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  1. Article ; Online: A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination.

    Masi, Stefano / Kobalava, Zhanna / Veronesi, Chiara / Giacomini, Elisa / Degli Esposti, Luca / Tsioufis, Konstantinos

    Advances in therapy

    2023  Volume 41, Issue 1, Page(s) 182–197

    Abstract: Introduction: The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/ ... ...

    Abstract Introduction: The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population.
    Methods: This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up.
    Results: The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999€) than in the FEC (2359€) cohort (p < 0.001).
    Conclusion: In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.
    MeSH term(s) Adult ; Humans ; Male ; Aged ; Female ; Perindopril/therapeutic use ; Antihypertensive Agents/therapeutic use ; Hypertension/drug therapy ; Bisoprolol/therapeutic use ; Retrospective Studies ; Delivery of Health Care ; Medication Adherence
    Chemical Substances Perindopril (Y5GMK36KGY) ; Antihypertensive Agents ; Bisoprolol (Y41JS2NL6U)
    Language English
    Publishing date 2023-10-21
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 632651-1
    ISSN 1865-8652 ; 0741-238X
    ISSN (online) 1865-8652
    ISSN 0741-238X
    DOI 10.1007/s12325-023-02707-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Letter to the Editor - Pilot proof for RNA biomarker-based minimally invasive endometrial receptivity testing using uterine fluid extracellular vesicles.

    Meltsov, Alvin / Giacomini, Elisa / Vigano, Paola / Zarovni, Natasa / Salumets, Andres / Aleksejeva, Elina

    European journal of obstetrics, gynecology, and reproductive biology

    2023  Volume 287, Page(s) 237–238

    MeSH term(s) Female ; Humans ; RNA ; Endometrium ; Embryo Implantation ; Uterine Diseases/diagnosis ; Extracellular Vesicles ; Biomarkers
    Chemical Substances RNA (63231-63-0) ; Biomarkers
    Language English
    Publishing date 2023-06-07
    Publishing country Ireland
    Document type Letter
    ZDB-ID 190605-7
    ISSN 1872-7654 ; 0301-2115 ; 0028-2243
    ISSN (online) 1872-7654
    ISSN 0301-2115 ; 0028-2243
    DOI 10.1016/j.ejogrb.2023.06.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cellular and Molecular Nature of Fragmentation of Human Embryos.

    Cecchele, Anna / Cermisoni, Greta Chiara / Giacomini, Elisa / Pinna, Monica / Vigano, Paola

    International journal of molecular sciences

    2022  Volume 23, Issue 3

    Abstract: Embryo fragmentation represents a phenomenon generally characterized by the presence of membrane-bound extracellular cytoplasm into the perivitelline space. Recent evidence supports the cellular and molecular heterogeneity of embryo fragments. In this ... ...

    Abstract Embryo fragmentation represents a phenomenon generally characterized by the presence of membrane-bound extracellular cytoplasm into the perivitelline space. Recent evidence supports the cellular and molecular heterogeneity of embryo fragments. In this narrative review, we described the different embryo fragment-like cellular structures in their morphology, molecular content, and supposed function and have reported the proposed theories on their origin over the years. We identified articles related to characterization of embryo fragmentation with a specific literature search string. The occurrence of embryo fragmentation has been related to various mechanisms, of which the most studied are apoptotic cell death, membrane compartmentalization of altered DNA, cytoskeletal disorders, and vesicle formation. These phenomena are thought to result in the extrusion of entire blastomeres, release of apoptotic bodies and other vesicles, and micronuclei formation. Different patterns of fragmentation may have different etiologies and effects on embryo competence. Removal of fragments from the embryo before embryo transfer with the aim to improve implantation potential should be reconsidered on the basis of the present observations.
    MeSH term(s) Apoptosis/physiology ; Blastomeres/physiology ; Cell Division ; Cell-Derived Microparticles/genetics ; Cell-Derived Microparticles/metabolism ; Cell-Derived Microparticles/physiology ; Embryo Implantation/physiology ; Embryo Transfer/methods ; Embryo, Mammalian/cytology ; Embryo, Mammalian/metabolism ; Embryonic Development/genetics ; Embryonic Development/physiology ; Humans ; Micronucleus, Germline/physiology
    Language English
    Publishing date 2022-01-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23031349
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  4. Article ; Online: Description of characteristics, management of care and healthcare direct costs of patients with HR+/HER2- early breast cancer in Italy: a real-world study involving administrative and pathological anatomy databases.

    Perrone, Valentina / Giacomini, Elisa / Sangiorgi, Diego / Tamma, Antonella / Giovannitti, Massimo / Buzzoni, Carlotta / Degli Esposti, Luca

    Expert review of pharmacoeconomics & outcomes research

    2023  Volume 23, Issue 9, Page(s) 1077–1085

    Abstract: Background: Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in ... ...

