Frequently Asked Questions

What is a chromosome abnormality or “aneuploidy?

Aneuploidy is a term used to describe an abnormal number of chromosomes.

Chromosomes are structures in each cell of our body that carry our genetic information, or genes, in the form of DNA.

Healthy humans normally have 46 chromosomes arranged in pairs: 22 pairs of ‘autosomes’ (numbered from 1 to 22) and one pair of ‘sex chromosomes’ (XX in females or XY in males). Thus, humans have a total of 24 different types of chromosomes (1-22, X, Y).

How are chromosome inherited?

A child receives one of each pair of chromosomes from the mother in the egg and one of each pair from the father in the sperm. Normally, the egg and the sperm each have 23 chromosomes so that the first cell of the child has a total of 46 chromosomes – half from the mother and half from the father.

Sometimes during the formation of the egg or sperm an error can occur, resulting in an egg or sperm with an abnormal number of chromosomes. This type of error is called ‘chromosome non-disjunction’. The result is aneuploidy in the embryo. Having an extra chromosome is called ‘trisomy’; a missing chromosome is called ‘monosomy’.

The vast majority of embryos with aneuploidy do not implant in the uterus or are lost in early miscarriage often before a woman even realizes she’s been pregnant. In fact, over half of all early miscarriages are due to aneuploidy. In some cases a baby can be born with an abnormal number of chromosomes, a situation usually associated with mental retardation and birth defects. The specific features found in a baby with aneuploidy depend on which chromosome is extra or missing. An example of a common type of aneuploidy is Down syndrome, caused by three copies of chromosome number 21 (Trisomy 21).

Some of the more common aneuploidy conditions that can occur in live born babies include:

• Trisomy 21 (Down Syndrome)

Down syndrome, or Trisomy 21, caused by an extra chromosome of the 21st pair, accounts for about half of chromosome abnormalities found in live born babies. Children with Down syndrome have characteristic facial features that most people recognize. Most children are mentally retarded with an average IQ of about 50, although this varies from person to person. The average life span of a person with Down syndrome is between 35 and 50 years.

• Trisomy 18

Trisomy 18, also called Edward syndrome, is caused by three copies of chromosome 18. The extra chromosome causes multiple severe birth defects including structural abnormalities of the brain, heart, kidneys and genitals. Most babies with Trisomy 18 are stillborn or die shortly after birth due to the severe brain and heart malformations.

• Trisomy 13

Trisomy 13, also called Patau syndrome, is caused by an extra copy of chromosome 13. Babies with Trisomy 13 have multiple severe birth defects of the brain, heart, kidneys, gastrointestinal tract and genitals. Most fetuses with trisomy 13 are lost in miscarriage, are stillborn, or die shortly after birth.

• Klinefelter Syndrome (XXY)

Klinefelter syndrome, also known as XXY, affects between 1 in 500 and 1 in 1,000 males. Boys with Klinefelter syndrome may have learning disabilities and difficulty with speech and language development. Most have low levels of testosterone during puberty which can lead to breast development (gynecomastia), reduced facial and body hair, and infertility. Testosterone replacement therapy starting at puberty can prevent many of these features, but the infertility is usually permanent.

• Turner Syndrome (XO)

Turner syndrome, also known as 45,XO, or “XO”, is caused by a missing sex chromosome. Turner syndrome occurs in about 1 in 2500 to 1 in 5000 female births. The rate of XO in embryos is much higher than this and nearly 99% of embryos with XO are lost in miscarriage early in pregnancy. Most girls with Turner syndrome have short stature, are infertile and do not develop secondary sex characteristics without hormone replacement. Some have more serious birth defects of the heart or kidneys. Most girls are of average intelligence, although many have specific learning disabilities and may need additional help in school.

• Triple X Syndrome (XXX)

47,XXX, also known as XXX or Triple X, affects about one in every thousand females. Most females with XXX do not look different in appearance but are often taller than average and may have minor coordination problems. Most girls are of average intelligence, although they are at increased risk for learning difficulties, speech and language delays, and behavioral and emotional problems to varying degrees. Women with XXX typically have normal fertility.

• Jacob Syndrome (XYY)

47, XYY, also known as XYY or Jacob syndrome, affects about one in every thousand males. Most males with XYY do not look different in appearance, although they may be taller than average. Most boys are of average intelligence although they are at increased risk for learning disabilities, speech and language delays, and behavior problems to varying degrees. Men with XYY typically have normal fertility.

