# Handbook of Genetic Counseling/Advanced Maternal Age - Chorionic Villus Sampling (CVS)

Advanced Maternal Age - Chorionic Villus Sampling (CVS)

## Introduction

* What are your main reasons for seeing us today for genetic counseling?
* Ask them if they have any particular questions or concerns they would like to discuss.
* Address any concerns or explain that they will be discussed later
* Provide an overview of what we will be doing including a discussion of their concerns or questions

## Obtain Pregnancy and Family History

* How far along is the pregnancy?
* How was that determined?
* Have you had any complications with your pregnancy?
* Have you had an ultrasound?
* When was prenatal care begun?
* Have you taken any medications since you were pregnant or before you realized you were pregnant?
* Have you had any alcoholic beverages since you were pregnant?
* Any drugs?
* Are you taking prenatal vitamins? When did you start them?
* How many total pregnancies have you had?
* Have you had any miscarriages or elective terminations?
* Do you work outside the home? What is your occupation?
* Husband's or partner's employment?
* Do you or your husband/partner have a religious preference?
* I would like to obtain some family medical history information. Some of the questions I will ask will help us determine if there are any hereditary disorders that we may want to discuss.
* Take basic 3 generation pedigree unless something else seems significant
* Ask about: her three pregnancy losses and may want to explain reason for most recent loss. Also ask about MR/learning difficulties in school, birth defects such as cleft lip or palate or heart defects, anyone die young or unexpectedly, anyone with bleeding disorders, cancers, any other health problems that you think might be hereditary?

## Explanation of Advanced Maternal Age

* Are you familiar with the age related risk associated with having a baby with some specific chromosomal abnormalities?
* As women get older their risk for having a baby with a change in the number of chromosomes in their cells increases. There is no magic age at which a woman goes from no risk to high risk. However, at age 35 the risk is considered high enough to offer some standard testing options that we will discuss today.
* Explain chromosomes and genes
* Explain nondisjunction
** Sometimes when the egg or sperm form, the chromosomes don't separate and an egg or sperm ends up with an extra copy of a chromosome
** This is called nondisjunction and it is a random, chance event that does not run in families
** Although it is a random event, it does occur more often as a woman gets older
** After fertilization, there are now 47 chromosomes rather than the usual 46
** When there is an extra copy we call it trisomy because there are three copies instead of the usual two copies
** Often when there is extra genetic material there are changes in the way the fetus grows and develops
** When a fetus has an extra chromosome there is also a higher risk of having a miscarriage as occurred in your last pregnancy
** However some fetuses with certain extra chromosomes may survive to birth.

## Down syndrome

* Discuss previous pregnancy loss due to trisomy 21 or Down syndrome
* Trisomy 21 (most common cause of Down syndrome) is the third most common autosomal trisomy to be observed in fetuses that don't survive
* Approximately 23% of fetuses with Down syndrome will be lost between midtrimester and term
* Trisomy 21 is the most common trisomy in babies that are born
* Are you familiar with the characteristics of Down syndrome?
* Children with Down syndrome are all unique, but often have distinguishable physical characteristics that you might recognized.
* They are all cognitively impaired and this is most often mild to moderate
* Nearly half of children born with Down Syndrome have heart defects and they are at an increased risk for some other specific birth defects or medical concerns

## Trisomy 18, 13

* Two of the other common trisomies are trisomy 18 and 13.
* Children with these conditions are more severely affected than those with Down Syndrome.
* They usually have a variety of birth defects and are severely cognitively impaired.
* Many miscarry and there is a high rate of mortality during infancy

## Other chromosome abnormalities involving the sex chromosomes

* Other chromosome abnormalities that you may be at an increased risk for due to age involves the sex chromosomes (Smith's quotes that there is a marked increase in maternal age associated with maternally derived 47XXY males where the error was in meiosis 1. However, the error can also be in maternal meiosis II and half of males with 47XXY result from paternal meiosis 1 errors)
* Babies can have an extra copy of one of the sex chromosomes and sometimes they remain undiagnosed until later in life
* They usually have an average IQ, but may experience learning difficulties in school.
* They don't usually have serious medical problems associated with having extra sex chromosomes, but they may be infertile.

