{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:31:38Z","timestamp":1792150298137,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Chorionic villus sampling (CVS) is a pivotal diagnostic tool for early prenatal detection of chromosomal and genetic abnormalities; however, the safety and diagnostic efficacy of different CVS approaches remain a subject of clinical interest. This monocentric study compares transcervical (TC-CVS), transabdominal (TA-CVS) and transvaginal (TV-CVS) techniques, focusing on procedure-related fetal loss and diagnostic yield. Methods: In this 15-year, single-operator prospective study, a total of 5500 women underwent CVS between 10 and 14 weeks of gestation at a single center. Sampling was performed via TA-CVS (n = 4500), TC-CVS (n = 850), or TV-CVS (n = 150). Outcomes assessed included fetal loss rates, sample adequacy, early complications and hemodynamic changes measured by Doppler ultrasound. A p-value &lt; 0.05 (two-tailed) was considered statistically significant. Results: Spontaneous abortion rates were significantly lower following TA-CVS (0.18%; 8\/4500) compared to TC-CVS (0.6%; 5\/850) and TV-CVS (1.3%; 2\/150) (\u03c72 = 24.56, p &lt; 0.001). Post hoc pairwise analysis showed significantly lower fetal loss in TA-CVS compared to TC-CVS, but not between TA-CVS and TV-CVS. Cytogenetic abnormalities were detected in 220 cases (4.0%), and clinically significant copy number variants (CNVs) were confirmed in fetuses with major structural malformations. Five-year follow-up showed no diagnosed intellectual disability among assessed children. Optimal tissue weight (10\u201320 mg) was more frequent with TA-CVS (66.7%) than TC-CVS (35.3%) or TV-CVS (36.7%) (\u03c72 = 350.92, p &lt; 0.001). In a Doppler subset (n = 400), uterine, spiral, and interplacental artery PI changes were non-significant; the umbilical (p = 0.032) and middle cerebral arteries (p &lt; 0.001) showed transient PI reductions after sampling. Conclusions: Transabdominal CVS demonstrated the most favorable balance of safety and diagnostic quality, suggesting it should be the preferred first-line technique in early prenatal diagnosis. Standardized technique and operator training remain critical to optimize outcomes.<\/jats:p>","DOI":"10.3390\/diagnostics15212750","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T02:48:28Z","timestamp":1761878908000},"page":"2750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcervical, Transabdominal and Transvaginal Chorionic Villus Sampling for Prenatal Diagnosis in Zagreb, Croatia: A Prospective Single-Operator Study on 5500 Cases"],"prefix":"10.3390","volume":"15","author":[{"given":"Petra","family":"Podobnik","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-8149","authenticated-orcid":false,"given":"Tomislav","family":"Me\u0161trovi\u0107","sequence":"additional","affiliation":[{"name":"DA VINCI Polyclinic, Petrovaradinska Ulica 110, 10000 Zagreb, Croatia"},{"name":"University Centre Vara\u017edin, University North, 42000 Vara\u017edin, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6484-7207","authenticated-orcid":false,"given":"Mario","family":"Podobnik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Bertovi\u0107-\u017dunec","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Lon\u010dar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Kurdija","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u017eenis","family":"Jel\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zlata","family":"Srebrenikovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slava","family":"Podobnik-\u0160arkanji","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Podobnik Special Hospital, Ul. Sveti Duh 112, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Canadian Collaborative CVS, Amniocentesis Clinical Trial Group (1989). Multicenter randomized clinical trial of chorionic villus sampling and amniocentesis: First report. Lancet, 1, 1\u20136.","DOI":"10.1016\/S0140-6736(89)91670-X"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1056\/NEJM199208273270903","article-title":"NICHD Chorion Villus Sampling and Amniocentesis Study Group. A randomized comparison of transcervical and transabdominal chorionic villus sampling","volume":"327","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Canadian Early and Midtrimester Amniocentesis Trial Group (1998). Randomized trial to assess safety and fetal outcome of early and midtrimester amniocentesis. Lancet, 351, 242\u2013247.","DOI":"10.1016\/S0140-6736(97)12346-7"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists Committee on Practice Bulletins\u2013Obstetrics, Committee on Genetics, and Society for Maternal-Fetal Medicine (2020). Screening for fetal chromosomal abnormalities. ACOG Practice Bulletin Number 226. Obstet. Gynecol., 136, e48\u2013e69.","DOI":"10.1097\/AOG.0000000000004084"},{"key":"ref_5","first-page":"CD014715","article-title":"Diagnostic accuracy of ultrasound screening for fetal structural abnormalities during the first and second trimester of pregnancy in low-risk and unselected