BlueCross and BlueShield of Montana Medical Policy/Codes
Preimplantation Genetic Testing (PGT)
Chapter: Maternity/Gyn/Reproduction
Current Effective Date: December 27, 2013
Original Effective Date: December 27, 2013
Publish Date: September 27, 2013

Preimplantation genetic testing (PGT) involves analysis of biopsied cells as part of an assisted reproductive procedure.  It is generally considered to be divided into two categories: 

  • Preimplantation genetic diagnosis (PGD) is used to detect a specific inherited disorder and aims to prevent the birth of affected children in couples at high risk of transmitting a disorder. 
  • Preimplantation genetic screening (PGS) uses similar techniques to screen for potential genetic abnormalities in conjunction with IVF for couples without a specific known inherited disorder.

PGT describes a variety of adjuncts to an assisted reproductive procedure, in which either maternal or embryonic DNA (deoxyribonucleic acid) is sampled and genetically analyzed, thus permitting deselection of embryos harboring a genetic defect prior to implantation of the embryo into the uterus.  The ability to identify preimplantation embryos with genetic defects before the initiation of pregnancy provides an attractive alternative to standard techniques, such as amniocentesis or chorionic villus sampling (CVS), with selective pregnancy termination of affected fetuses.  (Prenatal confirmation of normality can be performed using these standard techniques: CVS, amniocentesis, ultrasound, or fetal blood analysis.)  Preimplantation genetic testing is generally categorized as either PGD or PGS.  PGD is used to detect genetic evidence of a specific inherited disorder, in the oocyte or embryo, derived from mother or couple, respectively that has a high risk of transmission.  PGS is not used to detect a specific abnormality but instead uses similar techniques to identify genetic abnormalities that identify embryos at risk.  This terminology, however, is not used consistently, e.g., some authors use the term PGD when testing for a number of possible abnormalities in the absence of a known disorder.

Embryos are obtained by assisted reproductive technology in several ways: either by combining an egg and sperm in the laboratory (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICIS]), or transvaginal ultrasound guided oocyte (embryo) retrieval.  Once the embryo(s) is located, two different sources of genetic material may be sampled in PGT; either the first or second polar body of the oocyte may be sampled or the preimplantation embryo may be biopsied.  The first and second polar bodies are extruded from the oocyte as it completes meiotic division after ovulation (first polar body) and fertilization (second polar body).  This strategy thus focuses on maternal chromosomal abnormalities.  If the mother is a known carrier of a genetic defect and genetic analysis of the polar body is normal, then it is assumed that the genetic defect was transferred to the oocyte during meiosis.  Alternatively, single cells from the preimplantation embryo can also be sampled.  As PGT can be performed on cells from different developmental stages, the biopsy procedures will vary accordingly. 

Typically, preimplantation embryos undergo biopsy after the first few cleavage divisions when it is composed of eight cells, although some researchers have performed biopsies of blastocysts containing 120 cells.  At both of these stages, the cells are totipotent, and there is no damage to the resulting embryo.  Biopsy of preimplantation embryos or blastocysts can detect genetic abnormalities arising from the maternal or paternal genetic material.  Sampling of approximately five cells from blastocysts may reduce the likelihood of misdiagnosis of chromosomal abnormalities due to mosaicism within the embryo.  Mosaicism refers to genetic differences among the cells of the embryo that could result in an incorrect interpretation if the chromosomes of only a single cell are examined.  It is not yet known with certainty whether mosaicism is present at all stages of embryonic development or whether it disappears around the time of blastocyst formation.

The biopsied material can be analyzed in a variety of ways.  Polymerase chain reaction (PCR) or other amplification techniques can be used to amplify the harvested DNA with subsequent analysis for single genetic defects.  This technique is most commonly used when the embryo is at risk for a specific genetic disorder – PGD, such as Tay Sachs disease or cystic fibrosis.  Fluorescent in situ hybridization (FISH) is a technique that allows direct visualization of specific (but not all) chromosomes to determine the number or absence of chromosomes.  This technique is most commonly used to screen – PGS, such as aneuploidy, gender determination or to identify chromosomal translocations.  FISH cannot be used to diagnose single genetic defect disorders.  However, molecular techniques can be applied with FISH, such as microdeletions and duplications and thus, single-gene defects can be recognized with this technique.

Another approach that is becoming more common is array comparative genome hybridization (CGH) testing at either the eight -cell or more often, the blastocyst stage.  Unlike FISH analysis, this allows for 24 chromosome aneuploidy screening, as well as more detailed screening for unbalanced translocations and inversions and other types of abnormal gains and losses of chromosomal material.

Three general categories of embryos have undergone PGT:

1. Embryos at risk for a specific inherited single genetic defect:  Inherited single-gene defects fall into three general categories: autosomal recessive, autosomal dominant, and X-linked.  When either the mother or father is a known carrier of a genetic defect, embryos can undergo PGD to deselect embryos harboring the defective gene.  Gender selection of a female embryo is another strategy when the mother is a known carrier of an X-linked disorder for which there is not yet a specific molecular diagnosis.  The most common example is female carriers of fragile X syndrome.  In this scenario, PGD is used to deselect male embryos, half of which would be affected.  PGD could also be used to deselect affected male embryos.  While there is a growing list of single genetic defects for which molecular diagnosis is possible, the most common indications include cystic fibrosis (CF), beta thalassemia, muscular dystrophy (MD), Huntington's disease, hemophilia, and fragile X disease.  It should be noted that when PGD is used to deselect affected embryos, the treated couple is not technically infertile but are undergoing an assisted reproductive procedure for the sole purpose of PGD.  In this setting, PGD may be considered an alternative to selective termination of an established pregnancy after diagnosis by amniocentesis or CVS.

