Preimplantation Genetic Testing

Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS) 

To the point– Preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) are testing options that are only available to patients undergoing in vitro fertilization (IVF), which is the fertilization of an egg in a laboratory.  PGD and PGS are terms used to describe testing an embryo for a specific genetic disease(s) it is at risk of inheriting.  In general, PGD is testing for single gene disorders that one or both parents are known to “carry”, whereas, PGS is screening for an abnormal number of chromosomes (e.g. Down syndrome), which increase in risk as mom’s age increases.  PGD and PGS are typically performed on one cell from the embryo, which is removed most often at day 3 or 5 after the egg is fertilized and analyzed through genetic testing methods. Results are usually received within 1-2 days (possibly longer). Only an embryo(s) without the genetic condition(s) is then implanted into mom’s uterus (other embryos that do not have the genetic condition can be saved for future IVF cycles if desired).  Follow-up testing through CVS or amniocentesis during the pregnancy to confirm PGD/PGS findings is recommended. 

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THE BASICS 

Preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) are testing options that are only available to patients undergoing in vitro fertilization (IVF), which is the fertilization of an egg in a laboratory. PGD and PGS are performed after the egg has been fertilized in a laboratory and grown for several days (usually 3 or 5 days) but prior to placing the embryo(s) in mom’s uterus where hopefully it will eventually implant, hence the term, preimplantation.  For more detailed information on “How it Works”, keep reading below or click here.

Basically, PGD & PGS are the earliest forms of prenatal testing.  Embryos are tested for specific genetic conditions and only those embryos that do not have the genetic condition(s) are placed in mom’s uterus.

The core elements of PGD & PGS testing are the following:

  • 1-2 cells are removed from the embryo (often at 3 or 5 after fertilization)
  • The chromosomes and the genes in those 1-2 cells are usually the same as the chromosomes and genes in the remaining embyro cells*
  • By testing one cell from the embryo for genetic conditions one can then choose to implant only embryos presumed to not have the genetic condition(s) of concern

*The genetic information in the cell(s) removed is not always the same as that of the remaining embryo.  This is more of a concern with PGS than PGD and you can talk with your reproductive endocrinologist or genetic counselor about this further.

So, let’s talk about the differences between PGD & PGS….

Preimplantation genetic diagnosis (PGD) is generally the diagnosis of a genetic condition involving a single gene abnormality in the embryo for couples, where one or both parents (depending on the inheritance of the condition) are known carriers.  These couples are typically seeking this information because they want to have a baby without the genetic condition, however some individuals may seek out this technology to select for certain conditions such as deafness. Generally individuals seeking PGD have a 25 to 50% chance of having a child with the particular genetic condition.  Examples of some of the genetic conditions that have been tested through PGD include, cystic fibrosis, Tay-sachs, Huntington disease, sickle cell anemia and Fragile X.  PGD is currently available for most known genetic changes or mutations, meaning, if you and/or your partner are known carriers for a particular genetic condition and you have had genetic testing to determine the mutation involved, chances are good that PGD would be available.

Preimplantation genetic screening (PGS) generally refers to the testing of the embryo for an abnormal number of chromosomes, detecting conditions such as Down syndrome and other conditions that are increased in risk as mom’s age increases. PGS is the term used more often by doctors or genetic counselors when discussing infertility with couples struggling with issues involving increased age, repeated in vitro fertilization (IVF) failures, recurrent miscarriages, or having had a previous pregnancy with a chromosome abnormality.

For couples undergoing IVF, PGD/PGS may be offered when:

  • One or both partners has a history of heritable genetic disorders
  • One or both partners is a carrier of a chromosomal abnormality
  • The mother is of advanced maternal age*
  • The mother has a history of recurrent miscarriages*

*Research does not necessarily indicate that live birth rates are increased with PGS for these indications (ASRM 2008 Preimplantation genetic testing: a Practice Committee opinion)

In many cases, results will be received within 1-2 days of testing, however, it may take longer.  PGD/PGS does not replace prenatal testing, such as CVS or amniocentesis. Preimplantation genetic testing provides information based on the analysis of a single cell which, at the end of the day, is not as reliable as something like amniocentesis or CVS where many are analyzed. Therefore, prenatal diagnosis through CVS or amniocentesis is still recommended following PGD or PGS and currently remains the standard of care.