populations","volume":"5","author":"Buijtendijk","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"International Society of Ultrasound in Obstetrics and Gynecology, Bilardo, C.M., Chaoui, R., Hyett, J., Kagan, K.O., Karim, J.N., Papageorghiou, A.T., Poon, L.C., Salomon, L.J., and Syngelaki, A. (2023). ISUOG Practice Guidelines (updated): Performance of 11\u201314-week ultrasound scan. Ultrasound Obstet. Gynecol., 61, 127\u2013143.","DOI":"10.1002\/uog.26106"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00404-024-07881-9","article-title":"Clinical factors that influence chorionic villus sampling sample size","volume":"311","author":"Alamri","year":"2025","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13039-022-00607-z","article-title":"Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review","volume":"15","author":"Liu","year":"2022","journal-title":"Mol. Cytogenet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Podobnik, P., Me\u0161trovi\u0107, T., \u0110or\u0111evi\u0107, A., Kurdija, K., Jel\u010di\u0107, \u0110., Ogrin, N., Bertovi\u0107-\u017dunec, I., Gebauer-Vukovi\u0107, B., Ho\u0107evar, G., and Lon\u010dar, I. (2024). A decade of non-invasive prenatal testing (NIPT) for chromosomal abnormalities in Croatia: First national monocentric study to inform country\u2019s future prenatal care strategy. Genes, 15.","DOI":"10.3390\/genes15121590"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Giovannopoulou, E., Tsakiridis, I., Mamopoulos, A., Populidis, I., Anastanidis, A., and Dagklis, T. (2022). Invasive prenatal diagnostic testing for aneuploidies in singleton pregnancies: A comparative review of major guidelines. Medicina, 58.","DOI":"10.3390\/medicina58101472"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/pd.1970080506","article-title":"First trimester chorionic villus sampling versus mid-trimester genetic amniocentesis: Preliminary results of a controlled prospective trial","volume":"8","author":"Crane","year":"1988","journal-title":"Prenat. Diagn."},{"key":"ref_12","first-page":"e13","article-title":"Amniocentesis and chorionic villus sampling. Green-top Guideline No. 8","volume":"129","author":"Navaratnam","year":"2022","journal-title":"Int. J. Obstet. Gynaecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/uog.20353","article-title":"Risk of miscarriage following amniocentesis or chorionic villus sampling: Systematic review of literature and updated meta-analysis","volume":"54","author":"Salomon","year":"2019","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_14","first-page":"CD003252","article-title":"Amniocentesis and chorionic villus sampling for prenatal diagnosis","volume":"9","author":"Alfirevic","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/pd.6357","article-title":"Position statement from the International Society for Prenatal Diagnosis on the use of non-invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies","volume":"43","author":"Hui","year":"2023","journal-title":"Prenat. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.3346\/jkms.2021.36.e26","article-title":"Clinical Practice Guidelines for prenatal aneuploidy screening and diagnostic testing from Korean Society of Maternal-Fetal Medicine: (2) Invasive diagnostic testing for fetal chromosomal abnormalities","volume":"36","author":"Lee","year":"2021","journal-title":"J. Korean Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/pd.1970130307","article-title":"Risk of CVS","volume":"13","author":"Holzgreve","year":"1993","journal-title":"Prenat. Diagn."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"MRC Working Party on the Evaluation of Chorionic Villus Sampling (1991). Medical Research Council European trial of chorionic villus sampling. Lancet, 337, 1491\u20131499.","DOI":"10.1016\/0140-6736(91)93193-D"},{"key":"ref_19","first-page":"77","article-title":"Chorionic frondosum cultivation technique in antenatal detection of genetic disease","volume":"91","author":"Singer","year":"1989","journal-title":"Period. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/(SICI)1097-0223(199702)17:2<125::AID-PD43>3.0.CO;2-K","article-title":"Transabdominal chorionic villus sampling in the second and third trimester of high-risk pregnancies","volume":"17","author":"Podobnik","year":"1997","journal-title":"Prenat. Diagn."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/pd.1970131010","article-title":"Transabdominal chorionic villus sampling in the second and third trimester of pregnancy: Chromosome quality, reporting time, and feto-maternal bleeding","volume":"13","author":"Lundsten","year":"1993","journal-title":"Prenat. Diagn."