2. Embryos at a higher risk of translocations:  Balanced translocations occur in 0.2% of the neonatal population but at a higher rate in infertile couples or in those with recurrent spontaneous abortions.  PGD can be used to deselect those embryos carrying the translocations, thus leading to an increase in fecundity or a decrease in the rate of spontaneous abortion.

3. Identification of aneuploid embryos:  Implantation failure of fertilized embryos is a common cause for failure of assisted reproductive procedures; aneuploidy of embryos is thought to contribute to implantation failure and may also be the cause of recurrent spontaneous abortion.  The prevalence of aneuploid oocytes increases in older women.  These age-related aneuploidies are mainly due to nondisjunction of chromosomes during maternal meiosis.  Therefore, PGS of the extruded polar bodies from the oocyte has been explored as a technique to deselect aneuploid oocytes in older women.  The FISH technique is most commonly used to detect aneuploidy.

Children often serve as hematopoietic stem cell donors, most commonly for their siblings.  Human leukocyte antigen (HLA) matched biological siblings are generally preferred as donors due to the reduced risks of transplant-related complications compared to unrelated donors.  Parents of an affected child are requesting PGT to select embryos in the hope of conceiving an HLA identical donor sibling.  Only embryos HLA matched to the existing sibling in need of a compatible donor of hematopoietic stem cells would be transferred to complete the course of the pregnancy.


Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.


NOTE: Carefully check the member’s benefit plan, summary plan description or contract for language specific to assisted reproductive technologies (ART) and related services (including, but not limited to, in vitro fertilization [IVF], preimplantation genetic diagnosis [PGD], etc.).  If ART and its related services are determined to be eligible for member benefits then the following services that are listed as medically necessary should be considered for benefit coverage.  

Preimplantation genetic diagnosis (PGD) may be considered medically necessary as an adjunct to in vitro fertilization (IVF) in couples who meet any one of the following criteria subject to careful consideration of the technical and ethical issues involved:

  • For evaluation of an embryo at an identified elevated risk of a genetic disorder, such as when:
  1. Both partners are known carriers of a single-gene autosomal recessive disorder; or
  2. One partner is a known carrier of a single-gene autosomal recessive disorder and  the partners have one offspring that has been diagnosed with that recessive disorder; or
  3. One partner is a known carrier of a single-gene autosomal dominant disorder; or
  4. One partner is a known carrier of a single X-linked disorder; OR
  • For evaluation of an embryo at an identified elevated risk of chromosomal abnormality, e.g., unbalanced translocation, such as for a parent with balanced or unbalanced chromosomal translocation.

NOTE:  It is recommended that the provider and patient should carefully consider the technical and ethical issues involved in preimplantation genetic testing (PGT).

Preimplantation genetic diagnosis (PGD) as an adjunct to IVF is considered experimental, investigational and unproven in patients or couples who are undergoing IVF in all situations other than those specified above.

Preimplantation genetic screening (PGS) as an adjunct to IVF is considered experimental, investigational and unproven in patients or couples who are undergoing IVF in all situations. 

Diagnostic or screening preimplantation genetic testing (PGD or PGS) utilizing human leukocyte antigen (HLA) matching or other markers is considered not medically necessary to establish whether the embryo is a potential donor for a future stem cell transplantation.

Policy Guidelines

In 2004, specific CPT codes were issued describing the embryo biopsy procedure (89290-89291).  Additional CPT codes will be required for the genetic analysis.  The CPT codes used will vary according to the technique used to perform the genetic analysis.  

If performed to evaluate a specific genetic defect, a variable combination of CPT codes for molecular diagnostics will be used (CPT codes 83890-83913).  

If the technique is performed to detect aneuploidy or translocations, CPT codes for molecular cytogenetics will be used (CPT codes 88271-88275).


This policy was originally created in 2013.  The most recent literature search was performed through September 2011.  Issues addressed in the literature review include the technical feasibility of preimplantation genetic testing (PGT) to deselect embryos for different indications and the impact of the procedure on implantation rates, pregnancy and birth outcomes.  Following is a summary of the key literature to date.

Technical Feasibility

Preimplantation genetic diagnosis (PGD) has been shown to be a feasible technique to detect genetic defects and to deselect affected embryos.  A straightforward example is the ability to use PGD to distinguish male and female embryos as a technique to deselect male embryos at risk for X-linked disorders.  However, this policy is not designed to perform a separate analysis on every possible genetic defect.  Therefore, the determination of medical necessity will require a case by case approach to address the many specific technical and ethical considerations inherent in testing for genetic disorders, based on an understanding of the penetrance and natural history of the genetic disorder in question and the technical capability of genetic testing to identify affected embryos.  For example, several studies suggest that the role of PGT has expanded to a broader variety of conditions that have not been considered as an indication for genetic testing via amniocentesis or chorionic villus sampling (CVS).  The report of PGT used to deselect embryos at risk for early-onset Alzheimer’s disease prompted considerable controversy, both in lay and scientific publications.  Other reports focus on other applications of PGT for predispositions to late-onset disorders.  This contrasts with the initial use of PGD in deselecting embryos with genetic mutations highly predictive of lethal diseases.  PGD has also been used for gender selection and “family balancing.”  A representative sample of case series and reports on the technical feasibility of PGT to deselect embryos for different indications follows.

The European Society of Hormone Reproduction and Embryology (ESHRE) created a registry for PGD.  In 1999, the registry reported that PGD had been performed on 51 genetic defects with the most common diseases being cystic fibrosis (CF), beta thalassemia, myotonic dystrophy, muscular dystrophy (MD), hemophilia, and fragile X syndrome.  In this database pre- and postnatal confirmation of PGD was performed in 70 of 110 (64%) of the conceptuses, either through amniocentesis, CVS, or genetic testing on the live-birth.  Among these 70 conceptuses, there was one misdiagnosis, which was detected by an amniocentesis followed by pregnancy termination.  These registry data suggest that PGD, using PCR or fluorescence in situ hybridization (FISH), can be used to deselect affected embryos.

