Chorionic Villi Sampling with Traditional Chromosome Analysis
To the Point– CVS is a diagnostic test that can tell you, with very high accuracy, if your baby has an age-related chromosome abnormality such as Down syndrome, by looking at the chromosomes in the chorionic villi cells, which are part of the placenta. In general, the chromosomes of placental cells are the same as that of the baby/fetus. CVS is performed by inserting a catheter vaginally, or a very thin needle abdominally, into the chorionic villi of the placental tissue and removing a small amount of tissue. The needle/catheter are then immediately removed and the tissue is sent to the lab for analysis. CVS is generally considered fairly safe but not entirely risk-free; there is a risk of miscarriage associated with the procedure of approximately 1/200-1/300. The procedure is typically done at 10-12 weeks gestation and it takes about 7-10 days to receive results.
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Chorionic villus sampling (CVS) is a diagnostic test with results thought to be over 99% accurate or in most cases, yes or no. Chorionic villi are a part of the placenta, the structure that allows nutrients and waste to pass between mom and baby. The genetic information found in placental cells is typically the same as the genetic information found in fetal cells. The procedure itself is typically performed between 10-14 weeks gestation. There are 2 different methods of doing CVS; one method involves inserting a catheter vaginally through the cervix. The second method involves inserting a needle into your abdomen and obtaining some cells from the placental tissue. The placental cells each have a set of chromosomes (see genetics 101 for more info). So, with CVS, we can essentially open up the placental cells and look directly at the chromosomes! In general, the chromosomes from the placental cells are the same as that found in the fetus, however, < 1% of the time there may be areas of the placenta that are different. Often times this does not mean the baby has abnormal chromosomes but rather, it is something that is isolated to the placenta (this is termed confined placental mosaicism).
CVS is a procedure performed in the doctor’s office. Most women report that it does not hurt as badly as anticipated (we know….it looks and sounds like it would hurt). There is a risk of miscarriage associated with the procedure, which is thought to be less than 1%. Ultimately, over 99% of the time everything goes just fine. If you do have a CVS, you need to take it easy for 24-48 hours – ask your doctor for details. You will get results in approximately 7-10 days regarding all of the chromosomes, including the sex chromosomes. So, you will know if it is a boy or a girl. CVS does not look for or rule out all birth defects, but it does rule out chromosome abnormalities such as Down syndrome with over 99% accuracy. Historically, this test was offered only to high-risk pregnancies (e.g. advanced maternal age, abnormal screening test, etc.), however, new guidelines suggest that CVS be offered to all women, regardless of age.
HOW IT WORKS
CVS is a pretty quick procedure done in a doctor’s office. This procedure should only be performed by an experienced high-risk pregnancy doctor (perinatologist/Maternal-Fetal Medicine specialist). Basically, the doctor will use an ultrasound to guide as they insert the catheter vaginally or a very thin needle abdominally into the chorionic villi of the placental tissue. A small amount of tissue is taken out, and then the needle/catheter are immediately removed. Total time of this process is typically less than a few minutes.
The placental tissue is sent off to the laboratory where the cells are grown (that’s the part of the process that takes time) and then the chromosomes can be analyzed. The placental chromosomes are evaluated for any extra (trisomy, such as, Down syndrome) or missing chromosomes (monosomy, such as Turner syndrome). Large deletions (missing sections of a chromosome) or rearrangements of parts of chromosomes can also be determined. Sex chromosomes are obviously seen, so if you don’t want to know if you are having a boy or a girl, make sure you let your doctor know so they don’t spill the beans! The doctor’s office will likely call you or give you results within 7-10 days.
Unlike the amniocentesis, CVS does NOT look for evidence of open neural tube defects (ONTDs), such as, spina bifida. However, a simple blood draw on mom at approximately 15-20 weeks can screen for evidence of ONTD. High level (level II) ultrasound in the 2nd trimester is also highly sensitive in evaluating for open neural tube defects. ONTDs are a fairly common birth defect affecting approximately 1-2/1000 babies born. Risk for ONTD does not increase with age. For more information on ONTDs click here.
