Can the Reproductive Hospital Affiliated to Shandong University Perform Genetic Disease Screening? Screening Items and Process Description
The Reproductive Hospital Affiliated to Shandong University offers genetic disease screening, including PGT-A, PGT-M, PGT-SR, and chromosome karyotype analysis. It is suitable for individuals with a family history of genetic diseases, recurrent miscarriage, advanced maternal age, and chromosomal abnormalities. This article describes the screening items, applicable conditions, process steps, and precautions.
Opening: Real consultation scenario
"Doctor, we are both SMA carriers. Can we use third-generation IVF to screen out the pathogenic gene?" In the genetic counseling clinic, 35-year-old Ms. Lin and her husband spoke at the same time. They had previously conceived naturally, but prenatal diagnosis confirmed the fetus had Spinal Muscular Atrophy (SMA), forcing them to terminate the pregnancy. This time, they came to the Reproductive Hospital Affiliated to Shandong University to find out clearly — can the genetic disease screening technology here help them have a child who does not carry the pathogenic gene?
Genetic Disease Screening: What Can the Reproductive Hospital Affiliated to Shandong University Do
Yes. The Reproductive Hospital Affiliated to Shandong University has a complete genetic disease screening technology system, including Preimplantation Genetic Testing (PGT), chromosome karyotype analysis, gene sequencing, and carrier screening. For single-gene diseases (such as SMA, thalassemia, cystic fibrosis, etc.), PGT-M (Monogenic Disease Screening) can accurately screen for embryos that do not carry the paternal and maternal pathogenic genes. The hospital has a Reproductive Genetics Department, an Embryology Laboratory, and a Genetic Testing Center, capable of independently completing the entire process from genetic counseling and family verification to embryo biopsy, genetic testing, and transfer.
PGT technology is divided into three types:
- PGT-A: Detects whether the embryo has an abnormal number of chromosomes (aneuploidy), suitable for individuals of advanced maternal age, with recurrent miscarriage, or recurrent implantation failure.
- PGT-M: Detects whether the embryo carries a specific single-gene pathogenic gene, suitable for individuals with a family history of known single-gene diseases.
- PGT-SR: Detects whether the embryo has structural rearrangements of chromosomes (such as balanced translocation, Robertsonian translocation), suitable for carriers of chromosomal structural abnormalities.
For the SMA couple in the case above, the PGT-M approach is suitable. They first need to complete family verification to determine the pathogenic site, and then perform targeted testing on the embryos.
Reproductive Genetics Specialist: Who is Suitable and Who is Not
From a clinical decision-making perspective, PGT is not suitable for all genetic problems. Doctors focus on the following core conditions during evaluation:
Conditions Suitable for PGT
- Single-gene diseases (clear pathogenic gene, clear inheritance pattern, such as SMA, thalassemia, hemophilia, cystic fibrosis, etc.)
- Chromosomal structural abnormalities (balanced translocation, Robertsonian translocation, inversion, etc.)
- Recurrent spontaneous miscarriage (≥2 times, considering chromosomal factors)
- Advanced maternal age (female age ≥38 years, significantly increased risk of aneuploidy)
- Previous adverse pregnancy history (such as fetal malformation, history of chromosomal abnormality pregnancy)
Conditions Not Suitable or Requiring Careful Evaluation
- Diseases with unclear pathogenic genes or complex inheritance patterns (such as some intellectual disabilities, polygenic diseases)
- Low disease penetrance (carrying the pathogenic gene but low probability of developing the disease, making test results difficult to guide clinical decisions)
- Unreliable testing methods (such as regions with high gene homology, many repetitive sequences, etc.)
- Involving non-medical embryo selection (such as sex selection, which is explicitly prohibited by Chinese laws and regulations)
The doctor emphasizes that genetic counseling is the first and most important step of PGT. Both partners need to participate together, fully understand the scope of testing, accuracy, limitations, and potential risks, in order to make a decision that suits their own situation.
Six Most Easily Overlooked Details
In clinical work, the following details are often overlooked by patients but directly affect the feasibility and results of screening:
- Family verification requires blood samples from three generations. PGT-M usually requires collecting blood samples from the patient, their parents, children, and at least three generations of relatives to determine the pathogenic gene locus. Some families cannot complete verification due to relatives being unable to cooperate or complex blood relationships, thus preventing PGT-M.
- PGT has diagnostic errors. Limited by the number of biopsied cells (usually 5-10) and technical limitations (allele dropout, gene amplification failure, etc.), the accuracy of PGT-M is about 95%-98%, and PGT-A is about 95%-99%. All PGT pregnancies must undergo amniocentesis for prenatal diagnosis confirmation in the second trimester.
