Do IVF Babies Have Genetic Diseases? IVF Genetic Risk & PGT Screening Explained

Opening: Real Consultation Scenario

In the outpatient clinic, we encountered a couple, both 28 years old, married for two years, planning to undergo IVF. The woman presented a thalassemia genetic test report; she is a carrier of β-thalassemia. The man had not yet been tested. She asked, "Doctor, if we do IVF, will our child also get thalassemia? Is the probability of an IVF baby having a genetic disease higher than that of a naturally conceived baby?" This question is heard almost daily in the reproductive clinic.

IVF Technology Itself Does Not Increase the Risk of Genetic Diseases

IVF is an assisted reproductive technology where sperm and egg are fertilized in vitro to form an embryo, which is then transferred to the uterus. This process does not alter the gene sequence or induce gene mutations. The source of genetic diseases is the pathogenic genes carried by the parents, not the IVF technology itself. Whether conceived naturally or through IVF, the incidence of genetic diseases in offspring depends entirely on the parents' genetic background.

Why is there a question that "IVF babies are more prone to genetic diseases"?

This misconception may stem from several aspects: First, some couples undergoing IVF are themselves carriers of genetic diseases or have chromosomal issues, so their offspring's genetic risk is inherently high, but this is unrelated to the IVF technology. Second, early public misunderstanding of third-generation IVF (PGT) led to the belief that all IVF procedures lack genetic screening. Third, a few media outlets have linked "genetic diseases" with "IVF babies" in their reports, creating a cognitive bias.

How Third-Generation IVF (PGT) Reduces the Risk of Genetic Diseases

PGT (Preimplantation Genetic Testing) involves genetic analysis of a few cells from a blastocyst before embryo transfer, selecting embryos with normal chromosome number and structure that do not carry specific pathogenic genes for transfer. Based on the testing purpose, it is divided into three types:

PGT can significantly reduce the transmission risk of specific genetic diseases. Taking β-thalassemia as an example, if both partners are carriers, the risk of severe thalassemia in naturally conceived offspring is 25%. By using PGT-M to select embryos that do not carry the pathogenic gene for transfer, the risk can be reduced to nearly zero. However, this is contingent on the pathogenic gene being clearly identified and the testing protocol being feasible.

Accuracy and Limitations of PGT Screening

The accuracy of PGT is influenced by several factors: the number of cells biopsied from the embryo (usually 5-10 trophectoderm cells), the testing platform (NGS or aCGH), the proportion of mosaicism, and the type of gene mutation. For PGT-A, the concordance rate for detecting chromosomal aneuploidy is about 95%-98%. For PGT-M, family linkage analysis must first be constructed, and the accuracy can reach over 98%, but there is a possibility of misdiagnosis due to genetic recombination, allele dropout, etc.

When is PGT Suitable and When is it Not?

Suitable Candidates:

• One or both partners are carriers of a clearly identified pathogenic gene (e.g., thalassemia, spinal muscular atrophy, hereditary deafness)
• One partner is a carrier of a balanced translocation or Robertsonian translocation
• Advanced maternal age (≥38 years) combined with recurrent spontaneous abortion or recurrent implantation failure
• History of having a child with a genetic disease
• Carriers of X-linked recessive genetic diseases (can undergo PGT for sex selection or direct detection of the pathogenic gene)

Unsuitable Candidates:

• Genetic cause is unclear, making it impossible to establish an effective testing protocol
• The type of pathogenic gene mutation is complex and cannot be covered by current technology
• Severely diminished ovarian function with very few retrieved eggs, making it difficult to obtain enough embryos for biopsy
• Medical conditions that contraindicate PGT testing (e.g., uncontrolled severe infections, malignant tumors)

Easily Overlooked Details

There are several easily overlooked aspects in clinical practice:

• Comprehensive Collection of Family History: Many patients only focus on their own test reports, neglecting the family history of their spouse. In one case, the female carried a GJB2 gene mutation, the male was not tested, and it was only discovered after the child's birth that the male was also a carrier of the same mutation.
• Possibility of De Novo Mutations: About 15%-20% of single-gene disorders are caused by de novo mutations, where neither parent carries the mutation, but the child is affected. PGT-M cannot predict de novo mutations; these cases need to be identified through prenatal diagnosis or newborn screening.
• Assessment of Mosaic Embryos: Some embryos are chromosomal mosaics (coexistence of normal and abnormal cells). The cells biopsied for PGT may not fully represent the entire embryo's true status. Embryos with a mosaicism rate of <20% may still be considered for transfer, but full informed consent is required, and prenatal diagnosis is recommended.

