Comparative Genomic Hybridization (CGH)
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Coverage criteria and medical necessity guidance for use of comparative genomic hybridization (CGH)/chromosomal microarray analysis for prenatal and pediatric genetic evaluation, and certain dermatologic indications; applies to Aetna members and providers.
No material clinical or coverage changes in this revision.
Coverage Criteria
Prenatal and fetal indications
Covered when ANY of the following are met for prenatal and certain dermatologic indications:
Dermatologic (Spitzoid) indication
Covered when ANY of the following are met:
Molecular analysis (CGH or aCGH) is adjunctive to histopathologic assessment and immunostaining.
Children with congenital anomalies
Covered for diagnosing genetic abnormalities in children when ALL of the following are met:
See Appendix for specifics of major/minor malformations.
Developmental delay/intellectual disability or autism spectrum disorder
Covered for children with DD/ID or ASD when ALL of the following are met:
DSM-5 criteria referenced for DD/ID or ASD.
Supported clinical contexts
Contexts in which CMA/CGH is supported or specifically recommended by cited guidelines and studies
Does not detect balanced translocations or triploidy; counseling regarding variants of uncertain significance recommended.
Higher diagnostic yield than karyotype; requires genetics expertise for interpretation.
May be preferred when further cytogenetic analysis is desired for stillbirth >=20 weeks.
Spitzoid melanocytic neoplasms
Use of CGH for spitzoid melanocytic lesions:
Supported by multiple studies and UpToDate/NCCN guidance; Ki‑67 >30% favors melanoma but overlap exists.
Primary ovarian insufficiency (POI)
Use of array-CGH in primary ovarian insufficiency:
Study identified ovary-related CNVs in 32 of 67 patients; array‑CGH plus NGS may increase diagnostic yield.
Neurodevelopmental disorders / developmental delay
Chromosomal microarray testing for neurodevelopmental disorders:
Testing should follow validated laboratory standards; results require genetics expertise for interpretation.
Aetna considers comparative genomic hybridization (CGH) not medically necessary when a diagnosis of a disorder or syndrome is readily apparent from clinical evaluation alone. This policy also limits medically necessary CGH testing in the pediatric congenital anomaly and neurodevelopmental indications to cases that meet the specific criteria (e.g., non‑specific presentation, specialist evaluation, and potential for test results to impact management); evaluations that do not meet those criteria are considered not medically necessary. Only one CGH is considered medically necessary per lifetime when criteria are met.
Array genomic hybridization is not recommended for routine prenatal diagnosis in pregnancies at low risk for structural chromosomal abnormalities (for example: advanced maternal age alone, positive maternal serum screen, previous trisomy, or isolated soft ultrasound markers). When fetal structural anomalies are present, microarray may be appropriate and can be performed in lieu of karyotype if rapid aneuploidy screening is negative and an acceptable turnaround time for results is assured.
Several UpToDate topic reviews referenced in the policy do not list CGH as a management option for certain conditions. Specifically, UpToDate summaries for spontaneous primary ovarian insufficiency, short stature, and craniosynostosis do not mention comparative genomic hybridization as part of routine management, indicating limited support for CGH in these contexts.
Testing of products of conception for pregnancy losses is guided by gestational age and clinical context. Aetna considers chromosomal microarray analysis appropriate for evaluation of fetal tissue in intrauterine fetal death or stillbirth at ≥20 weeks gestation; however, testing products of conception in pregnancy losses at <20 weeks in structurally normal embryos/fetuses (including first‑trimester and recurrent losses) is considered experimental and investigational and therefore not covered.
Array genomic hybridization is not recommended for routine use in pregnancies at low risk for structural chromosomal abnormalities (eg, advanced maternal age alone, positive maternal serum screen, previous trisomy, or isolated soft ultrasound markers). Professional guidance recommends pre‑test consultation with a medical geneticist for pregnant women who qualify for microarray testing to discuss benefits, limitations, and possible outcomes.