    Abstract Background: Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in clinical practice.
    Methods: This retrospective analysis, based on 9.4 million of Italian National Health Service beneficiaries, included adult patients with hospitalization discharge diagnosis for EBC in 01/2015-12/2020. Those with HR+/HER2- status were selected; among them, patients that underwent removal of lymph nodes (LN) were analyzed.
    Results: Of 24,137 patients with EBC and HR+/HER2- status, 3619 patients (15%) had documented LN removal. Overall, 4.7% of HR+/HER2- patients and 9.9% of patients with LN removal experienced distant relapse over a median follow-up of 33.2 months (Q1-Q3: 17.0-50.6). Local relapse occurred in approximately 9.1-9.3% of patients in each group. Among the 1,175 patients with LN removal that had available pathological anatomy data, 399 (34.0%) had pathological high-risk characteristics and 13.3% experienced distant relapse.
    Conclusions: One in ten patients with EBC who underwent LN removal experienced a relapse, highlighting the strong need to prevent early recurrence.
    MeSH term(s) Adult ; Humans ; Female ; Breast Neoplasms/pathology ; Receptor, ErbB-2 ; Retrospective Studies ; State Medicine ; Neoplasm Recurrence, Local/pathology ; Health Care Costs ; Recurrence
    Chemical Substances Receptor, ErbB-2 (EC 2.7.10.1)
    Language English
    Publishing date 2023-08-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2208481-2
    ISSN 1744-8379 ; 1473-7167
    ISSN (online) 1744-8379
    ISSN 1473-7167
    DOI 10.1080/14737167.2023.2246652
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Real-world analysis of the economic and therapeutic burden in advanced breast cancer patients in Italy.

    Palladino, Simona / Perrone, Valentina / Giacomini, Elisa / Sangiorgi, Diego / Premoli, Eleonora / Valsecchi, Diletta / Degli Esposti, Luca / Suter, Matteo Basilio

    Expert review of pharmacoeconomics & outcomes research

    2023  Volume 23, Issue 9, Page(s) 1041–1048

    Abstract: Background: This real-world analysis evaluated drug utilization focusing on wastage and healthcare costs for treatment of patients with advanced breast cancer (aBC) hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) ...

    Abstract Background: This real-world analysis evaluated drug utilization focusing on wastage and healthcare costs for treatment of patients with advanced breast cancer (aBC) hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) in Italy.
    Methods: A retrospective analysis was conducted on administrative data covering about 13.3 million health-assisted individuals. Across January/2017-June/2021, all patients with HR+/HER2-aBC were identified by ≥ 1 prescription for cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). Cost analysis was performed and updated referring to the prices of November 2021.
    Results: Overall, 3,647 HR+/HER2-aBC patients were included (2,627 palbociclib treated, 729 ribociclib treated, and 291 abemaciclib treated). After 12 months of follow-up, 35% of palbociclib patients had a dose reduction (on average 8.9 wasted pills/patient), 44.7% of abemaciclib patients had a dose reduction (on average 6.7 wasted pills/patient), 22.1% of ribociclib patients had a dose reduction (no wasted pills). Therapy wastage added up to 528,716€ for palbociclib-treated patients (524€/patient) and 5,738€ in abemaciclib-treated patients (151€/patient). No wastage was attributed to ribociclib.
    Conclusions: Dose reduction was associated with drug wastage in palbociclib and abemaciclib-treated patients, but not in ribociclib-treated ones. These findings might be helpful to policy decision-makers who, for healthcare strategies implementation, among several variables should consider the possible restraining of drug wastage.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/drug therapy ; Retrospective Studies ; Aminopyridines/pharmacology ; Aminopyridines/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Protein Kinase Inhibitors/pharmacology ; Benzimidazoles ; Purines
    Chemical Substances ribociclib (TK8ERE8P56) ; abemaciclib (60UAB198HK) ; Aminopyridines ; Protein Kinase Inhibitors ; Benzimidazoles ; Purines
    Language English
    Publishing date 2023-07-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2208481-2
    ISSN 1744-8379 ; 1473-7167
    ISSN (online) 1744-8379
    ISSN 1473-7167
    DOI 10.1080/14737167.2023.2234637
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  6. Article ; Online: Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells.