PGD and PGS are not without controversy and there are ethical considerations.  For some, PGD and PGS in and of themselves pose a moral/ethical dilemma (e.g. those that feel that life begins at conception). Some of the questions that the medical and professional communities are continually wrestling with, and it would be worthwhile for you to consider if you are contemplating IVF with PGD or PGS, include the following:

  • For which conditions should PGD/PGS be performed?
    • early-onset severe conditions
    • mild conditions
    • adult-onset conditions, for example, predisposition to breast cancer
    • Should certain genetic conditions or traits be positively selected for?
      • Parents are deaf and they choose to have a deaf child through PGD
      • Should PGD be used to create a baby that can help save an existing child in the family by HLA matching and tissue donation?
      • Should gender selection be used for non-medical reasons?
        • This could be the only reason the couple decided to do IVF with PGS and is termed “family balancing”
        • Couple has IVF and PGD for other reasons but is then given the option of whether to implant male or female embryos
      • Should other ‘social traits’ be selected for or against (this is down the road, but when we learn more about the genes involved in intelligence, athleticism, height, etc. should we allow this to be a part of PGD)?

PGS is relatively new compared to PGD and although it is often utilized among patients undergoing IVF treatment, its indications (knowing when to offer/recommend it), utility (how useful and beneficial it is in given situations), and outcomes (the end result- how accurate it is and how does it affect the number of babies who are born without disease, etc.) remain an active area of research in reproductive medicine.

HOW IT WORKS

To the point– Preimplantation genetic diagnosis (PGD) and preimplantation genetic screening are both done in the context of a patient undergoing in vitro fertilization.  The gist of this testing is the following:

  • 1-2 cells are removed from embryo (on day 3 or 5 after egg is fertilized) 
  • The chromosomes and the genes in those 1-2 cells are the same as the chromosomes and genes in the remaining embyro cells*
  • By testing one cell from the embryo for genetic conditions you can then choose to implant only embryos without the genetic conditions being screened

*The genetic information in the cell is not always the same as that of the remaining embryo.  This is more of a concern with PGS than PGD and you can talk with your reproductive endocrinologist or genetic counselor about this further. 

Preimplantation genetic testing (PGD & PGS) can only be offered to individuals who are undergoing in vitro fertilization (IVF).  IVF involves ovary stimulation through medication, egg retrieval, and fertilization in a laboratory. Once the egg is fertilized by the sperm in the laboratory it starts dividing, first into 2 cells, then 4, then 8, etc.  By day 3 of this process (day 1 is fertilization), the embryo is at the 8-cell stage. Although it can be done at other stages, PGD/PGS often done on day 3 or day 5 after fertilization and includes the following:

1. First, one (possibly 2 cells) are removed from the embryo.

2. Next, the genetic material or DNA is retrieved from the cell and copied through a process known as polymerase chain reaction (PCR).

3. The next step in the process depends on whether or not the patient is pursuing PGS or PGD.

  • PGD– For PGD and looking for single gene genetic conditions, the specific area of DNA of interest (or the gene involved) is copied over and over again so the sample can be analyzed for the presence of a specific sequence of DNA or gene and also for linkage markers, other sequences of DNA, known to be near the gene.  They can identify whether or not the embryo has inherited the genetic condition or not through this process.  PGD does not look for other chromosome abnormalities, such as Down syndrome.
  • PGS– As stated above, the genetic material (DNA) within the cell is copied or amplified using the technique called polymerase chain reaction (PCR). This amplification produces enough DNA to use a second technique, known as array comparative genomic hybridization (aCGH). Array CGH assesses the amount of DNA that comes from each chromosome, revealing whether or not there are both a normal amount and correct number of chromosomes. aCGH can be used to screen for any extra chromosomes (e.g. Down syndrome which is an extra chromosome 21), missing chromosomes (e.g. Turner syndrome which is a missing X) and/or known rearrangements of chromosomes (translocations). Array CGH does not detect all types of chromosome abnormalities and does not look for all genetic conditions or birth defects.  Utilization of array CGH technology allows the laboratory to look at all of the chromosomes and is also referred to as Comprehensive Chromosomal Screening (CCS). Some laboratories may utilize a techonology called FISH (florescent in situ hybridization) instead or in addition to aCGH to screen for chromosome abnormalities.  This technology is not as comprehensive as CCS as it does not look at all of the chromosomes, but it allows for a quicker turnaround time.