UpToDate reviews for several topics (including atypical/dysplastic nevi in the context of melanoma history, primary ovarian insufficiency, short stature, and craniosynostosis) do not include comparative genomic hybridization as a management option, reinforcing that CGH is not routinely recommended for these indications in current clinical summaries.
Specified Covered Indications
Summary of covered indications
Only one CGH is considered medically necessary per lifetime; specialist evaluation and, in prenatal cases, genetic consultation are recommended as noted in policy.
Evaluation of fetuses with structural anomalies
Does not detect balanced translocations or triploidy; counseling about VOUS recommended.
Postnatal first-tier testing for intellectual disability/ASD/multiple congenital anomalies
Higher diagnostic yield than karyotype; interpretation requires genetics expertise.
Evaluation of intrauterine fetal death or stillbirth
ACOG Committee Opinion and NICHD stillbirth research support CMA utility in stillbirth evaluation.
Adjunct diagnostic aid for histologically equivocal spitzoid melanocytic neoplasms
Absence of chromosomal aberrations or isolated 11p amplification favors benign lesion; multiple melanoma‑typical alterations (eg, deletions in 9p, 10q; gains in Chr7) suggest malignancy.
Histologically equivocal spitzoid melanocytic neoplasms
Ki‑67 labeling index >30% favors melanoma but overlap exists; molecular testing is adjunctive.
Genetic evaluation of autism spectrum disorder, developmental delay, and intellectual disability
Reported FSDX yields: pathogenic 9.5%, VOUS 20.2%, overall 29.7%.
Evaluation of primary ovarian insufficiency to identify ovary-related CNVs
Study identified 32 patients with ovary‑related CNVs among 67 cases; combined approaches recommended.
Genetic evaluation in specified clinical contexts
Testing and interpretation should follow established laboratory standards and clinical genetics evaluation.
Coding and Billing
| 81228 | Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (eg, bacterial artificial chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis). |
| 81229 | Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities. |
| 81277 | Cytogenomic neoplasia (genome-wide) microarray analysis, interrogation of genomic regions for copy number and loss-of-heterozygosity variants for chromosomal abnormalities. |
| 81349 | Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number and loss-of-heterozygosity variants, low-pass sequencing analysis. |
| 0156U | Copy number (eg, intellectual disability, dysmorphology), sequence analysis. |
| S3870 | Comparative genomic hybridization (CGD) microarray testing for developmental delay, autism spectrum disorder and/or intellectual disability. |
| D22.0 - D22.9 | Melanocytic nevi [Spitzoid melanocytic neoplasms]. |
| F01 - F99 | Mental, behavioral and neurodevelopmental disorders. |
| O35.0xx0 | Maternal care for (suspected) central nervous system malformation in fetus. |
| P95 | Stillbirth. |
| Q00.0 - Q99.9 | Congenital malformations, deformations and chromosomal abnormalities. |
| Z36.0 - Z36.9 | Encounter for antenatal screening of mother. |
| Z37.1 | Single stillbirth. |
| C43.0 - C43.9 | Malignant melanoma of skin (listed as not covered indication). |
| D89.82 | Autoimmune lymphoproliferative syndrome [ALPS] (listed as not covered indication). |
| E28.310 - E28.39 | Primary ovarian failure [evaluation of primary ovarian insufficiency] (listed as not covered indication). |
| G40.001 - G40.919 | Epilepsy and recurrent seizures (listed as not covered indication). |
| N96 | Recurrent pregnancy loss (listed as not covered indication). |
| Q75.0 | Craniosynostosis (listed as not covered indication). |
| not specified | No specific CPT/HCPCS/ICD codes are provided in this segment of the document. |
Provider Actions and Administrative Guidance
Code coverage contingent on criteria
CPT/HCPCS codes for CGH are covered only when the clinical selection criteria in this policy are met; prior authorization may be required per payer processes. Documentation should show how the clinical indications meet policy criteria (e.g., prenatal structural abnormalities, DD/ID/ASD criteria, histologically equivocal spitzoid lesions).
