# Invasive Prenatal Diagnostics: A Cornerstone of Perinatal Management
## 2 Techniques of Invasive Diagnostics
### Chorionic Villus Sampling (CVS)  
Chorionic villus sampling (CVS) is an alternative procedure for invasive prenatal diagnostics. Its superiority over amniocentesis is the timing of its feasibility. It can be conducted from 10 to 14 weeks of gestation [178]. It provides an early genetic diagnosis and assessment of pregnancy management and, eventually, a less traumatic experience for the patient if termination of pregnancy is considered. The idea is to sample chorionic villi with an 18- or 20-gauge needle, from either a transabdominal or transvaginal approach. This way, it is possible to obtain a specimen of trophoblastic cells. In the vast majority of cases, the placental tissue DNA will be the same as that of a footus. Therefore, the aforementioned methods of genetic analysis, such as CGH or NGS, can be used to assess chromosomal or subchromosomal aberrations. However, the main weakness of this method is the inability to detect cases of confined placental mosaicism (CPM). According to guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) from 2022 [179] regarding CVS, the overall prevalence of CPM is approximately 1-2%. Therefore, in the absence of structural anomalies, only the examination of amniotic fluid should be considered. However, if mosaicism is observed in amniotic fluid, the reliable way to rule out true foetal mosaicism (TFM) is the karyotyping of foetal lymphocytes collected in cordocentesis [180].  
Credible data regarding the procedure-related risk for complications of CVS is limited. In a systematic review of 29 studies by [PERSON] et al. [66] published in 2007, it was shown that the overall risk of pregnancy loss was similar to that related to amniocentesis, and it was 0.7% within 14 days after the procedure. In an update from 2017 [181], [PERSON] confirmed the previous findings. However, it is worth noting that the risk of CVS will always be at least slightly higher because of a higher rate in 10-13 weeks of gestation. Moreover, [PERSON] et al. [182] noticed that the learning curve of the CVS procedure is significantly longer and that an operator's expertise has a considerable influence on the outcome. Other less worrying complications are transient leakage of amniotic fluid, vaginal spotting, and culture failure. The overall incidence is reported to be lower than 0.5% [183].  
It is also worth noting, that the aforementioned procedures are also applicable in multiple pregnancies. The technique of amniocentesis and CVS does not differ from singleton pregnancies; however, frequently, two samples are required. Therefore, the procedure-related risk is likely to be higher [179]. The most recent data come from a paper from 2022 by [PERSON] et al. [184]. Their retrospective cohort study assessed the risk of foetal loss following amniocentesis and transabdominal CVS in both DCDA and MCDA twins. Their study indicated a significant increase in miscarriage both in the DCDA and MCDA groups versus uncomplicated control twin pregnancies. However, if only genetically and structurally normal foetuses were considered, the increase in pregnancy loss was not statistically significant. These findings underline a substantial limitation of their study, which was the construction of the control group. The most appropriate control group should be composed of twin pregnancies with similar indications for invasive testing that had declined genetic diagnosis. However, such a group would be challenging to assemble; therefore, their results must be interpreted cautiously.