2010 Group Project 2

From Embryology
Revision as of 14:44, 19 August 2014 by Z8600021 (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Notice - Mark Hill
This page is an undergraduate science embryology student Group Project 2010.
Embryo 11-14 weeks.jpg

Chorionic Villus Sampling (CVS)



Chorionic villus sampling or CVS is a type of prenatal diagnosis test performed in the first trimester to detect major fetal abnormalities such as down syndrome, cystic fibrosis and tay-sachs disease, among many others. In the procedure, tissue is withdrawn from small finger like projections on the placenta called chorionic villi and tested for chromosomal defects. It is commonly performed between 10 and 12 weeks of pregnancy. The advantage of CVS over other procedures is that the result is available approx 6 weeks earlier in the pregnancy, so if a termination is needed, it can be done earlier which is much safer, rather than later in the pregnancy, which can carry more risks. [1]

Reasons for getting chorionic villus sampling can include:

-History of genetic disorders in the family

-Parents have already had a child with a disorder such as down syndrome or cystic fibrosis

-Abnormal ultrasound result

-Maternal age of 35 or older, which increases the risk of chromosomal defects such as down syndrome

Historic background

Brief timeline of CVS use

  • 1968 - Mohr in Scandinavia introduced the concept of prenatal diagnosis using chorionic villi sampling [2]
  • 1973 - Kullander and Sandahl and Hahnemann in 1974 showed further study into chromosomal analysis from CVS [3]
  • 1975 - from the Department of Obstetrics and Gynaecology at the Tietung Hospital in Anshan, China was successful in using CVS to determine sex of fetuses for sex pre selection. [4]
  • 1980 - Kazy et al. were the first to use ultrasound guidance during chorionic villi sampling. [5]
  • 1981 - Niazi et al. improved methods for culturing of fibroblasts from trophoblast villi. [6]
  • 1983 - Ward performed transcervical CVS with 67% success rate. In the same year, the Brombati group demonstrated and 96% success rate with obtaining villi with the aid of ultrasound guidance [7]
  • 1984 - Smidt-Jensen and Hahnemann introduced transabdominal CVS under ultrasound guidance [8]
  • 1986 - The Golbus group had a 3.8% miscarriage rate, and subsequently many other clinics started reporting a much lower rate of miscarriage at 1.7% making the procedure safe for routine use [9]

Jan Mohr (1921-2009)

Jan Mohr

1968 -- Concept of CVS introduced

In 1968 Jan Mohr introduced the concept of prenatal diagnosis using the CVS technique. [10] He used the transcervical method to get a biopsy of the chorion using an endoscope as the source of vision. The current technique differs by using mostly transabdominal access with ultrasound instead of an endoscope. He reported a 96% success rate in obtaining chorionic material but with a high incidence of bleeding and infection. The approach was abandoned as amniocentesis became more popular due to higher safety levels

1973-1975 -- Further study into chromosomal analysis from CVS

Kullander and Sandahl in 1973 and Hahnemann in 1974 further researched fetal chromosome analysis using transcervical biopsy before termination in early pregnancies. [11] In 1975 the first successful diagnostic use of chorionic villi was reported at the Tietung Hospital in China. [12] This is where fetal sex was diagnosed for the purpose of sex pre-selection. They claimed to have 94% diagnosis success and only 4% miscarriage rate. Researchers in the United States were, however unable to duplicate the results and so the idea of CVS diagnosis was again abandoned for some time.

1980-1983 -- Change from endoscopic examination to ultrasound to guide CVS

With the invention of the ultrasound and advancement in molecular genetics, an earlier prenatal diagnosis was now sought after. So Kazy et al. in 1980, began using both the endoscope and the ultrasound for fetal sexing on chorion biopsies. This was the first report of using ultrasound guidance during chorion sampling. After Kazy et.al. began using the ultrasound for guidance, many others followed. Niazi et al., Ward and the Brombati group all started using ultrasound guided CVS. Techniques quickly improved and success rate of obtaining chorionic material rose from 75% to 96% [13]

1984-1986 -- The introduction of transabdominal CVS

In 1984, Smidt-Jensen and Hahnemann in Copenhagen introduced transabdominal CVS using ultrasound guidance. [14] With less chance of infective complications the procedure has become more popular than the transcervical method in many prenatal diagnostic centers. Other ultrasonic techniques and modifications were explored by the Brambati and Simoni group and the Golbus group in 1985. [15] The Golbus group reported in 1986 a miscarriage rate of 3.8%. [16] Subsequently, many other centres reported a much lower miscarriage rate of 1.5% which made the procedure safe for routine use.

Table Comparing Prenatal Diagnosis Techniques

This table shows invasiveness and timeframe for some prenatal diagnostic techniques
Invasiveness Diagnostic technique Comments Time that procedure can be performed Diagram
Non Invasive Ultrasound Tests for: neural tube defects, chromosomal abnormalities and congenital heart abnormalities

Risks: No risks currently indicated for ultrasound use in prenatal diagnosis.

This test uses high frequency sound waves through a transmitting device, which construct a picture of the fetus when the waves are reflected and received back by the transmitter. Due to no known risks, ultrasound use is used routinely in pregnancies and is the first port of call for prenatal diagnosis. If a potential abnormality is found or the parents are high risk, then a more invasive diagnostic technique may be recommended. The type of diagnostic technique used depends on the potential abnormality found. [17]More about Ultrasound

Weeks 18-20
ZConvex Array Transducer.jpg
Invasive Chorionic Villus Sampling Tests for: chromosomal abnormalities and genetic abnormalities

Risks: Miscarriage (1%), some of the side effects include dizziness, abdominal discomfort, cramping, haemorrhage, infection, ruptured amniotic sac, increased risk of limb defects if the test was performed at nine weeks’ gestation or earlier [18]

With the guidance of Ultrasound, a needle is inserted in to the abdomen or through the cervix and a small sample of chorionic villi from the placenta are obtained. This sample is sent to a cytogenetics laboratory where the cells are cultured and stained, and photographed to view chromosomes

Weeks 10-12
Transabdominal CVS.jpg
Invasive Amniocentesis Tests for: chromosomal abnormalities, fetal infections, and genetic abnormalities

Risks: Miscarriage <1%, stillbirths 3%, and small risk of infection. [19]

A needle is inserted in to the uterus where a sample of the amniotic fluid surrounding the fetus is taken. This procedure is usually done with the guidance of ultrasound so the physician can see where the needle is being inserted. The amniotic fluid is analysed for abnormalities. More about Amniocentesis

Weeks 15-16
Process of amniocentesis.jpeg
Invasive Percutaneous Umbilical Cord Blood Sampling Tests for:chromosomal abnormalities, blood disorders, some metabolic disorders, fetal infections, and some causes of structural problems.