What are the chances of having an aneuploid embryo?

Aneuploidy can happen in any pregnancy just by a chance error in the formation of the sperm or egg, or early during embryo development, resulting in too few or too many chromosomes in the embryo. Although anyone can have an embryo with aneuploidy, the chance increases with the age of the mother. Additionally, due to the fact that the majority of fetuses with aneuploidy miscarry, the chance of aneuploidy is higher if testing an embryo, and decreases when testing a fetus (during the pregnancy), or a newborn baby.

About 1 in every 500 live born babies has some type of chromosome abnormality. The rate of aneuploidy in embryos is much higher, reaching 80% in women over 40 years of age. Most of these chromosomally abnormal embryos will either not attach to the uterus or will be miscarried early in pregnancy. This is likely the reason that women, as they age, have more difficulty conceiving and continuing a pregnancy. The risk of aneuploidy in an embryo or baby is illustrated in the chart to the right.

Do you screen the embryos for autism?

Parental Support tests for chromosome abnormalities – missing or extra chromosomes that can prevent implantation, cause miscarriage or result in the birth of a baby with a chromosome syndrome. Most cases of autism are not associated with chromosome abnormalities.

There are many, many different theories as to the causes of autism and there are likely multiple factors that contribute the development of this condition in any particular child. However, at this time, the majority of children with autism have no identifiable genetic cause, and no form of PGD, including Parental Support, can screen for autism in preimplantation embryos.

About 15-20% of children with autism can be found to have a gene mutation (a change in the code of one or more genes) that is thought to contribute to or cause the condition. If a family has a child with autism who has already been found to have a causal gene mutation, it may be possible to set up a custom Preimplantation Genetic Diagnosis (PGD) test to test specifically for this mutation. This type of testing only detects the mutation already known to be present in the family and may take time to develop depending on the mutation. Contact GSN at info@genesecurity.net if you have a known autism-related gene mutation in the family and have questions about PGD for this gene.

How many chromosome problems do you test for?

Any chromosome out of the 24 different kinds of chromosomes can be extra or missing. Most embryos that have extra or missing chromosomes do not implant or result in early miscarriages. Some of the more common chromosome problems that can occur in liveborn babies are Trisomy 21 (Down syndrome), Trisomy 18, Trisomy 13, Turner syndrome and Klinefelter syndrome. Parental Support PGD for aneuploidy screens for extra or missing copies across all chromosomes, in addition to large extra or missing chromosome segments and uniparental disomy.

Why is aneuploidy more common as women get older?

The cells that will eventually become eggs each have 46 chromosomes. These ‘pre-eggs’ are stored in the female ovaries from birth and women do not make more during their lifetime. After ovulation each month, one of the pre-eggs divides in half, giving one chromosome from each chromosome pair to the mature egg, for a total of 23 chromosomes. As women get older their pre-eggs get older, too, and the process of chromosome division does not work as well. Thus, as a woman ages, the mature eggs released at ovulation have a higher chance of dividing abnormally and containing extra or missing chromosomes instead of the normal number of 23. The process of abnormal division is called chromosome non-disjunction.

What is chromosome mosaicism?

Chromosome mosaicism is a situation in which the cells of an embryo have different numbers of chromosomes. In some cases, a portion of the cells may have a normal number of chromosomes while another portion may be aneuploid. In other cases all the cells of the embryo may be aneuploid to different degrees.

Embryos with mosaicism may be lost in early miscarriage. Others result in perfectly healthy babies with no identifiable effects. In rare cases, an embryo with mosaicism may result in a liveborn baby with some degree of physical, mental or medical effects.

Preimplantation Genetic Diagnosis (PGD) cannot detect mosaicism because testing is done on only one cell from the embryo and mosaicism can only be detected by testing the chromosomes of multiple individual cells. Although the actual risk is unknown, the chance to miss clinically significant mosaicism when performing PGD for aneuploidy is considered to be lower than the overall rate of mosaicism. This is because most embryos with mosaicism have been found to either contain mainly aneuploid cells, or the abnormal cell(s) ‘self-correct’ over time resulting in an embryo or fetus with normal chromosomes. Due to the fact that PGD cannot rule out mosaicism, prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis is recommended in all pregnancies achieved through PGD and IVF.