Several smaller case series have reported on individual diseases.  For example, Goossens and colleagues reported on 48 cycles of PGD in 24 couples at risk for CF.  Thirteen patients became pregnant, and 12 healthy babies have been born.  Other anecdotal studies have reported successful PGD in patients with osteogenesis imperfecta, Lesch-Nyhan syndrome, bulbar muscular atrophy, and phenylketonuria (PKU).

Efficacy and Safety

PGD with IVF in otherwise fertile couples:

An area of clinical concern is the impact of PGD on overall IVF success rates.  For example, is the use of PGT associated with an increased number of IVF cycles required to achieve pregnancy or a live-birth?  The Centers for Disease Control and Prevention (CDC) routinely collects and reports on IVF success rates; these data may be compared to the ESHRE registry data.  The following table summarizes the success rates for IVF overall and PGT associated with IVF based on these two data sources.

Clinical Pregnancy Rate Per:

IVF (%)

PGD + IVF (%)




Egg retrieval 






Although this table only provides a very rough estimate, the data suggest that use of PGT lowers the success rate of an IVF cycle, potentially due to any of a variety of reasons such as inability to biopsy an embryo, inability to perform genetic analysis, lack of transferable embryos, and effect of PGT itself on rate of clinical pregnancy or live-birth.  In addition, the CDC database presumably represents couples who are predominantly infertile compared to the ESHRE database, which primarily represents couples who are not necessarily infertile but are undergoing IVF strictly for the purposes of PGD.

An important general clinical issue is whether PGD is associated with adverse obstetric outcomes, specifically fetal malformations related to the biopsy procedure.  Strom and colleagues addressed this issue in an analysis of 102 pregnant women who had undergone PGD with genetic material from the polar body.  All PGDs were confirmed postnatally; there were no diagnostic errors.  The incidence of multiple gestations was similar to that seen with IVF.  PGD did not appear to be associated with an increased risk of obstetric complications compared to the risk of obstetric outcomes reported in data for IVF.  However, it should be noted that biopsy of the polar body is considered biopsy of extra-embryonic material, and thus one might not expect an impact on obstetric outcomes.  The patients in this study had undergone PGD for both unspecified chromosomal disorders and various disorders associated with a single-gene defect (i.e., CF, sickle cell disease, and others).

In the setting of couples with known translocations, the most relevant outcome of PGD is the live-birth rate per cycle or embryo transfer.  Munne and colleagues reviewed 35 couples in which one partner was known to carry a translocation.  Of the 47 cycles of PGD, there were 13 completed or ongoing pregnancies.  There was no embryo transfer in 14 of the cycles; thus the pregnancy rate per embryo transfer was 39%.  A total of 15 patients in this group had 16 pregnancies, only two of which ended in spontaneous abortion.  Prior to PGD, this same group of patients had 38 previous pregnancies, 35 of which ended in spontaneous abortion.

PGS with IVF:

Several meta-analyses of randomized controlled trials (RCTs) on PGS have been published.  A meta-analysis published in 2009 by Checa and colleagues identified ten trials with a total of 1,512 women.  PGS was performed for advanced maternal age in four studies, for previous failed IVF cycles in one study, and for single embryo transfer in one study; the remaining four studies included the general IVF population.  A pooled analysis of data from seven trials (346 events) found a significantly lower rate of live-birth in the PGS group compared to the control group.  The unweighted live-birth rates were 151 of 704 (21%) in the PGS group and 195 of 715 (27%) in the control group, p=0.003.  Findings were similar in subanalyses including only studies of the general IVF population and only the trials including women in higher-risk situations.  The continuing pregnancy rate was also significantly lower in the PGS group compared to the control group in a meta-analysis of eight trials.  The unweighted rates were 160 of 707 (23%) in the PGS group and 210 of 691 (30%) in the control group, p=0.004.  Again, findings were similar in subgroup analyses.

Another meta-analysis was published in 2011 by Mastenbroek and colleagues.  They included RCTs that compared the live-birth rate in women undergoing IVF with and without PGS for aneuploidies.  Fourteen potential trials were identified; five trials were excluded after detailed inspection, leaving nine eligible trials with 1,589 women.  All trials used FISH to analyze the aspirated cells.  Five trials included women of advanced maternal age, three included “good prognosis” patients, and one included women with repeated implantation failure.  When data from the five studies including women with advanced maternal age were pooled, the live-birth rate was significantly lower in the PGS group (18%) compared to the control group (26%), p=0.0007.  There was not a significant difference in live-birth rates when data from the three studies with good prognosis patients were pooled; rates were 32% in the PGS group and 42% in the control group, p=0.12.  The authors concluded that there is no evidence of a benefit of PGS as currently applied in practice; they stated that potential reasons for inefficacy include possible damage from the biopsy procedure and the mosaic nature of analyzed embryos.

Technical and Ethical Issues 

The complicated technical and ethical issues associated with PGT will frequently require case by case consideration.  For example, such consideration may be required, particularly for couples who are known carriers of potentially lethal or disabling genetic mutations and are seeking PGD as an alternative to conventional conception, with the possibility of an elective abortion if a subsequent amniocentesis identifies an affected fetus.  The diagnostic performance of the individual laboratory tests used to analyze the biopsied genetic material is rapidly evolving, and evaluation of each specific genetic test for each abnormality is beyond the scope of this policy.  However, in general, to assure adequate sensitivity and specificity for the genetic test guiding the embryo deselection process, the genetic defect must be well characterized.  For example, the gene or genes responsible for some genetic disorders may be quite large, with mutations spread along the entire length of the gene.  The ability to detect all or some of these genes, and an understanding of the clinical significance of each mutation (including its penetrance, i.e., the probability that an individual with the mutation will express the associated disorder), will affect the diagnostic performance of the test.  An ideal candidate for genetic testing would be a person who has a condition that is associated with a single well-characterized mutation for which a reliable genetic test has been established.  In some situations, PGT may be performed in couples in which the mother is a carrier of an X-linked disease, such as fragile X syndrome.  In this case, the genetic test could focus on merely deselecting male embyros.

