In the era of prenatal ultrasound and biochemical screening and also due to the increase of noninvasive prenatal testing and screening (NIPT, NIPS), invasive prenatal techniques are the most appropriate procedures for diagnosing chromosomal, metabolic, and genetic fetal anomalies. Chorionic villous sampling (CVS) in the first trimester of pregnancy is currently the technique of choice for women at high genetic risk. Amniocentesis is more frequently employed in the second trimester while fetal blood sampling (FBS) by cordocentesis is rarely used nowadays. Women who choose to avoid the termination of pregnancy (TOP) of an affected fetus can opt for preimplantation genetic diagnosis (PGD) by assisted reproductive techniques (ART) by transferring in utero only the microbiopsied non-affected embryos or blastocysts. All invasive prenatal diagnosis procedures are performed under continuous ultrasound monitoring and can be done both free-hand or by insertion of a spinal needle in the ultrasound probe. Chorionic villous sampling can be performed by transcervical or transabdominal route; this last one is preferred mostly because it can be employed in any trimester of pregnancy but also because it is simpler and therefore easier for hands-on training, faster, less invasive; it is also associated with lower risks of infections and fetal loss. In antenatal diagnosis, the first step is non-directive pretest counseling to explain the risks and efficacy and to provide information about the procedures and the disease. The new laboratory analysis techniques are in continuous progress and their efficacy and success are very high for chromosomal anomalies using traditional karyotype by direct analysis of cytotrophoblastic and cultured metaphases of chorionic tissue. Alternatively, quantitative fluorescent polymerase chain reaction (QF-PCR) and array comparative genetic hybridization (aCGH) can be utilized. DNA amplification by PCR and, recently, next-generation sequencing (NGS) have shown high sensitivity and specificity for single-gene diseases. Audit of clinicians and adequate training of fellows are of paramount importance to have the highest quality results. The authors of this manuscript would like to thank Fondazione di Sardegna; Sardinia Regional Department for Programming; Boyana Petrova Tsikalova, MA in English Philology.
Milunsky A, Milunsky JM, ed. Genetic disorders and the fetus. 6th ed., Chicester, UK: Wiley- Blackwell; 2010.
Monni G, Zoppi MA, Axiana C, et al. Changes in the approach for invasive prenatal diagnosis in 35,127 cases at a single center from 1977 to 2004. Fetal Diagn Ther 2006;21(4):348–354. DOI: 10.1159/000092464.
Kuliev A, Rechitsky S, Verlinsky O, et al. Preimplantation diagnosis of thalassemias. J Assist Reprod Genet 1998;15(5):219–225. DOI: 10.1023/a:1022571822585.
Traeger-Synodinos J. Pre-implantation genetic diagnosis. Best Pract Res Clin Obstet Gynaecol 2017;39:74–88. DOI: 10.1016/j.bpobgyn.2016.10.010.
Cao A, Cossu P, Monni G, et al. Chorionic villus sampling and acceptance rate of prenatal diagnosis. Prenat Diagn 1987;7(7):531–533. DOI: 10.1002/pd.1970070710.
Ghi T, Sotiriadis A, Calda P, et al. On behalf of the International Society of Ultrasound in Obstetrics and Gynecology, ISUOG practice guidelines: invasive procedures for prenatal diagnosis in obstetrics. Ultrasound Obstet Gynecol 2016;48(2):256–268. DOI: 10.1002/uog.15945.
Brambati B, Lanzani A, Tului L. Transabdominal and transcervical chorionic villus sampling: efficiency and risk evaluation of 2,411 cases. Am J Med Genet 1990;35(2):160–164. DOI: 10.1002/ajmg.1320350204.
Monni G, Olla G, Rosatelli MC, et al. Second-trimester placental biopsy versus amniocentesis for prenatal diagnosis of beta-thalassemia. N Engl J Med 1990;322(1):60–61. DOI: 10.1056/NEJM199001043220115.
Monni G, Olla G, Cao A. Patient's choice between transcervical and transabdominal chorionic villus sampling. Lancet 1988;7(8593):1057. DOI: 10.1016/s0140-6736(88)91880-6.