Risks:Miscarriage <2%, Preterm labour, fetal bradycardia, bleeding of the umbilical cord. [20]

A small needle is inserted in to the abdomen of the mother and a sample of blood is taken from the umbilical vein in the umbilical cord. This technique is often used when other diagnostic techniques are inconclusive, but should be used with caution as carries higher risk rates. The benefit of Percutaneous Umbilical Cord Blood Sampling is that the results are available much faster, within 72 hours of testing. CVS and amniocentesis tests need culturing and therefore take up to 11 days for a result. More about Percutaneous Umbilical Cord Blood Sampling

Weeks 18-22
Placenta Anterior.jpg
Less Invasive Fetal Fibronectin Tests for:determines the likelihood of premature birth in women of high risk

Risks:No known risks for the testing of Fetal Fibronectin, as is it less invasive than other techniques.

Fetal Fibronectin is only found in the uterus until the onset of labour when is secretes in through the cervix. In this procedure, a sample of the cervico-vaginal secretions are taken and sent to the lab for testing. If the test comes out positive for Fetal Fibronectin in the vagina, the mother has a chance of going into premature labour. More about Fetal Fibronectin

Weeks 24-34
Non Invasive Maternal serum alpha-fetoprotein Tests for:AFP is a type of screening test and do not diagnose problems, but signal whether further testing is needed. Normal AFP levels are increased in Neural Tube Defects and Omphalocoele & decreased in Down Syndrome.

Risks:No known risks as Maternal serum alpha-fetoprotein is non invasive

A blood sample is taken from the mother and alpha-fetoprotein levels are measured in the lab. These measurements can determine the risk level of certain abnormalities in the fetus. The advantage is that it is non invasive, but the disadvantage is that it has a very high false positive rate, so many mothers have gone on to have amniocentesis or chorionic villus sampling to find nothing is wrong with the baby. This can be overcome by having another alpha-fetoprotein test before getting amniocentesis or chorionic villus sampling. More about Maternal serum alpha-fetoprotein

Weeks 15-20
Enzyme immunoassay.jpg

Description of technique

Sample is taken from the chorionic villi
Transabdominal Technique
Transcervical Technique

The CVS procedure involves taking a sample of the chorion frondosum — the part of the chorionic membrane containing the villi. Between 10-12 weeks of pregnancy, the developing gestational sac is composed of a thick, outer chorionic membrane surrounding the amniotic cavity, a thin amniotic membrane and the chorionic cavity. The chorionic villi have now degenerated over most of the outer membrane, forming the chorion laeve, and the remaining villi fuses and embeds loosely into the decidua basalis. This forms the chorion frondosum, which will ultimately become the placenta. At this stage, the villi float freely in the blood of the intervillus space. Each villi is branched, and is composed of an outer syncytiotrophoblast and an inner cytotrophoblast layer. Within the centre of each villus is a mesenchymal core which contain capillaries carrying fetal blood. In CVS, usually samples of both cells lines (cytotrophoblasts and mesenchymal cells) are obtained. Chromosomal analysis of these cell lines can be performed by means of direct preparations, short-term cultures (cytotrophoblasts), or long-term cultures (mesenchymal cells) of the chorionic villi.[21]

CVS can be performed in two ways, through the cervix (transcervical) or through the abdomen (transabdominal). Both techniques are equally safe when performed by an experienced technician, however miscarriage rates are somewhat higher when done through the cervix. Prior to the procedure, an abdominal ultrasound can be performed to locate the position of the uterus, and the placenta. A full bladder is not required. Depending on the type of method performed, the vulva, vagina, cervix or abdomen are cleaned with antiseptic. The procedure normally takes only 1-2 minutes to perform and the patient is able to leave the clinic within the hour after the fetus is checked.[22]

Transabdominal Procedure

  1. A local anaesthetic is first applied to the abdomen.
  2. A thin hollow needle is then inserted through the abdomen into the uterus and into the edge of the placenta where the chorion is located. An ultrasound transducer is commonly used to guide the needle during the procedure.
  3. A finer syringe needle is then passed through the outer needle, and the tissue is then drawn.
  4. The sample is taken to the laboratory for testing.

Transcervical Procedure

  1. A speculum is inserted in the vagina and the area is cleaned with antiseptic.
  2. With the help of ultrasound imaging, a thin cannula is then inserted through the cervix and uterus and into the placenta.
  3. The tissue sample is then taken up through the cannula.


After the sample is taken to the laboratory, the cells are grown until there are enough cells for chromosome testing. The results normally take up to 2 weeks to complete.


Some of the side effects and complications after a CVS procedure can include:

  • Dizziness
  • Abdominal discomfort
  • Cramping
  • Haemorrhage
  • Infection
  • Ruptured amniotic sac
  • Increased risk of limb defects if the test was performed at nine weeks’ gestation or earlier
  • Premature delivery


Additional complications can involve technical errors such as failure of the specimen to grow sufficiently in the laboratory and uncertain laboratory results. If this occurs, amniocentesis is still an option after 15 weeks.