CVS results with traditional chromosome analysis are typically considered to be very accurate with regard to looking for chromosome conditions, such as Down syndrome. Results are also very accurate if you are having the procedure to look for other specific genetic conditions based on family history, such as cystic fibrosis or Tay-Sachs disease. There are rare cases when the results are hard to interpret and the doctor may recommend you consider amniocentesis. There are also rare cases of lab error. With CVS chromosome results, there is a small chance that the results will indicate that some of the cells have an abnormal number of chromosomes and some have the typical number. This may be a true representation of the fetus or may be confined to the placenta. In order to sort this out, amniocentesis is recommended. CVS final results typically take around 7-10 days to receive. You will receive information on the chromosomes (looking for evidence of Down syndrome and other Trisomies, etc.) and gender (if you want to know if it is a boy or a girl). CVS does not look for all birth defects or genetic conditions.
My CVS results are abnormal….what to consider….
Historically, CVS was offered to women 35 or older at delivery to look for Down syndrome, as this was one of the first conditions known to increase in incidence as mom’s age increases. As time has passed and technology has improved, the CVS with traditional chromosome analysis is now capable of detecting a variety of chromosome abnormalities with various levels of severity. If you are reading this and you have received a result indicating a chromosome condition, it may be that you are finding out that your baby has Down syndrome or it may be something more severe, such as Trisomy 13 or Trisomy 18, or something potentially more mild, such as Turner syndrome (45, X) or Klinefelter syndrome (47,XXY) or some other chromosome or genetic condition. No matter what condition has been diagnosed, we know that this is not necessarily an easy time or what you expected.
If your results indicate a chromosome condition or birth defect, it is often very helpful to take time to talk to your provider, a genetic counselor if you are able, friends and family if you are comfortable, and even get a second opinion if you feel like that may be helpful. Taking time and consulting with others is especially important if your results are confusing, unclear, or if you don’t know much about the condition that has been diagnosed.
Even if you know a bit about the condition, it’s often helpful to get up-to-date information as things have changed dramatically for some conditions. For example, in the case of individuals with Down syndrome, quality of life and life expectancy is quite different than it was 2 generations ago. Also, depending on what website you go to, who you talk to, what you read, you are going to find differing opinions on what life may be like for a child with the condition that has been diagnosed, what it is like to parent a child with the condition, etc. Some people benefit from finding someone who has a child with the same diagnosis and speaking with them directly. Your provider or genetic counselor may be able to help facilitate this.
Ultimately, you have 3 options if you find out through amniocentesis that your baby has a chromosome abnormality, genetic condition or birth defect….
- Continue the pregnancy and prepare – READ MORE
- Continue and place the baby for adoption – READ MORE
- Choose to not continue the pregnancy – READ MORE
HOW TO DECIDE
To The Point– Deciding about invasive testing like CVS can be tough. If you feel like either way you would continue your pregnancy and raise your child AND you are doing ok mentally with the uncertainty, then the invasive testing may not be for you. If you aren’t sure what you would do if a chromosome abnormality was found AND/OR you are not doing well mentally with the uncertainty, then invasive testing may be the way to go. Read on for more information to help you in this process…..
Deciding whether or not to have a diagnostic test, such as, CVS, is a big decision. For some, it may be a fairly easy call. For others, it may be agonizing. Either way, it warrants thoughtful consideration.
Patients often ask their doctors or genetic counselors, “would you have the CVS?” This is a great question, however, the answer is different for each individual and circumstance. One of the most important aspects of prenatal genetic counseling is that whatever the patient decides is based on their personality, beliefs and values, not the providers. So, instead we offer you some questions to consider.
- Do you feel like you need yes or no answers to be able to enjoy the rest of the pregnancy (i.e. eat, sleep, etc)?
- Do you feel like you are ok waiting until the baby arrives to know for sure?
- If you feel like you need more definitive answers, are you ok with the risk of miscarriage associated with this procedures (CVS, <1/200)?
- If you knew that the baby had a chromosome condition, would it affect your decision to continue the pregnancy and raise the child?
- Would you consider other options if there was a chromosome condition present in your baby, such as, placement of the baby for adoption (which is a realistic option) or choosing not to continue the pregnancy?
- Have you thought about these two scenarios- 1) you don’t have the CVS and you find out at delivery that the baby has a chromosome condition and 2)you do have the CVS and you end up miscarrying the baby. Both situations may be unsettling, but which scenario is more unsettling to you? …these are ethically challenging things to think about and talk about….this is part of why your provider will allow you to make these decisions based on your own personality, beliefs, needs and values.
- Are there other trusted people in your life that you can turn to for advice and perspective (i.e. religious leader, family member, friend, etc.)?
Another way to look at this is… “What do other people decide to do?”
- Don’t get the CVS because….“I wouldn’t do anything even if the test came back indicating that the baby had a chromosome condition.”