Prenatal testing: use with structural anomalies
In prenatal cases with fetal structural abnormalities detected on ultrasound or fetal MRI, chromosomal microarray (array CGH) may be used in lieu of karyotype if rapid aneuploidy screening is negative and an appropriate turnaround time is assured. This use should be accompanied by specialist consultation and informed discussion of benefits and limitations.
- Array CGH is not recommended in pregnancies at low risk for structural chromosomal abnormality.
- Pre-test genetic consultation by a medical geneticist is recommended for pregnant women who qualify for microarray testing.
Prior authorization guidance
Prior authorization guidance is not explicitly listed in the excerpt for specific CPT/HCPCS codes; however, prior authorization may be required per payer processes and is recommended when clinical documentation or histopathology is equivocal (for example, spitzoid lesions) or when policy-specified indications are used.
- If your plan requires prior authorization, submit clinical notes, specialist evaluation, and evidence that policy criteria are met.
- When histopathology is equivocal for spitzoid lesions, include dermatopathology reports and documentation of multi-disciplinary review.
Prior authorization not specified in excerpt
The document excerpt does not state specific prior authorization requirements for CGH in this section; check payer-specific procedures and prior authorization tools for any required submission steps before testing.
- Absence of explicit PA language in the excerpt does not preclude payer-level PA requirements.
- Contact the payer or use the payer portal to confirm prior authorization rules and required documentation.
Experimental / Investigational exclusions
Aetna considers CGH experimental and investigational (and therefore not covered) for certain indications due to insufficient evidence (e.g., detection of balanced rearrangements, diagnosis of melanoma, evaluation of primary ovarian insufficiency, testing products of conception in structurally normal embryos/fetuses <20 weeks, and other listed indications).
- Do not submit claims for CGH for indications listed as experimental/investigational; include alternative diagnostic rationale if disputing coverage.
- Refer to the policy's Experimental and Investigational section for the not-covered list before ordering.
Use of array genomic hybridization is not recommended in low-risk pregnancies
Array genomic hybridization is not recommended in pregnancies at low risk for structural chromosomal abnormality and is intended primarily for cases with structural anomalies or other policy-specified indications.
- Low-risk indications (advanced maternal age alone, positive serum screen, soft markers) do not by themselves justify array CGH per guidance.
- Ensure the indication aligns with policy criteria to avoid denials.
Policy bulletins are intended to assist administration of plan benefits
Clinical Policy Bulletins are intended to assist in administering plan benefits and provide only a partial description of plan or program benefits. They do not guarantee coverage and do not substitute for plan benefit documents or medical advice.
- Plan benefit terms and member-specific coverage determinations prevail over the bulletin.
- Providers remain responsible for medical advice and should confirm coverage with the payer.
Pre-test genetic consultation recommended
Pregnant women who qualify for microarray genomic hybridization testing should have pre-test consultation with a medical geneticist so that benefits, limitations, and interpretation challenges (including variants of uncertain significance) are discussed to support informed decision-making.
- Document that pre-test counseling occurred and that the patient was informed of possible outcomes and limitations.
- Include the consulting geneticist's evaluation in the authorization/claims submission when required.
Products of conception evaluation
For evaluation of fetal tissue (products of conception, placenta, or other fetal tissue) in intrauterine fetal death or stillbirth (≥ 20 weeks gestation), chromosomal microarray analysis is recommended because it increases the likelihood of obtaining informative results compared with conventional cytogenetics.
- Testing of products of conception in pregnancy losses < 20 weeks in structurally normal embryos/fetuses is listed as experimental/investigational and not covered.
- When ordering for ≥ 20 weeks stillbirth or intrauterine fetal death, include gestational age and clinical context in documentation.