Brambati B, Terzian E, Tognoni G. Randomized clinical trial of transabdominal versus transcervical chorionic villus sampling methods. Prenat Diagn 1991;11(5):285–293. DOI: 10.1002/pd.1970110503.
Monni G, Ibba RM, Lai R, et al. Early transabdominal chorionic villus sampling in couples at high genetic risk. Am J Obstet Gynecol 1993;168(1 Pt 1):170–173. DOI: 10.1016/s0002-9378(12)90908-4.
Monni G, Ibba RM, Zoppi MA. Prenatal genetic diagnosis through chorionic villus sampling. In: Genetic disorders and the fetus Milunsky A, Milunsky JM, ed. 6th ed., Hoboken, NJ, USA: Wiley-Blackwell; 2010. pp. 160–193.
Monni G, Pagani G, Stagnati V, et al. How to perform transabdominal chorionic villus sampling: a practical guideline. J Matern Fetal Neonatal Med 2015(9):1–7. DOI: 10.3109/14767058.2015. 1051959.
Monni G, Iuculano A. Re: ISUOG practice guidelines: invasive procedures for prenatal diagnosis. Ultrasound Obstet Gynecol 2017;49(3):414–415. DOI: 10.1002/uog.17375.
Ward RH, Modell B, Petrou M, et al. Method of sampling chorionic villi in first trimester of pregnancy under guidance of real time ultrasound. Br Med J (Clin Res Ed) 1983;286(6377):1542–1544. DOI: 10.1136/bmj.286.6377.1542.
Monni G, Ibba RM, Olla G, et al. Chorionic villus sampling by rigid forceps: experience with 300 cases at risk for thalassemia major. Am J Obstet Gynecol 1987;156(4):912–914. DOI: 10.1016/0002-9378(87)90352-8.
Firth HV, Boyd PA, Chamberlain P, et al. Severe limb abnormalities after chorion villus sampling at 56–66 days’ gestation. Lancet 1991;337(8744):762–763. DOI: 10.1016/0140-6736(91)91374-4.
Monni G, Ibba RM, Lai R, et al. Limb-reduction defects and chorion villus sampling. Lancet 1991;337(8749):1091–1092. DOI: 10.1016/0140-6736(91)91735-D.
Froster UG, Jackson L. Limb defects and chorionic villus sampling: results from an international registry, 1992–94. Lancet 1996;347(9000):489–494. DOI: 10.1016/s0140-6736(96)91136-8.
Tabor A, Alfirevic Z. Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther 2010;27(1):1–7. DOI: 10.1159/000271995.
Akolekar R, Beta J, Picciarelli G, et al. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015;45(1):16–26. DOI: 10.1002/uog.14636.
Wulff CB, Gerds TA, Rode L, et al. The risk of fetal loss associated with invasive testing following combined first trimester risk screening for down syndrome – a national cohort of 147 987 singleton pregnancies. Ultrasound Obstet Gynecol 2016;47(1):38–44. DOI: 10.1002/uog.15820.
Monni G, Ibba RM, Laj R, et al. Transabdominal chorionic villus sampling: fetal loss rate in relation to maternal and gestational age. Prenat Diagn 1992;12(10):815–820. DOI: 10.1002/pd.1970121007.
Monni G, Pagani G, Illescas T, et al. Training for transabdominal villous sampling is feasible and safe. Am J Obstet Gynecol 2015;213(2):248–250. DOI: 10.1016/j.ajog.2015.04.019.
Monni G, Zoppi MA. Improved first-trimester aneuploidy risk assessment: An evolving challenge of training in invasive prenatal diagnosis. Ultrasound Obstet Gynecol 2013;41(5):486–488. DOI: 10.1002/uog.12461.
Jackson LG, Zachary JM, Fowler SE, et al. A randomized comparison of transcervical and transabdominal chorionic-villus sampling. The U.S. National Institute of Child Health and Human Development chorionic-villus sampling and amniocentesis study group. N Engl J Med 1992;327(9):594–598. DOI: 10.1056/NEJM199208273270903.
