Clinical UM Guideline

Preimplantation embryo biopsy is performed to allow for genetic testing (PGT), which encompasses a variety of adjunctive techniques to assisted reproductive procedures, in which embryonic DNA is sampled and genetically analyzed, thus permitting deselection of embryos harboring a genetic defect prior to implantation of the embryo into the uterus. These procedures may be performed as part of assisted reproductive technology (ART).

Note: This document addresses preimplantation embryo biopsy only. This document does not address genetic testing, including for aneuploidies (PGT-A), monogenic disorders (PGT-M), or structural rearrangements (PGT-SR). For criteria related to genetic testing, please refer to the applicable guidelines used by the plan.

Note: The use of in vitro fertilization (IVF) services is subject to separate Benefit Determination, independent of this position statement. Not all benefit contracts or certificates include benefits for IVF services, including preimplantation embryo biopsy. Preimplantation embryo biopsy is only covered when IVF services are covered benefits. Benefit language supersedes this document.

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

Medically Necessary:

Preimplantation embryo biopsy is considered medically necessary when conducted for preimplantation genetic testing that meets the applicable guidelines used by the plan.

Not Medically Necessary:

Preimplantation embryo biopsy is considered not medically necessary when the criteria above have not been met.

This document describes clinical studies and expert recommendations, and explains when it is medically appropriate to remove cells from an early embryo created outside of the body (called in vitro fertilization or IVF) before it is placed in the uterus (called preimplantation embryo biopsy). The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Preimplantation embryo biopsy is a procedure used during IVF to remove a small number of cells from an embryo before it is implanted into the uterus. These cells are then used for genetic testing to help identify embryos that may carry harmful inherited health conditions or chromosomal abnormalities. This testing helps choose embryos that are most likely to result in a healthy pregnancy. The most common and preferred method involves taking cells from the outer layer of the embryo at the blastocyst stage (day 5-6 of development), which provides more DNA for testing and is less likely to harm the embryo. This procedure is typically done when genetic testing is needed and covered by the health plan. However, the procedure itself is only covered when IVF services are also included in the person's health benefits.

What the Studies Show

Research shows that removing cells from the outer layer of the embryo at the blastocyst stage is safer for embryo development than removing a single cell earlier at the cleavage stage (day 3). Studies found that blastocyst biopsy gives more genetic material for testing and is less likely to affect the future development of the embryo. Professional groups, including the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM), recommend the blastocyst method because it avoids removing cells that would become the fetus and has a smaller effect on overall embryo health. A newer approach, called noninvasive preimplantation genetic testing (niPGT), collects DNA that the embryo releases into its surrounding fluid. This method does not involve taking cells from the embryo, so it may reduce the chance of harming it. However, studies show this method is less accurate and may be affected by contamination from other sources, such as the mother’s DNA. More research is needed to understand how well this method works.

When is Preimplantation Embryo Biopsy Clinically Appropriate?

Preimplantation embryo biopsy may be appropriate when it is performed as part of genetic testing that meets the specific criteria used by the health plan.

When is this not Clinically Appropriate?

Preimplantation embryo biopsy is not appropriate when the genetic testing does not meet the health plan’s requirements. This type of test is not clinically appropriate in scenarios other than those listed above. Unnecessary or unproven tests may lead to complications or care that does not actually help.

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The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure codes listed above when criteria are not met.

Summary:

This document addresses preimplantation embryo biopsy, which is used to obtain embryonic cells for genetic analysis as part of assisted reproductive technology. The evidence reflects current clinical understanding that blastocyst-stage biopsy provides more DNA for testing and is less disruptive to embryo development compared with earlier cleavage-stage biopsy. Professional guidance from the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) indicates that trophectoderm biopsy is generally associated with better embryo viability than cleavage-stage biopsy and supports its preferential use. Additional emerging evidence regarding noninvasive or minimally invasive testing methods is noted, though current data highlight limitations in accuracy and potential contamination. Overall, the discussion outlines current biopsy techniques, their relative advantages, and the professional society recommendations that inform practice.

Embryo biopsy for PGT is conducted to evaluate DNA from embryos in order to significantly reduce the risk of inherited diseases and chromosomal abnormalities, for example, aneuploidy and structural rearrangements. PGT starts with IVF followed by embryo biopsy and preparation of DNA from the embryonic cells for testing. Subsequently, the healthiest embryos selected based on the results of genetic testing are transferred into the uterus to continue development.