- Get the CVS because…. “I wouldn’t do anything differently if the test came back indicating that the baby had a chromosome condition, but I want to have the information to prepare.”
- Get the CVS because…”I am not sure what I would do if the test came back indicating a chromosome condition, but if it indicated a serious disorder I may consider choosing not to continue the pregnancy.”
CVS is now offered to women of all ages and some may choose to have CVS simply because they want as much definitive information regarding age-related chromosome abnormalities as early as possible in the pregnancy. Other reasons you may consider having a CVS include the following:
- You had positive/abnormal results from a prenatal screening test, such as first trimester screening (FTS) or non-invasive prenatal testing (NIPT). In these situations, if you want yes or no answers, it is recommended to consider having CVS or amniocentesis.
- You have a family history of a chromosome abnormality (eg. child or previous pregnancy). This puts you at higher risk and you also may mentally feel like you need to know earlier than later if your baby is going to have something similar to your previous pregnancy.
- You are 35 or older at delivery. Historically, women 35 or older (Advanced Maternal Age or AMA) have been routinely offered CVS because of the higher chance of chromosomal conditions, such as Down syndrome as mom ages.
- You have a family history of a specific genetic condition, or you and/or your partner are known carriers of a genetic condition. If the genetic changes are known in your family, you may be able to have additional testing through CVS to determine if your baby has a specific genetic condition, for example, Tay-Sachs disease, cystic fibrosis, spinal muscular atrophy, Fragile X, etc.
Great question. Short answer- you get answers with similar accuracy earlier in the pregnancy (first trimester).
Both CVS and amniocentesis are considered to be the gold-standard diagnostic tests for looking for chromosome abnormalities in the baby. In general, with CVS the results are reported more quickly (7-10 days versus 10-14 days). Also, CVS is performed in the first trimester at 10-14 weeks versus the amniocentesis, which is performed at 16-20 weeks. So, if you want information regarding the chromosomes of the baby as early as possible, CVS may be the test for you.
There are a few disadvantages to CVS.
- CVS is considered more risky than amniocentesis by some. However, in the hands of a specialist who regularly performs CVS, the risks are nearly equivalent.
- CVS is looking at the chromosomes from placental cells (chorionic villi is part of the placenta) whereas amniocentesis is looking at chromosomes from fetal bladder and skin cells. There can be differences seen in areas of the placenta cell chromosomes, which may not reflect the fetus. When this occurs, amniocentesis is recommended to evaluate whether the results truly reflect the fetus or are limited to areas of the placenta (this is called confined placental mosaicism).
- CVS does not look for evidence of open neural tube defects (for example, spina bifida). However, there are other ways to assess chances of this, including, level II ultrasound in the second trimester and a blood draw on mom in the second trimester called, maternal serum alpha-fetoprotein (MSAFP). Open neural tube defects occur in approximately 1/500 to 1/1000 babies born and chances of these do not increase as mom ages.
It is not necessarily unusual for doctors to perform amniocentesis but not CVS. CVS requires special training and experience. Typically, only Maternal-Fetal Medicine specialists have the experience. Not all Maternal-Fetal Medicine specialists are trained in CVS. You should inquire from the office how often the provider performs CVS. If the answer is less than 10 per year, it may be wise to keep looking for a different provider to perform the test.
Early research on CVS indicated a possible increase in risk for birth defects involving the baby’s limbs due to the procedure if performed < 10 weeks gestation. There is no evidence that CVS causes limb defects when performed at 10 weeks or beyond
To the point:
- Both traditional chromosome analysis and chromosomal microarray can evaluate conditions that are increased in risk as mom’s age increases (e.g. Down syndrome).
- Both traditional chromosome analysis and chromosomal microarray can identify other conditions involving missing chromosomes or major chromosome rearrangements
- Unlike traditional chromosome analysis, chromosomal microarray testing has the capability to detect smaller regions of extra or missing portions of the chromosome, called microduplications or microdeletions which may be associated with mental retardation and birth defects
- Both traditional chromosome analysis and chromosomal microarray may identify a change where outcome is uncertain, however, this is arguably more likely with chromosomal microarray.
- Chromosomal microarray testing has approximately a 1-2% chance of identifying what is called a variant of unknown significance (VOUS), meaning, there is not enough data to know whether or not the genetic change will results in abnormalities in the baby; this information may result in substantial anxiety for mom and dad.
- Chromosomal microarray may detect non-paternity (different father of baby) and consanguinity (parents are closely related to each other, i.e. cousins).
