two bichorionic twin pregnancies RESULTS: One thousand five hundred and thirty-nine transabdominal chorionic villus sampling (TA-CVS) procedures were conducted on 1524 pregnant women. As many as 1449 were performed without manipulation with the transvaginal probe and in 90 cases the manipulation was carried out. In 89 cases, access to the trophoblast was difficult and the uterus was manipulated, which enabled an adequate TA-CVS to be performed with a single aspiration. In one case, TA-CVS was not performed due to significant pelvic pain in a patient with a fixed, retroflexed uterus and a previous history of endometriosis. CONCLUSIONS: Uterine manipulation with the transvaginal probe may be a useful solution in cases where TA-CVS is limited by difficult access to the trophoblast. Copyright © 2011 John Wiley & Sons, Ltd.

2011 - Vermian biometric parameters in the normal and abnormal fetal posterior fossa: three-dimensional sonographic study [Articolo su rivista]
Bertucci, Emma; Gindes, Liat; Mazza, Vincenzo; Re, Claudia; Lerner Geva, Liat; Achiron, Reuven
abstract

The purposes of this study were to describe a 3-dimensional sonographic technique for evaluation of the fetal vermis and to compare vermian biometric parameters in fetuses with a normal and an abnormal posterior fossa. A prospective study was conducted from 2006 through 2008 on 12 fetuses with an abnormal posterior fossa and 73 healthy control fetuses from 18 to 35 weeks' gestation. Three-dimensional scans of the fetal head were performed in the axial plane, using static volume contrast imaging in the C-plane. The vermian perimeter, cross-sectional area, and superoinferior diameter were measured and compared between abnormal and normal fetuses using the Wilcoxon nonparametric test. Linear regression analysis was used to describe trends of the vermis during gestation. The z scores for perimeter, cross-sectional area, and superoinferior diameter measurements in the abnormal posterior fossa group in each 2-week interval were calculated. Twelve fetuses with an abnormal posterior fossa were recruited: 3 with a Blake pouch cyst, 1 vermian cyst, 1 enlarged cisterna magna, 2 Dandy-Walker malformation, 4 partial vermian agenesis, and 1 hemicerebellar hypoplasia. The vermian cross-sectional area was reduced significantly in the fetuses with an abnormal posterior fossa compared with the control fetuses starting at 18 to 19 weeks' gestation (P = .01); the mean vermian superoinferior diameter was lower only from 22 to 23 weeks (P = .01); and the mean vermian perimeter was decreased from 28-29 weeks' gestation (P = .03). Linear regression analysis of the parameters showed that fetuses with an abnormal posterior fossa had a statistically significantly lower growth rate than control fetuses during gestation (P < .001). Measurements of the cross-sectional area were more useful than those of the perimeter and superoinferior diameter in distinguishing between fetuses with a normal and an abnormal posterior fossa during the early stages of gestation.

2008 - Familial Beckwith-Wiedemann syndrome due to CDKN1C mutation manifesting with recurring omphalocele [Articolo su rivista]
Percesepe, Antonio; Bertucci, Emma; Ferrari, Paola; Lugli, Licia; Ferrari, Fabrizio; Mazza, V; Forabosco, Antonino
abstract

no abstract

2007 - Age-specific risk of fetal loss post second trimester amniocentesis: analysis of 5043 cases [Articolo su rivista]
V., Mazza; M., Pati; Bertucci, Emma; C., Re; A., Ranzi; Percesepe, Antonio; Forabosco, Antonino; Volpe, Annibale
abstract

AbstractObjectives To assess the risk of fetal loss attributable to second trimester amniocentesis in singleton pregnancies through a cross-sectional study. Methods Records of 5043 consecutive second trimester amniocentesis, performed by a single operator between 1997 and 2003, were analyzed. Fetal loss post amniocentesis was calculated by grouping pregnant women in age classes and assessing observed/expected (O/E) rate. Results Total fetal losses were 40 (0.81%): 33 cases (0.67%) occurred before the 24th week, 37 cases (0.76%) before the 28th gestational week, and 3 cases (0.06%) after the 28th week of pregnancy. An age-dependent increase of the rate of fetal loss, not statistically significant (Chi-Square = 0.349, p = 0.505) was observed. The total O/E ratio values did not show any statistically significant risk (O/E ratio = 1.25, Cl = 0.86-1.64). The analysis of the single age classes did not detect any statistical significance. The excess fetal loss rate associated with amniocentesis was 0.16%. Conclusions No effect of the 2nd trimester amniocentesis was noted on fetal loss.

2007 - Anti-Mullerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology [Articolo su rivista]
LA MARCA, Antonio; Giulini, S; Tirelli, A; Bertucci, Emma; Marsella, T; Xella, S; Volpe, Annibale
abstract

BACKGROUND: Recently, a new marker, the anti-Mullerian hormone (AMH), has been evaluated as a marker of ovarian response. Serum AMH levels have been measured at frequent time-points during the menstrual cycle, suggesting the complete absence of fluctuation. The aim of this study was to evaluate whether serum AMH measurement on any day of the menstrual cycle could predict ovarian response in women undergoing assisted reproductive technology (ART). METHODS: This study included 48 women attending the IVF/ICSI programme. Blood withdrawal for AMH measurement was performed in all the patients independently of the day of the menstrual cycle. RESULTS: Women in the lowest AMH quartile (< 0.4 ng/ml) were older and required a higher dose of recombinant FSH than women in the highest quartile (> 7 ng/ml). All the cancelled cycles due to absent response were in the group of the lowest AMH quartile, whereas the cancelled cycles due to risk of ovarian hyperstimulation syndrome (OHSS) were in the group of the highest AMH quartile. This study demonstrated a strong correlation between serum AMH levels and ovarian response to gonadotrophin stimulation. CONCLUSION: For the first time, clinicians may have a reliable serum marker of ovarian response that can be measured independently of the day of the menstrual cycle.