- Some genetic diseases have incomplete penetrance. Carrying the pathogenic gene does not necessarily mean the disease will develop, but PGT-M currently cannot distinguish between "carriers" and "healthy individuals"; it can only distinguish between "carrying the pathogenic gene" and "not carrying the pathogenic gene".
- Embryo freezing and thawing have loss rates. After biopsy, embryos need to be stored by vitrification, waiting for test results for about 2-4 weeks. About 5% of embryos may not survive the thawing and transfer process.
- Low-level mosaicism may be missed. When the chromosome mosaicism ratio is below 20%, PGT-A may not detect it, but mosaic embryos can still potentially develop into normal fetuses.
- Single carrier of autosomal dominant disease can be screened. Even if only one partner carries an autosomal dominant pathogenic gene, PGT-M can screen for embryos that do not carry that gene, preventing the offspring from developing the disease.
Actual Process and Timeline for Genetic Disease Screening
From the initial consultation to transfer, the entire process usually takes 3-5 months. The specific steps are as follows:
| Step | Content | Approximate Time |
|---|---|---|
| ① Initial Genetic Counseling | Assess the type of genetic disease, inheritance pattern, clarity of the pathogenic gene, confirm PGT indications, and issue test orders | 1 day |
| ② Carrier Screening and Family Verification | Blood draw for screening both partners, collect blood samples from relatives if necessary for family verification, determine the pathogenic locus, and design detection probes | 4-8 weeks |
| ③ Develop PGT Plan and Sign Informed Consent | Doctor formulates a specific PGT plan based on genetic test results, informs about the scope of testing, accuracy, limitations, and costs, and signs the informed consent form | 1-2 days |
| ④ Ovarian Stimulation and Egg Retrieval | Female partner undergoes ovarian stimulation (about 10-14 days), follicle monitoring via ultrasound, egg retrieval surgery (intravenous anesthesia, about 15-20 minutes), male partner provides sperm sample simultaneously | 2-3 weeks |
| ⑤ In Vitro Fertilization and Embryo Culture | ICSI fertilization, embryo culture to blastocyst stage (day 5-6) | 5-6 days |
| ⑥ Embryo Biopsy and Genetic Testing | Take 5-10 cells from the trophectoderm of the blastocyst, perform whole genome amplification followed by genetic testing (NGS or SNP array) | 2-4 weeks |
| ⑦ Transfer of Normal Embryo | Select an embryo with normal chromosomes and not carrying the pathogenic gene for frozen or fresh transfer | 1 day |
| ⑧ Prenatal Diagnosis Confirmation | Perform amniocentesis in the second trimester (18-22 weeks) for prenatal genetic diagnosis to confirm the fetal genotype | Weeks 18-22 of pregnancy |
Overall, it is prudent to reserve a cycle of 4-6 months from family verification to final transfer. For some patients with ovarian reserve issues requiring multiple stimulation cycles to accumulate embryos, the time may be longer.
Key Test Indicators and Their Clinical Significance
The following indicators have important reference value in the evaluation before genetic disease screening:
| Test Item | Normal Reference Range | Abnormal Indication |
|---|---|---|
| AMH (Anti-Müllerian Hormone) | 1.0-4.0 ng/ml | <1.0 ng/ml indicates diminished ovarian reserve, may affect the number of eggs retrieved |
| FSH (Follicle-Stimulating Hormone) | 3-10 IU/L | >10 IU/L indicates decreased ovarian function, may have poor response to ovarian stimulation |
| Antral Follicle Count (AFC) | Total bilateral count >7 | <5 indicates insufficient ovarian reserve, limited number of retrievable eggs |
| Chromosome Karyotype Analysis | 46,XX or 46,XY | Abnormal karyotype (e.g., balanced translocation, Robertsonian translocation, mosaicism, etc.) requires genetic counseling |
| Gene Sequencing Depth | ≥30X | Insufficient depth affects the sensitivity and specificity of variant detection |
| Blastocyst Formation Rate | 40%-60% | <30% indicates poor embryo developmental potential, may affect the number of biopsiable embryos |
These indicators are not the only factors determining whether PGT can be performed, but they help doctors and patients estimate the approximate range of ovarian stimulation outcomes, embryo numbers, and overall success rates.
Screening Decisions in Three Real Scenarios
Case 1: SMA Carrier Couple
Both partners are SMA carriers. AMH 2.3 ng/ml, FSH 6.8 IU/L, antral follicle count 12. After ovarian stimulation, 14 eggs were retrieved, forming 7 blastocysts. Biopsy and testing revealed 2 embryos did not carry the pathogenic gene, 1 was a carrier, and 4 were affected. After transferring one normal embryo, blood HCG was positive on day 14. Amniocentesis at 18 weeks confirmed a normal fetal genotype. The pregnancy was stable, and a healthy infant was delivered at term.
