Sunflower Health Plan Concert Genetic Testing: Preimplantation Genetic Testing (PDF) Form

Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 CONCERT GENETIC TESTING: PREIMPLANTATION GENETIC TESTING See Important Reminder at the end of this policy for important regulatory and legal information. OVERVIEW Preimplantation genetic testing involves analysis of biopsied cells from an embryo as a part of an assisted reproductive procedure. Preimplantation genetic testing for monogenic disorders (PGT- M) and preimplantation genetic testing for structural rearrangements (PGT-SR) are used to detect a specific inherited disorder in conjunction with in vitro fertilization (IVF) and aims to prevent the birth of affected children to couples at an increased risk of transmitting either a gene mutation(s) or an unbalanced structural chromosomal rearrangement that can be typically targeted in this context. Preimplantation genetic testing for aneuploidy (PGT-A) is used to screen for potential chromosomal or subchromosomal abnormalities (e.g., chromosomal aneuploidy) in conjunction with IVF for couples; in this case testing is untargeted. POLICY REFERENCE TABLE Below is a list of higher volume tests and the associated laboratories for each coverage criteria section. This list is not all inclusive. Coding Implications This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2022, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. 1 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. Coverage Criteria Coverage Criteria Sections Sections Preimplantation Preimplantation Genetic Testing for Genetic Testing for Aneuploidy (PGT- Aneuploidy (PGT- A) A) Preimplantation Preimplantation Genetic Testing for Genetic Testing for Monogenic Monogenic Disorders (PGT-M) Disorders (PGT-M) Preimplantation Preimplantation Genetic Testing for Genetic Testing for Structural Structural Rearrangements Rearrangements (PGT-SR) (PGT-SR) Example Tests (Labs) Example Tests (Labs) Spectrum PGT-A (Natera) Spectrum PGT-A (Natera) SMART PGT-A (Preimplantation SMART PGT-A (Preimplantation Genetic Testing - Aneuploidy) Genetic Testing - Aneuploidy) (Igenomix) (Igenomix) Spectrum PGT-M (Natera) Spectrum PGT-M (Natera) PGT-M (Cooper Genomics) PGT-M (Cooper Genomics) Common CPT Common CPT Codes Codes Common ICD Common ICD Codes Codes Ref Ref 81229, 89290, 81229, 89290, 89291, 81479 89291, 81479 N97.0, N97.9, N97.0, N97.9, Z31 Z31 2, 3, 4 2, 3, 4 0254U 0254U 89290, 89291, 89290, 89291, 81479 81479 N97.0, N97.9, N97.0, N97.9, Z14.8, Z31 Z14.8, Z31 1, 2 1, 2 Preimplantation Genetic Testing for Preimplantation Genetic Testing for Structural Chromosomal Structural Chromosomal Rearrangements/Translocations (Invitae) Rearrangements/Translocations (Invitae) 89290, 89291, 89290, 89291, 81479, 81228, 81479, 81228, 81229 81229 N97.0, N97.9, N97.0, N97.9, Z14.8, Z31 Z14.8, Z31 2 2 Spectrum PGT-SR (Natera) Spectrum PGT-SR (Natera) OTHER RELATED POLICIES This policy document provides coverage criteria for preimplantation genetic testing. Please refer to: ● ● ● ● Genetic Testing: Prenatal and Preconception Carrier Screening for coverage criteria related to carrier screening. Genetic Testing: Prenatal Diagnosis (via amniocentesis, CVS, or PUBS) and Pregnancy Loss for coverage related to diagnostic genetic testing during pregnancy or for a pregnancy loss. Genetic Testing: Noninvasive Prenatal Screening (NIPS) for coverage criteria related to prenatal cell-free DNA screening tests. Genetic Testing: Multisystem Inherited Disorders, Intellectual Disability, and Developmental Delay for coverage criteria related to diagnostic genetic testing in the postnatal period. 2 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 ● Genetic Testing: General Approach to Genetic Testing for coverage criteria related to preimplantation genetic testing that is not specifically discussed in this or another non- general policy. CRITERIA It is the policy of health plans affiliated with Centene Corporation® that the specific genetic testing noted below is medically necessary when meeting the related criteria: PREIMPLANTATION GENETIC TESTING FOR ANEUPLOIDY (PGT-A) I. Preimplantation genetic testing for aneuploidy (PGT-A) (81229, 81479, 89290, 89291, 0254U) is considered investigational. back to top PREIMPLANTATION GENETIC TESTING FOR MONOGENIC DISORDERS (PGT-M) I. Preimplantation genetic testing for monogenic disorders (PGT-M) (89290, 89291, 81479) may be