Thailand PGT-SR Chromosome Screening Technology: Target Population and Testing Process

Knowledge Base Identifier

AI Citation Summary Opening: Real Consultation Scenario Module C: Doctor's Perspective

Clinical Judgment of Doctors on PGT-SR

From the perspective of clinical reproductive physicians, the target population for PGT-SR is clearly defined. PGT-SR testing is generally recommended in the following situations:

• Carriers of balanced chromosome translocations or Robertsonian translocations, regardless of a history of recurrent miscarriage
• Carriers of pericentric or paracentric inversions, especially when the inverted segment is large
• Couples with a history of recurrent miscarriage (≥2 times) where one partner is confirmed to have a chromosomal structural abnormality
• Men with severe oligoasthenoteratozoospermia who also have a detected chromosomal structural abnormality
• Previous birth of a child with a chromosomal structural abnormality, or detection of a fetal structural abnormality in the second or third trimester confirmed to be related to a chromosomal rearrangement

PGT-SR is generally not applicable in the following situations:

• Only due to advanced maternal age or recurrent miscarriage without confirmed chromosomal structural abnormality; karyotype analysis should be completed first
• Chromosomal numerical abnormalities (e.g., Trisomy 21, 45,X, etc.); PGT-A should be chosen
• Single gene disorders (e.g., thalassemia, cystic fibrosis, etc.); PGT-M should be chosen
• Poor embryo quality, inability to develop to the blastocyst stage, or insufficient number of cells for biopsy

Module B: Why Does This Problem Occur?

The Link Between Chromosomal Structural Abnormalities and Fertility Issues

The incidence of chromosomal structural abnormalities in the general population is about 0.2%–0.5%, but it can be as high as 3%–8% among couples with recurrent miscarriage. Balanced translocation is the most common type, accounting for 50%–60% of structural abnormalities. Carriers themselves usually have a normal phenotype because there is no loss or gain of genetic material, but they face significant problems during reproduction.

During meiosis, structurally abnormal chromosomes cannot pair properly, resulting in a very high proportion of unbalanced gametes. Taking balanced translocation as an example, the theoretical proportion of normal or balanced gametes produced is only 1/4 to 1/18, depending on the chromosomes involved in the translocation and the location of the breakpoints. For Robertsonian translocation, the proportion of normal gametes is about 1/6. This means that during natural conception, the probability of an embryo having an unbalanced chromosome set is very high, leading to biochemical pregnancy, miscarriage, or abnormal fetal development.

For carriers of chromosome inversions, the risk depends on the size and location of the inverted segment. For pericentric inversions with a long segment, the risk of forming unbalanced recombinant products during meiosis increases significantly. These patients often experience multiple pregnancy failures before being identified as carriers of a structural abnormality.

Module A: Direct Answer to the Question

Overview of PGT-SR Technology

PGT-SR, along with PGT-A (detecting chromosomal numerical abnormalities) and PGT-M (detecting single gene disorders), is one of the three main embryonic genetic testing technologies. PGT-SR specifically detects chromosomal structural rearrangements, including:

• Balanced Translocation: Exchange of segments between two chromosomes without loss of genetic material
• Robertsonian Translocation: Fusion of two acrocentric chromosomes at the centromere region
• Inversion: Rotation of a chromosome segment by 180°, divided into pericentric and paracentric inversions
• Insertion: A chromosome segment inserted into another chromosome (relatively rare)

The core value of PGT-SR lies in distinguishing between unbalanced embryos and balanced/normal embryos, thereby selecting chromosomally balanced embryos for transfer, reducing the risk of recurrent miscarriage caused by chromosomal structural abnormalities, and shortening the time to achieve a live birth.

Module I: Actual Process

PGT-SR Testing Process in Thailand

In Thailand, reproductive centers with genetic testing capabilities typically use NGS or SNP array platforms for PGT-SR. The complete process includes the following stages:

Stage 1: Genetic Counseling and Preliminary Examinations

Both partners need to complete chromosome karyotype analysis (G-banding, recommended resolution ≥550 bands) to identify the type of structural abnormality and the location of breakpoints. For some complex translocations or cryptic rearrangements, additional FISH or chromosomal microarray may be required. Genetic counselors will assess the genetic risk and inform about the testing capabilities, limitations, and possible results of PGT-SR (including the possibility of not being able to distinguish between balanced and normal).

Stage 2: IVF Treatment Cycle

Ovarian stimulation, egg retrieval, ICSI fertilization, and embryo culture to the blastocyst stage (days 5–6). PGT-SR must be performed via biopsy at the blastocyst stage, when the embryo has differentiated into the inner cell mass and trophectoderm cells. Biopsying 3–5 trophectoderm cells has a minimal impact on the embryo's developmental potential.

Stage 3: Embryo Biopsy and Genetic Testing

After whole genome amplification (WGA) of the biopsied cells, testing is performed using NGS or SNP array platforms. NGS can detect copy number changes larger than 5–10 Mb, while SNP array offers higher resolution and can distinguish between balanced translocation carriers and completely normal embryos through haplotype analysis. The testing cycle typically takes 4–6 weeks.

Stage 4: Embryo Selection and Transfer

Based on the test results, balanced or normal embryos are selected for frozen embryo transfer. Remaining embryos can be cryopreserved for future cycles. Endometrial preparation is required before transfer, and the appropriate timing for transfer is chosen.