The severity of the genetic disorder is also a consideration.  At the present time, many cases of PGD have involved lethal or severely disabling conditions with limited treatment opportunities, such as Huntington's chorea or Tay Sachs disease.  CF is another condition for which PGD has been frequently performed.  However, CF has a variable presentation and can be treatable.  The range of genetic testing that is performed on amniocentesis samples as a possible indication for elective abortion may serve as a guide.

This policy does not attempt to address the myriad ethical issues associated with PGT that, it is hoped, have involved careful discussion between the treated couple and the physician.  For some couples, the decision may involve the choice between the risks of an IVF procedure and deselection of embryos as part of the PGT treatment versus normal conception with the prospect of amniocentesis and an elective abortion.  In some cases involving a single X-linked disorder, determination of the gender of the embryo provides sufficient information for excluding or confirming the disorder; thus guiding the couple in their decision making process.

Previous PGS Study Trials

In 2007, Mastenbroek et al., in an RCT, found that PGS reduced the rates of ongoing pregnancies and live-births after IVF in women of advanced (aged 35 through 41 years) maternal age.  In this study, 408 women (206 assigned to PGD and 202 assigned to the control group) underwent 836 cycles of IVF (434 cycles with and 402 cycles without PGS).  The ongoing pregnancy rate was significantly lower in the women assigned to PGS (52 of 206 women [25%]) than in those not assigned to PGS (74 of 202 women [37%]; rate ratio, 0.69; 95% confidence interval [CI]: 0.51–0.93).  The women assigned to PGS also had a significantly lower live-birth rate (24% vs. 35%, respectively; rate ratio, 0.68; 95% CI: 0.50–0.92).  In 2011, a follow-up study was published when surviving children were two years-old.  Forty-nine pregnancies in the PGS group and 71 in the control group resulted in live-births of at least one child.  Forty-five couples with 54 children (36 singletons and nine twins) in the PGS group and 63 couples with 77 children (49 singletons and 14 twins) in the control group were available for follow-up.  The groups of children did not differ significantly in scores on an infant development scale and child development checklist variables.  For example, median scores on the total Child Behavior Checklist were 43.0 among children born after PGS and 46.0 in control children, p=0.44.  However, the neurologic optimality score (NOS) was significantly lower in the PGS group than the control group, p=0.20.  In the PGS group, there were four children (7%) classified as having simple minor neurologic dysfunction (MND), two (4%) with complex MND and one (2%) with cerebral palsy.  In the control group, three (4%) children had simple MND, one (1%) had complex MND, and there were no cases of cerebral palsy.  Simple MND referred to the isolated presence of fine motor, gross motor of visuomotor dysfunction, or mild dysregulation of muscle tone and complex MND to dysfunction in two or more of these domains.

Debrock and colleagues, in Belgium, published a trial in 2010 that included women of advanced (at least 35 years) maternal age who were undergoing IVF to undergo PGS or implantation without PGS.  Randomization was done by cycle; 52 cycles were randomized to the PGS group and 52 to the control group.  Cycles were excluded if two or fewer fertilized oocytes were available on day one after retrieval or if two or fewer embryos of six or more cells were available on day three.  Individuals could participate more than once, and there was independent randomization for each cycle.  More cycles were excluded postrandomization in the control group; outcome data were available for 37 cycles (71%) in the PGS group and 24 cycles (46%) in the control group.  Study findings did not confirm the investigators’ hypothesis that the implantation rate would be higher in the group receiving PGS.  The implantation rate was 15.1% in the PGS group and 14.9% in the control group; p=1.  Moreover, the live-birth rate per embryo transferred did not differ significantly between groups; rates were 9.4% in the PGS group and 14.9% in the control group; p=0.76.  An intention-to-treat (ITT) analysis of all randomized cycles (included and excluded) did not find any significant differences in outcomes including the implantation rate which was 11 of 76 (14.5%) in the PGS group and 16 of 88 (18.2%) in the control group, p=0.67.  In the ITT, the live-birth date per embryo transferred was seven of 47 (14.9%) in the PGS group and ten of 49 (20.4%) in the control group, p=0.60.

A randomized trial published in 2009 included good prognosis patients (similar to the general IVF population in the Checa et al. meta-analysis) undergoing IVF.  This was defined as women with age younger than 39 years, normal ovarian reserve, body mass index (BMI) less than 30 kg/m2, presence of ejaculated sperm, normal uterus and no more than two previous failed IVF cycles.  Women were randomly assigned to receive PGS (n=23) or implantation without PGS on day three (n=24) after oocyte retrieval.  There was no significant difference between groups in PGS and control groups in terms of clinical pregnancy rate (52.4% vs. 72.7%, respectively).  However, there was a significantly lower rate of embryo implantation in the PGS group than the control group (31.7% vs. 62.3%, respectively, p=0.004).  There was also a significantly lower live-birth rate in the PGS group (28.6% vs. 68.2%, respectively, p=0.009).  The investigators originally planned to enroll 100 women per group, but the study was terminated early because of results from a planned interim analysis.

In a 2008 editorial commentary, Fritz commented that while PGS should work, after a decade of experience, there is no substantive evidence to indicate that it does work.  Possible reasons for this lack of benefit include potential adverse effects of biopsy on implantation or developmental potential, transfer of presumed normal embryos that were aneuploid for one or more chromosomes that were not analyzed, and misdiagnoses due to interpretation errors or due to mosaicism.  In another commentary, Fauser noted that well-designed studies failed to demonstrate a clinical benefit of PGS in IVF.  Issues that need to be addressed, in Fauser’s view, include better understanding of mosaicism, improving PGS related to studying all chromosomes in a reliable manner, and determining the optimal timing for removal of one or more cells.