Results and Accuracy

The accuracy of CVS to detect chromosome abnormalities is quite high, at around 98-99% [25]. Although it has a high accuracy rate to diagnose most major chromosomal problems, CVS does have some limitations. Having a negative result for an abnormality does not rule out ALL genetic defects the baby may have. Comparatively to amniocentesis, CVS does NOT detect neural tube defects such as spina bifida, or anencephaly. The type of chromosome abnormalities detected by CVS will be further discussed in detail below.


Example of a child with double tetrasomy 18+ mosaicism.

Maternal contamination

Since the villus sample also involves maternal cells, there is a possibility that they may take over the laboratory culture instead, consequently leading to the mother's cells being tested instead of the fetus's cells. The risk of this happening is low however and is decreased when the sample contains an adequate amount of fetal cells.[26]


"Mosaicism" occurs when both abnormal and normal cells are found in the chorionic villi. Mosaicism can involve both the fetus (true fetal mosaicism) and the placental tissues or the placental tissues alone. When this happens, cells that multiply from these abnormal cells may develop a chromosome anomaly. What can result is that in certain body organs the fetus has a combination of cells that are abnormal and normal in genetic structure. The rate of the placental type occuring is found in 1-2% of pregnancies detected by CVS.[27] When mosaicism is detected by CVS, the limitation lies in the inability to conclude that the baby itself and not just the placental tissues will share the mosaicism. Even if the baby is affected, it will be unclear as to what percentage of the fetal cells and the type of organs that will be affected.[28]


When Chorionic Villus Sampling is performed, a small sample of the placenta is removed for analysis. The placenta contains fetal material, therefore can reveal genetic defects which may lead to problems or abnormalities. [29] This prenatal test can be performed as early as 11 weeks into the pregnancy, this is earlier than many prenatal diagnosis tests, which is why many parents choose CVS as they can have solid information earlier in the pregnancy. Some common risks which are not under current research include: Cramping, light blood spotting, pain, fever and chills, leakage (which can be a major concern as it can lower amniotic fluid to a dangerous level for the infant), and potential for missing fingers and toes in the newborn. For this reason, the procedure is only recommended for women who are at least 11 weeks pregnant. [30] The other major risks that are currently being researched are outlined below

Transabdominal vs Transcervical CVS. Comparison of risks

Transabdominal vs Transcervical risks

This table shows the symptoms of women approximately 3 days after sampling. Women who had transcervical sampling had higher occurrence of fluid leakage and spotting. When a tenaculum is not used, the occurrence of vaginal spotting and bleeding continued. [31]


One of the biggest risks of Chorionic Villus Sampling is miscarriage. In one to 100 or 200 cases, the procedure is linked with miscarriage. [32] In an experienced clinic, this rate may go down to one in 300 to 400. To lower the risk of miscarriage with Chorionic Villus Sampling, it is recommended the procedure be performed by an experienced clinician


Oligohydramnios is a condition due to low amniotic fluid level, which is caused by amniotic fluid leakage. Amniotic fluid leakage is typically caused by fetal urinary tract abnormalities such as Potter's syndrome, polycystic kidneys, or genitourinary obstruction. But leakage can sometimes be caused by sampling of the chorionic villi due to insertion of the needle. If the resulting oligohydramnios is not treated and the amniotic fluid continues to leak it can result in the baby developing hypoplastic lungs (underdeveloped lungs). [33]

Why would you use CVS over other techniques?

Advantages and Disadvantages of Chorionic Villus Sampling
Advantages Disadvantages
Can be performed earlier in pregnancy than amniocentesis (at around ten weeks).

Results are available faster

Cells obtained are mitotically active

Amount of tissue obtained is preferable for DNA analysis.

It is almost 100% reliable in detecting chromosomal and genetic defects.

It carries a slightly higher risk of miscarriage (1%-2%) than does amniocentesis

It's less commonly available than amniocentesis, and fewer doctors are experienced in the procedure.

It entails a greater risk of distorted results than does amniocentesis due to presence of mother's cells in the sample and discrepancies between chorionic villi and fetal genes.

Metabolic disorders are difficult to diagnose and must be confirmed with amniocentesis.

Because of the early gestational age at which the test is performed, fetal anatomy cannot be seen as well as it can at the time amniocentesis is performed.


Abnormalities found by CVS prenatal diagnostic technique

third copy of chromosome 21

The cells collected by CVS are sent to a cytogenetics laboratory, which is a laboratory that analyses the number and shape of the chromosomes in cells. At the laboratory the cells are cultured (stimulated to grow and divide) for approximately 12 days. After enough cells are cultured, a banded karyotype is completed. This is where the fetal chromosomes in the cultured cells are stained and then photographed. The photographed chromosomes are then ordered, counted and checked for abnormalities.[35]

This table shows what disorders CVS detects, the cause, frequency and any comments
Disorder Cause Comments Frequency Picture
Down Syndrome A third copy of chromosome 21

Normally, there are only two copies of this chromosome

The average IQ of children with Down syndrome is around 50, compared to normal children with an IQ of 100. Complications for people with down syndrome include: congenital heart defects, gastroesophageal reflux disease, recurrent ear infections, obstructive sleep apnea, and thyroid dysfunctions. [36] The picture shows a newborn infant with Down Syndrome (Trisome 21) Approximately 1 in 1,000 births [37]
Trisomy 21 newborn.jpg
Trisomy 13 A third copy of chromosome 13

Normally, there are only two copies of this chromosome

Also called Patau syndrome. This abnormality causes mental and motor abnormalities, polydactyly (extra digits), kidney defects, abnormal genitalia and heart defects, among many others. [38] The picture shows an infant with polydactyly, a potential complication of Trisome 13 Less than 1%
Trisomy 18 A third copy of chromosome 18

