Chorionic Villus Sampling

Indications

According to the American College of Obstetrics and Gynecology, women of all ages should be offered prenatal assessment for aneuploidy by screening or diagnostic testing regardless of maternal age or other risk factors.[1][2] Prenatal genetic testing cannot identify all abnormalities, so testing should be focused on the patient’s risk, reproductive goals, and preferences. Ideally, genetic testing should be discussed at the first obstetric visit.

Indications for chorionic villus sampling include.[1][3]

• Abnormal early genetic screening on a non-invasive prenatal screening, first trimester combined screening, or abnormalities on ultrasound
• A prior child with a structural birth defect 
• A prior child with autosomal trisomy or sex chromosome aneuploidy 
• Advanced maternal or paternal age 
• Parental carrier of a chromosomal rearrangement 
• Parental aneuploidy or aneuploidy mosaicism 
• Parental carrier of a genetic disorder, such as Tay Sachs, Sickle Cell Disease, or Neurofibromatosis

Contraindications

Caution is advised in patients receiving anticoagulation. Maternal alloimmunization is a relative contraindication since the procedure may cause more severe fetal hemolytic disease.[4] In addition, patients with bloodborne infectious diseases, such as human immunodeficiency virus and hepatitis, should be advised of the possible risk of vertical transmission with prenatal diagnostic testing.

Equipment

The procedure is performed under continuous ultrasound guidance using an aseptic technique. Apart from an ultrasound machine, the following equipment is required: 

Transabdominal Approach

• Sterile drape 
• Sterile ultrasound probe cover
• Chlorhexidine or iodine preparation 
• A local anesthetic of your choice (optional)
• 10 cc and 20 cc syringe
• 18 gauge or 20 gauge spinal needle 
• Sample collection container with transport media 

Transcervical Approach

• Sterile speculum
• Single tooth tenaculum
• Iodine preparation 
• 10 cc and 20 cc syringe 
• Transcervical CVS catheter
• Sample collection container with transport media

Personnel

The procedure requires a sonographer to scan in real time.

Preparation

Before the Procedure 

• Formal consult with a maternal-fetal medicine specialist  
• If possible, referral for prenatal genetic counseling 
• Informed consent after a thorough discussion of risks and benefits with the opportunity for patients to ask questions 
• Evaluation of the need for Rhogam in Rh-negative patients 
• Ultrasound to confirm fetal heart activity, gestational age assessment with crown-rump length measurement, site of cord insertion, and location of the placenta
• Ensure all necessary materials are available, including transport media

At the Time of the Procedure

• Skilled provider and ultrasonographer 
• Ensure the patient is comfortable on the examination table 
• Make sure lighting is appropriate 
• Prepare the abdomen or cervix, depending on the approach
• Explain steps to the patient, if they would like, to help alleviate anxiety

Technique or Treatment

The procedure's route is based on provider preference, but the placental location may influence the decision.[5] In the transabdominal approach, the ideal site exposing the longest axis of the placenta is identified. The patient is supine, and the abdomen is cleaned with a chlorhexidine or iodine solution. Sterile drapes are placed to create a sterile field. A local anesthetic may be used. An 18 or 20-gauge spinal needle is inserted into the placenta under continuous ultrasound guidance. A 20 cc syringe containing collection media is attached to the end of the needle once the stylet is removed. Negative pressure is created, and the needle is moved up and down through the placenta, collecting the tissue. Once the sample is collected, it is evaluated to ensure sufficient chorionic villi are aspirated.

In the transcervical approach, the patient is placed in a lithotomy position, and a sterile speculum is inserted into the vagina. The cervix is cleaned with an iodine solution. A single tooth tenaculum may be applied to the anterior lip of the cervix to facilitate the passage of the catheter. Under continuous ultrasound guidance, a transcervical CVS catheter is inserted into the placenta. The catheter contains a malleable guidewire with an echogenic tip, which can be identified on ultrasound. Once in the proper location, the stylet is removed, a 20 cc syringe containing media is attached to the end of the catheter, and negative pressure is created. The sample is evaluated for adequacy before ending the procedure. Transcervical CVS can also be performed using small biopsy forceps.[6] Tissue samples are sent to the laboratory for culturing and further testing, including conventional karyotype, fluorescence in situ hybridization, and chromosomal microarray. Rapid assessment results return in 2 to 4 days, and cultured samples result in 1 to 2 weeks. Families should meet with their providers to discuss further management. Additional ultrasounds may be performed, and MSAFP may be collected at 16 weeks to screen for open neural tube defects.

Complications

The risks of chorionic villus sampling are similar to those of amniocentesis and include pregnancy loss, bleeding, infection, rupture of membranes, and uncertain results. The pregnancy loss rate has decreased with ultrasound guidance and increasing skill and technique; however, chorionic villus sampling has a long learning curve. A systematic review of the complications of chorionic villus sampling determined a total fetal loss of 0.7 percent within 14 days using a transabdominal approach, 1.3 percent within 30 days, and 2 percent for loss anytime during pregnancy. In the amniocentesis group, the total rate of fetal loss within 14 days was 0.6 percent.[7] Predictors of increased fetal loss include the number of times the needle or catheter is introduced, the experience and skill of the operator, pregnancies after assisted reproductive techniques, and the use of transcervical cannula instead of biopsy forceps.[8][9] With chorionic villus sampling, there is a possibility of identifying confined placental mosaicism, which occurs in 1-2% of cases.[10] This occurs when there is a discrepancy between the chromosomal makeup of the placenta and the fetus. The fetus is truly mosaic in 10% of cases, however, the finding of mosaicism is associated with an increased risk of poor placental function and perinatal complications including fetal growth restriction and maternal hypertension.[11] Mosaicism should be followed by amniocentesis in the second trimester. 

Additionally, limb reduction defects and oromandibular hypogenesis have been described in the literature as risks of chorionic villus sampling.[12] Early CVS (before 10 weeks gestation) has been identified as a risk factor for these complications. For example, the World Health Organization estimates the risk of limb defects to be about 6 per 10,000, which does not differ from the general population risk.[1][13] Although the risk is low, it is important to counsel patients about the data when CVS is considered before 10 weeks. Vaginal spotting has been reported in up to 32% of women and is more common after transcervical CVS.[1][14] The incidence of culture failure, leakage of amniotic fluid, or infection after CVS is reported to be less than 0.5%.

Clinical Significance

Chorionic villus sampling is a safe and established early diagnostic prenatal genetic testing option. With a skilled provider and the advancement of ultrasound, complications are minimal. The results can help families make informed decisions about their pregnancy.

Enhancing Healthcare Team Outcomes

A maternal-fetal medicine specialist generally performs chorionic villus sampling. Some pregnant patients who are candidates for CVS may present for care to a general obstetrician, family medicine, or internal medicine provider. Given the specific time frame in which a CVS can be performed, early referral to MFM is a key factor in ensuring patients have access to the procedure. Genetic counselors are an additional resource for families, helping them understand risks and options for prenatal testing. Clear and efficient communication between maternal-fetal medicine specialists and the referring provider is crucial to ensure a timely discussion of results and outline further pregnancy management recommendations.