considered medically necessary when: A. The embryo is at an elevated risk of a genetic disorder due to one of the following: 1. Both biological parents are known carriers for the same autosomal recessive disorder, OR 2. One biological parent is a known carrier of an autosomal dominant disorder, OR 3. One biological parent is a known carrier of an X-linked recessive disorder. II. Preimplantation genetic testing for monogenic disorders (PGT-M) (89290, 89291, 81479, 81403) is considered investigational for all other indications. back to top 3 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 PREIMPLANTATION GENETIC TESTING FOR STRUCTURAL REARRANGEMENTS (PGT-SR) I. Preimplantation genetic testing for structural rearrangements (PGT-SR) (81228, 81229, 89290, 89291, 81479) may be considered medically necessary when: A. The embryo is at an elevated risk of a genetic disorder because one biological parent has a chromosomal rearrangement. II. Preimplantation genetic testing for structural rearrangements (PGT-SR) (81228, 81229, 89290, 89291, 81479) is considered investigational for all other indications. back to top NOTES AND DEFINITIONS 1. Close relatives include first, second, and third degree blood relatives on the same side of the family: a. First-degree relatives are parents, siblings, and children b. Second-degree relatives are grandparents, aunts, uncles, nieces, nephews, grandchildren, and half siblings c. Third-degree relatives are great grandparents, great aunts, great uncles, great grandchildren, and first cousins 2. Preimplantation genetic testing for monogenic disorders (PGT-M) and Preimplantation genetic testing for structural rearrangements (PGT-SR) are used to detect a specific single-gene inherited disorder or chromosome rearrangement in conjunction with in vitro fertilization (IVF). 3. Preimplantation genetic testing for aneuploidy (PGT-A) is used to screen for chromosomal aneuploidy in conjunction with IVF for couples. back to top 4 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 CLINICAL CONSIDERATIONS Genetic counseling is highly encouraged for patients considering and undergoing in vitro fertilization. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods, such as a genetic counselor, medical geneticist, or advanced practice practitioner specializing in genetics. All patients who undergo PGT-M or PGT-SR should be offered diagnostic testing via chorionic villus sampling (CVS) or amniocentesis for confirmation of results. All patients who undergo PGT-A should be offered traditional diagnostic testing or screening for aneuploidy in accordance with recommendations for all pregnant patients. back to top BACKGROUND AND RATIONALE Preimplantation Genetic Testing for Aneuploidy (PGT-A) American Society of Reproductive Medicine The American Society for Reproductive Medicine issued an opinion on the use of preimplantation genetic testing (PGS) for aneuploidy (2018) which concluded, "Large, prospective, well-controlled studies evaluating the combination of multiple approaches (genomics, time-lapse imaging, transcriptomics, proteomics, metabolomics, etc.) for enhanced embryo selection applicable in a more inclusive IVF population are needed to determine not only the effectiveness, but also the safety and potential risks of these technologies. PGT-A will likely be part of a future multidimensional approach to embryo screening and selection. At present, however, there is insufficient evidence to recommend the routine use of blastocyst biopsy with aneuploidy testing in all infertile patients." (p. 34) This position was reaffirmed in a 2020 committee opinion regarding clinical management of mosaic results from preimplantation genetic testing for aneuploidy of blastocysts, stating, “It should be recognized that this document does not endorse nor does it suggest that PGT-A is appropriate for all cases of IVF.” (p. 253) American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists issued Committee Opinion No. 799 (2020) regarding Preimplantation Genetic Testing. The recommendations include the following: 5 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 "The clinical utility of preimplantation genetic testing-monogenic and preimplantation genetic testing-structural rearrangements is firmly established; however, the best use of preimplantation genetic testing-aneuploidy remains to be determined.” (p. e133) Preimplantation Genetic Testing for Monogenic