Ongoing Clinical Trials for PGS and PGD

PGS in women of advanced maternal age (NCT00795795): This non-blinded RCT is comparing the outcome of IVF cycles with and without PGS among women of advanced maternal age (38-44 years).  Primary outcomes are ongoing implantation per embryo and per patient.  The study is being conducted in Spain and is sponsored by the Instituto Valenciano de Infertilidad.  The estimated study completion date is December 2011.

Implantation failure and PGD (NCT00547781): This non-blinded RCT will include patients with repetitive implantation failure (at least two previous failures).  It will compare standard IVF with day five transfer with and without PGD.  PGD will include aneuploidy screening.  The study is being conducted in Spain and is sponsored by the Instituto Valenciano de Infertilidad.  The expected completion date for data collection is July 2011.

PGD by array comparative genome hybridization (CGH) (NCT01332643): This RCT is comparing single embryo transfer with and without array CGH.  The treatment group will undergo embryo biopsy at the blastocyst stage (day five) and analysis of the biopsied cells with a comprehensive chromosome analysis technique.  The primary outcome is implantation rate, and secondary outcomes include miscarriage rate and live-birth rate.  To be included, women need to be between 35 and 42 years-old.  The study is being conducted in Peru; the expected date of study completion is May 2012.

Efficacy of 24 chromosome preimplantation genetic diagnosis (NCT01219283): This is a RCT comparing embryo transfer with and without 24-chromosome PGD.  Embryos in the treatment group will undergo biopsy at day five and two normal embryos will be transferred.  In the control group, the two morphologically best embryos will be transferred.  Inclusion criteria include attempting conception through IVF and a maximum of one prior failed IVF cycle.  The study is being conducted at several centers in the United States.  The expected date of study completion is July 2012.

Practice Guidelines and Position Statements on PGS

In 2009, the American College of Obstetricians and Gynecologists issued an opinion on PGS for aneuploidy.  They state that current data do not support the use of PGS to screen for aneuploidy due solely to maternal age.

A 2007 practice committee opinion issued by the American Society for Reproductive Medicine concluded that available evidence did not support the use of PGS as currently performed to improve live-birth rates in patients with advanced maternal age, previous implantation failure, or recurrent pregnancy loss, or to reduce miscarriage rates in patients with recurrent pregnancy loss related to aneuploidy.

Practice Guidelines and Position Statements on PGT with IVF for Donor Suitability

In 2009, the American Academy of Pediatrics (AAP) issued an opinion on utilizing PGT with IVF to ensure an HLA matched donor of stem cells, either by umbilical cord blood donation or future stem cell donations, for a sibling requiring stem cell rescue due to a disease, such as leukemia.  The parents often request PGD to be done simultaneously to the HLA matching to avoid the birth of a child with a similar genetic defect, such as Fanconi anemia.  The AAP site a 2005 study of five PGD centers in four countries that have performed HLA genotyping in 180 IVF cycles.  In 122, the goal was to avoid a genetic condition.  But in 58 cycles, PGD was done solely for HLA typing.  The AAP further expressed the following statement, “The willingness of health care professionals to collect cord blood for stem cells in the delivery room must be ensured before delivery, although the pregnant woman and couple must also understand that the health of both the newborn infant and the pregnant woman have priority and that peripartum events may preclude collection.  To avoid exposing the newborn infant to any risks from the donation, the delivery should not be modified to maximize the number of cells collected.” 


PGT has been shown to be technically feasible in detecting single-gene defects, structural chromosomal abnormalities, and aneuploid embryos using a variety of biopsy and molecular diagnostic techniques.  In terms of health outcomes, small case series have suggested that PGD is associated with the birth of unaffected fetuses when performed for detection of single genetic defects and a decrease in spontaneous abortions for patients with structural chromosomal abnormalities.  For couples with single genetic defects, these beneficial health outcomes are balanced against the probable overall decreased success rate of the PGD procedure compared to IVF alone.  However, the alternative for couples at risk for single genetic defects is prenatal genetic testing, i.e., amniocentesis or CVS, with pregnancy termination contemplated for affected fetuses.  (It should be noted that many patients undergoing PGD will also undergo a subsequent amniocentesis or CVS to verify PGD accuracy.)  Ultimately, the choice is one of the risks (both medical and psychologic) of undergoing IVF with PGD, compared to the option of normal fertilization and pregnancy with the possibility of a subsequent elective abortion.  Thus, PGD is considered medically necessary, as noted in the coverage, when the evaluation is focused on a known disease or disorder, and the decision to undergo PGD is made upon careful consideration of the risks and benefits.  There is insufficient evidence that PGS improves ongoing pregnancy and live-birth rates; thus, PGS as an adjunct to IVF is considered experimental, investigational and unproven.  Since PGD or PGS testing for HLA typing is not required for the maintenance of a healthy embryo, PGD with IVF is not medically necessary to determine if the healthy embryo is a suitable potential donor for a sibling requiring stem cell transplantation.