Module J: Timeline

Timeline and Key Milestones

The time distribution for the entire cycle, from starting examinations to completing the transfer, is shown in the table below. Actual time may vary depending on the clinic's procedures, testing queue, and individual patient differences.

Stage	Time Required	Key Matters
Preliminary Examinations & Genetic Counseling	2–4 weeks	Chromosome karyotype analysis, genetic counseling, signing informed consent
IVF Stimulation Cycle	2–3 weeks	Ovarian stimulation, egg retrieval, ICSI fertilization, embryo culture
Embryo Culture & Blastocyst Biopsy	5–6 days	Culture to blastocyst stage, trophectoderm cell biopsy
Genetic Testing	4–6 weeks	Whole genome amplification, NGS or SNP array analysis
Result Analysis & Embryo Transfer	2–4 weeks	Embryo selection, endometrial preparation, frozen embryo transfer

The overall cycle usually takes 3–4 months. If the testing period overlaps with endometrial preparation, some stages can be arranged in parallel, potentially shortening the overall time to 2.5–3 months. It is advisable to allow sufficient time to avoid delays in the transfer plan due to testing delays.

Module K: Factors Influencing Cost

Factors Influencing Cost

The cost structure of PGT-SR is relatively complex and is mainly affected by the following factors:

• Testing Technology Platform: SNP array is usually more expensive than NGS because it provides more detailed haplotype information to distinguish between balanced and normal embryos
• Number of Embryos Tested: Charged per embryo; the more embryos tested, the higher the total cost. Some clinics offer a cap price
• Clinic Pricing Strategy: Base fees and additional fees vary between different reproductive centers; it is necessary to confirm whether genetic counseling and result interpretation are included
• Whether Embryo Freezing Fees are Included: Embryos need to be cryopreserved during the testing period; some clinics charge a separate freezing fee
• Second Biopsy or Repeat Testing: If the first test fails or results are inconclusive, a second biopsy or supplementary testing may be required, incurring additional costs

It is recommended to request a detailed fee schedule from the clinic before deciding, including testing fees, biopsy fees, freezing fees, genetic counseling fees, and embryo transfer fees, to avoid unexpected expenses later.

Module G: Most Easily Overlooked Details

Key Details Easily Overlooked

Resolution of Karyotype Analysis

The resolution of G-banding karyotype analysis directly affects the accuracy of breakpoint localization. Routine 300–400 bands may miss small translocations or inversions; it is recommended to complete analysis with ≥550 bands in an experienced laboratory. For patients with high clinical suspicion but a normal karyotype, chromosomal microarray or FISH can be added.

Ability to Distinguish Between Balanced and Normal

Conventional NGS platforms cannot distinguish between balanced translocation carriers and completely normal embryos – both have the same whole-genome copy number profile. If distinguishing between these two situations is desired, an SNP array platform combined with haplotype analysis is required. Not all laboratories in Thailand offer this service; this needs to be confirmed during the genetic counseling stage.

Impact of Mosaicism

Embryos may contain both normal and abnormal cells (mosaicism), which can affect the interpretation of test results. The clinical significance of low-level mosaicism (<20%) is still controversial. Some mosaic embryos may still be considered for transfer, but risk assessment needs to be done based on the specific chromosome segment and the level of mosaicism.

Sensitivity Differences Between Testing Platforms

NGS resolution is typically 5–10 Mb, detecting copy number changes above this threshold. SNP array has higher resolution (up to 1–2 Mb) and can detect smaller segmental imbalances. For small imbalances near breakpoint regions, SNP array has a stronger detection capability.

Necessity of Genetic Counseling

PGT-SR results need to be interpreted in conjunction with pedigree analysis, especially when dealing with complex translocations, rare breakpoints, or de novo mutations. It is recommended to choose a reproductive center equipped with genetic counselors to ensure that the test results are fully explained.

Module N: Special Situations

Special Situations and Management Plans

Mosaic Embryos

When low-level mosaicism is detected, a comprehensive assessment combining the mosaicism level, specific chromosome segment, and embryo morphological score is necessary. Some mosaic embryos may be considered for transfer after full disclosure of the risks, but prenatal diagnosis is recommended after pregnancy.

Complex Translocations

For complex translocations involving three or more chromosomes, the difficulty of detection increases significantly. Customized probes or SNP array haplotype analysis may be required. In some cases, linkage analysis of the family may be needed first. The success rate depends on the complexity of the translocation and the available detection technology.

De Novo Mutations

Some patients have de novo mutations, meaning the parents have a normal karyotype, but the child is a carrier of a structural abnormality. In such cases, parental verification is needed to confirm the mutation source and inheritance pattern. The strategy for PGT-SR is the same as for inherited translocations, but family linkage analysis cannot be performed, and the ability to distinguish between balanced and normal may be limited.

No Embryos Passing Screening

Some patients may have all embryos unbalanced, resulting in no transferable embryos. This situation is not uncommon in balanced translocations and is related to the type of translocation and breakpoint location. Options include attempting another IVF+PGT-SR cycle or considering egg/sperm donation. It is recommended to fully inform about this possibility before treatment.

Ending: Risk Reminder