Normally, there are only two copies of this chromosome

Also known as Edwards syndrome. It has a very low survival rate, due to: kidney and heart defects, intestines protruding outside the body, mental abnormalities, growth disorders, feeding and breathing difficulties. [39] The picture shows a clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth finger, characteristically seen in Trisomy 18. 1 in 3,000 conceptions and approximately 1 in 6,000 live births
200px-Overlapping fingers.JPG
Cystic Fibrosis A mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR) in chromosome 7. An autosomal recessive disease that causes excessive sticky mucous to form on mucosal surfaces effecting the digestive and respiratory organs. [40] The picture shows clubbing of the fingers in a person with cystic fibrosis Approx 1 in 3,000
Hemoglobinopathy Structural abnormalities in the globin proteins Multiple types of abnormal haemoglobins exist including Haemoglobin S, C E and D that alter the structure of these proteins. A common defect is sickle cell disease.[41] Hemoglobinopathies are a genetic defect and therefore an inherited disorder, frequency depends on which particular hemoglobinopathy is being discussed, eg. in the case of Sickle cell disease, it is estimated that 7% of worlds population are carriers
Series 10-09.jpg
Tay Sachs Disease mutations on chromosome 15 in the HEXA gene It is a rare autosomal recessive defect inherited from parents that are carriers for the disease. Affected individuals suffer from premature nerve cells death in the brain. [42] Approx 1 in 300 are carriers


Since CVS is able to detect a variety of chromosome abnormalities, there is a chance that the baby may be affected with a defect. If the test results are normal however, this does not exclude other congenital defects and neural tube defects that can occur that can be detected by other prenatal diagnosis methods. IF the test result is positive and a defect is detected by CVS, the mother has several options available. One is to terminate the pregnancy and the other is to seek treatment after the baby is born. If the mother chooses to terminate the pregnancy, doctors have a responsibility to educate the mother and offer counseling.

Doctors should:

  • Give parents information about the defect so that they can be prepared.
  • Talk to parents about the baby's predicted quality of life.
  • Should explain any procedures that will be done to the baby after he is born.
  • Doctors should do their best to tell parents what the problem is and how serious it is.
Suction Aspiration technique. Enlarge for labels.

Abortion is the termination of pregnancy, with the removal of the fetus and placenta from the uterus. In Australia, abortion laws vary by state and usually allow this up to a range of about 12 - 20 weeks into the pregnancy, on the grounds of fetal abnormalities, endangerment of the mother and other socio-economic factors.[43] If the mother chooses to terminate the pregnancy, counselling is usually done to make sure the parents understand the issues and ethics surrounding abortion. There are currently two ways to perform an abortion:

Surgical abortion - Also called suction aspiration, or suction currette, this is the most common procedure used for first trimester abortion(up to 12 weeks) The cervix is dilated, and a tube is inserted through the cervix and a suction removes the fetus and the placenta. A curette is then used to scrape the wall of the uterus to ensure any remains are not left inside. If later in pregnancy, other surgical techniques are used.

Medical abortion - (Note: Not applicable in this case due to CVS being performed at 10-12 weeks.)This involves administration of a drug called mifepristone (RU486). Available for abortions earlier than 2-9 weeks, it is a low-risk and effective method instead of the surgical method earlier in pregnancy. Usage of the drug is available in many countries but is currently restricted in Australia.


If the mother decides to continue on with the pregnancy, treatment options are necessary for the baby after birth to maintain the health and symptoms associated with a defect. Some of these management options for some of the defects will be discussed below.

Down Syndrome

Treatment and therapies for Down syndrome available include the physical, medical and cognitive problems associated with Down Syndrome. Medical treatment such as surgery or medications, while early intervention programs and therapies help babies and children achieve better quality of life. For example, children with Down Syndrome have a higher risk for having many conditions such as congenital heart defects, problems with the thyroid, muscles, joint, vision and hearing problems.[44] Medications can be used to treat these different problems, such as if the thyroid is affected, a child will benefit from taking thyroid replacement hormones. Medications aim to control the symptoms and reduce the impact the condition will have on the baby. There is no medication that can cure chromosome abnormalities. Some individuals affected with cardiac and gastrointestinal problems may also need surgery soon after birth. Regular screening for vision problems, hearing, hypothyroidism, and other medical conditions should be performed.

Cognitive development can be assisted with physiotherapy and speech therapy for example. Since children with Down Syndrome can have speech problems due to their relatively small mouths and large tongue, speech therapy can help the child to communicate properly. Physical therapy is often needed since individuals with Down Syndrome have hypotonia (low muscle tone)which needs to be improved by developing motor skills.[45]

Trisomy 13

Since Trisomy 13 causes a range of serious complications like congenital heart disease and brain and spinal cord abnormalities, the survival rate is low, with a median survival time of 2.5 days. [46] Treatment is usually directed towards the specific symptoms that are present in the affected child, which differs to each individual. In some cases, treatment may include surgical procedures to correct cleft lip and palate, or surgery to correct heart defects. This will depend upon the severity and nature of the abnormalities and symptoms.[47]

Cystic fibrosis

There is currently no cure for cystic fibrosis, but various treatment methods can manage the symptoms of lung and digestive problems, liver and gallbladder diseases and infertility. Digestive problems can be corrected by having a diet that is low in fat and high in protein, with vitamin supplements. Regular antibiotics are prescribed to prevent and to treat lung infections, and mucolytics are needed to make the mucous less sticky. Other methods to dislodge and remove mucous is manual chest physiotherapy, where it consists of bronchial drainage done manually or mechanically. Manual drainage can be done by performing controlled breathing techniques or the chest is vibrated or clapped to dislodge the mucous out of the airways. [48]

Tay-sachs disease

The prognosis for babies with the condition is usually poor, with children living to the age of 4-5.[49] Therefore treatment for Tay-sachs disease is usually to help alleviate symptoms associated with the disease. Spasticity and siezures can be helped by administering anticonvulsants, while other supportive methods include respiratory care to keep the airway open and proper nutrition and hydration.

Ethical concerns


The Bioethics involved in Health Care that encompasses medical practices including prenatal diagnosis methods aim to ensure that human values are respected in terms of healthcare institutions, life technology, health professions and clinical practices.[50] Maintaining good practices in CVS testing and any other prenatal testing is essential to exercise the duty of care and to reduce any sort of harm upon the expectant mother. CVS:

  • Should not be performed under 10 weeks gestation.
  • Should be performed by an experienced, well trained technician
  • Written consent should be obtained before testing
  • Clinicians should use the CVS technique with which they are competent, using local anaesthesia for transabdominal CVS.