4.  It depends a bit on what type of testing you have done, but sometimes results are received within 1-2 days, other times it can take longer.  Either way, you receive your results prior to implantation of the embryos.

5.  Once the PGD/PGS procedure has been performed and embryos have been selected, they are then inserted into mom’s uterus.

6. Confirmation of PGD/PGS results through either CVS or amniocentesis during the pregnancy is recommended.

RESULTS

Results from PGD/PGS take 1-2 days (possibly longer) to receive.

Results are not as accurate as other prenatal testing options, such as amniocentesis and CVS.  There are many factors that contribute to this, but one of them is simply that they are analyzing genetic information from only ONE or a couple of cells versus many with amniocentesis and CVS.  The limited amount of genetic material can affect the accuracy of the test, as well as concerns that one cell from the embryo may or may not represent what is going on with the rest of the embryo (this is especially of concern with PGS).

In general, approximately 3-4% of all babies born have some type of birth defect or genetic condition.  PGD/PGS does not rule out all birth defects or genetic conditions. Results from PGD/PGS should be confirmed during the pregnancy through amniocentesis or CVS for more definitive information.

HOW TO DECIDE

Deciding to undergo IVF with PGD/PGS is a big decision.  You may be undergoing IVF for infertility and PGD or PGS has been presented as an option based on your family history, age, etc.  For others, PGD may be the main reason you have decided to consider IVF in the first place.  Either way, deciding to pursue PGD/PGS takes thoughtful consideration.

One thing to keep in mind is that you are definitely not alone.  There are hundreds of other couples who have been in your situation and struggled through the process to determine the “right” decision…..for them.

Each circumstance for considering PGD/PGS involves a unique story, one that we do not presume to know or understand fully.  And, we all come at this from different beliefs, values, and personalities that play into our decisions.  So, here are just a few things to consider if you are trying to decide whether or not to undergo PGD and/or PGS with IVF.

  • Do you feel like all of your questions have been answered regarding the reliability/accuracy of PGD/PGS?
  • The embryos that have been identified as having a genetic condition will be discarded.  Is this something you and your partner have discussed?
  • Do you feel like you have up-to-date information on the condition(s) PGD/PGS is testing for?  Would you like more information about the condition(s)? Would it help you to talk with other families who have a child with this condition?
  • If you are considering PGS, do you feel like your provider has clearly communicated the limitations of this testing, including the fact that it may not improve your live-birth rate chances, there is a chance of the test being a false positive or false negative, etc.?

Considering the cost of IVF and the emotional and time commitment, if you are undergoing IVF with PGD or PGS, you and your partner have likely thought through almost all sides of this decision and may be at a point where you are comfortable with your decision.

IVF with PGD/PGS allows couples to look for genetic conditions prior to more traditional prenatal testing timelines and therefore, may prevent them from going through some of the difficult decisions involved with determining this information later in the pregnancy.

Questions? Get in touch




FAQs


Will my insurance cover PGD/PGS?

You will have to check with your insurance, but some insurance companies are covering parts of the PGD or PGS testing.  For example, they may pay for the genetic analysis but not necessarily the biopsy portion of the testing.  The cost of PGD/PGS varies but may be an additional $3,000-$7,000 or more (beyond IVF costs), depending on what type of testing is performed.

 





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