Thailand Third-Generation IVF PGT Technology: Disease Screening Scope and Limitations
What diseases can Thailand third-generation IVF screen for?
Thailand's third-generation IVF technology, Preimplantation Genetic Testing (PGT), can analyze the chromosome number, structure, and specific single-gene pathogenic sites of embryos before transfer. Clinically, it is divided into three types based on testing purpose: PGT-A (aneuploidy screening), PGT-M (monogenic disease testing), and PGT-SR (chromosomal structural rearrangement testing). There are clear differences in the disease coverage, detection accuracy, and applicable populations for each technology.
I. Chromosomal abnormalities detectable by PGT-A
PGT-A (formerly PGS) is used to screen embryos for numerical chromosomal abnormalities (aneuploidy) and is currently the most widely used PGT technology. The following chromosomal abnormalities can be detected by PGT-A:
| Abnormality Type | Specific Disease / Syndrome | Chromosome Karyotype |
|---|---|---|
| Autosomal Trisomy | Down Syndrome | 47,XX,+21 or 47,XY,+21 |
| Autosomal Trisomy | Edwards Syndrome | 47,XX,+18 or 47,XY,+18 |
| Autosomal Trisomy | Patau Syndrome | 47,XX,+13 or 47,XY,+13 |
| Sex Chromosome Abnormality | Turner Syndrome | 45,X |
| Sex Chromosome Abnormality | Klinefelter Syndrome | 47,XXY |
| Sex Chromosome Abnormality | Triple X Syndrome | 47,XXX |
| Sex Chromosome Abnormality | XYY Syndrome | 47,XYY |
| Chromosomal Microdeletion | 22q11.2 Deletion Syndrome (DiGeorge Syndrome) | del(22)(q11.2) |
| Chromosomal Microdeletion | 1p36 Deletion Syndrome | del(1)(p36) |
| Chromosomal Microdeletion | Angelman Syndrome (some types) | del(15)(q11-q13) maternal |
The detection resolution of PGT-A is typically 5–10 Mb, with some platforms able to detect microdeletions larger than 1 Mb. Structural abnormalities such as balanced translocations and inversions require screening via PGT-SR.
II. Monogenic diseases detectable by PGT-M
PGT-M (formerly PGD) targets genetic diseases with known causative genes. It requires identifying the pathogenic mutation carried by one or both partners, followed by customized probe development. The following monogenic diseases have established PGT-M testing protocols clinically:
| Disease Category | Specific Disease | Causative Gene |
|---|---|---|
| Hemoglobinopathy | Alpha-thalassemia, Beta-thalassemia | HBA1/HBA2, HBB |
| Hemoglobinopathy | Sickle Cell Disease | HBB |
| Neuromuscular Disease | Spinal Muscular Atrophy (SMA) | SMN1 |
| Neuromuscular Disease | Duchenne Muscular Dystrophy (DMD) | DMD |
| Neuromuscular Disease | Huntington's Disease | HTT |
| Hereditary Cancer Syndrome | Hereditary Breast and Ovarian Cancer (HBOC) | BRCA1, BRCA2 |
| Hereditary Cancer Syndrome | Lynch Syndrome | MLH1, MSH2, MSH6, PMS2 |
| Hereditary Cancer Syndrome | Familial Adenomatous Polyposis (FAP) | APC |
| Coagulation Disorder | Hemophilia A, Hemophilia B | F8, F9 |
| Connective Tissue Disease | Marfan Syndrome | FBN1 |
| Skeletal Dysplasia | Osteogenesis Imperfecta (some types) | COL1A1, COL1A2 |
| Hereditary Hearing Loss | Autosomal Recessive Hearing Loss | GJB2, SLC26A4, etc. |
| Metabolic Disease | Phenylketonuria (PKU) | PAH |
| Metabolic Disease | Gaucher Disease | GBA |
The detection scope of PGT-M depends on the clearly identified pathogenic mutation within the family. It cannot screen for genetic diseases with unknown causative genes, nor can it screen for polygenic diseases (such as type 2 diabetes, essential hypertension, schizophrenia, etc.).
III. Chromosomal structural abnormalities detectable by PGT-SR
PGT-SR is used to detect whether embryos carry chromosomal structural rearrangements, including reciprocal translocations, Robertsonian translocations, inversions, and insertions. Such abnormalities are common in patients with recurrent miscarriage, infertility, or oligoasthenozoospermia.
- Reciprocal Translocation: Exchange of segments between two non-homologous chromosomes, can lead to unbalanced embryos
- Robertsonian Translocation: Fusion of two acrocentric chromosomes at the centromere, commonly involving chromosomes 13, 14, 15, 21, 22
- Pericentric / Paracentric Inversion: Inversion of a segment within a single chromosome, can produce unbalanced gametes during meiosis
- Insertion: A segment from one chromosome inserted into another, relatively rare
PGT-SR is typically performed using SNP arrays or next-generation sequencing to distinguish between balanced and unbalanced embryos, helping carriers select chromosomally normal embryos for transfer.