A World Map showing the legal status of abortion in different countries. Enlarge for legend.


Abortion is a subject that brings about a wide number of ethical concerns whether morally, religiously and politically around the world. Usually a community's beliefs and moral views are reflected in political decisions, although debate continues to be ongoing whether it is morally right to terminate a pregnancy before a normal childbirth, given a range of different circumstances people believe is acceptable. In Australia, abortion laws are present and differ by state, and is usually based on the mother's choice, given that she conforms to the restrictions of the law.

Current associated research

Chorionic Villus Sampling (CVS) is one of many prenatal diagnostic tools for expectant mothers, it is popular since it can be used to identify potential problems with a fetus at a very early stage. However, the procedure does carry some risks, as does any invasive diagnostic procedure. As chorionic villus sampling is a relatively new technique, made available for safe routine use only 20 years ago, the current associated research is mainly associated with risks associated with the procedure, and ways to overcome these risks. The next section in this page will discuss the current research on CVS and the risks involved in the procedure, and not what the test results may find.

Hypertensive disorders of pregnancy

Hypertension, or high blood pressure, is a condition where systemic arterial blood presssure is elevated. Hypertension is one of the most common medical problem during pregnancy, affecting about 2-3% of pregnancies.[52] Pregnancy induced hypertension is a condition that can occur during and after the 20th week of pregnancy. The types of hypertensive disorders can include:

Enamel hypoplasia due to maternal toxemia
  • Pre-eclampsia or toxemia – Characterised as high blood pressure above 140/90 with proteinuria (protein in the urine that is above 300mg)
  • Eclampsia - Developed in a pregnant woman who has had pre-eclampsia and is characterised by seizures
  • Gestational hypertension – arterial hypertension that occurs after the 20th week of gestation

If untreated, the condition may develop into HELLP syndrome which is a serious complication noted by hemolytic aneamia, elevated liver enzymes and a low platelet count.

There has been conflicting evidence in literature that suggests that CVS is associated with hypertensive disorders in pregnancy such as pre-clampsia and gestational hypertension. In several studies, such as data from the National Institute of Health that compared late CVS procedures with early amniocentesis, showed a higher rite of gestational hypertension and preeclampsia in pregnant mothers.[53] (5.4% for mothers who had CVS and 3.5% that had amniocentesis.) It was hypothesized that disruption and disturbance of the placenta at 13-14 weeks may increase the risk of maternal hypertension. In addition, another recent study in 2006 also reported that there was an increase in the rate of pre-clampsia in first-time expectant mothers who have had CVS.[54]

However, in a very recent data investigation of among 9098 women that were pregnant between 1990 and 2006, the overall incidence of hypertensive disorders with women who have had CVS was 2.7% compared to the control group that did not have the procedure done which was 7.1%.[55] Similarly, in a study conducted by The American College of Obstetricians and Gynecologists,[56] 31, 138 women were that were included in the investigation showed that 2.2% developed preeclampsia and 2.8% developed gestation hypertension. Only 7.8% of those individuals had previously had CVS procedure performed.

Although it can be said that some woman may develop hypertensive disorders during pregnancy that have also had the CVS procedure done in the past, there is no conclusive evidence so far that definitively associates CVS with hypertensive disorders such as pre-clampsia and gestation hypertension.


Craniosynostosis .jpg

Many malformations were thought to be a result of more invasive prenatal diagnostic techniques such as chorionic villus sampling. These malformations include, but are not limited to, cardiac malformations, hypospadias, craniosynostosis, pyloric stenosis, inguinal hernia, polydactyly, syndactyly, hydrocephalus and cleft lip and palate. Although these studies have now confirmed no known relationship with CVS, we will mention some below. [57]

Craniosynostosis is a condition where one of the sutures of the skull prematurely fuses, this causes the other sutures to compensate in growth for the fused suture. In normal development of the skull, the sutures allow for brain growth, so if one suture fuses prematurely, the brain can not grow normally, and the other sutures over expand in compensation. In the shown image, pictures a1 and a2 show the normal development and fusing of the infant skull. b2 shows how a suture is prematurely fused and b1 shows how the abnormality shows in an infant child. Craniosyntosis may result in increased pressure on the brain and developmental delays. Treatment of craniosynostosis usually consists of surgery to the skull where a zigzag incision is made to make the hair look more natural than the scar left by a straight incision. The surgery separates the sutures that have joined together to allow the head to develop normally.



Polydactyly is a congenital condition where an extra digit is formed. Mostly it occurs on only one hand or foot, but sometimes can occur on all limbs. The extra digit is mostly a small non-function appendage of skin, less often it is an extension of the adjacent digit, and rarely it is a fully functioning finger that arises from the wrist or ankle joint like the other digits. Polydactyly can be described as:

● postaxial polydactyly (arising from the little finger)

● preaxial polydactyly (arising from the thumb) or

● central polydactyly (arising from anywhere between the other digits)

Polydactyly is seen in 1 in every 500 births, but the extra digit is usually surgically removed shortly after birth [59]


Syndactyly is also a congenital condition, but is seen when digits are fused together. Syndactyly can be described as:

● simple syndactyly (where only skin is fused to the adjacent finger)

● complex syndactyly (where the bone is fused together)

● incomplete syndactyly (where fusion is only part of the way up the digit), and,

● complete syndactyly (where fusion is to the tip of the digit)

The picture on the left shows an example of polysyndactyly, where the digits are both fused, and there is an extra digit. [60]



A hemangioma is a benign tumour growth of endothelial cells that can occur in newborns and infants. Hemangiomas can occur anywhere in the body but are often localised on the skin of the face and neck, and are characterised by a red to reddish purple raised lesion on the skin, similarly to a "strawberry" like appearance. Its red appearance is due to the newly formed blood vessels, which result from the malformation of angioblastic tissues of fetal life.[61] Most hemangiomas do not cause any serious complications, and regress later on in life, where 90% of hemangiomas in children would disappear by the age of 9.