},{"key":"ref_22","first-page":"358803","article-title":"Factors influencing the decision-making process for undergoing invasive prenatal testing","volume":"16","author":"Tzela","year":"2024","journal-title":"Cureus"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1080\/14767058.2018.1555807","article-title":"Detection of structural abnormalities in fetuses with normal karyotype at 11\u201313 weeks using the anatomic examination protocol of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)","volume":"33","author":"Petousis","year":"2020","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/pd.1970130305","article-title":"Mosaicism in chorionic villus sampling: An analysis of incidence and chromosomes involved in 2612 consecutive cases","volume":"13","author":"Wang","year":"1993","journal-title":"Prenat. Diagn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/tog.12850","article-title":"Pitfalls of prenatal diagnosis associated with mosaicism","volume":"25","author":"Reilly","year":"2023","journal-title":"Obstetrician Gynaecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396.e1","DOI":"10.1016\/j.ajog.2020.10.037","article-title":"Routine first-trimester ultrasound screening using a standardized anatomical protocol","volume":"224","author":"Liao","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00404-022-06477-5","article-title":"Antenatal screening for chromosomal abnormalities","volume":"305","author":"Kagan","year":"2022","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/uog.27538","article-title":"ISUOG Practice Guidelines: Performance of third-trimester obstetric ultrasound scan","volume":"63","author":"Khalil","year":"2024","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/uog.26157","article-title":"Complication rate after termination of pregnancy for fetal defects","volume":"62","author":"Spingler","year":"2023","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_30","unstructured":"Maines, J., and Montero, F.J. (2025). Chorionic villus sampling. StatPearls, StatPearls."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/uog.14636","article-title":"Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: A systematic review and meta-analysis","volume":"45","author":"Akolekar","year":"2015","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/uog.15986","article-title":"Total pregnancy loss after chorionic villus sampling and amniocentesis: A cohort study","volume":"49","author":"Bakker","year":"2017","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.3390\/jcm11133624","article-title":"Prenatal diagnosis using chromosomal microarray analysis in high-risk pregnancies","volume":"11","author":"Chen","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref_34","first-page":"9","article-title":"Doppler assessment of fetal circulation during late chorionic villus sampling in high-risk pregnancies","volume":"3","author":"Podobnik","year":"1998","journal-title":"Prenat. Neonatal Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/(SICI)1097-0223(199803)18:3<255::AID-PD255>3.0.CO;2-C","article-title":"First 10,000 chorionic villus samplings performed on singleton pregnancies by a single operator","volume":"3","author":"Brambati","year":"1998","journal-title":"Prenat. Diagn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0301-5629(90)90140-8","article-title":"Uterine blood flow velocity waveforms before and after transcervical chorionic villus sampling","volume":"16","author":"Jahoda","year":"1990","journal-title":"Ultrasound Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jcu.1870190603","article-title":"Umbilical artery velocity waveforms in early pregnancy: A transvaginal color Doppler study","volume":"19","author":"Arduini","year":"1991","journal-title":"J. Clin. Ultrasound"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0140-6736(91)91374-4","article-title":"Severe limb abnormalities after chorionic villus sampling at 56\u201366 days gestation","volume":"337","author":"Firth","year":"1991","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/pd.1970100708","article-title":"Risk of transabdominal chorionic villus sampling before 12 weeks of amenorrhea","volume":"10","author":"Saura","year":"1990","journal-title":"Prenat. Diagn."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0140-6736(86)90894-9","article-title":"Why confine chorionic villus (placental) biopsy to the first trimester","volume":"1","author":"Nicolaides","year":"1986","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Liu, L., Yang, Y., Huo, H., Hu, N., and Wang, F. (2025). The relationship between fetal tissue chromosomal karyotype and clinical characteristics in patients with spontaneous abortion: A retrospective study. BMC Pregnancy Childbirth, 25.","DOI":"10.1186\/s12884-025-08106-w"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Podobnik, P., Me\u0161trovi\u0107, T., Podobnik, M., Lon\u010dar, I., Bertovi\u0107-\u017dunec, I., Kurdija, K., Jel\u010di\u0107, D., Srebrenikovi\u0107, Z., and Podobnik-\u0160arkanji, S. (2025). Genetic and sonographic insights into first-trimester fetal cystic hygroma: A retrospective 30-year analysis using 3D\/4D ultrasound and cytogenetic evaluation in Croatia (1993\u20132023). Genes, 16.","DOI":"10.3390\/genes16080980"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:18:41Z","timestamp":1774340321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":42,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15212750"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15212750","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]}}}