How clinicians view the indications for PGT
From a reproductive medicine perspective, PGT is not a routine option for all IVF patients. In clinical decision-making, we primarily recommend PGT based on the following indications:
- Female age ≥ 38 years (significantly increased risk of embryonic aneuploidy)
- Recurrent pregnancy loss (≥ 2 miscarriages, excluding uterine anatomical and endocrine factors)
- Previous pregnancy with chromosomal abnormality
- One partner is a carrier of chromosomal structural rearrangement
- Family history of known monogenic genetic disease
- Repeated implantation failure (some studies suggest PGT-A may improve live birth rates)
It is important to clarify that PGT cannot improve embryo quality nor increase the number of available embryos. It only helps select chromosomally normal embryos from the existing pool. For patients with diminished ovarian reserve (low AMH, reduced antral follicle count), the number of obtainable embryos is limited, and the value of PGT needs individualized assessment.
Differences in PGT policies between Thailand and mainland China
Thailand's clinical application of PGT technology is relatively open, mainly reflected in the following aspects:
| Item | Thailand | Mainland China |
|---|---|---|
| PGT-A Application | Applicable for advanced age, recurrent miscarriage, repeated implantation failure, etc. | Must meet medical indications and require ethical approval |
| PGT-M Disease Scope | Covers most monogenic diseases, including some tumor susceptibility genes | Limited to severe genetic diseases, requires approval |
| Sex Selection | Permitted (under certain legal frameworks) | Non-medical sex selection prohibited |
| Embryo Biopsy Timing | Usually blastocyst biopsy on days 5–6 | Blastocyst biopsy, must comply with national standards |
| Genetic Testing Platform | Next-generation sequencing (NGS), SNP arrays, qPCR | NGS, SNP arrays, FISH, etc. |
Before undergoing PGT in Thailand, patients still need genetic counseling, informed consent, and necessary ethical review. For PGT-M, genetic test reports of both partners and family history of genetic diseases must be provided. Testing platforms and data analysis capabilities vary among different reproductive centers, directly affecting the range and accuracy of detectable diseases.
Easily overlooked testing limitations
Furthermore, PGT cannot replace prenatal diagnosis. After pregnancy, amniocentesis or chorionic villus sampling for chromosomal karyotype analysis or genetic testing is still recommended to confirm the actual fetal condition.
Common cognitive pitfalls patients fall into
Actual testing process and timeline
From ovarian stimulation to obtaining PGT results, it typically takes 4–6 weeks. The specific steps are as follows:
- Ovarian Stimulation and Egg Retrieval (about 10–14 days): Use gonadotropins for controlled ovarian stimulation, followed by transvaginal ultrasound-guided egg retrieval.
- In Vitro Fertilization and Embryo Culture (5–6 days after egg retrieval): Conventional IVF or ICSI insemination, culture to blastocyst stage.
- Trophectoderm Biopsy (Days 5–6): Use a laser to create an opening in the zona pellucida of the blastocyst and aspirate 5–8 trophectoderm cells.
- Embryo Freezing (after biopsy): All biopsied blastocysts are immediately vitrified and stored while awaiting test results.
- Genetic Testing (7–14 days): Perform NGS, SNP array, or qPCR analysis based on the test type.
- Result Interpretation and Transfer (after testing): Select embryos that are chromosomally normal or do not carry the pathogenic mutation for frozen embryo transfer.
Throughout the cycle, genetic counseling should be completed before ovarian stimulation. For PGT-M testing, family samples need to be submitted 1–2 months in advance for probe design and validation.
Frequently asked questions
Practitioner observations: Real clinical experience
In daily work at the reproductive center, I have observed the following noteworthy situations:
- Some patients have overly high expectations of PGT, believing it guarantees a healthy child. It is necessary to fully inform them of the testing scope and technical limitations.
- For carriers of chromosomal structural abnormalities (e.g., balanced translocations), the rate of identifying normal embryos through PGT-SR is typically only 20–35%, requiring mental preparation for multiple stimulation cycles.
- Although the aneuploidy rate in advanced-age patients (≥40 years) is as high as 60–80%, PGT-A can still effectively screen for transferable embryos if a sufficient number of blastocysts are obtained.
- In PGT-M testing, the availability of family samples directly affects the feasibility of the testing protocol. Some genetic diseases require cooperation from multiple family members, including parents and the proband.
- The qualifications of genetics laboratories vary significantly among different reproductive centers in Thailand. It is advisable to choose a center with an NGS platform and a genetic counseling team.
Risk Reminder: PGT technology has inherent limitations, including misdiagnosis due to mosaicism, technical testing errors, and inability to cover polygenic diseases. All PGT results should be interpreted under the guidance of a genetic counselor or reproductive doctor. After pregnancy, formal prenatal diagnosis (amniocentesis or chorionic villus sampling) is still recommended to confirm the fetal chromosome and gene status. This content is for medical science reference only. Please consult a formal reproductive center for specific diagnosis and treatment plans.