How can PGD for aneuploidy help?

PGD allows the testing of each embryo separately so that those with 46 chromosomes are transferred to the mother’s uterus. Transferring those embryos with the correct number of chromosomes may increase the chance that a couple will become pregnant during a particular cycle. It may also decrease the chance for miscarriage during the pregnancy and reduce the chance for the couple to have a liveborn baby with a chromosome abnormality such as Down syndrome.

There are several technologies currently used to perform PGD for aneuploidy screening. GSN’s Parental Support is the newest and most advanced technology and enables testing of all 24 chromosomes for aneuploidy with results returned in time for transfer on Day 5 with no embryo freezing required. The other commonly used technologies, both with their own benefits and limitations, are FISH and CGH.

What is Preimplantation Genetic Diagnosis (PGD)?

Preimplantation Genetic Diagnosis, or PGD, is a specialized laboratory test that is performed during In Vitro Fertilization (IVF) to evaluate one cell of an embryo, called a blastomere, for specific genetic diseases or chromosome abnormalities. Each embryo created in an IVF cycle is tested separately. The tests will give the doctors information on whether or not the specified genetic diseases or chromosome abnormalities are not, or may not, be present. Physicians can then use the results of these tests to help select embryos for transfer to the mother’s uterus.

What is Preimplantation Genetic Diagnosis (PGD) for Aneuploidy?

Preimplantation Genetic Diagnosis (PGD) for aneuploidy is a specific type of PGD used with IVF to identify embryos with an abnormal number of chromosomes, a condition called ‘aneuploidy’. One blastomere of each embryo is evaluated for aneuploidy. This testing allows IVF physicians to transfer to the mother’s uterus those embryos with no detectable chromosome abnormalities. This may increase the chance that a couple will become pregnant during a particular cycle. It may also decrease the chance for miscarriage during the pregnancy and reduce the chance for the couple to have a liveborn baby with a chromosome abnormality such as Down syndrome.

Who should consider PGD for Aneuploidy?

The clinical benefits of PGD are an active area of research. Aneuploidy can occur in any embryo from any couple just by chance, although some couples are at a higher risk. A number of studies using FISH, which until recently had been the industry standard, have demonstrated that PGD may be particularly beneficial for couples meeting any of the criteria below. Traditional FISH testing has known limitations; thus, given the recent advances in PGD technology, including the ability to deliver results on all 24 chromosomes with high levels of accuracy, an even greater benefit from PGD is expected with these newer testing methods. Due to the fact that these technologies are new, clinical data is still pending.

• Women aged 35 and older
• Couples who have had a previous pregnancy with a confirmed chromosome abnormality
• Couples who have had multiple early miscarriages

Studies of couples who have had more than one miscarriage have shown a higher number of embryos with chromosome abnormalities than expected. Some studies have shown an increased rate of pregnancy, a decreased rate of miscarriage, and an increased rate of livebirth following the use of PGD in couples with recurrent pregnancy loss. Others have shown a clear benefit with PGD only in couples with recurrent miscarriage where the mother is 35 years of age or more.

Before considering PGD, couples with a history of 3 or more miscarriages are encouraged to have their own chromosomes evaluated for the presence of inherited chromosome rearrangements, which can be done with a blood test. In approximately 5% of couples with recurrent pregnancy loss one member of the couple is found to have a balanced chromosome rearrangement. A balanced chromosome rearrangement does not affect a person’s health, but it does increase greatly the risk for having chromosomally abnormal embryos, the majority of which will be lost in early miscarriage. If a chromosome rearrangement is found, there are specialized Preimplantation Genetic Diagnosis (PGD) methods that can be used to analyze embryos for the unbalanced rearrangement.

• Couples who have had previously unsuccessful IVF cycles

There is data to suggest that aneuploidy rates are increased in the embryos of couples who have experienced repeated IVF cycle failure. Some studies show an increased rate of pregnancy in these couples when PGD is used, although other studies show no clear indication that these couples benefit from PGD. In some of these couples, there may be reasons other than aneuploid embryos for unsuccessful IVF cycles.

How and when is PGD performed?