Disclaimer for coding information on Medical Policies          

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes
V18.9, V26.31, V26.32, V26.33, V26.34, V26.35, V26.39, V82.79, V82.89    
ICD-10 Codes

Z13.79, Z13.89, Z84.81, Z31.430, Z31.438, Z31.5, Z31.440, Z31.441, Z31.448

Procedural Codes: 81200, 81220, 81221, 81222, 81223, 81224, 81242, 81243, 81244, 81250, 81251, 81255, 81257, 81260, 81265, 81266, 81291, 81292, 81293, 81294, 81295, 81296, 81297, 81298, 81299, 81300, 81301, 81302, 81303, 81304, 81317, 81318, 81319, 81330, 81332, 81400, 81401, 81402, 81403, 81404, 81405, 81406, 81408, 88261, 88262, 88263, 88264, 88271, 88272, 88273, 88274, 88275, 88280, 88283, 88285, 88289, 88291, 88299, 89290, 89291, 96040, S0265
  1. Harper, J.C.  Preimplantation diagnosis of inherited disease by embryo biopsy: an update of the world figures.  Journal of Assisted Reproduction and Genetics (1996 February) 13(2):90-5.
  2. Munne, S., Dailey, T., et al.  Reduction in signal overlap results in increased FISH efficiency implications for preimplantation genetic diagnosis.  Journal of Assisted Reproduction and Genetics (1996 February) 13(2):149-56.
  3. Verlinsky, Y., Cieslak, J., et al.  Birth of healthy children after preimplantation diagnosis of common aneuploidies by polar body fluorescent in situ hybridization analysis.  Preimplantation Genetics Group. Fertility and Sterility (1996 July) 66(1):126-9.
  4. Grifo, J.A., Tang, Y.X., et al.  Update in preimplantation genetic diagnosis.  Age, genetics, and infertility.  Annals of the New York Academy of Science (1997 September 26) 828:162-5.
  5. Gianaroli, L., Magli, M.C., et al.  Preimplantation genetic diagnosis increases the implantation rate in human in vitro fertilization by avoiding the transfer of chromosomally abnormal embryos.  Fertility and Sterility (1997 December) 68(6):1128-31.
  6. - Fact Sheet: Preimplantation Genetic Diagnosis (1998).  Prepared by The American Society for Reproductive Medicine.  Available at (accessed on 24 March 1999).
  7. - AFT Cycles Using Fresh, Nondonor Eggs and Embryos. (1998) Section 2: 1-6. Prepared by Division of Reproductive Health of US Department of Health and Human Services, Centers for Disease Control.  Available at <http:> (accessed on 24 January 2003).
  8. Nagy, A.M., De Man, X., et al.  Scientific and ethical issues of preimplantation diagnosis.  Annals of Medicine (1998 February) 30(1):1-6.
  9. Verlinsky, Y., Cieslack, J., et al.  Preimplantation diagnosis of common aneuploidies by the first- and second-polar body FISH analysis.  Journal of Assisted Reproduction and Genetics (1998 May) 15(5):285-9.
  10. Munne, S., Marquez, C., et al.  Chromosome abnormalities in embryos obtained after conventional in vitro fertilization and intracytoplasmic sperm injection.  Molecular Human Reproduction (1998 May) 69(5):904-8.
  11. Mennuti, M.T., Thomson, E., et al.  Screening for cystic fibrosis carrier state.  Obstetrics & Gynecology – Clinical Commentary (1999 March) 93(3):456-61.
  12. Munne, S., Magli, C., et al.  Positive outcome after preimplantation diagnosis of aneuploidy in human embryos.  Human Reproduction (1999 September) 14(9):2191-9.
  13. Gianaroli, L., Magli, M.C., et al.  Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed.  Fertility and Sterility (1999 November) 72(5):837-44.
  14. Geraedts, J., Handyside, A., et al.  ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: preliminary assessment of data from January 1997 to September 1998.  ESHRE PGD Consortium Steering Committee.  Human Reproduction (1999 December) 14(12):3138-48.
  15. Ray, P.F., Harper, J.C., et al.  Successful preimplantation genetic diagnosis for sex Link Lesch-Nyhan Syndrome using specific diagnosis.  Prenatal Diagnosis (1999 December) 19(13):1237-41.
  16. Geraedts, J., Handyside, A., et al.  ESHRE preimplantation genetic diagnosis (PGD) consortium: data collection II – May 2000.  Human Reproduction (2000 December) 15(12):2673-83.
  17. Strom, C.M., Strom, S., et al.  Obstetric outcomes in 102 pregnancies after preimplantation genetic diagnosis.  American Journal of Obstetrics and Gynecology (2000 June) 182(6):1629-32.
  18. De Vos, A., Sermon, K., et al.  Two pregnancies after preimplantation genetic diagnosis for osteogenesis imperfecta type I and type IV.  Human Genetics (2000 June) 106(6):605-13.
  19. Munne, S., Sandalinas, M., et al.  Outcome of preimplantation genetic diagnosis of translocations. Fertility and Sterility (2000 June) 73(6):1209-18.
  20. Goossens, V., Sermon, K., et al.  Clinical application of preimplantation genetic diagnosis for cystic fibrosis. Prenatal Diagnosis (2000 July) 20(7):551-71.
  21. Gianaroli, L., Plachot, M., et al.  ESHRE guidelines for good practice in IVF laboratories.  Committee of the Special Interest Group on Embryology of the European Society of Human Reproduction and Embryology.  Human Reproduction (2000 October) 15(10):2241-6.
  22. Ouhibi, N., Olson, S., et al.  Preimplantation genetic diagnosis.  Current Women’s Health Reports (2001) 1:138-42.
  23. Georgiou, I., Sermon, K., et al.  Preimplantation genetic diagnosis for spinal and bulbar muscle atrophy (SBMA).  Human Genetics (2001 June) 108(6):494-8.
  24. Preimplantation Genetic Diagnosis – Practice Committee Report.  Birmingham, Alabama: American Society for Reproductive Medicine and Society for Assisted Reproductive Technology (2001 June).