Recently, research has linked the increase in the incidence of hemangiomas in infants following CVS. It has been postulated that the mechanism of hemangioma formation is associated with the embolisation of angioblasts or endothelial cells from the placenta to the fetal skin.[62] Although this may link hemangiomas to placental origin, it is unclear how, or whether CVS directly interferes or enhances the formation of these lesions. However, a recent study that compared the effects of CVS and amniocentesis on the prevalence of hemangiomas in infants showed that 27% of the study group had hemangiomas with CVS compared to 9.4% in children with hemangiomas and amniocentesis. [63] Furthermore, in an previous study conducted in 1995, there was a threefold increase in incidence after trancervical procedure was done, compared to amniocentesis.[64][65]

Future of Chorionic Villus Sampling and Prenatal diagnosis techniques

FISH technique
Comparative Genomics

Prenatal diagnosis has been used to detect chromosomal abnormalities, especially Down’s syndrome, for over 30 years. As we have discussed on this page, the most common forms of prenatal diagnosis are amniocentesis, CVS and ultrasound. The type of test used depends on the history of the parents, any abnormalities detected in the initial ultrasound examination, and preferences of the parents. Testing for chromosomal abnormalities using amniocentesis and CVS is invasive and somewhat time consuming. Some recent advancements in this field include the use of fluorescence in situ hybridisation (FISH), quantitative fluorescence-PCR techniques, and comparative genomics. Although these techniques are currently still invasive, the waiting time for these tests is usually only 1 to 2 days for chromosomal abnormalities. [66] This waiting time would mean a much less stressful waiting period for the parents. The future of prenatal diagnosis certainly lies in the field of non invasive techniques, and research in the field of prenatal diagnosis is looking toward making detection of abnormalities non invasive, using the fetal cells from maternal circulation. [67]

Fluorescence in situ hybridisation (FISH): FISH is a cytogenetic technique, involving analysing the number and shape of the chromosomes of cells. FISH detects the addition or deletion of specific DNA sequences on chromosomes using florescent probes that bind to a similar sequence of chromosomes. Once the florescence probes are attached, fluorescence microscopy is used to view the chromosomes and detect the abnormality. In prenatal diagnosis, FISH is useful for detecting trisomy and monosomy conditions.More about FISH

Comparative genomics: Comparative Genomics is a very new research field where the genome sequence of different organisms are compared. This comparison between organisms shows where a species genomes have been conserved (stabilising selection) and where differences occur (positive selection). Many species share the same genes, and comparative genomics can show what species share genes and which genes are different among species. This information can help us understand the function of different genes and identify and control diseases. The purpose is to gain a better understanding of how species have evolved and to determine the function of genes. In prenatal diagnosis, fetal cells can be viewed and compared against both parents genome, any change that deviates from the normal pattern due to too much or too little DNA can be seen, this deviation of the normal pattern means a certain chromosome has either been copied or deleted, causing disease. More about Comparative Genomics

Useful links

Search Bookshelf Chorionic villus sampling

Search Pubmed Chorionic villus sampling

WikipediaChorionic villus sampling

Fact sheets Chorionic villus sampling

Images Chorionic villus sampling

You tube video of procedure Chorionic villus sampling


Amniocentesis - A prenatal diagnostic test involving sampling of amniotic fluid by needle aspiration for genetic analysis.

Amnion - An extraembryonic membrane ectoderm and extraembryonic mesoderm in origin and forms the innermost fetal membrane, produces amniotic fluid. This fluid-filled sac initially lies above the trilaminar embryo disc and with embryoic disc folding this sac is drawn ventrally to enclose (cover) the entire embryo, then fetus.

Amniotic cavity - The fluid-filled (amniotic fluid) extraembryonic coelom (cavity) formed initially by epiblast and then ectoderm and surrounding extraembryonic mesoderm. In humans, it forms the innermost fetal membrane, produces amniotic fluid expanding to fuse with the chorionic membrane during week 8 of development.

Amniotic fluid - The fluid that fills amniotic cavity totally encloses and cushions the embryo.

Cannula - A flexible medical tube with a sharp-pointed part at one end that is inserted into a duct, vein, or cavity in order to drain away fluid or to administer drugs

Chorion - The extraembryonic membrane generated from trophoblast and extraembryonic mesoderm that forms placenta. chorion and amnion are made by the somatopleure. The chorion becomes incorporated into placental development. The avian and reptilian chorion lies beside the egg shell and allows gas exchange.

Chorionic villus sampling (CVS) - The taking a biopsy of the placenta, usually at the end of the second month of pregnancy, to test the fetus for genetic abnormalities.

Chromosome - double stranded DNA coiled around histones. Condenses during mitosis and meiosis.

Ectoderm - One of the initial 3 germ cell layers, which will form the nervous system from the neural tube and neural crest and also generates the entire epithelial layer of the skin covering the embryo.

Endoscope - a long slender medical instrument for examining the interior of a bodily organ or performing minor surgery

Endoderm - One of the initial 3 germ cell layers (ectoderm, mesoderm and endoderm) formed by the process of gastrulation. The endoderm forms as a cuboidal epithelium and contributes not only to the trilaminar embryo, but also lines the yolk sac. It will form the entire epithelial lining of the gastrointestinal tract (GIT), contribute to the accessory organs of GIT and also forms the epithelial lining of the respiratory tract.

Fetus - In mammals, term describes the period of development following the embryonic period. In humans, the development week 9 to 36 is the fetal stage (second and third trimester). (see fetal period above). This term is also used non-scientifically to describe the human conceptus at both embryonic and fetal stages of development.

Gene - A DNA sequence that is transcribed as a single unit and encodes a single polypeptide (protein) or a set of closely related polypeptides. There are approximately 20,000-25,000 protein encoding genes in the human genome. In each cell, DNA is found within the nucleus and also within mitochondria.

Gestation - The period of time from conception to birth. A pregnancy with multiple fetuses is referred to as a multiple gestation.

