Preimplantation Genetic Diagnosis (PGD) With PREIMPLANTATION GENETIC SCREENING (PGS) FOR ANEUPLOIDY
PGD is highly specialized testing designed for couples who have an increased risk of having a child with a specific genetic disorder or chromosomal abnormality based on their own genetic status. CombiPGD is available for:
Single Gene Disorders
Individuals who are identified as carriers of a recessive disorder or who are at risk for/have a dominant genetic disorder are at increased risk of having an affected child. Using DNA samples from your patient, her partner, and a reference family member, PGD determines the unique chromosomal background of the disease-causing mutation(s), and utilizes this information to determine the disease status of an embryo.
Individuals with a balanced chromosomal translocation typically do not experience any symptoms associated with their chromosomal alteration, however, their gametes have a significantly increased chance of carrying a chromosomal imbalance. PGD determines whether or not a chromosomal imbalance is present in an embryo.
PGS for Aneuploidy Screening
As part of the PGD process (for both single gene disorders and chromosome translocations), embryos are also screened for chromosomal abnormalities. Chromosomal abnormalities are one of the most common reasons for implantation failure and first trimester miscarriages. Approximately 50-60% of miscarriages under 12 weeks have a major fetal chromosomal abnormality. Because chromosomally abnormal embryos may not differ in overall microscopic appearance from chromosomally normal embryos, it is difficult to identify the optimal embryo(s) for transfer. By implanting a chromosomally normal embryo, the possibility of a successful implantation and pregnancy is significantly enhanced.
How Is PGD With Aneuploidy Screening Performed?
CombiMatrix utilizes a technique called Karyomapping, which investigates hundreds of thousands of points along all 23 pairs of chromosomes. For single gene disorders, Karyomapping utilizes information from the parents and a reference family member to identify the exact chromosomal background of the mutation(s), and uses this information to determine whether or not an embryo has inherited the mutation(s). For chromosomal translocations, Karyomapping is able to identify how many copies of the chromosomes involved in the translocation are present, which determines whether or not the embryo has a chromosomally unbalanced form of the balanced parental translocation. Karyomapping is also used to simultaneously determine how many copies of any given region of a chromosome are present. Although the focus is on whole chromosome aneuploidy, which is the most common cause of failed implantation and/or early miscarriage, gains and losses of chromosomal segments larger than 30 Mb in size (segmental aneuploidy) may also be detected, and are anticipated to be associated with a similar risk.
Genetic Counseling Services
Genetic counseling is an integral part of the PGD process. Our board-certified genetic counselors will work closely with your patient to prepare and guide them through the process.
Timeline for PGD With PGS for Aneuploidy
Because each patient’s situation is unique, there is a necessary preparatory period prior to initiating PGD. Karyomapping allows us to significantly reduce that time compared to other techniques of PGD. Below is an outline of the PGD referral and testing process:
- Initial Referral Complete and submit the PGD Patient Referral Form, enclosing all relevant patient genetic testing results (i.e. mutation analysis for single gene disorders or karyotype reports for chromosome translocations). Please note that if a specific mutation has not yet been identified in the family, PGD cannot be performed.
- Initial Genetic Counseling Within 72 hours, a CombiMatrix genetic counselor will contact your patient to schedule an initial telephone consultation with the patient and her partner. The purpose of this initial consultation is to review the test results, obtain a detailed family and medical history, and for single gene disorders, identify any suitable family members who could serve as a test reference. Although appointments are typically available for the same or the following day, please note that the timing of this consultation is up to the discretion of the patient, which will affect the overall time required to complete the PGD pre-test process.
- Medical Team Review The CombiMatrix Medical Team will review the case and evaluate your patient’s case to determine whether there are sufficient markers within and surrounding the gene (single gene disorders) or chromosomal region (chromosomal translocations) of interest. The vast majority of cases will be suitable for PGD by Karyomapping, however, it is possible that a case may not be accepted due to decreased coverage of the region of concern or, for single gene disorders, a lack of a suitable reference. Both you and your patient will then be immediately informed of the Medical Team’s decision.
- Second Genetic Counseling Consultation Once a case has been approved, the patient will be asked to schedule a second genetic counseling telephone consultation to review the design of the testing for their specific situation, discuss the requested reference family member (for single gene disorders only), and review the risks and benefits of PGD With PGS for Aneuploidy. Following this consultation, the patient and her partner will sign a consent form, pay a deposit of $500 (which is applied to the cost of the testing) and receive DNA collection kits. You and your patient will receive a personalized summary letter from the genetic counselor following the consultation. Again, while appointments are typically available for the same or the following day, please note that the timing of this consultation is up to the discretion of the patient, which will affect the overall time required to complete the PGD pre-test process.
- PGD Test Set Up For single gene disorder cases, the patient, partner and reference family member’s DNA will be analyzed together to optimize the testing. If the reference sample provided is not suitable, a sample from another family member(s) may be requested. If there are any concerns regarding the unique PGD test setup for the family, our medical team will inform both you and your patient. Since chromosome translocation cases do not require a reference family member, there is no additional test set-up step required for these cases. Patients may begin their cycle at this point.
- Embryo Testing and Post-Test Genetic Counseling Once we receive the embryo biopsies in our laboratory, testing will be initiated, with results typically available in 12-14 calendar days. After you have discussed the results with your patient, a CombiMatrix genetic counselor will follow-up with your patient to answer any additional questions.
Provider PGD Test Process
PGD Patient Referral Form
PGD & PGS Rinse and Loading Instructions
PGD & PGS Shipping Instructions
Embryo Biopsy Worksheet