## Age Related Risks

* Age related risks (refer to chart in visual aids)
** Live born baby with Down Syndrome 1 in 112 almost 1%
** at age 42 risk of a live born with any chromosomal abnormality is 1 in 65 around 1.6%
** chance of having a liveborn child without a chromosomal abnormality detected is 98.4%
** risks are higher of having an affected fetus during pregnancy though because of the high miscarriage rates in fetuses with a chromosome abnormality
* quote risks at amnio and CVS if interested at amnio risk is 1 in 41 for all chromosome abnormalities and at time of CVS risk for all is 1 in 28 and at amnio risk for Down syndrome is 1 in 86

## Prenatal Testing Options During First and Second Trimester

* Two tests that are diagnostic and can tell us with greater than 99% [source?] accuracy whether the fetus has a chromosomal abnormality
* CVS (10-12 weeks)
* Amniocentesis around 15 weeks
* (Have you read any information about CVS or amniocentesis?)
* Option to undergo no testing
* Screening
* First trimester prenatal screening plus ultrasound
* blood test and ultrasound combined will detect 91% of Down syndrome and 97% for trisomy 18, 40% of heart defects and some other birth defects
* blood tests measures levels of 2 proteins freeBeta-hCG and PAPP-A
* ultrasound measures nuchal translucency (increased neck width)
* not diagnostic of a chromosome abnormality but shows whether risks are increased
* Level II ultrasound in second trimester will help in determining the overall development of the major organs. It will show some birth defects, which may provide a clue about whether or not there is a chromosomal abnormality. However, not all birth defects are detected by amnio, and the presence of a birth defect will not indicate for certain if there is a chromosomal abnormality

## Chorionic Villus Sampling Overview

* Often referred to simply as CVS
* CVS is a technique in which a sample of placental tissue is obtained
* The little fingerlike projections of the placenta that are sampled are called chorionic villi
* The villi are derived from the same original cells as the fetus so these cells should have the same genes and chromosomes as the fetus and we can look at the chromosomes in these cells and detect the chromosomal abnormalities discussed earlier
* CVS is performed between 10 and 12 weeks gestation
(CVS has been around since 1983 in US)

## What Information CVS Can Provide

* It is a diagnostic test that can determine if the fetus has one of the chromosomal abnormalities we discussed with 98-99% accuracy.
* It can also determine the sex of the fetus if you would like to know.
* DNA obtained from the sample can also be used to test for certain specific genetic disorders if the fetus is at risk

## Limitations: Information CVS Does Not Provide

* Most birth defects cannot be detected by CVS or amnio. (Amnio can detect about 10% of birth defects). For example cleft lip, cleft palate, congenital heart defects, and many types of mental retardation will not be detected.
* CVS doesn't routinely test for heritable disorders such as cystic fibrosis unless there is a risk for a specific disorder and a special test is ordered.
* CVS does not test for whether the fetus has a neural tube defect (i.e. spina bifida or anencephaly
* About 95% of women who undergo a CVS will have a negative test result. However, a negative test result from CVS does not guarantee a healthy baby. (3-5 out of every hundred babies have a birth defect).
* There is a 1-2% chance that the test will be inaccurate (reasons for this will be discussed later)

## Associated Risks

* 1% additional risk for pregnancy loss. This is above the baseline risk of miscarriage that all women have. (At 10-12 weeks this spontaneous loss rate is 2-3%) In other words, about 1 out of every 100 women who have CVS will have a miscarriage that is due directly to the procedure.
* Extremely low risk of uterine infection
* Some studies reported a possible risk of limb defects while other studies have not. Most of the defects were noted if the procedure was performed before 10 weeks because the limbs develop between 4-10 wks. The increased risk of limb defects is about 1 in 3000 compared with the norm of 6 per 10,000.

## Amniocentsis VS. CVS

* Amniocentesis is another option that can be performed later in the pregnancy and will test for the same chromosomal abnormalities as well as neural tube defects, but ONTD's can be detected 85% of the time with MSAFP (blood test performed after 14 weeks)
* Review visual aid that compares the two procedures on timing, risk, accuracy etc.

