Patient Consent for Preimplantation Genetic Screening (PGS)
TEST DESCRIPTION
What is Preimplantation Genetic Screening?
Preimplantation Genetic Screening (PGS) is a test performed on a small sample of cells from an embryo to evaluate the embryo’s
chromosomes. Chromosomes are the structures inside of our cells that contain the genetic information needed for our bodies to grow,
develop, and maintain our health. There are 23 pairs of chromosomes (46 total). Chromosomes 1-22 are called autosomes, and are present
in both males and females. The 23rd pair of chromosomes determines whether we are male (XY) or female (XX). Changes to the number or
structure of the chromosomes may cause failure of an embryo to implant, result in a miscarriage, or lead to the birth of a baby with a
genetic disorder. The goal of PGS is to identify embryos with normal chromosomes in order to improve your chances of a healthy
pregnancy. CombiMatrix utilizes a technique called Chromosomal Microarray Analysis (CMA) to evaluate the embryo for chromosomal
abnormalities.
BENEFITS, RISKS AND LIMITATIONS
Benefits of PGD with PGS for Aneuploidy
Chromosomal abnormalities are one of the most common reasons for implantation failure and miscarriages that occur within the first 12
weeks of pregnancy. Approximately 50-60% of miscarriages that occur in the first trimester are due to a fetal chromosomal abnormality.
Chromosomally abnormal embryos may not differ in overall microscopic appearance from chromosomally normal embryos, thus making it
difficult to identify which embryo(s) have the best chance of resulting in successful implantation and pregnancy. By implanting a
chromosomally normal embryo, the possibility of a successful implantation and pregnancy is significantly enhanced.
Risks and Limitations of PGS
Embryo Biopsy-Related Risks
Although in vitro fertilization (IVF) has been used successfully in tens of thousands of pregnancies worldwide with no documented increase
in risk for congenital malformations or developmental disorders, the PGS process requires an embryo biopsy, and this biopsy process is not
without risk. Biopsies are typically performed at either 3 days following fertilization or 5/6 days following fertilization. Day 3 (blastomere)
biopsies involve the removal of a single cell from the embryo at the 8-10 cell stage of development. Day 5/6 (trophectoderm) Biopsies
involve the removal of approximately 5-10 cells from the outer cell layer of the embryo, leaving the inner cell mass, which will become the
developing baby, intact. Embryo biopsy-related risks include:
• An embryo may be damaged during the biopsy process
• One or more cells may not be obtained from the embryo for testing
• In the case of a Day 3 biopsy, the biopsied cell may not contain a nucleus (the part of the cell that contains the chromosomes)
• For a discussion of the risks and benefits associated with Day 3 versus Day 5/6 biopsies, please consult your fertility specialist. Please
note that although the biopsy samples will be sent to CombiMatrix for testing, your embryos will remain at your fertility specialist’s
facility.
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Patient’s Initials
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Partner’s Initials
Risks and Limitations of PGD with PGS for Aneuploidy
Embryo Biopsy-Related Risks
Although in vitro fertilization (IVF) has been used successfully in tens of thousands of pregnancies worldwide with no documented increase
in risk for congenital malformations or developmental disorders, the PGD process requires an embryo biopsy, and this process is not
without risk. Biopsies are typically performed at either 3 days following fertilization or 5/6 days following fertilization. Day 3 (blastomere)
biopsies involve the removal of a single cell from the embryo at the 8-10 cell stage of development. Day 5/6 (trophectoderm) biopsies
involve the removal of approximately 5-10 cells from the outer cell layer of the embryo (trophectoderm), leaving the inner cell mass, which
will become the developing baby, intact. Although the biopsied cell(s) are sent to CombiMatrix for testing, your embryos will remain at your
fertility specialist’s facility. Embryo biopsy-related risks include:
• An embryo may be damaged during the biopsy process
• One or more cells may not be obtained from the embryo for testing
• In the case of a Day 3 biopsy, the biopsied cell may not contain a nucleus (the part of the cell that contains the chromosomes)
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Patient’s Initials
ASR-F-05092016
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Partner’s Initials
Patient: ___________________________________________________
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Patient Consent for Preimplantation Genetic Screening (PGS)
BENEFITS, RISKS AND LIMITATIONS (cont’d)
IVF Specialist / Clinic-Related Risks
There are also risks associated with the clinical process of IVF:
• It is possible that no embryos (normal or abnormal) will be available for transfer following biopsy
• It is possible that the wrong embryo is transferred to the uterus
• Transfer of a chromosomally normal embryo does not guarantee a successful implantation or pregnancy
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Patient’s Initials
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Partner’s Initials
Technical and Analytic Risk
CombiMatrix employs individual bar-code labeling of embryos and stringent sample tracking and control procedures to minimize the risk
of technical errors, however, errors may occur that result in no diagnosis or a misdiagnosis.