Mesoderm - The middle layer of the 3 germ cell layers of the trilaminar embryo.

Miscarriage - A general clinical term for the loss of embryo or fetus by spontaneous abortion.

Mitosis - The normal division of all cells, except germ cells, where chromosome number is maintained (diploid).

Prenatal diagnosis - any of the diagnostic procedures used to determine whether a fetus has a genetic abnormality

Tenaculum - instrument used to grasp the cervix and keep the uterus in place during gynecological procedures.

Termination - The spontaneous or artificially induced expulsion of an embryo or fetus. As used in legal context, the term usually refers to induced abortion.

Transabdominal - In the transabdominal CVS technique, the physician inserts a needle through the abdomen into the placenta. This is also done with ultrasound, to guide the physician

Transcervical - In the transcervical CVS technique, the physician inserts a small tube through the cervix into the placenta. This is done while ultrasound guides the physician

Ultrasound - A non-invasive technique for visualizing and prenatal diagnosis of several features of development including: follicles in the ovaries, the gestational sac, fetus in the uterus, fetal parameters, and the placenta. The technique uses high-frequency sound waves that are reflected off internal structures. These reflections can then be analysed and displayed by computer.

Villi - Plural of villus, which is a thin projection from a surface. A term used to describe the many functional units together of the fetal placenta.

Vitelline arteries and veins - The blood vessels which form in the extraembryonic mesoderm of the yolk sac and anastomose are called vitelline arteries (flow away from the embryo) and vitelline veins (flow toward the embryo).

Prenatal Diagnosis Terms

false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.

false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.

negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.

positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.

pre-implantation genetic diagnosis - (PGD) a screening procedure for embryos produced through in vitro fertilisation (IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.

prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.

prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.

Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers


  1. Rhoads, G.G., Jackson, L.G., Schlesselman, S.E., de, l.C., Desnick, R.J., Golbus, M.S., Ledbetter, D.H., Lubs, H.A., Mahoney, M.J., Pergament, E., Simpson, J.L., Carpenter, R.J., Elias, S., Ginsberg, N.A., Goldberg, J.D., Hobbins, J.C., Lynch, L., Shiono, P.H., Wapner, R.J. & Zachary, J.M. 1989, "The Safety and Efficacy of Chorionic Villus Sampling for Early Prenatal Diagnosis of Cytogenetic Abnormalities", New England Journal of Medicine, vol. 320, no. 10, pp. 609-617.
  2. <pubmed>5691288</pubmed>
  3. <pubmed>4766093</pubmed>
  4. <pubmed>811431</pubmed>
  5. <pubmed>7208019</pubmed>
  6. <pubmed>7208019</pubmed>
  7. <pubmed>6463023</pubmed>
  8. <pubmed>4088973</pubmed>
  9. <pubmed>3717235</pubmed>
  10. <pubmed>5691288</pubmed>
  11. <pubmed>4766093</pubmed>
  12. <pubmed>811431</pubmed>
  13. <pubmed>7208019</pubmed>
  14. <pubmed>6463023</pubmed>
  15. <pubmed>4088973</pubmed>
  16. <pubmed>3717235</pubmed>
  17. Kremkali, F.W. (2006) Diagnostic Ultrasound Principles and Instruments (7th ed.) St Louis: Saunders Elsevier. pp3-5
  18. Alfirevic, Z., K. Sundberg, et al. 2008. "Amniocentesis and chorionic villus sampling for prenatal diagnosis (Review)." Cochrane Database of Systematic Reviews 4: 1-134.
  19. <pubmed>PMC2464303</pubmed>
  20. <pubmed>16530195</pubmed>
  21. Jenkins, T.M, Wapner, R.J, 1999. First trimester prenatal diagnosis: Chorionic villus sampling. Seminars in Perinatology. pp403-413.
  22. Melbourne Ultrasound for Women. Chorionic Villus Sampling. Accessed 5 September 2010. http://www.nevdgp.org.au/info/melb_us/cvs_melb.htm
  23. <pubmed>20154617</pubmed>
  24. Alfirevic, Z., K. Sundberg, et al. 2008. "Amniocentesis and chorionic villus sampling for prenatal diagnosis (Review)." Cochrane Database of Systematic Reviews 4: 1-134.
  25. Hall, Judith G. "Chromosomal Clinical Abnormalities." In Nelson Textbook of Pediatrics. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.
  26. <pubmed>6855813</pubmed>
  27. <pubmed>9316125</pubmed>
  28. Trofatter. K.F. 2008. Chromosomal Mosaicism Detected at the Time of Chorionic Villus Sampling. Accessed on 15 September 2010. http://www.healthline.com/blogs/pregnancy_childbirth/2008/03/chromosomal-mosaicism-detected-at-time.html
  29. <pubmed>20664398</pubmed>
  30. <pubmed>20051662</pubmed>
  31. Jackson, L.G., Zachary, J.M., Fowler, S.E., Desnick, R.J., Golbus, M.S., Ledbetter, D.H., Mahoney, M.J., Pergament, E., Simpson, J.L., Black, S. & Wapner, R.J. 1992, "A Randomized Comparison of Transcervical and Transabdominal Chorionic-Villus Sampling", New England Journal of Medicine, vol. 327, no. 9, pp. 594-598.
  32. <pubmed>19155918</pubmed>
  33. <pubmed>17694578</pubmed>
  34. Malone, F.D., Canick, J.A., Ball, R.H., Nyberg, D.A., Comstock, C.H., Bukowski, R., Berkowitz, R.L., Gross, S.J., Dugoff, L., Craigo, S.D., Timor-Tritsch, I., Carr, S.R., Wolfe, H.M., Dukes, K., Bianchi, D.W., Rudnicka, A.R., Hackshaw, A.K., Lambert-Messerlian, G., Wald, N.J. & D'Alton, M.E. 2005, "First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome", New England Journal of Medicine, vol. 353, no. 19, pp. 2001-2011.
  35. Rhoads, G.G., Jackson, L.G., Schlesselman, S.E., de, l.C., Desnick, R.J., Golbus, M.S., Ledbetter, D.H., Lubs, H.A., Mahoney, M.J., Pergament, E., Simpson, J.L., Carpenter, R.J., Elias, S., Ginsberg, N.A., Goldberg, J.D., Hobbins, J.C., Lynch, L., Shiono, P.H., Wapner, R.J. & Zachary, J.M. 1989, "The Safety and Efficacy of Chorionic Villus Sampling for Early Prenatal Diagnosis of Cytogenetic Abnormalities", New England Journal of Medicine, vol. 320, no. 10, pp. 609-617.
  36. Malone, F.D., Canick, J.A., Ball, R.H., Nyberg, D.A., Comstock, C.H., Bukowski, R., Berkowitz, R.L., Gross, S.J., Dugoff, L., Craigo, S.D., Timor-Tritsch, I., Carr, S.R., Wolfe, H.M., Dukes, K., Bianchi, D.W., Rudnicka, A.R., Hackshaw, A.K., Lambert-Messerlian, G., Wald, N.J. & D'Alton, M.E. 2005, "First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome", New England Journal of Medicine, vol. 353, no. 19, pp. 2001-2011.
  37. Malone, F.D., Canick, J.A., Ball, R.H., Nyberg, D.A., Comstock, C.H., Bukowski, R., Berkowitz, R.L., Gross, S.J., Dugoff, L., Craigo, S.D., Timor-Tritsch, I., Carr, S.R., Wolfe, H.M., Dukes, K., Bianchi, D.W., Rudnicka, A.R., Hackshaw, A.K., Lambert-Messerlian, G., Wald, N.J. & D'Alton, M.E. 2005, "First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome", New England Journal of Medicine, vol. 353, no. 19, pp. 2001-2011.
  38. Driscoll, D.A. & Gross, S. 2009, "Prenatal Screening for Aneuploidy", New England Journal of Medicine, vol. 360, no. 24, pp. 2556-2562.
  39. Driscoll, D.A. & Gross, S. 2009, "Prenatal Screening for Aneuploidy", New England Journal of Medicine, vol. 360, no. 24, pp. 2556-2562.
  40. Levison, J.H., Barbieri, R.L., Katz, J.T. & Loscalzo, J. 2010, "Hard to Conceive", New England Journal of Medicine, vol. 363, no. 10, pp. 965-970.
  41. Abboud, M.R. 2009, "Hematopoietic Stem-Cell Transplantation for Adults with Sickle Cell Disease", New England Journal of Medicine, vol. 361, no. 24, pp. 2380-2381.
  42. <pubmed>20100466</pubmed>
  43. Cica. N., 1998. Abortion Law in Australia. Parliament of Australia, Parliamentary Library. Accessed September 29. 2010. <http://www.aph.gov.au/library/pubs/rp/1998-99/99rp01.htm>
  44. Medline Plus: Trusted Health Information for You. 2010. Down's Syndrome. Accessed Septemeber 28, 2010.<http://www.nlm.nih.gov/medlineplus/ency/article/000997.htm>
  45. Roizen, N., Patterson, D., 2003. Down's syndrome. The Lancet. 361:1281-1289
  46. <pubmed>11310997</pubmed>
  47. Stewart, K. B., 2007. Trisomy 13 - Patau Syndrome. [Fact sheet] Centre for Genetics Education. Accessed 29 September, 2010. <http://www.genetics.com.au/pdf/factsheets/fs29.pdf>
  48. <pubmed>18079549</pubmed>
  49. National Institute of Neurological Disorders and Stroke. 2007. Tay-Sachs Disease Information Page. Accessed September 29, 2010. <http://www.ninds.nih.gov/disorders/taysachs/taysachs.htm>
  50. Southern Cross Bioethics Institute. 2008. Bioethical Issues. Accessed 6 October, 2010. <http://www.bioethics.org.au/Resources/Bioethical%20Issues.html>
  51. Royal Collage of Obstetricians and Gynaecologyists. 2010. Green-top Guideline No. 8 Amniocentesis and Chorionic Villus Sampling. Accessed 6 October, 2010. <http://www.rcog.org.uk/files/rcog-corp/GT8Amniocentesis0610.pdf>
  52. Gibson, P., Carson, M.P, 2010. Hypertension and Pregnancy. Accessed 29 September, 2010. <http://emedicine.medscape.com/article/261435-overview>
  53. <pubmed>15738029</pubmed>
  54. <pubmed>19455602</pubmed>
  55. <pubmed>19918960</pubmed>
  56. <pubmed>20664398</pubmed>
  57. <pubmed>7937577</pubmed>
  58. Silver, R.K., Macgregor, S.N., Muhlbach, L.H., Knutel, T.A. & Kambich, M.P. 1994, "Congenital malformations subsequent to chorionic villus sampling: Outcome analysis of 1048 consecutive procedures", Prenatal diagnosis, vol. 14, no. 6, pp. 421-427.
  59. <pubmed>20661588</pubmed>
  60. <pubmed>20811188</pubmed>
  61. <pubmed>7063565</pubmed>
  62. <pubmed>19218861</pubmed>
  63. <pubmed>20824891</pubmed>
  64. Lo, K., Mihm, M. & Fay, A. 2009, "Current Theories on the Pathogenesis of Infantile Hemangioma", Seminars in ophthalmology, vol. 24, no. 3, pp. 172-177.
  65. <pubmed>7784377</pubmed>
  66. <pubmed>20014413</pubmed>
  67. <pubmed>20014413</pubmed>

2010 ANAT2341 Group Projects

Project 1 - Ultrasound | Project 2 - Chorionic villus sampling | Project 3 - Amniocentesis | Group Project 4 - Percutaneous Umbilical Cord Blood Sampling | Project 5 - Fetal Fibronectin | Project 6 - Maternal serum alpha-fetoprotein | Students Page

Cite this page: Hill, M.A. (2024, June 17) Embryology 2010 Group Project 2. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/2010_Group_Project_2

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G