{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:17:31Z","timestamp":1793377051838,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72\/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 \u00b1 3.8 million\/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications\/microcalcifications, and enlarged\/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors.<\/jats:p>","DOI":"10.3390\/jcm13154399","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T09:50:05Z","timestamp":1722246605000},"page":"4399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Seminological, Hormonal and Ultrasonographic Features of Male Factor Infertility Due to Genetic Causes: Results from a Large Monocentric Retrospective Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Rossella","family":"Mazzilli","sequence":"first","affiliation":[{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Petrucci","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Zamponi","sequence":"additional","affiliation":[{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Golisano","sequence":"additional","affiliation":[{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pecora","sequence":"additional","affiliation":[{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1839-133X","authenticated-orcid":false,"given":"Camilla","family":"Mancini","sequence":"additional","affiliation":[{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"},{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6597-1452","authenticated-orcid":false,"given":"Gerardo","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Alesi","sequence":"additional","affiliation":[{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"De Santis","sequence":"additional","affiliation":[{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Libi","sequence":"additional","affiliation":[{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rossi","sequence":"additional","affiliation":[{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7839-9125","authenticated-orcid":false,"given":"Marina","family":"Borro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9501-7638","authenticated-orcid":false,"given":"Salvatore","family":"Raffa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"},{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-3121","authenticated-orcid":false,"given":"Vincenzo","family":"Visco","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"},{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2425-5609","authenticated-orcid":false,"given":"Giuseppe","family":"Defeudis","sequence":"additional","affiliation":[{"name":"Department of Theoretical and Applied Sciences, eCampus University, 22060 Novedrate, Italy"},{"name":"Unit of Endocrinology and Diabetes, Department of Medicine, University Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-247X","authenticated-orcid":false,"given":"Maria","family":"Piane","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"},{"name":"UOD Medical Genetics and Advanced Cell Diagnostics, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9324-3946","authenticated-orcid":false,"given":"Antongiulio","family":"Faggiano","sequence":"additional","affiliation":[{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant\u2019Andrea Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"ref_1","unstructured":"(2024, June 10). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/infertility."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/cen.15093","article-title":"One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice","volume":"101","author":"Boeri","year":"2024","journal-title":"Clin. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1111\/andr.13380","article-title":"Clinical parameters associated with altered sperm DNA fragmentation index among primary infertile men: Findings from a real-life cross-sectional study","volume":"11","author":"Pozzi","year":"2023","journal-title":"Andrology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/rmb2.12336","article-title":"Genetic disorders and male infertility","volume":"19","author":"Kuroda","year":"2020","journal-title":"Reprod. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00439-019-02101-w","article-title":"The X chromosome and male infertility","volume":"140","author":"Vockel","year":"2021","journal-title":"Hum. Genet."},{"key":"ref_6","first-page":"baab049","article-title":"Male Infertility Knowledgebase: Decoding the genetic and disease landscape","volume":"2021","author":"Joseph","year":"2021","journal-title":"Database"},{"key":"ref_7","unstructured":"Jungwirth, A., Diemer, T., Feng, Z., Krausz, C., Minhas, S., and Tournaye, H. (2018). EAU Guidelines on Male Infertility, EAU Guidelines Office."