  25. Verlinsky, Y., Rechitsky, S., et al.  Preimplantation testing for phenylketonuria.  Fertility and Sterility (2001 August) 76(2):346-9.
  26. Towner, D., and R.S. Loewy.  Ethics of preimplantation for a woman destined to develop early-onset Alzheimer disease.  The Journal of the American Medical Association (2002) 287(8):1038-40.
  27. ESHRE Preimplantation Genetic Diagnosis Consortium: data collection III – May 2001.  Human Reproduction (2002 January) 17(1):233-46.
  28. Malpani, A., Malpani, A., et al.  The use of preimplantation genetic diagnosis in sex selection for family balancing in India.  Reproductive Biomedicine Online (2002 January-February) 4(1):16-20.
  29. Sermon, K.  Current concepts in preimplantation genetic diagnosis (PGD): A molecular biologist’s view.  Human Reproduction Update (2002 January – February) 8(1):11-20.
  30. Verlinsky, Y., Rechitsky, S., et al.  Preimplantation diagnosis for early-onset Alzheimer disease caused by V717 mutation.  Journal of the American Medical Association (2002 February 27) 287(8):1018-21.
  31. Pennings, G., Schots, R., et al.  Ethical considerations on preimplantation genetic diagnosis for HLA typing to match a future child as a donor of hematopoietic stem cells to a sibling.  Human Reproduction (2002 March) 17(3):534-8.
  32. Rechitsky, S., Verlinsky, O., et al.  Preimplantation genetic diagnosis for cancer disposition.  Reproductive Biomedicine Online (2002 September-October) 5(2):148-55.
  33. Hanson, C., Hamberger, L., et al.  Is any form of gender selection ethical?  Journal of Assisted Reproduction and Genetics (2002 September) 19(9):431-2.
  34. Sills, E.S., and G.D. Palermo.  Preimplantation genetic diagnosis for elective sex selection, the IVF market economy, and the child – another long day’s journey into night?  Journal of Assisted Reproduction and Genetics (2002 September) 19(9):433-7.
  35. Spriggs, M.  Genetically selected baby free of inherited predisposition to early-onset Alzheimer’s disease.  Journal of Medical Ethics (2002 October) 28(5):290.
  36. Kuliev, A., Cieslak, J., et al.  Chromosomal abnormalities in a series of 6,733 human oocytes in preimplantation diagnosis for age-related aneuploidies.  Reproductive Biomedicine Online (2003 January – February) 6(1): 54-9.
  37. Kuliev, A., and Y. Verlinsky. The role of preimplantation genetic diagnosis in women of advanced reproductive age.  Current Opinion in Obstetrics and Gynecology (2003 June) 15(3):233-5.
  38. Pehlivan, T., Rubio, C., et al.  Preimplantation genetic diagnosis by fluorescence in situ hybridization: Clinical possibilities and pitfalls.  Journal of the Society for Gynecologic Investigation (2003 September) 10(6):315-22.
  39. Verlinsky, Y., and A. Kuliev.  Current status of preimplantation diagnosis for single gene disorders.  Reproductive Biomedicine Online (2003 September) (2):145-50.
  40. Devroey, P., and A. Van Steirteghem.  A review of ten years experience of ICSI.  Human Reproduction Update (2004 January – February) 10(1):19-28.
  41. Los, F.J., Van Opstal, D., et al.  The development of cytogenetically normal, abnormal, and mosaic embryos: A theoretical model.  Human Reproduction Update (2004 January – February) 10(1):79-94.
  42. Kuliev, A., and Y. Verlinsky.  Thirteen years’ experience of preimplantation diagnosis: Report of the Fifth International Symposium on Preimplantation Genetics.  Reproductive Biomedicine Online (2004 February) 8(2):229-35.
  43. Watt, H.  Preimplantation genetic diagnosis: choosing the ‘good enough’ child.  Health Care Analysis (2004 March) 12(1):51-60.
  44. Nyboe Anderson, A., Gianaroli, L., et al.  Assisted reproductive technology in Europe, 2000.  Results generated from European registers by ESHRE.  Human Reproduction (2004 March) 19(3):490-503.
  45. Baart, E.B., Van Opstal, D., et al.  Fluorescence in situ hybridization analysis of two blastomeres from day 3 frozen-thawed embryos followed by analysis of the remaining embryo on day 5.  Human Reproduction (2004 March) 19(3):685-93.
  46. Ferraretti, A.P., Magli, M.C., et al.  Prognostic role of preimplantation genetic diagnosis for aneuploidy in assisted reproductive technology outcome.  Human Reproduction (2004 March) 19(3):694-9.
  47. Aran, B., Veiga, A., et al.  Preimplantation genetic diagnosis in patients with male meiotic abnormalities.  Reproductive Biomedicine Online (2004 April) 8(4):470-6.
  48. Allan, J., Edirisinghe, R., et al.  Dilemmas encountered with preimplantation diagnosis of aneuploidy in human embryos.  Australian and New Zealand Journal of Obstetrics and Gynecology (2004 April) 44(2):117-23.
  49. Wilding, M., Forman, R., et al.  Preimplantation genetic diagnosis for the treatment of failed in vitro fertilization – embryo transfer and habitual abortion.  Fertility and Sterility (2004 May) 81(5):1302-7.
  50. Verlinsky, Y., Rechitsky, S., et al.  Preimplantation HLA testing.  Journal of the American Medical Association (2004 May 5) 291(17):2079-85.
  51. Verlinsky, Y., and A. Kuliev.  Preimplantation diagnosis for aneuploidies in assisted reproduction.  Minerva Ginecologica (2004 June) 56(3):197-203.
  52. Sampson, J.E., Ouhibi, N.  The role for preimplantation genetic diagnosis in balanced translocation carriers.  American Journal of Obstetrics and Gynecology (2004 June) 190(6):1707-11.
  53. Wells, D. Advances in preimplantation genetic diagnosis.  European Journal of Obstetrics, Gynecology, and Reproductive Biology (2004 July 1) 115 Supplement 1:S97-101.