    Makieva, Sofia / Giacomini, Elisa / Scotti, Giulia Maria / Lazarevic, Dejan / Pavone, Valentina / Ottolina, Jessica / Bartiromo, Ludovica / Schimberni, Matteo / Morelli, Marco / Alteri, Alessandra / Minetto, Sabrina / Tonon, Giovanni / Candiani, Massimo / Papaleo, Enrico / Viganò, Paola

    Human reproduction open

    2024  Volume 2024, Issue 2, Page(s) hoae014

    Abstract: Study question: Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?: Summary answer: ... ...

    Abstract Study question: Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?
    Summary answer: Aneuploid embryo-derived EVs contain transcripts of
    What is known already: We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown.
    Study design size duration: Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy.
    Participants/materials setting methods: EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs.
    Main results and the role of chance: Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes
    Large scale data: Raw data have been uploaded to GEO (accession number GSE234338).
    Limitations reasons for caution: The findings of the study will require validation utilizing a second cohort of EV samples.
    Wider implications of the findings: The discovery that the transcriptomic profile of EVs secreted from aneuploid cleavage stage embryos differs from that of euploid embryos supports the possibility to develop a non-invasive methodology for PGT-A. The upregulation of
    Study funding/competing interests: The study was supported by a Marie Skłodowska-Curie Actions fellowship awarded to SM by the European Commission (CERVINO grant agreement ID: 79620) and by a BIRTH research grant from Theramex HQ UK Ltd. The authors have no conflicts of interest to declare.
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article
    ISSN 2399-3529
    ISSN (online) 2399-3529
    DOI 10.1093/hropen/hoae014
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  7. Article ; Online: Extracellular vesicles as a potential diagnostic tool in assisted reproduction.

    Giacomini, Elisa / Makieva, Sofia / Murdica, Valentina / Vago, Riccardo / Viganó, Paola

    Current opinion in obstetrics & gynecology

    2020  Volume 32, Issue 3, Page(s) 179–184

    Abstract: Purpose of review: Extracellular vesicles have emerged as a promising field of research for their potential to serve as biomarkers. In the pathophysiology of reproduction, they have attracted significant attention because of their diverse roles in ... ...

    Abstract Purpose of review: Extracellular vesicles have emerged as a promising field of research for their potential to serve as biomarkers. In the pathophysiology of reproduction, they have attracted significant attention because of their diverse roles in gametogenesis and embryo-endometrial cross-talk. Advances in extracellular vesicle translational potential are herein reviewed with a particular focus in oocyte competence, semen quality diagnostics, embryo selection and detection of endometrial receptivity.
    Recent findings: Specific miRNAs present in follicular fluid-derived extracellular vesicles have been associated with follicle development and oocyte maturation. Some proteins known to regulate sperm function and capacitation such as glycodelin, and CRISP1 have been found as overrepresented in semen exosomes isolated from severe asthenozoospermic compared to normozoospermic men. In vitro developed human embryos can secrete extracellular vesicles whose propitiousness for preimplantation genetic testing is being increasingly investigated. Endometrial cell-derived extracellular vesicles recovered from uterine flushings might represent a reservoir of molecular markers potentially exploited for monitoring the endometrial status.
    Summary: Accumulated knowledge on extracellular vesicles deriving from endometrium, follicular fluid, embryos or male reproductive system may be translated to clinical practice to inform diagnostics in assisted reproduction technology (ART). Validation studies and technology developments are required to implement the profiling of extracellular vesicles as diagnostic tests in ART.
    MeSH term(s) Biomarkers/analysis ; Cell Communication/physiology ; Extracellular Vesicles/physiology ; Female ; Follicular Fluid/cytology ; Follicular Fluid/physiology ; Humans ; Infertility/diagnosis ; Male ; MicroRNAs/metabolism ; Oocytes/cytology ; Oocytes/pathology ; Pregnancy ; Reproductive Techniques, Assisted ; Spermatozoa/cytology ; Spermatozoa/physiology
    Chemical Substances Biomarkers ; MicroRNAs
    Language English
    Publishing date 2020-03-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1049382-7
    ISSN 1473-656X ; 1040-872X
    ISSN (online) 1473-656X
    ISSN 1040-872X
    DOI 10.1097/GCO.0000000000000621
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies.

    Giacomini, Elisa / Minetto, Sabrina / Li Piani, Letizia / Pagliardini, Luca / Somigliana, Edgardo / Viganò, Paola

    International journal of molecular sciences

    2021  Volume 22, Issue 16

    Abstract: According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, ...