The embryo biopsy procedure (Embryo Biopsy Kit [CooperSurgical Fertility Solutions, Ballerup, Denmark]) required for PGT involves two steps: the opening of the zona pellucida (the membrane covering the embryo) and retrieval of the cells for genetic testing. Biopsy can be performed at day 3 of cleavage-stage embryo development when the embryo is at the six- to the eight-cell stage, with either one or two cells (blastomeres) being removed for analysis (Vlajkovic, 2022). However, the most common method of embryo biopsy entails collecting cells at the blastocyst stage of development. The blastocyst stage is reached at 5-6 days following fertilization and usually contains more than 100 cells. During the biopsy, approximately 5-10 cells are removed from the trophectoderm layer, the outer portion of the blastocyst that gives rise to the placenta, without disrupting the inner cell mass that is destined to become the fetus (ACOG, 2020). Compared with other methods for obtaining DNA for PGT, including sampling polar bodies or a blastomere from a cleavage-stage embryo, blastocyst biopsy is the least disruptive to subsequent embryo development while providing the most DNA for testing (Scott, 2013). Addressing the potential for embryo damage caused by biopsy, the ASRM (2018) states that:

There are few data on embryo biopsy techniques used in PGT-A; however, it is generally accepted that trophectoderm biopsy has less impact on embryo viability than cleavage-stage biopsy. This is because even though more cells are removed during trophectoderm biopsy, it represents a smaller percentage of embryo mass and, by definition, trophectoderm biopsy removes only trophectoderm cells and not cells that have any fetal fate. Conversely, cleavage-stage biopsy occurs at a time when cell lineage has not yet been established and the cell removed could potentially impact viability of the embryo and the fate of the fetus.

Noninvasive and/or minimally invasive PGT (niPGT) is an emerging technique involving collection of cell-free DNA released from preimplantation embryos, including fluids in the blastocysts, spent culture medium, or both. This technique does not involve embryo biopsy and thus has the potential to reduce embryo damage. However, lower detection rates and DNA contamination from maternal cells may be associated with this technique. Prospective, large-scale studies are needed to determine the accuracy and detection value of niPGT (Huang, 2023).

Aneuploidy: A condition where there are either fewer or more than the normal number of chromosomes present in cells of a person’s body.

Embryo biopsy: A procedure conducted during an assisted reproduction process where, following the fertilization process, cells are removed from the developing embryo and used for genetic testing.

In vitro fertilization (IVF): A type of assisted reproductive procedure where an egg is fertilized outside a woman’s body and then implanted into the womb.

Oocyte: An egg before maturation.

Preimplantation genetic testing (PGT): A technique in which embryonic DNA is sampled via embryo biopsy and genetically analyzed to identify abnormal embryos and to select only genetically normal embryos for implantation.

Zona pellucida: A thick specialized membrane that surrounds mammalian oocytes.

Peer Reviewed Publications:

1. Huang B, Luo X, Wu R, et al. Evaluation of non-invasive gene detection in preimplantation embryos: a systematic review and meta-analysis. J Assist Reprod Genet. 2023; 40(6):1243-1253.
2. Scott RT, Jr., Upham KM, Forman EJ, et al. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril. 2013; 100(3):624-630.
3. Vlajkovic T, Grigore M, van Eekelen R, Puscasiu L. Day 5 versus day 3 embryo biopsy for preimplantation genetic testing for monogenic/single gene defects. Cochrane Database Syst Rev. 2022; 11(11):CD013233.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Obstetrics and Gynecology. Preimplantation genetic testing: ACOG committee opinion, Number 799. Obstet Gynecol. 2020; 135(3):e133-137.
2. National Institutes of Health (NIH). DEVICE: Embryo Biopsy Kit (60888937021815). Available at: https://accessgudid.nlm.nih.gov/devices/60888937021815.Accessed on December 3, 2025.
3. 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. Fertl Steril. 2018; 109:429-436.

1. Centers for Disease Control (CDC). Genetic Testing. Genomics and your health. Last updated May 15, 2024. Available at: https://www.cdc.gov/genomics-and-health/counseling-testing/genetic-testing.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fgenomics-and-health%2Fabout%2Fgenetic-testing.html. Accessed on December 3, 2025.

Federal and State law, as well as contract language including definitions and specific coverage provisions/exclusions, and Medical Policy take precedence over Clinical UM Guidelines and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Clinical UM Guidelines, which address medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Clinical UM Guidelines periodically. Clinical UM guidelines are used when the plan performs utilization review for the subject. Due to variances in utilization patterns, each plan may choose whether or not to adopt a particular Clinical UM Guideline. To determine if review is required for this Clinical UM Guideline, please contact the customer service number on the back of the member's card.