American College of Obstetricians and Gynecologists. ACOG practice bulletin no.88, December 2007. Invasive prenatal testing for aneuploidy. Obstet Gynecol 2007;110(6):1459–1467. DOI: 10.1097/01.AOG.0000291570.63450.44.
Technical and clinical assessment of fluorescence in situ hybridization: an ACMG/ASHG position statement. Technical considerations. American College of Medical Genetics. Genet Med 2000;2(6):356–361. DOI: 10.1097/00125817-200011000-00011.
Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012;367(23):2175–2184. DOI: 10.1056/NEJMoa1203382.
Jansen FA, Blumenfeld YJ, Fisher A, et al. Array comparative genomic hybridization and fetal congenital heart defects: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015;45(1):27–35. DOI: 10.1002/uog.14695.
Grande M, Jansen FA, Blumenfeld YJ, et al. Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015;46(6):650–658. DOI: 10.1002/uog.14880.
Rosatelli MC, Falchi AM, Tuveri T, et al. Prenatal diagnosis of beta-thalassaemia with the synthetic-oligomer technique. Lancet 1985;1(8423):241–243. DOI: 10.1016/s0140-6736(85)91026-8.
Saiki RK, Bugawan TL, Horn GT, et al. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature 1986;324(6093):163–166. DOI: 10.1038/324163a0.
Batanian JR, Ledbetter DH, Fenwick RG. A simple VNTR-PCR method for detecting maternal cell contamination in prenatal diagnosis. Genet Test 1998;2(4):347–350. DOI: 10.1089/gte.1998.2.347.
Lo YMD, Chan KCA, Sun H, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2010;2(61):61ra91. DOI: 10.1126/scitranslmed. 3001720.
Monni G, Zoppi MA, Iuculano A, et al. Invasive or non-invasive prenatal genetic diagnosis? J Perinat Med 2014;42(5):545–548. DOI: 10.1515/jpm-2014-0135.
Odibo AO, Dicke JM, Gray DL, et al. Evaluating the rate and risk factors for fetal loss after chorionic villus sampling. Obstet Gynecol 2008;112(4):813–819. DOI: 10.1097/AOG.0b013e3181875b92.
Palini S, De Stefani S, Primiterra M, et al. Pre-implantation genetic diagnosis and screening: now and the future. Gynecol Endocrinol 2015;31(10):755–759. DOI: 10.3109/09513590.2015.1068752.
Handyside AH, Pattinson JK, Penketh RJ, et al. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1989;1(8634):347–349. DOI: 10.1016/s0140-6736(89)91723-6.
Monni G, Peddes C, Iuculano A, et al. From prenatal to preimplantation genetic diagnosis of β-thalassemia. Prevention model in 8748 cases: 40 years of single center experience. J Clin Med 2018;7(2):35. DOI: 10.3390/jcm7020035.
Scott Jr RT, Upham KM, Forman EJ, et al. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril 2013;100(3):624–630. DOI: 10.1016/j.fertnstert.2013.04.039.
Monni G, Cau G, Usai V, et al. Preimplantation genetic diagnosis for beta-thalassaemia: the sardinian experience. Prenat Diagn 2004;24(12):949–954. DOI: 10.1002/pd.1051.
De Wert G, Dondorp W, Shenfield F, et al. ESHRE task force on ethics and Law22: preimplantation genetic diagnosis. Hum Reprod 2014;29(8):1610–1617. DOI: 10.1093/humrep/deu132.
Fiorentino F, Kahraman S, Karadayi H, et al. Short tandem repeats haplotyping of the HLA region in preimplantation HLA matching. Eur J Hum Genet 2005;13(8):953–958. DOI: 10.1038/sj.ejhg.5201435.
Tur-Kaspa I, Jeelani R. Clinical guidelines for IVF with PGD for HLA matching. Reprod Biomed Online 2015;30(2):115–119. DOI: 10.1016/j.rbmo.2014.10.007.