Case 2: Balanced Translocation Carrier
The male partner is a carrier of a balanced translocation between chromosomes 11 and 22, with a history of 3 spontaneous miscarriages. The female partner has AMH 1.8 ng/ml, age 33. After ovarian stimulation, 10 eggs were retrieved, forming 5 blastocysts. PGT-SR testing found 2 embryos with normal chromosome structure and 3 with unbalanced translocation. After transferring one normal embryo, pregnancy was achieved, and prenatal diagnosis confirmed a normal fetal chromosome structure.
Case 3: Advanced Maternal Age with Recurrent Miscarriage
The female partner is 42 years old, with 2 recurrent miscarriages and no clear genetic history. AMH 0.6 ng/ml, FSH 11.2 IU/L, antral follicle count 4. After ovarian stimulation, 6 eggs were retrieved, forming 3 blastocysts. PGT-A testing showed only 1 was euploid (normal chromosomes), and 2 were aneuploid. Transfer of the euploid embryo did not result in implantation. The doctor assessed that this was related to age-related decline in endometrial receptivity and poor embryo potential, suggesting consideration of another stimulation cycle to accumulate embryos or discussion of other options.
These three cases illustrate that the success of PGT depends on multiple dimensions including genetic factors, ovarian reserve, embryo developmental potential, and uterine environment. Each family's outcome is unique and requires individualized assessment.
Frequently Asked Questions About Genetic Disease Screening
- Q: Can PGT screen for all genetic diseases?
A: No. PGT is only applicable to single-gene diseases and chromosomal structural abnormalities with clear pathogenic genes, clear inheritance patterns, and reliable detection methods. Polygenic complex diseases (such as diabetes, hypertension, etc.) and genetic diseases with unclear pathogenic genes cannot currently be screened by PGT. - Q: How accurate is PGT testing?
A: The accuracy of PGT-A is about 95%-99%, and PGT-M is about 95%-98%. Errors mainly arise from the limited number of biopsied cells, gene amplification failure, and allele dropout (ADO). Therefore, all PGT pregnancies must undergo prenatal diagnosis for confirmation. - Q: Is amniocentesis still necessary after PGT?
A: Yes. Prenatal diagnosis is an essential part of the PGT process. It is recommended to undergo amniocentesis at 18-22 weeks of pregnancy for final confirmation of the fetal genotype. - Q: What is the approximate cost of genetic screening?
A: PGT-A costs about 3000-5000 RMB per embryo, and PGT-M and PGT-SR cost about 5000-8000 RMB per embryo. This fee does not include basic treatment costs such as ovarian stimulation, egg retrieval, embryo culture, and transfer. The specific amount is subject to the actual charges of the hospital. - Q: What materials should I bring for genetic counseling?
A: Previous medical records, genetic disease diagnosis reports (if any), family genetic history information, and ID cards and marriage certificates of both partners. If genetic testing has been done, please bring the test report as well. - Q: How many embryos available for screening can typically be obtained from one ovarian stimulation cycle?
A: On average, women under 35 retrieve 10-15 eggs, forming 5-8 blastocysts; women aged 35-40 retrieve 6-10 eggs, forming 2-5 blastocysts; women over 40 retrieve 3-6 eggs, forming 1-3 blastocysts. Individual variation is significant and directly related to ovarian reserve.
Practitioner Observation: Common Cognitive Misconceptions in Genetic Counseling
In genetic counseling clinics, several recurring cognitive biases are worth noting:
- Misconception 1: "PGT guarantees a completely healthy child." In reality, PGT only screens for specific genetic diseases and cannot detect all genetic diseases, chromosomal abnormalities, or birth defects. The birth of a healthy infant still relies on standard prenatal examinations and pregnancy care.
- Misconception 2: "Family verification is troublesome; can we skip it?" For PGT-M, family verification is a crucial step for determining the pathogenic locus. Skipping this step and directly testing embryos could lead to errors in locus identification, resulting in false-negative or false-positive results.
- Misconception 3: "Embryo biopsy harms the embryo." Current clinical data indicate that trophectoderm biopsy at the blastocyst stage has a limited impact on the embryo's subsequent developmental potential. The transfer success rate of biopsied embryos after vitrification and thawing is not significantly different from that of non-biopsied embryos.
- Misconception 4: "If PGT fails once, the technology is not good." Whether an embryo can develop normally and implant successfully is influenced by multiple factors including egg quality, sperm quality, uterine environment, and endocrine status. PGT only addresses the genetic aspect and cannot compensate for deficiencies in other areas.
The general feeling among practitioners is that genetic disease screening is a decision requiring full collaboration between doctors and patients. Patients provide accurate family medical history and cooperate with family verification, while doctors provide clear testing plans and risk explanations; both are indispensable.
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