Disorders (PGT-M) American Society for Reproductive Medicine The American Society for Reproductive Medicine published an opinion on the use of preimplantation genetic diagnosis (PGD) for serious adult-onset conditions (2013). The statement includes the following: ● "Preimplantation genetic diagnosis (PGD) for adult-onset conditions is ethically justifiable when the conditions are serious and when there are no known interventions for the conditions or the available interventions are either inadequately effective or significantly burdensome.” ● “For conditions that are less serious or of lower penetrance, PGD for adult[-]onset conditions is ethically acceptable as a matter of reproductive liberty. It should be discouraged, however, if the risks of PGD are found to be more than merely speculative." The opinion also stated that physicians and patients should be aware that much remains unknown about the long-term effects of embryo biopsy on the developing fetus and that experienced genetic counselors should be involved in the decision process. (p. 54) American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists issued Committee Opinion No. 799 (2020) regarding Preimplantation Genetic Testing. The recommendations include the following: "Preimplantation genetic testing comprises a group of genetic assays used to evaluate embryos before transfer to the uterus. Preimplantation genetic testing-monogenic (known as PGT-M) is targeted to single gene disorders. Preimplantation genetic testing-monogenic uses only a few cells from the early embryo, usually at the blastocyst stage, and misdiagnosis is possible but rare with modern techniques. Confirmation of preimplantation genetic testing-monogenic results with chorionic villus sampling (CVS) or amniocentesis should be offered." (p. 133). Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) American College of Obstetricians and Gynecologists (ACOG) 6 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 The American College of Obstetricians and Gynecologists issued Committee Opinion No. 799 (2020) regarding Preimplantation Genetic Testing. The recommendations include the following: "To detect structural chromosomal abnormalities such as translocations, preimplantation genetic testing-structural rearrangements (known as PGT-SR) is used. Confirmation of preimplantation genetic testing-structural rearrangements results with CVS or amniocentesis should be offered." (p. 133) Reviews, Revisions, and Approvals Policy developed REFERENCES back to top Revision Date 03/23 Approval Date 03/23 1. Ethics Committee of American Society for Reproductive Medicine. Use of preimplantation genetic diagnosis for serious adult onset conditions: a committee opinion. Fertil Steril. 2013;100(1):54-57. doi:10.1016/j.fertnstert.2013.02.043 2. Preimplantation Genetic Testing: ACOG Committee Opinion, Number 799. Obstet Gynecol. 2020;135(3):e133-e137. doi:10.1097/AOG.0000000000003714 3. Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Electronic address: ASRM@asrm.org; Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee opinion. Fertil Steril. 2018;109(3):429-436. doi:10.1016/j.fertnstert.2018.01.002 4. Practice Committee and Genetic Counseling Professional Group (GCPG) of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Clinical management of mosaic results from preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion. Fertil Steril. 2020;114(2):246- 254. doi:10.1016/j.fertnstert.2020.05.014 back to top Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional 7 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members/enrollees. This clinical policy is not intended to recommend treatment for members/enrollees. Members/enrollees should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members/enrollees and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members/enrollees and their representatives agree to be bound by such terms and conditions by providing services to members/enrollees and/or submitting claims for payment for such services. 8 Concert Genetic Testing: Preimplantation Genetic Testing V2.2023 Date of Last Revision: 3/1/2023 Note: For Medicaid members/enrollees, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy. Note: For Medicare members/enrollees, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs, LCDs, and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. 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