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.fertnstert.2006.12.020","article-title":"Aneuploidy study in sperm and preimplantation embryos from nonmosaic 47, XYY men","volume":"88","author":"Hans","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s40618-022-01741-6","article-title":"Management of male factor infertility: Position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS): Endorsing Organization: Italian Society of Embryology, Reproduction, and Research (SIERR)","volume":"45","author":"Ferlin","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.21037\/tau-19-599","article-title":"Y-microdeletions: A review of the genetic basis for this common cause of male infertility","volume":"10","author":"Witherspoon","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1093\/humrep\/dead125","article-title":"Anti-M\u00fcllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study","volume":"38","author":"Pozzi","year":"2023","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4103\/aja.aja_53_21","article-title":"Severe male factor in in vitrofertilization: Definition, prevalence, and treatment. An update","volume":"24","author":"Mazzilli","year":"2022","journal-title":"Asian J. Androl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s40618-022-02000-4","article-title":"Male factor infertility and assisted reproductive technologies: Indications, minimum access criteria and outcomes","volume":"46","author":"Mazzilli","year":"2023","journal-title":"J. Endocrinol. Investig."},{"key":"ref_14","unstructured":"WHO (2010). Laboratory Manual for the Examination and Processing of Human Semen, Cambridge University Press. [5th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/andr.13260","article-title":"The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: An overview on male genital tract ultrasound reference ranges","volume":"10","author":"Lotti","year":"2022","journal-title":"Andrology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1439-0272.2000.tb02859.x","article-title":"Clinical findings in congenital absence of the vasa deferentia","volume":"32","author":"Weiske","year":"2000","journal-title":"Andrologia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.eururo.2021.08.014","article-title":"European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility","volume":"80","author":"Minhas","year":"2021","journal-title":"Eur. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4081\/aiua.2014.3.171","article-title":"Impact of Cystic Fibrosis Transmembrane Regulator (CFTR) gene mutations on male infertility","volume":"86","author":"Elia","year":"2014","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.21037\/tau.2020.04.05","article-title":"Genetics of CFTR and male infertility","volume":"10","author":"Bieniek","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1093\/humrep\/dey110","article-title":"Prevalence of XXY karyotypes in human blastocysts: Multicentre data from 7549 trophectoderm biopsies obtained during preimplantation genetic testing cycles in IVF","volume":"33","author":"Mazzilli","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.reprotox.2006.04.016","article-title":"Genetic causes of male infertility","volume":"22","author":"Ferlin","year":"2006","journal-title":"Reprod. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13039-018-0367-3","article-title":"Human ring chromosome registry for cases in the Chinese population: Re-emphasizing Cytogenomic and clinical heterogeneity and reviewing diagnostic and treatment strategies","volume":"11","author":"Hu","year":"2018","journal-title":"Mol. Cytogenet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1210\/jc.2006-1981","article-title":"Molecular and Clinical Characterization of Y Chromosome Microdeletions in Infertile Men: A 10-Year Experience in Italy","volume":"92","author":"Ferlin","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/humupd\/dmx008","article-title":"Sperm recovery and ICSI outcomes in Klinefelter syndrome: A systematic review and meta-analysis","volume":"23","author":"Corona","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jcf.2022.04.020","article-title":"Clinical outcomes of a large cohort of individuals with the F508del\/5T;TG12 CFTR genotype","volume":"21","author":"Tosco","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s40618-018-0989-7","article-title":"Incidence of Y chromosome microdeletions in patients with Klinefelter syndrome","volume":"42","author":"Sciarra","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1007\/s00261-016-0713-z","article-title":"Testis ultrasound in Klinefelter syndrome infertile men: Making the diagnosis and avoiding inappropriate management","volume":"41","author":"Rocher","year":"2016","journal-title":"Abdom. Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Barbonetti, A., Martorella, A., Minaldi, E., D\u2019Andrea, S., Bardhi, D., Castellini, C., Francavilla, F., and Francavilla, S. (2019). Testicular cancer in infertile men with and without testicular microlithiasis: A systematic review and meta-analysis of case-control studies. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00164"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12938","DOI":"10.1111\/and.12938","article-title":"Y chromosome microdeletions and varicocele as aetiological factors of male infertility: A cross-sectional study","volume":"50","author":"Christofolini","year":"2018","journal-title":"Andrologia"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/15\/4399\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:25:04Z","timestamp":1760109904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/15\/4399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,27]]},"references-count":30,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["jcm13154399"],"URL":"https:\/\/doi.org\/10.3390\/jcm13154399","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,27]]}}}