• No Diagnosis: Technical difficulties with the test or the sample itself may fail to yield adequate quality data that may result in test
failure. Common causes include absent or poor quality DNA from the embryo biopsy.
• Misdiagnosis: The risk of misdiagnosis is generally considered to be <4%. This includes the risk for either a false negative (the PGS
results are normal but the embryo is chromosomally abnormal) or a false positive (the PGS results are abnormal but the embryo is
chromosomally normal). One recognized source of misdiagnosis is embryo mosaicism; a phenomenon in which the cell or cells
biopsied for analysis are not genetically representative of the remainder of the embryo. Mosaicism may or may not be detected by
this assay.
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Patient’s Initials
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Partner’s Initials
Technical Limits of Detection
PGS is designed to detect gains and losses of entire chromosomes or large regions of a specific chromosome. PGS does not detect:
• Single Gene Disorders – PGS does not detect single gene disorders. If this testing is desired, Preimplantation Genetic Diagnosis (PGD)
must be performed, if available, in addition to PGS.
• Polyploidy – The current method of CMA cannot detect when an entire extra set of chromosomes is present within an embryo (69
instead of 46).
• Balanced chromosomal rearrangements – The presence of a balanced chromosomal rearrangement cannot be identified by the
current method.
• Small Chromosomal gains/losses <30 Mb – PGS cannot identify gains or losses of chromosomal material that are less than 30 Mb in
size, even though such abnormalities have the potential to cause a chromosomal disorder.
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Patient’s Initials
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Partner’s Initials
Other Pregnancy-Associated Risks
The general population risk for having a child with a congenital malformation is approximately 2-3%. PGS does not reduce this risk.
Developmental delay, intellectual disability and autism/autism spectrum disorders have many different possible causes. PGS does not test
for or decrease the risks of these conditions.
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Patient’s Initials
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Partner’s Initials
Follow-Up Recommendation for Prenatal Diagnosis
Due to the risks associated with PGS testing, PGS should not be viewed as a replacement for prenatal diagnostic testing by chorionic villus
sampling (CVS) or amniocentesis. If you do not wish to pursue confirmatory diagnostic testing, you can discuss other options for screening
with your prenatal care provider.
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Patient’s Initials
ASR-F-05092016
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Partner’s Initials
Patient: ___________________________________________________
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Patient Consent for Preimplantation Genetic Screening (PGS)
TEST RESULTS AND INTERPRETATION
PGS for Aneuploidy
• Abnormal: one or more whole chromosome or segmental chromosome abnormalities were detected
• Normal: no whole chromosome or segmental chromosome abnormalities were detected
• No result*: the chromosomal status of the embryo was not able to be determined
NOTE: A “No Result” call may occur for a number of reasons, including a cell with no nucleus (Day 3 biopsy), failure of DNA within the
sample to amplify, or poor quality amplification of the DNA.