PGD is only performed as part of IVF. On the third day after fertilization (Day 3), when the embryos have reached about six to ten cells in size, one blastomere of each embryo is removed for testing in a process called ‘embryo biopsy’. With current technologies, the blastomeres are prepared using a difficult procedure called ‘fixation’ and then packaged separately in custom tubes and shipped by medical courier to the testing laboratory. With Parental Support, we have eliminated the fixation step, making the preparation and packaging of the blastomeres simpler and easier. At the laboratory, each blastomere is individually tested. Results are reported back to the doctor at the IVF center in time for the embryos to be transferred to the mother’s uterus on Day 5.

Does biopsy harm the embryo?

On Day 3 when embryo biopsy is performed, all of the cells of the embryo are similar and are not yet separated into different cell types. Removing one cell for testing does not appear to disrupt or interfere with subsequent fetal development and has not been associated with an increased risk of birth defects. Babies born after PGD that include embryo biopsy have had a similar rate of birth defects as compared to all other babies in the general population.

Embryo biopsy in the absence of PGD has been shown in some studies to be associated with a reduced rate of implantation. However most doctors feel that if the biopsy procedure is correctly performed, aneuploidy screening more than compensates for this reduced rate of implantation resulting in equivalent or better implantation rates.

No other known adverse effects associated with embryo biopsy or PGD have been reported to date. However, as embryo biopsy is still a relatively new procedure the potential for unknown consequences to a liveborn baby cannot be entirely excluded.

Should I have a day 3 or a day 5 biopsy?
If you choose to have a day 3 biopsy you will have results on the morning of day 5, in time for a fresh transfer (no embryos will be frozen prior to transfer). Day 3 testing analyzes a single cell that has been biopsied from each embryo. Testing a single cell cannot detect or rule out the possibility of chromosome mosaicism (a condition in which some cells of an embryo have a different number of chromosomes than other cells).

If you choose to have a day 5 biopsy, a cluster of two to ten cells are removed from the mass of cells called the trophectoderm, the tissue that will become the placenta. Since embryos do not survive well outside of the mother’s uterus beyond Day 5 or 6, the embryos are frozen until results are available (1 to 2 weeks from receipt of cells). Embryos with normal chromosome results can be considered for thawing and transfer. Early data suggests aneuploidy screening of trophectoderm (TE) cells may be associated with lower mosaicism rates and higher euploidy rates (likely a product of negative selection in that aneuploid embryos are less likely to survive to Day 5) [1,2]. It is increasingly used in clinics with specialized expertise in embryo freezing and good recovery rates of frozen embryos. Not all IVF Clinics perform day 5 biopsies so please check with your IVF center if you’re interested in more information about this option.

If you are interested in further reading, please click here for an article regarding D5 data published by GSN in HMR in Oxford Journals, July 2010.

What is my chance of getting pregnant after PGS with Parental Support?

There are many different factors that influence whether or not you become pregnant during your IVF cycle. The data that Gene Security Network (GSN) currently has on pregnancy rates following testing is reported by IVF centers and was not collected under a formal clinical study. These rates may change as more data is collected.
• For Day 3 blastomere biopsy with fresh transfer there is approximately a 50% ongoing pregnancy rate with embryo transfer following testing; this rate is closer to 60% in patients aged 35 and younger and 45% in patients aged 36 and older.
• For Day 5 trophectoderm biopsy with Frozen Embryo Transfer (FET) there is approximately a 75% ongoing pregnancy rate with embryo transfer. This rate appears to be slightly higher in patients 35 and younger and slightly lower in patients aged 36 and older.

How does conventional FISH testing work?

In most centers FISH is the still the standard technology used for PGD. FISH works by using segments of DNA, called probes, that hybridize, or attach, to a specific chromosome. The DNA probes have been treated with a fluorescent dye so that they light up under a microscope with a different color for each chromosome tested. FISH is used to test a single cell by applying the probes and then using a microscope to count the colored dots: if two dots of a specific color are seen then that chromosome has two copies; if three colored dots are seen then that chromosome has three copies indicating that the cell is aneuploid and abnormal.

The key limitations with FISH are:

1. Only a few probes can be used at a time

Only a maximum of five probes can be applied to one cell at one time, which means that only five chromosomes can be evaluated at once. Though the cell can be washed and a second set of probes applied to test additional chromosomes, the ability for the probes to successfully hybridize weakens. Consequently, it is only possible to test a subset of the chromosomes in a blastomere, and if a probe doesn’t successfully hybridize it may result in a misdiagnosis.