2007 - Preterm delivery and exposure to active and passive smoking during pregnancy: a case-control study from Italy [Articolo su rivista]
Fantuzzi, Guglielmina; Aggazzotti, Gabriella; Righi, Elena; Facchinetti, Fabio; Bertucci, Emma; S., Kanitz; F., Barbone; G., Sansebastiano; M. A., Battaglia; V., Leoni; L., Fabiani; M., Triassi; S., Sciacca
abstract

The aim of this study was to assess the relationship between preterm/early preterm delivery and active smoking as well as environmental tobacco smoke (ETS) exposure in a sample of pregnant Italian women. A case-control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of preterm birth were singleton babies born before the 37th gestational week; babies born before the 35th gestational week were considered early preterm births. Controls were babies with gestational ages ≥ 37th week. A total of 299 preterm cases (including 105 early preterm) and 855 controls were analysed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Multivariable logistic regression analysis showed a relationship between active smoking during pregnancy and preterm/early preterm delivery [adjusted ORs: 1.53; 95% CI 1.05, 2.21 and 2.00; 95% CI 1.16, 3.45, respectively]. A dose-response relationship was found for the number of cigarettes smoked daily. The adjusted ORs were 1.54 and 1.69 for preterm babies and 1.90 and 2.46 for early preterm babies for 1-10 and >10 cigarettes/day respectively. ETS exposure was associated with early preterm delivery [adjusted OR 1.56; 95% CI 0.99, 2.46] with a dose-response relationship with the number of smokers in the home. Smoking during pregnancy was strongly associated with preterm delivery with a dose-response effect. ETS exposure in non-smoking women was associated only with early preterm delivery.

2006 - Corticotropin-releasing hormone, its binding protein and receptors in human cervical tissue at preterm and term labor in comparison to non-pregnant state [Articolo su rivista]
Klimaviciute, Aurelija; Calciolari, Jacopo; Bertucci, Emma; Abelin Tornblöm, Susanne; Stjernholm Vladic, Ylva; Byström, Birgitta; Petraglia, Felice; Ekman Ordeberg, Gunvor
abstract

Preterm birth is still the leading cause of neonatal morbidity and mortality. The level of corticotropin-releasing hormone (CRH) is known to be significantly elevated in the maternal plasma at preterm birth. Although, CRH, CRH-binding protein (CRH-BP), CRH-receptor 1 (CRH-R1) and CRH-R2 have been identified both at mRNA and protein level in human placenta, deciduas, fetal membranes, endometrium and myometrium, no corresponding information is yet available on cervix. Thus, the aim of this study was to compare the levels of the mRNA species coding for CRH, CRH-BP, CRH-R1 and CRH-R2 in human cervical tissue and myometrium at preterm and term labor and not in labor as well as in the non-pregnant state, and to localize the corresponding proteins employing immunohistochemical analysis. Cervical, isthmic and fundal (from non-pregnant subjects only) biopsies were taken from 67 women. Subjects were divided in 5 groups: preterm labor (14), preterm not in labor (7), term labor (18), term not in labor (21) and non-pregnant (7). Real-time RT-PCR was employed for quantification of mRNA levels and the corresponding proteins were localized by immunohistochemical analysis. The levels of CRH-BP, CRH-R1 and CRH-R2 mRNA in the pregnant tissues were lower than those in non-pregnant subjects. No significant differences were observed between preterm and term groups. CRH-BP and CRH-R2 mRNA and the corresponding proteins were present at lower levels in the laboring cervix than in the non-laboring cervix, irrespective of gestational age. In most of the samples, with the exception of four myometrial biopsies the level of CRH mRNA was below the limit of detection. All of these proteins could be detected and localized in the cervix and the myometrium by immunohistochemical analysis. Expression of CRH-BP, CRH-R1 and CRH-R2 in uterine tissues is down-regulated during pregnancy. The most pronounced down-regulation of CRH-BP and CRH-R2 occurred in laboring cervix, irrespective the length of gestation. The detection of substantial expression of the CRH and its receptor proteins, as well as receptor mRNA in the cervix suggests that the cervix may be a target for CRH action. Further studies are required to elucidate the role of CRH in cervical ripening.

2006 - L'induzione della crescita follicolare nelle donne con anovulazione [Ovulation induction in anovulatory women] [Articolo su rivista]
LA MARCA, Antonio; Bertucci, Emma; Giulini, Simone; Tirelli, Alessandra; Malavasi, Barbara; Volpe, Annibale
abstract

Ovulation induction therapy is administered to stimulate follicular growth and induce ovulation in anovulatory infertile women. In anovulatory women with polycystic ovary syndrome, the treatment of choice is clomiphene citrate, whereas in clomiphene nonresponders, gonadotrophins are given as secondary therapy. Currently, insulin-sensitizing agents are used in the treatment of polycystic ovary syndrome to restore menstrual cyclicity. In selected patients, laparoscopic drilling has also been suggested. In anovulatory patients affected with hypogonadotropic hypogonadism, treatment is based on gonadotrophin replacement therapy or pulsatile gonadotrophin-releasing hormone infusion. In ovulation induction therapy the clinician's attention should be directed at restoring normal ovary function. When pharmacotherapy is required, monofollicular growth should be induced to reduce the risk of multiple pregnancy.