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Patient’s Initials
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Partner’s Initials
GENDER DISCLOSURE
PGS automatically provides gender information based on the evaluation of the sex chromosomes (X and Y). Please indicate your preference:
 We DO wish to know fetal gender
 We DO NOT wish to know fetal gender
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Patient’s Initials
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Partner’s Initials
CONFIDENTIALITY AND GENETIC COUNSELING
• Genetic counseling regarding the benefits, risks and limitations of PGS is recommended prior to testing. Once the PGS results are
complete, genetic counseling is also recommended to review your results. Depending upon the results of the PGS, further testing
and/or diagnostic evaluations may be indicated.
• To protect patient confidentiality, test results can only be released to authorized entities, such as the: referring physician, genetic
counselor, reference laboratory, patient, or patient’s personal representative.
• No testing apart from that which is ordered by your physician will be performed on your sample. Additional testing requires your
further expressed consent.
• All samples are destroyed after 60 days, however, any remaining extracted DNA is retained for 5 years. You have the option of
allowing CombiMatrix to completely de-identify the sample and strip it of all protected health information in order to use this sample
for validation or educational purposes.
If you do not consent to having your de-identified sample being used for laboratory validation and educational purposes, please
initial here: _________ (patient) _________ (partner)
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Patient’s Initials
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Partner’s Initials
ALTERNATIVES TO PGS
The risks, benefits and limitations of PGS should be discussed with your fertility specialist and/or a genetic counselor. PGS is an optional test
that is offered to improve the likelihood of having a successful pregnancy and a healthy child. You are not obligated to undergo PGS, even if
your fertility specialist recommends it. If you do not wish to undergo PGS, but do wish to know the chromosomal status of your pregnancy,
diagnostic testing can be performed on a prenatal sample obtained by chorionic villus sampling or amniocentesis.
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Patient’s Initials
ASR-F-05092016
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Partner’s Initials
Patient: ___________________________________________________
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Patient Consent for Preimplantation Genetic Screening (PGS)
COST OF TESTING
Fees for PGS are in addition to any other costs associated with your IVF cycle. Testing cannot be initiated until CombiMatrix has received
your payment and your signed consent form. If you pay for PGS, but it is not performed (cancellation of testing prior to receipt of samples
by CombiMatrix or lack of suitable embryos for biopsy) your payment will be refunded in full.
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Patient’s Initials
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Partner’s Initials
AGREEMENT TO ARBITRATION
You acknowledge that any legal controversy, dispute or disagreement arising from the services provided by CombiMatrix shall be settled by
binding arbitration by the American Arbitration Association, under the applicable rules in effect at that time. Any award of the arbitrator
may be entered as judgment in any court of competent jurisdiction. Information may be obtained and claims may be filed in any California
office of the American Arbitration Association. Any such arbitration shall take place at the American Arbitration Association office closest to
CombiMatrix’s corporate headquarters at the time of filing. All disputes shall be decided under the laws of the State of California.
By signing below, I/we hereby:
• Agree to the arbitration agreement set forth above and give up the right to a jury trial as to all claims covered by such arbitration
agreement.
• Waive the right to have evidence admitted only if it is deemed admissible under the application rules of evidence.
• Waive the right to certain discovery procedures available under the California Code of Civil Procedure.
• Acknowledge that I/we have been advised to and have had the opportunity to consult with independent counsel concerning this
arbitration agreement.
• Acknowledge that my signature on this Patient Consent Form obligates me to participate in Arbitration should any dispute arise out of
this agreement.
Patient’s Name: ______________________________________________
DOB: ____________________
Patient’s Signature: ___________________________________________
Date: ____________________
Partner’s Name: ______________________________________________
DOB: ____________________
Partner’s Signature: ___________________________________________
Date: ____________________
WITNESSING HEALTH CARE PROVIDER
I certify that I have reviewed the risks, benefits and limitations associated with PGS with the patient and her partner, and that they have
been offered an opportunity to ask additional questions, which have been answered to their satisfaction.
Name: _____________________________________________________
Signature: ________________________________________
Institution/Clinic/Lab: _________________________________________________________________
ASR-F-05092016
Patient: ___________________________________________________
Date: _____________________
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