2. The process of applying and visualizing the probes is prone to error

Ultimately, determining whether the blastomere is normal or aneuploid is done by a person looking through a microscope. If the chromosomes are arranged in such a way that the dots overlap, or are difficult to see, it may not be possible to get a good read and a misdiagnosis may result.

Due to these and other limitations, the accuracy of FISH for single cell diagnosis is only around 90%.

What about other, newer technologies like CGH?

Comparative Genomic Hybridization, or CGH, is another new technology capable of evaluating all 24 chromosomes in a single cell. However, it cannot produce results in time for Day 5 embryo transfer.

CGH is usually done by labeling the DNA from a blastomere and DNA from a normal control cell with different colored fluorescent dyes. The samples are mixed and added to a slide with either a set of normal chromosomes or a set of defined DNA probes matching each chromosome. The blastomere and control DNA will hybridize, or attach, to the sections of the slide that are an exact match. If there is an imbalance in chromosome number between the blastomere and the normal control the results will show a different color. For example, when the chromosomes of the blastomere and control cell are balanced, all the probes/chromosomes will be the same color; when there is a missing chromosome in the blastomere, the control DNA color predominates for those probes/chromosomes; when there is an extra chromosome in the blastomere, the blastomere color predominates.

There are a number of limitations with CGH that make it less than ideal for blastomere analysis. First, the processing time for CGH is much longer than for FISH or Parental Support, precluding transfer of the embryos during the same IVF cycle. CGH can take several weeks to produce results, which means that the embryos must be frozen until results are available, a process which may be associated with a reduction in embryo survival.

Secondly, CGH can only detect unbalanced chromosome changes; it cannot detect a complete additional or missing set of chromosomes, such as haploidy and polyploidy which occur in up to 10% of embryos.

Why is prenatal diagnosis recommended after PGD?

Prenatal diagnosis is recommended after PGD for two reasons:

1. Although PGD has been performed for years, the technology is still considered investigational
2. Risk of chromosome mosaicism

For these reasons prenatal diagnosis through chorionic villus sampling (CVS) or amniocentesis is recommended to confirm the results

• Chorionic Villus Sampling (CVS)
  Chorionic villus sampling (CVS) is typically performed in the first trimester of pregnancy, between 10 and 12 weeks gestation, by a specially trained obstetrician or perinatologist who removes a small amount of tissue, called chorionic villi, from the placenta either via a catheter placed through the cervix or a thin needle placed through the abdomen. The cells in this tissue come from the same cells that created the fetus and, thus, should have the same chromosome make-up. The cells are tested for chromosome abnormalities.

• Amniocentesis
  Amniocentesis is usually done in the second trimester of pregnancy, between 15 and 20 weeks of pregnancy, by a specially trained obstetrician or perinatologist who removes a small amount of the fluid in the amniotic sac via a thin needle inserted into the mother’s uterus. Fetal cells that float freely within the amniotic fluid are cultured and tested for chromosome abnormalities.

What is Parental Support?

Parental Support is a new technology for Preimplantation Genetic Diagnosis (PGD) to test all 24 chromosomes in a single cell from an embryo (called a blastomere) for a variety of genetic abnormalities within 24 hours. Test reliability typically exceeds 99% and results are returned in time for Day 5 embryo transfer. Parental Support is a proprietary technology developed by Gene Security Network.

Why screen all 24 chromosomes?

Aneuploidy can affect any chromosome. When only a portion of the chromosomes are evaluated, as with FISH, there is still a chance for aneuploidy of one or more of the untested chromosomes. Studies comparing analysis of nine chromosomes to 24 chromosomes have found that up to 25% of aneuploid embryos would test normal with FISH simply because the other chromosomes were not tested. This means that 1 in 4 blastomeres with a problem would not be detected using FISH.

Accurate screening of each embryo across all 24 chromosomes greatly decreases the chance that an aneuploid embryo will be transferred to the mother. As embryos with aneuploidy are prone to miscarriage or often fail to implant at all, this should in theory improve the chance of a successful IVF cycle and pregnancy.

Why is 24-hour turnaround so important?

While there are some technologies, such as CGH, that can screen all 24 chromosomes, delivering results can take up to several weeks. This means that the embryos must be frozen until the testing is completed. Embryo freezing may be associated with a reduction in embryo survival. For couples who may only have one or two viable embryos, this may be a significant problem.