    Abstract According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, in the interaction between cytokines and their receptors, cellular adhesion and apoptosis have been demonstrated in endometriotic lesions. The objective of this narrative review is to provide an overview of the components and mechanisms at the intersection between inflammation and genetics that may constitute vanguard therapeutic approaches in endometriosis. The GWAS technology and pathway-based analysis highlighted the role of the MAPK and the WNT/β-catenin cascades in the pathogenesis of endometriosis. These signaling pathways have been suggested to interfere with the disease establishment via several mechanisms, including apoptosis, migration and angiogenesis. Extracellular vesicle-associated molecules may be not only interesting to explain some aspects of endometriosis progression, but they may also serve as therapeutic regimens per se. Immune/inflammatory dysfunctions have always represented attractive therapeutic targets in endometriosis. These would be even more interesting if genetic evidence supported the involvement of functional pathways at the basis of these alterations. Targeting these dysfunctions through next-generation inhibitors can constitute a therapeutic alternative for endometriosis.
    MeSH term(s) Endometriosis/genetics ; Endometriosis/immunology ; Endometriosis/metabolism ; Endometriosis/therapy ; Extracellular Vesicles/metabolism ; Female ; Humans ; Inflammation/genetics ; Inflammation/metabolism ; MAP Kinase Signaling System ; Molecular Targeted Therapy ; Wnt Signaling Pathway
    Language English
    Publishing date 2021-08-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22169033
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  9. Article: Evidence of Antibiotic Resistance from Population-Based Studies: A Narrative Review.

    Giacomini, Elisa / Perrone, Valentina / Alessandrini, Davide / Paoli, Daniela / Nappi, Carmela / Degli Esposti, Luca

    Infection and drug resistance

    2021  Volume 14, Page(s) 849–858

    Abstract: The 20th century witnessed the dawn of the antibiotic revolution and is now facing the rising phenomenon of antibiotic resistance. In this narrative review, we aim to describe antibiotic resistance in clinical practice settings through population-based ... ...

    Abstract The 20th century witnessed the dawn of the antibiotic revolution and is now facing the rising phenomenon of antibiotic resistance. In this narrative review, we aim to describe antibiotic resistance in clinical practice settings through population-based studies from different countries reporting the role of misuse of antibiotics in the development of resistance and the clinical and economic burden associated. The misuse of antibiotics was documented in the wide population as well as in hospitals and care facilities. It was mainly reported as over-use and inappropriate prescribing. Improper dosage regimens and longer treatment duration were regarded as pivotal factors related to antibiotic resistance; the emerging strategy of "antibiotic-de-escalation" could be the key to overcome these issues. The investigation of the self-medication attitude revealed widespread antibiotic use without following medical instructions or medical consultation. Moreover, several studies established the association of antibiotic resistance with increased risk of longer hospitalizations and mortality, highlighting the heavy clinical and economic burden of this phenomenon. In this narrative review, the widespread inappropriate use of antibiotics emerged as one of the main causes of antibiotic resistance, which negative outcomes call for the development of antibiotic stewardship programs and global surveillance networks.
    Language English
    Publishing date 2021-03-03
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2494856-1
    ISSN 1178-6973
    ISSN 1178-6973
    DOI 10.2147/IDR.S289741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Association between short-term exposure to particulate matter air pollution and outcomes of assisted reproduction technology in Lombardy, Italy: A retrospective cohort study.

    Iodice, Simona / Pagliardini, Luca / Cantone, Laura / Giacomini, Elisa / Candiani, Massimo / Viganò, Paola / Bollati, Valentina

    Reproductive toxicology (Elmsford, N.Y.)

    2021  Volume 105, Page(s) 148–155

    Abstract: The harmful effect of polluted air on spontaneous fertility has been consistently reported. However, the specific pollutants involved in determining this effect are still to be clarified. The study of Assisted Reproductive Technology (ART) populations is ...

    Abstract The harmful effect of polluted air on spontaneous fertility has been consistently reported. However, the specific pollutants involved in determining this effect are still to be clarified. The study of Assisted Reproductive Technology (ART) populations is particularly helpful in this context since it allows to monitor the key events of the reproductive process. We analyzed the medical records of 2122 patients who underwent fresh or frozen ART cycles during 2014-2017 in the Lombardy region, north-west Italy. Each subject was assigned the daily PM
    MeSH term(s) Adult ; Air Pollutants/adverse effects ; Air Pollutants/analysis ; Air Pollution/adverse effects ; Air Pollution/analysis ; Environmental Exposure/adverse effects ; Environmental Exposure/analysis ; Female ; Humans ; Italy ; Particulate Matter/adverse effects ; Particulate Matter/analysis ; Pregnancy ; Reproductive Techniques, Assisted ; Retrospective Studies ; Treatment Outcome
    Chemical Substances Air Pollutants ; Particulate Matter
    Language English
    Publishing date 2021-09-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639342-1
    ISSN 1873-1708 ; 0890-6238
    ISSN (online) 1873-1708
    ISSN 0890-6238
    DOI 10.1016/j.reprotox.2021.08.008
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