  54. Shahine, L.K., Cedars, M.I.  Preimplantation genetic diagnosis does not increase pregnancy rates in patients at risk for aneuploidy.  Fertility and Sterility (2006) 85(1):51-6.
  55. Sierra, S., Stephenson, M.  Genetics of recurrent pregnancy loss.  Seminars in Reproductive Medicine (2006) 24(1):17-24.
  56. Donoso, P., Devroey, P.  PGD for aneuploidy screening: An expensive hoax?  Best Practice & Research Clinical Obstetrics & Gynaecology (2007) 21(1):157-68.
  57. Mastenbroek, S., Twisk, M., et al.  In vitro fertilization with preimplantation genetic screening.  New England Journal of Medicine (2007 July) 357(1):9-17.
  58. Fritz, M.A.  Perspectives on the efficacy and indications for preimplantation genetic screening: where are we now?  Human Reproduction (2008) 23(12):2617-21.
  59. Fauser, B.C.J.M.  Preimplantation genetic screening: the end of an affair?  Human Reproduction (2008) 23(12):2622-5.
  60. CDC – Annual Assisted Reproductive Technology Reports (2008).  Available at http:/// (accessed on 2011 September 21).
  61. Mastenbroek, S., Scriven, P., et al.  What next for preimplantation genetic screening?  More randomized controlled trials needed?  Human Reproduction (2008 December) 23(12):2626-8.  (Epub 2008 October 23).
  62. Preimplantation genetic screening for aneuploidy.  ACOG Committee Opinion No. 430.  American College of Obstetricians and Gynecologists.  Obstetrics and Gynecology (2009 March) 113:766-7.
  63. Samuel, G.N., Strong, K.A., et al.  Establishing the role of preimplantation genetic diagnosis with human leukocyte antigen typing: what place do “savior siblings” have in pediatric transplantation.  Archives of Disease in Childhood (2009 April) 94(4):317-20. (Epub 2008 August 6).
  64. Meyer, L.R., Klipstein, S., et al.  A prospective randomized controlled trial of preimplantation genetic screening in the “good prognosis” patient.  Fertility and Sterility (2009 May) 91(5):1731-8.
  65. Checa, M.A., Alonso-Coello, P., et al.  IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis.  Journal of Assisted Reproduction and Genetics (2009 May) 26(5):273-83.
  66. Hanson, C., Hardarson, T., et al.  Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication.  Human Reproduction (2009 November) 24(11):2960-4.  (Epub 2009 July 22).
  67. – In Vitro Fertilization (IVF) with Preimplantation Genetic Diagnosis (PGD) for Single Gene Disorders (Mutations) (2009 December).  The Reproductive Genetics Institute – Informational Packet.  Available at (accessed on 2011 October 20).
  68. Karatas, J.C., Strong, K.A., et al.  Psychological impact of preimplantation genetic diagnosis: a review of the literature.  Reproduction and Biomedicine Online (2010 January) 20(1):83-91.  (Epub 2009 November 10).
  69. Debrock, S., Melotte, C., et al.  Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial.  Fertility and Sterility (2010 February) 93(2):364-73.
  70. Children as Hematopoietic Stem Cell Donors – Policy Statement prepared by The Committee on Bioethics.  Pediatrics (2010 February 1) 125(2):392-404.  (Epub 2010 January 25).
  71. Mir, P., Rodrigo, L., et al.  Improving FISH diagnosis for preimplantation genetic aneuploidy screening.  Human Reproduction (2010 May 19).  (Epub ahead of print).
  72. Milan, M., Cobo, A.C., et al.  Redefining advanced maternal age as an indication for preimplantation genetic screening.  Reproduction and Biomedicine Online (2010 November) 21(5):649-57.  (Epub 2010 June 19).
  73. Cooper, A.R., and E.S. Jungheim.  Preimplantation genetic testing: indications and controversies Clinical Laboratory Medicine (2010 September) 30(3):519-31.  (Epub 2010 June 12).
  74. Adiga, S.K., Kalthur, G., et al.  Preimplantation diagnosis of genetic diseases.  Journal of Postgraduate Medicine (2010 October-December) 56(4):317-20.
  75. – Implantation Failure and PGD (NCT00547781) (2011 March 3).  National Institutes of Health – Clinical Trials.  Available at (accessed on 2011 September 21).
  76. – Preimplantation Genetic Screening in Women of Advanced Maternal Age (NCT00795795) (2011 May 13).  National Institutes of Health – Clinical Trials.  Available at (accessed on 2011 September 21).
  77. – Preimplantation Genetic Diagnosis (PGD) by Array Comparative Genome Hybridization (CGH) and Blastocyst Biopsy (NCT01332643) (2011 June 13).  National Institutes of Health – Clinical Trials.  Available at> (accessed on 2011 September 21).
  78. Middelburg, K.J., van der Heide, M., et al.  Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial.  Fertility and Sterility (2011 July) 96(1):165-9.
  79. – Study of the Efficacy of 24 Chromosome Preimplantation Genetic Diagnosis (PGD) (NCT01219283) (2011 July 15).  National Institutes of Health – Clinical Trials.  Available at> (accessed on 2011 September 21).
  80. Mastenbroek, S., Twisk, M., et al.  Preimplantation genetic screening: a systematic review and meta-analysis of RCTs.  Human Reproduction Update (2011 July-August) 17(4):454-66.
  81. Preimplantation Genetic Testing.  Chicago, Illinois: Blue Cross Blue Shield Medical Policy Reference Manual (2011 July) OB/GYN/Reproduction 4.02.05.
September 2013  Policy formatting and language revised.  Policy statement unchanged.  Title changed from "Genetic Testing - Preimplantation Genetic Diagnosis" to "Preimplantation Genetic Testing (PGT)".
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Preimplantation Genetic Testing (PGT)