Specialist evaluation and documentation required
Ordering of CGH should be informed by evaluation from an appropriate specialist (Board‑Certified or Board‑Eligible Medical Geneticist, Developmental/Behavioral Pediatrician, Pediatric or Adult Neurologist, or other relevant specialist) when required by the policy, and documentation of that evaluation should be included with any authorization request.
- Specialist evaluation is required for pediatric congenital anomalies and for DD/ID or ASD indications per the policy criteria.
- The excerpt does not explicitly restrict ordering to specialty providers only, but specialist documentation is an explicit policy requirement.
Not Covered / Experimental Indications
Comparative genomic hybridization (CGH) is considered experimental, investigational, and not covered for a number of indications due to insufficient evidence of clinical effectiveness. Examples listed include detection of balanced rearrangements, diagnosis of melanoma, evaluation of autoimmune lymphoproliferative syndrome, atypical nevi in individuals with a history of melanoma, craniosynostosis, primary ovarian insufficiency, short stature, unexplained epilepsies, and testing products of conception for pregnancy losses at less than 20 weeks in structurally normal embryos/fetuses.
Routine use of CGH for low‑risk prenatal diagnosis is not recommended because of limitations in detecting balanced rearrangements, the potential to identify variants of uncertain significance, and higher costs compared with conventional cytogenetics. CGH does not replace classic karyotype for routine prenatal diagnosis; when used in prenatal cases it is most appropriate for pregnancies with identified fetal structural anomalies or when invasive diagnostic testing is being performed for other indications.
CGH is not described as a management option in several UpToDate reviews (for atypical nevi, primary ovarian insufficiency, short stature, and craniosynostosis), indicating limited or insufficient support in those clinical areas and contributing to the policy designation of CGH as investigational for those indications.
Eligibility Requirements
Eligibility for CGH testing depends on meeting the policy's covered‑indication criteria. The policy provides top‑level guidance on medically necessary indications (prenatal structural anomalies, invasive prenatal diagnostic testing, stillbirth ≥20 weeks, histologically equivocal spitzoid lesions, and certain pediatric congenital anomalies and neurodevelopmental disorders) and on investigational/not covered uses; details and specific documentation requirements are described in the coverage criteria and related sections.
The policy excerpt does not specify detailed family history thresholds. It emphasizes that interpretation of CGH results requires genetics expertise and recommends pre‑test consultation or counseling by a medical geneticist in prenatal cases. Clinical and family history should guide any indicated targeted testing (for example, FMR1) prior to array testing when appropriate.
No additional top‑level eligibility nodes are specified in the provided excerpt beyond the medical necessity criteria already outlined; eligibility decisions should follow the policy criteria and supporting documentation requirements.
No additional top‑level eligibility nodes are specified in the provided excerpt beyond the medical necessity criteria already outlined; see coverage criteria for specific clinical scenarios and documentation requirements.
In prenatal settings, chromosomal microarray may be performed instead of karyotype when fetal structural anomalies are identified and rapid aneuploidy screening is negative, provided that an appropriate turnaround time for results is assured. The policy and cited guidance note that not all prenatal cases require microarray and that counseling about possible variants of uncertain significance is important prior to testing.
No additional top‑level eligibility nodes are specified in the provided excerpt beyond the medical necessity criteria already outlined; eligibility decisions should follow the policy criteria and supporting documentation requirements.
Background and Definitions
Background: Comparative genomic hybridization (CGH), also referenced as chromosomal microarray analysis (CMA or aCGH), is a genome‑wide method to detect copy number variants (microdeletions and microduplications) across the genome with greater resolution than conventional karyotype. CGH is used in prenatal and postnatal settings to increase detection of clinically significant chromosomal imbalances, though it does not reliably detect balanced rearrangements and may identify variants of uncertain clinical significance that require genetics expertise for interpretation.
Revision History
Policy effective date established.
Policy was last reviewed.
Scheduled next policy review date.
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