## Reasons Some Women Choose CVS

(This is a personal decision and each woman places different emphasis on the things that are important to her)
* Permits termination at earlier gestational age
* 1st trimester and people often don't know that she is pregnant
* Early termination has been reported to be easier emotionally and physically
* They want reassurance that the fetus does not have a chromosomal abnormality
** Allows treatment for a fetus with 21-hydroxylase deficiency (CAH) autosomal recessive condition in which shots of dexamethosone can be given

## Reasons Some Women Choose Amniocentesis

* Lower risk of pregnancy loss 0.5% instead of 1%
* Results are slightly more accurate >99% compared to 98-99%
* Offers detection of open neural tube defects (90-96%)
* However, a maternal blood test (MSAFP) can be performed later in pregnancy (14-22 wks) and will detect 85% of open NTD's
* Procedure is easier and more hospitals perform it
* With CVS there is a greater likelihood of needing further testing due to
** Laboratory failure
** Maternal cell contamination
*** Frequency 1.9%
*** Not problematic for cytogenetics because they do maternal karyotype also, can be problem for DNA or biochemical testing
** Mosaic or ambiguous results
*** Presence of two or more groups of cells that differ in their chromosome make up
*** Occurs in 1-2% of CVS samples
*** less concerning in CVS than amnio because the placental cells are more distantly related they split off from the cells in the embryo early on so fetus might not share same genetic make up
** Insufficient sample

## Reasons Women Choose Not to Undergo Either Procedure

* They don't want to take that added risk of miscarriage
* They are more anxious about the procedure than they are about having a child with a chromosomal abnormality
* They feel comfortable not knowing if there is one of these problems until they deliver the child
* They don't feel a need for reassurance and would not abort the fetus regardless of the result
* Moral or religious views

## Description OF CVS

* There are two ways the procedure can be performed: Transcervical and Transabdominal Transcervical is the way Dr. Sedicke will usually perform it.
* Contraindications for both types include:
** Active vaginal bleeding (must have stopped at least 1 week ago)
** Don't worry about Rh sensitization because she is O positive
** Maternal bleeding disorder
** Fibroids not avoidable
** Multiple gestation? (usually not attempted)
* Transcervical
** Procedure is similar to a pap smear
** Vagina and cervix are cleaned
** Under the visual guidance of ultrasound, a thin tube (catheter) inserted through the vagina, cervix, and into the placenta
** Once the catheter is in place a syringe is attached
** Suction is applied to remove the villi while the catheter is removed
** After the sample is obtained it is viewed under a microscope to be sure the size and quality is sufficient and another sample is not needed
** Sample is placed in a tube of tissue culture medium and sent to a lab for testing
** Most women report minimal discomfort during the procedure although it varies
** The actual procedure only takes about 5 minutes
** The baby's heart beat will be monitored
** Bleeding occurs in up to 10% of women
** (Easiest to perform with posterior placenta close to cervix)
** (Contraindications for transcervical CVS include: cervical polyps, overly curved sampling pathway, active genital herpes or other infections)
** (Large sample is obtained including whole villi)
* Transabdominal
** Abdomen is cleansed and xylocaine injection is given to numb the upper layers (similar to shot given at the dentist)
** Using ultrasound as visual guidance, spinal needle is guided through the abdominal wall, uterine wall, and into the placenta
** Once in place a syringe is attached to supply suction
** While suction is supplied the needle is moved back and forth through the placenta
** After sample is obtained it is viewed to make sure there is enough and another sample is not required
** Sample is then placed in a tube of tissue culture medium and sent to a lab for testing
** There is a wide range of responses when it comes to how women report the procedure felt. When the needle is inserted it may burn for a few seconds. Women report everything from mild cramping to painful, heavy cramping.
** The actual procedure takes about 5 minutes
** The heartbeat of the fetus will be monitored
** Bleeding is rare
** Contraindications for transabdominal CVS include: interceding bowel, the placenta is too far from the maternal abdominal surface (obesity)
** (Easiest to perform with anterior or fundal placenta)
** (Smaller sample size (pieces of the villi) obtained)
** (Can be performed after 12 weeks, but usually only if there is not enough amniotic fluid for an amniocentesis)

