In the last several posts, I have discussed amniocentesis as a means of fetal diagnosis for chromosomal or genetic problems. Amniocentesis is considered to be an ‘invasive diagnostic procedure.’ We actually have to stick a needle through the fetal membranes (chorion and amnion) and into the sac surrounding the baby to obtain the fluid and cells we need to perform the diagnostic studies. Another common ‘invasive’ procedure we perform is chorionic villus sampling, or CVS. This procedure can best be thought of as a placental biopsy, sampling fetal placental tissues that lie outside the amniotic cavity. It is usually performed during the latter part of the first trimester (10-13 weeks) for reasons I will discuss later on, but actually is a procedure that can be done anytime, preferably, after 10 weeks, when technically feasible, and may be the procedure of choice when fetal chromosomal or genetic studies are indicated and there is little or no fluid surrounding the baby.
Like amniocentesis, we perform CVS under direct ultrasound visualization or ‘guidance.’ The procedure can be done transcervically or transabdominally and the route that is selected is determined by the position of the cervix and uterus and, most importantly, the placental location. When conditions are favorable for CVS to be done transcervically, the perineum, vagina, and cervix are first ‘prepped’ with an antiseptic solution such as povidone-iodine. The cervix is then grasped with an instrument such as a tenaculum that, with gentle traction, can be used to straighten the cervical canal, aligning the cervical canal and the uterine cavity. A catheter containing a semi-rigid stylet is then placed through the cervix to just inside the junction of the cervix and uterus. Then, using ultrasound to follow the path of the catheter tip, it is advanced until positioned beneath the placenta. The stylet is then removed, a syringe is attached to the catheter, and the catheter slowly withdrawn as negative pressure is applied with the syringe. Placental villi can be readily identified as feathery tissue in the tissue culture fluid. In the laboratory, the fetal chromosomal studies can be done by both direct preparations and tissue culture with results available within 3-4 days and 6-10 days, respectively. More cells are usually obtained by CVS than amniocentesis and the cells are usually more metabolically active, allowing a more rapid turn-around time for both chromosomal and biochemical analyses.
If the placenta is not in an accessible location for a transcervical CVS, the transabdominal route may be considered. In many ways, when the placental location lends itself to this approach, it is and often less uncomfortable procedure for the patient. This is also done under aseptic conditions and direct ultrasound guidance. Usually a 19 or 20 gauge spinal needle is used and, because of the large caliber needle, local anesthesia is generally injected at the needle insertion site. Once the needle is positioned under the placenta, a syringe is used to aspirate a sample of villi just as in the transcervical approach.
Although CVS can be done earlier in the pregnancy than amniocentesis, thereby providing results sooner, it is not without risks. Based on early studies, we have generally quoted patients an ‘excess loss rate (= background loss rate minus the procedure-related rate)’ related to CVS of about 1%, or twice the oft-quoted 1 in 200 risk of an amniocentesis later in pregnancy, a number also based on earlier studies. However, as is now the case with amniocentesis, more recent studies have shown that the risk of CVS has decreased with time and, especially, with the experience of the operators. Caughey and colleagues (Obstet Gynecol 2006;108:612-16) recently published a review of 20 years’ experience (1983-2003) with CVS (9,886 procedures) and amniocentesis (30,893 procedures) at a single institution. They found that while the risk of CVS was 4-fold that of amniocentesis over the entire time period, in the recent years between 1998 and 2003, the risks of the two procedures were equivalent and estimated to be about 1 in 370. The results from the FASTER trial, cited previously in our discussion of amniocentesis, also suggest the risk of CVS is only about 1 in 360, but when compared to that study’s results for amniocentesis (risk of 1 in 1600), CVS is still 4-fold riskier for losing a baby as a consequence of the procedure.
Immediate complications of CVS such as bleeding, rupture of membranes, and introduction of infection are surprisingly rare. However, as with early amniocentesis, other consequences of CVS were found during our early experience with the procedure. In 1991, Firth and colleagues reported 5 cases of limb reduction abnormalities among 289 CVS pregnancies (Lancet 1991;337:762-3), 4 of which were associated with ‘oromandibular hypogenesis (basically poor development of the lower face).’ Since the background risk of this complex of abnormalities is approximately only 1 in 175,000 live births, these findings following CVS were considered to be quite significant. Interestingly, all of these abnormalities occurred after transabdominal CVS procedures performed between gestational ages of 55 and 66 days. To make a long story short, the general consensus today is that there is not a significant risk of limb-reduction defects when CVS is performed between 10-13 weeks, but that the risk may be as high as 1-2% if done prior to this time, particularly when done in the 6 to 9 week time period (Jenkins and Wapner. Semin Perinatol 1999;23:403-13).
The only other issue that we typically discuss with women before they undergo CVS relates to the accuracy of the diagnosis. Vejerslev and Mikkelsen reported a 1% frequency of chromosomal mosaicism in CVS specimens (Prenat Diagn 1989;9:575-88). Chromosomal mosaicism indicates two (or more) populations of chromosomally divergent (different) cells, generally, those that are chromosomally normal and those that are not. A baby can have ‘generalized chromosomal mosaicism,’ thought to arise from a mutational event that occurs during the early divisions of the fertilized egg, and have all (or most) body tissues affected. While generalized mosaicism is a relatively rare event, it appears that similar mutations, occurring in the cells that are destined only to become the placental tissues, is not infrequent at all and when this occurs it is defined as “confined placental mosaicism (CPM).”
When mosaicism is found in a CVS specimen, it is recommended that another invasive diagnostic study, either amniocentesis or percutaneous umbilical blood sampling (yet, another post) be performed to rule out generalized fetal mosaicism. However, even if it appears that this is ruled out (there is still a small chance the baby could have a more limited distribution of mosaicism with fewer tissues involved), the finding of CPM still may indicate a pregnancy ‘at risk’ for complications related to placental ‘insufficiency’, including fetal loss, intrauterine growth restriction, and pregnancy-induced hypertensive disorders. Life is never as simple as it seems, is it?!?