Chorionic Villus Sampling
Thursday, May 03, 2007
Kenneth F. Trofatter, Jr., MD, PhD
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 The stylet is then removed, a syringe is attached to the catheter, and the catheter slowly withdrawn as negative pressure is applied with the syringe.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?!?
Labels: amniocentesis, ChorionicVillusSampling, CVS
12 Comments:
At Sun Jul 20, 02:44:00 PM 2008,
Eveline said…
Dear dr. T, I had a CVS done last Wednesday through the vagina (transcervical) at 13.2 weeks gestation.
Now I am very worried as I think I have (and had at that time) a candida (fungus) infection of the vagina. I saw the thrush just a day after the CVS was done so I did not mention it to the doctor. Now I am worried that the candida could have been travelled up to the uterus through the CVS procedure and is that harmful to the baby??
Off course the vagina was cleaned with Iodine before, but I can't stop to worry.
Can you please tell me what to do?
Many thanks Eveline
At Tue Jul 22, 06:58:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Eveline: That is something you need to call your primary provider or the physician who did the CVS about. That's what they are there for and I am sure they would want to know. Please do that! Best wishes! Dr T
At Thu Jul 24, 07:40:00 PM 2008,
Anonymous said…
Dear Doc,
I had a CVS done and the results are mosaic. The two cell lines are 46,XX(96%) and 46,XY(4%), which totally freaks me out. I googled that 23% of the mosaic results turn out to be (i) maternal cell contamination or (ii) confined placenta mosaicism. Is this consistent with what you know? If so, would this apply in my case? In other words, absent any additional information, is it 77% likely that my fetus will have both XX and XY?
The only additional fact I can give you is that my doctor commented that my sample was very small when he took it. He sighed when it was taken. Then he said, oh, it's perfect. It will be enough.
Thank you and I'm terribly stressed!!!!!! Any information that you have would be very appreciated.
At Sat Jul 26, 05:08:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 24: The odds are that the sample was poor, just as your doctor suspected initially. In other words, it is probably a male fetus with the sample contaminated by lots of your cells. Is the other a possibility? Yes, but that is much less likely. So don't get overly stressed out. Unfortunately, if you want to know for sure, you will probably need an amniocentesis performed. Good luck and please let us know what you find out! Dr T
At Mon Jul 28, 05:05:00 AM 2008,
Anonymous said…
My husband and I are confused and worried. I had a CVS done and the results showed a female karyotype with a Robertsonian translocation. The technician noted hat "there is concern that this result may represent the maternal karyotype as the cells from the CVS grew rapidly. The rapid growth is atypical for CVS samples. The mother is known to be a carrier of the same type of translocation." The lab analyzed 6 cells and karyotyped 3. The approximate GTG band level was 450-500. Please, what is the likelihood that the results don't match the fetus? How could a mistake happen? The literature is vague about this and only says that mistakes happen 1 out 100 times. I know that amnio would be the next step, but I feel uncomfortable waiting that long. Financially, I am not sure I can pay for it anyway.
At Mon Jul 28, 04:09:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 28: It is not so much a "mistake" as it may simply be a 'sampling error'. It does not sound like they got much tissue so that increases the likelihood (based on the description you give) that these are only your cells being analyzed. An amnio is probably the least risky "next step" other than just taking your chances. By the way, what type of translocation do you carry? Best wishes! Dr T
At Tue Jul 29, 05:30:00 PM 2008,
Anonymous said…
Dear Dr. Trofatter,
Thank you SO MUCH for replying to my question about the ambigous CVS. The translocation is a Robertsonian. Results: 45, XX, der (13;14)(q10;q10). My husband was upset because he called the lab and asked why a paternity test couldn't be done, since all family members have been karyotyed, but the lab had already thrown away the sample. Please bare with me for long explanation. My first son, who has the same translocation, is autistic. My second son has a normal karotype and is fine. Now we are expecting our third child. My husband and I are well read on autism - mercury, MMR, gut problems, genetics, etc. Of course, so one knows the cause, but genetics seem to play a part. There are famalies who have 50% autistic children, so we are convinced that genetics plays a part. We also know that Robertsonian translocations usually produce normal kids; nevertheless, it is statistically more likely that the fetus would develop autism with this translocation than if it had a normal karotype. What also concerns my husband is the clinical note that "the cells grew faster than normal fetal cells." If the CVS results are a mistake, then OK; but if an amnio shows that the initial results were fine, then we are both freaked out about the unusual growth. A characteristic of autism is that the brain grows to fast. We witnessed this with our first son who grew at the 95% percentile, way beyond the norm. So there you have the long explanation... We will probably do the amnio as you suggested, although this is a real financial burden (no insurance), and an abortion will be much more difficult in four or five weeks.
PLEASE DO NOT POST THIS MESSAGE, IT IS PRIVATE FOR DR. TROFATTER. You are welcome to respond to our private e-mail at kramer@nwmissouri.edu
Thank you for your wonderful webpage. You are a Godsend!
At Thu Aug 07, 05:03:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 29: I am sorry the message ended up getting posted...they get screened by someone but not closely read. Good luck with the amnio. Just remember, you carry this translocation and are NOT autistic! I will be thinking about you! Kind regards, Dr T
At Thu Aug 21, 03:43:00 PM 2008,
Anonymous said…
Dear Dr. T.,
I am 32 years old and pregnant with my second child. With my first, I did not have a nuchal since it was not routine at my dr. However, it is now routine that all pregnancies have a nuchal done prior to 13 weeks.
I also had the combined screening with the blood drawn from my finger. I received the call that my nuchal results were in normal range but my blood came back abnormal; I have a 1:31 risk as I was told. I went to a perinatal specialist and he too performed a nuchal and said that the baby looks great, within noraml limits. To know for sure he also suggested having a CVS done. I did; the results have not come in yet.
I guess I am confused at how the nuchal translucency is normal, but the blood results are so abnormal. I asked both my ob/gyn as well as the perinatal specialist, but the answers seem to be inconsistent and I am still confused. Please help me understand how this is possible??? I have been so stressed with anxiety the past week.
At Wed Aug 27, 06:09:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Aug 21: I am assuming the 1 in 31 risk is for Down syndrome and not trisomy 18. If we use the NT measurement alone to try to screen for Down syndrome, we will only pick up about 50% or less of those babies. In other words, at least half of all Down's babies do not have a widened nuchal traslucency. Indeed, we are not even sure what causes the widened NT in babies that do! Adding the serum markers increases the detection rate to about 90% with a false-positive rate of about 5%. So many Down's babies are only piced up because of the blood tests. I hope that helps. It IS acomplicated issue for patients as well as doctors to understand and to explain. Best wishes and let us know how things turn out. Dr T
At Thu Aug 28, 12:05:00 PM 2008,
Anonymous said…
Thank you for your response Dr. T! you did help make the entire process more understandable.
My placenta sample was tested and everything came back fine. Apparently I was one of the 5% having a false positive. I also found out that I was already in my second trimester when the 1st Trimester Combination Screening was performed. I found out at the perinatal specialist. I can't help but wonder if that played any part in the false positive results....
Thank you again for your response!!!!
At Wed Sep 03, 05:24:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Aug 28: You're welcome and thanks for the feedback. Best wishes for the rest of the pregnancy. Let us know how things turn out! Dr T
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