## Recommendations for After CVS

* No exercise or strenuous activity for 24 hours
* No sexual intercourse, douching, tub baths, or tampon use for 72 hours
* Notify the OB in any of the following occur:
** Fever greater than 100.4 degrees F
** Heavy bleeding or cramping
** Amniotic fluid leakage
* Return for follow up ultrasound ?????
* Blood test (MSAFP) at 16-18 weeks to check for ONTD's
* Ultrasound is recommended at 18-20 weeks
* Shot of Rho-gam if Rh negative

## Test Results

* Results will be available anywhere between 1-2 weeks
* More than 95% of women receive reassuring news
* Remind them that sometimes further follow-up testing is needed to confirm a result.
* Ask them how they would like to receive their results and if they want to know the sex of the fetus

## Psychosocial Considerations

* May be nervous about pregnancy loss and may have beliefs that she did something to cause
* Explain that sometimes women are concerned about how something they did was responsible for pregnancy losses
* Be reassuring if possible especially about the last one where we know the cause had nothing to do with what she did or didn't do before or during pregnancy
* May have difficulty deciding on whether to have prenatal test due to risks so help her look at risks and benefits and judge whether the benefit associated with likely reassurance of a normal pregnancy is worth the risk
* Sometimes the anxiety of the procedure is greater than the anxiety over the risks or vice versa and helping them determine this may be helpful in the decision making process.
* May feel bad or be very concerned about having a child at an older age so assess what is worrisome. Reassure that many women are having children at that age and the age women have children is increasing. There are many benefits to having children at an older age such as (maturity, financial stability, prior time for career or other goals)
* May be concerned about alcohol exposures. Can be very reassuring if the alcohol was early on before pregnancy was known. Usually large amount of alcohol or continual exposure is necessary to harm fetus.
* May be nervous about needles. Explore this and discuss the fear and support she will have present during procedure. Or ask if she would like one of us to accompany her if time will allow.
* Anxiety and other emotions are likely to be present, but some individuals try to keep them from surfacing.

## CF Carrier Screening

* Are you familiar with cystic fibrosis?
* CF is one of the most common inherited diseases (affects 1 in 3300 live births in US)
* Occurs more frequently in Caucasians than other ethnicities (one in 25,000 affected and 1 in 28 are carriers)
* causes body to produce thick mucus which leads to a greater risk of infections that sometimes requires hospitalization
* can affect digestion and cause diarrhea and failure to grow normally
* with the advancement of treatments over year life span increased average age in the 30's
* may cause decreased fertility in females and often causes infertility in males
* AR inheritance, both parents must be carriers to have child with CF
* a blood test is offered that can determine if an individual is a carrier of CF
* assess whether interested in this testing
* testing at CHMC screens for 25 of most common mutations \
* cost ??
* cost is $265 when done through CHMC, but sent to Genzyme
* carrier detection rate with the 97 mutation panel is 90% if of Northern European Descent and 70% if of Southern European descent
* The 97 mutation analysis by Genzyme detects 85-90% of carriers if Caucasian.
* Turnaround Time: 5-8 days (when cell culture is required, add ~2 weeks)
http://www.genzymegenetics.com/Our-Services/Reproductive-Testing/cf-plus.aspx

## Review

* Assess if there are any questions or other concerns about the procedure that were not addressed.
* Assess again how she feels about the test options.
* Acknowledge that it can be a difficult decision and does not need to be made today unless time constraints for testing require a decision right away.
* Offer patient literature
* If a decision is reached have her explain how she arrived at that decision to check for understanding.

## References

* Lecture by Kristine Jarrett, M.S., C.G.C. Feb, 2002
* Bianchi, D.W., Crombleholme T.M., D'alton, M.E. Fetology: Diagnosis & Management of the Fetal Patient. McGraw Hill, New York, 2000.

## Notes

The information in this outline was last updated in 2001.