With Parental Support, results on all 24 chromosomes are returned early on the morning of Day 5. This means that the embryos do not need to be frozen and can be transferred during the same IVF cycle.

How does Parental Support work?

Parental Support overcomes many of the limitations typically associated with the testing of just a single cell. Because so little genetic material is available from a single cell, results on one blastomere from an embryo are inherently error-prone, even with the best testing and laboratory methods. Although new microarray testing technologies can analyze DNA from all 24 chromosomes using thousands of probes, these technologies require a greater volume of DNA than the amount retrieved from a single cell. DNA from a blastomere can be amplified (copied) to create a greater volume for testing; however, the quality of the amplified sample is poor, which increases the chance for testing errors.

Parental Support compensates for the limitations of single cell amplification and testing by using DNA from both parents to enhance the results on each embryo. Many cells can be easily collected from the parents through a painless cheek swab, providing ample DNA for a full, accurate analysis on both parents. Since the DNA in the embryo is derived from the mother and father, Parental Support leverages the availability of parent samples to create a much more effective test on single blastomeres.

Parental Support works in the following way:

1. First, Parental Support uses a state-of-the-art Illumina microarray testing platform to screen all 24 chromosomes. The DNA from the single blastomere is amplified and added to an array that contains hundreds of thousands of tiny DNA probes. Each DNA probe binds to a specific area of a specific chromosome. These probes are much smaller than FISH probes, so small that they cannot be seen under a microscope and are instead read by a machine called a scanner.
2. The microarray scanner results cover all 24 chromosomes but are ‘noisy’, or difficult to interpret, due to the poor quality of the DNA sample produced through amplification of just one cell. However, genetic data produced through microarray analysis of thousands of cells from the cheek swab samples of the biological parents can be used to clarify the blastomere results. Parental Support uses a sophisticated bioinformatic algorithm that incorporates genetic data from both parents to clean and correct errors produced during the laboratory analysis. The final results are a highly accurate representation of the genetic composition of the blastomere.

This two step testing process significantly increases PGD test accuracy and is vastly superior to previous methods.

What makes Parental Support different from other types of PGD?

Parental Support offers two key advantages over conventional PGD:

1. Screening of all 24 chromosomes in 24 hours
2. 99% test accuracy

Historically, the technology used for PGD, called fluorescent in-situ hybridization (FISH), only screens nine chromosomes, leaving the rest of the chromosomes untested. Additionally the accuracy of FISH is considered to be approximately 90% for the chromosomes tested. This means that one in every ten blastomeres may be misdiagnosed due to test error, resulting in either the disposal of a healthy embryo, or the transfer of an abnormal embryo.

Parental Support provides a more accurate test covering more chromosomes than conventional FISH testing methods. More effective testing may improve the chance for IVF success and the birth of a healthy baby.

Do I need to use ICSI to have Parental Support testing?
GSN recommends that you use ICSI during your cycle (intracytoplasmic sperm injection of the eggs) to eliminate the risk of sperm contamination, however, we do not require it. In several cases when ICSI has not been used we have seen triploidy ( a complete extra set of 23 chromosomes) of paternal origin. Since paternal triploidy is rare, we suspect that most of these cases are due to sperm contamination (an extra sperm outside of the embryo that contaminated the biopsy sample). GSN will notify your doctor of possible sperm contamination on the test results report, but this means that there are No Results for the tested embryo. You and your doctor can decided whether you are comfortable with this increased chance of No Results and whether or not you wish to do ICSI.

Who should consider PGD with Parental Support?

PGD for aneuploidy may be recommended by your doctor if you are at increased risk for aneuploidy in your pregnancies. Couples with one or more of the following have a higher chance for aneuploidy in future pregnancies:

• Women aged 35 and older
• Recurrent miscarriages of unknown cause
• A previous child or pregnancy with a chromosomal abnormality
• Previous unsuccessful IVF cycles

If your doctor is recommending PGD for aneuploidy during your IVF cycle, Parental Support offers the most advanced way to evaluate all 24 chromosomes with high reliability. If you have been informed that you have an increased chance for aneuploidy, or if you’re already using IVF and wish to increase the chance to have a healthy pregnancy, you should consider testing with Parental Support.

Does PGD guarantee a successful IVF cycle and healthy baby?

No. There are many different factors affecting the chance of IVF success and no test can guarantee the birth of a healthy baby. Although Parental Support offers the most advanced PGD technology available, there are limitations to all PGD tests in part because the single cell analyzed from the embryo may differ genetically from the other cells in the embryo, a condition called mosaicism.