- Traditional chromosome analysis still considered standard of care, however, recent guidelines from The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have opened the doors for all women to be offered microarray if they are undergoing diagnostic testing, such as CVS or amniocentesis.
“The potential for complex results and detection of clinically uncertain findings identified by prenatal chromosomal microarray testing can result in substantial patient anxiety. This underscores the critical need for comprehensive patient pretest and posttest genetic counseling from qualified personnel about the benefits, limitations, and results of testing so that patients can make informed decisions.”- American College of Obstetrics & Gynecology/Society for Maternal Fetal Medicine statement
Traditional chromosome analysis, also known as karyotype analysis or cytogenetic analysis, can evaluate the number of chromosomes and the basic structure of each chromosome (e.g. any extra or missing chromosomes or any major rearrangements of the chromosomes). Traditional chromosome analysis can rule out common chromosome conditions like Down syndrome, Trisomy 18, Trisomy 13 and sex chromosome conditions. It can also detect large deletions and duplications of chromosomal material that are visible under the microscope. Traditional chromosome analysis is still considered the standard of care. However, recent guidelines from The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have opened the doors for all women to be offered microarray if they are undergoing diagnostic testing, such as CVS or amniocentesis.
Besides detecting the vast majority of things that traditional chromosome analysis can detect, microarray testing has the capability to zoom in on parts of the chromosomes that are too small to visualize using a microscope, allowing detection of smaller regions of extra or missing portions of the chromosome. Conditions in which several instructions or genes are missing are called microdeletion syndromes. Conditions in which there are several genes duplicated are called microduplication syndromes. Microdeletion and microduplication syndromes are typically associated with mental retardation and birth defects. There are over 150 genetic conditions that can be detected with microarray testing. These conditions are not typically increased in risk as mom’s age increases.
In terms of detecting chromosome abnormalities involving an extra chromosome, such as Down syndrome, CMA is just as good as traditional chromosome analysis. The differences come in when detecting abnormalities involving smaller genetic changes. Among fetuses with an abnormal ultrasound finding, CMA found clinically relevant chromosomal deletions or duplications approximately 4% of cases that were not detected with traditional chromosome analysis. In cases sampled for advanced maternal age or positive screening results, microarray analysis picked up an abnormality in 1.7% of pregnancies that had a normal traditional chromosome analysis1.
Besides the possibility of detecting conditions like Down syndrome and other genetic conditions, microarray testing may also detect what are called variants of unknown significance (VOUS). These are changes in the baby’s DNA that may or may not affect the baby’s development but there is not enough data to know for sure. Recent studies have shown that approximately 1-2% of patients receive a result that is a VOUS1. Many labs request samples of mom and dad’s blood to look at their DNA to help interpret the meaning of a VOUS; in some cases this can be helpful but not always. When a VOUS is found in the baby during the pregnancy, it may cause a lot of anxiety in mom and dad as the outcome for baby may be very uncertain. This is one of the main reasons that genetic counseling and informed consent prior to having prenatal chromosomal microarray is very important.
Prenatal chromosomal microarray results take approximately 7-10 days to receive, compared to 10-14 days for traditional karyotype analysis, and may be called out over the phone or given to you in person by your provider. Chromosomal microarray may be offered to all women undergoing invasive testing, such as amniocentesis or CVS, but this is an optional test and is always your choice.
There are certain situations where microarray will be offered or recommended based on abnormalities on ultrasound. However, if you are being offered microarray for no specific indication here are some thoughts to consider…
Microarray is an exciting technology that is relatively new within the arena of prenatal testing. Before assuming that more is better, you need to take a step back and think about a few things. First of all, do you want to know all of this information in the first place and would it change your decisions about how you would proceed with the pregnancy, etc. Secondly, and often understated, there is a real chance, 1/50 or greater1, that you may get results that indicate there is a difference or change found in the baby’s DNA, but we don’t know exactly what it means because technology is ahead of us. This can cause a lot of anxiety. Microarray testing during pregnancy cannot necessarily be equated with microarray testing after the baby is born, when you can actually see the baby, know what he/she looks like, etc. Finding out uncertain information about the prognosis of the baby during the pregnancy can be especially challenging and make decision-making extremely difficult. Microarray testing may also reveal information about the future health of the parents and also may detect things like non-paternity (if the father is someone other than previously thought) and consanguinity (if parents are closely related to each other). Microarray testing does not rule out all birth defects or genetic conditions. Like other prenatal testing options, the choice is always up to you to make.
1. Hillman et al. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol 2013; 41: 610–620.