With any pregnancy, there is a 3-5% risk for birth defects or genetic conditions and many of these are not detectable prior to implantation or even during pregnancy. Parental Support detects the portion of birth defects caused by aneuploidy (extra or missing chromosomes) but does not identify other structural chromosome abnormalities such as balanced translocations or small rearrangements of chromosome material. Also, as with all types of PGD, Parental Support does not analyze specific genes unless specifically requested, so it will not routinely identify single gene disorders like cystic fibrosis, muscular dystrophy, or Tay-Sachs disease.

Why does GSN ask about ethnic background?

The PGD for aneuploidy screening or Parental Support testing done by GSN is able to detect chromosome aneuploidy in all 24 chromosomes, but is not able to detect single gene disorders. Some single gene disorders are more common in specific ethnic backgrounds and screening for these disorders should be discussed with your doctor. For example, it is known that individuals of Ashkenazi Jewish descent are at a higher risk to be a carrier for Tay Sachs disease and Caucasian individuals are at a higher risk to be a carrier of Cystic Fibrosis (CF). The genetic counselors at GSN may inquire about your ethnic background in order to suggest further discussion of specific carrier screening with your doctor.

Is there anything else I should know about Parental Support?

In addition to analysis of all 24 chromosomes, Parental Support offers several unique advantages:

• Detection of haploidy and polyploidy:
  Haploidy and Polyploidy occur when a whole set of chromosomes is missing or extra in the cells of an embryo. With haploidy the cell has only one copy of each chromosome for a total of 23, and with polyploidy the cell has three or more copies of each chromosome for a total of 69 (triploidy) or 92 (tetraploidy), instead of the normal 46. Data suggests that these types of abnormalities are found in up to 10% of embryos created during IVF. Embryos with haploidy and polyploidy almost never implant to create a pregnancy, and those that do almost always result in miscarriage. In rare cases a baby may be born with triploidy, but the condition is always fatal soon after birth.
• Individually calculated test error rates:
  Parental Support calculates a test reliability specific to each individual blastomere and chromosome analyzed. This means that if the results on a given blastomere cannot be reported with confidence, the doctor will know which chromosome is responsible, along with the degree of risk, and can use this information to make the best clinical decisions.
• Detection of Uniparental Disomy:
  Uniparental Disomy (UPD) is a rare condition in which both chromosomes of a particular chromosome pair come from the same parent, instead of one from each parent. UPD can be associated with specific genetic disorders depending on the particular chromosome involved and the parent of origin of the two copies. The most common genetic disorder associated with UPD is Prader-Willi syndrome which occurs in about 1 of every 10,000 children and is characterized by mental retardation, childhood obesity and severe behavioral and emotional problems. Thirty percent of children with Prader-Willi have maternal UPD for chromosome 15, having received two copies of chromosome 15 from their mother and none from their father.

  Parental Support is able to detect the presence of uniparental disomy and will report this finding for those chromosomes in which UPD is known to result in a serious genetic condition.

• Detection of DNA contamination:
  Any time the DNA of a single cell such as a blastomere is amplified for testing, there is a risk of also amplifying foreign DNA that was inadvertently present along with the sample cell. Contamination may result when one or more additional sperm are present in the tube with the blastomere, or when foreign DNA from the lab environment gets into the tube with the blastomere DNA. Both of these situations can affect the results.

  Parental Support performs a number of unique quality control checks to detect the presence of foreign DNA and assure the highest reliability and accuracy of our results.

  Additionally, by referencing the DNA from the blastomere sample with DNA from each parent, DNA from a source other than the blastomere becomes easily identifiable. Other PGD technologies do not perform these measures and cannot rule out contamination in their samples.

• Determination of the parental origin of a trisomy or monosomy
  In some cases if a couple repeatedly has aneuploid embryos, it may be helpful to understand the parental origin for the extra or missing chromosome to determine whether aneuploidy may be occurring for a reason other than chance chromosome non-disjunction. Although not routinely reported in the testing results, information on parental origin is captured as part of the Parental Support process and is available upon request by the IVF doctor.
• Fast turnaround time:
  Results are available in time for embryo transfer on “Day 5”, so the ‘fresh’ embryo can be transferred. Embryo freezing is not required.

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