Common Pitfalls

In counseling and clinical practice, the following common misconceptions are observed:

• Misconception 1: "If we do third-generation IVF, the child will definitely not have a genetic disease." — As mentioned above, PGT has technical blind spots and cannot prevent de novo mutations. Prenatal diagnosis is still needed after screening.
• Misconception 2: "If there is no family history, genetic counseling is unnecessary." — Carriers of recessive genetic diseases are usually asymptomatic but can pass the pathogenic gene to their offspring. The carrier rate for genetic diseases in the general population is about 1%-2%, and in some regions (e.g., Guangdong, Guangxi), the thalassemia carrier rate is over 10%.
• Misconception 3: "PGT can screen for all known genetic diseases." — Currently, PGT-M can only detect diseases with clearly identified causative genes, and each embryo can only be tested for a specific set of diseases; it cannot perform "whole-genome screening."

Case Scenario Analysis

Case 1: Couple Both Carriers of Thalassemia

Both the man and woman are carriers of α-thalassemia (--SEA/αα). In naturally conceived offspring, the risk of severe α-thalassemia (Hb Bart's) hydrops fetalis syndrome is 25%, which is not viable. By using PGT-M to select embryos without the --SEA deletion for transfer, a healthy offspring was eventually achieved. In this case, PGT-M successfully blocked the transmission of the genetic disease, but this was contingent on the clear identification of the mutation type in both partners and the feasibility of the testing protocol.

Case 2: Carrier of a Balanced Chromosomal Translocation

A 35-year-old woman with a history of three recurrent spontaneous abortions was found to be a carrier of a balanced translocation, 46,XX,t(4;8)(p15;q22). Approximately 70% of her eggs were chromosomally unbalanced gametes, leading to embryonic chromosomal abnormalities and miscarriages. Through PGT-SR, embryos with balanced or normal chromosomes were selected for transfer, resulting in a successful pregnancy and delivery. In this case, PGT-SR resolved the issue of recurrent miscarriage caused by the chromosomal structural abnormality, but it could not completely eliminate the risk of miscarriage (there is still a natural miscarriage rate of about 5%-10%).

Frequently Asked Questions

Q: Are IVF babies more likely to have genetic diseases than naturally conceived babies?
A: No. IVF procedures do not increase the risk of genetic diseases. The occurrence of genetic diseases depends on the parents' genes, not the method of conception.

Q: Is prenatal diagnosis still necessary after PGT screening?
A: Yes. PGT has technical errors (e.g., mosaicism, allele dropout) and cannot detect de novo mutations. Amniocentesis or chorionic villus sampling is recommended during pregnancy for verification.

Q: Can all genetic diseases be screened by PGT?
A: No. PGT-M requires that the causative gene be clearly identified and detectable. For diseases with high genetic heterogeneity, unidentified causative genes, or polygenic disorders (e.g., congenital heart disease, schizophrenia), PGT is currently not feasible.

Q: Is carrier screening necessary if there is no family history of genetic disease?
A: It is recommended to undergo carrier screening for common genetic diseases (e.g., thalassemia, SMA, deafness genes) before attempting pregnancy or IVF. Carriers are usually asymptomatic, but if both partners are carriers of the same recessive genetic disease, there is a 25% risk of the child being affected. In some regions of China, the thalassemia carrier rate is high, making screening clinically significant.

Doctor's Perspective on Genetic Disease Risk Management

In reproductive medicine clinical practice, the core of genetic disease risk management is "diagnosis before treatment": The first step is to identify the source of risk through history taking and genetic testing; the second step is to assess the risk level and formulate intervention strategies; the third step is to choose the appropriate technical pathway (PGT or prenatal diagnosis). Not all genetic diseases require PGT; some can be screened during the second trimester through prenatal diagnosis (amniocentesis, cord blood sampling), avoiding the potential damage of embryo biopsy.

For women of advanced maternal age (≥38 years), the rate of embryonic chromosomal aneuploidy increases significantly (about 30% at age 35-40, about 50% at age 40-45). PGT-A can effectively select euploid embryos, reducing the miscarriage rate and birth defect rate. However, PGT-A cannot detect microdeletions, microduplications, or single-gene disorders, requiring combination with other testing methods.

Special Situations: Mosaicism and De Novo Mutations

When PGT results indicate mosaicism (e.g., 20% trisomy, 80% normal), decisions should be made considering the mosaicism rate, embryo morphological score, patient age, and other factors. General principles: A mosaicism rate of <20% may be considered for transfer; 20%-40% requires caution; >40% is not recommended for transfer. De novo mutations cannot be prevented by PGT, and early screening and intervention through prenatal diagnosis or the neonatal period are recommended.

Specific Process: From Genetic Counseling to PGT Implementation

A complete PGT cycle typically includes the following steps:

1. Genetic Counseling Clinic: Collect family history and previous reproductive history, assess genetic risk, and determine the testing protocol.
2. Carrier Screening: Both partners undergo genetic testing for common genetic diseases to determine carrier status.
3. Family Verification: For single-gene disorders, blood samples from both partners and the proband (if available) are collected to construct a linkage analysis model, verifying the validity and polymorphism of the testing site.
4. IVF + PGT Cycle: Ovarian stimulation, egg retrieval, fertilization, blastocyst culture (5-6 days).
5. Embryo Biopsy: Biopsy 5-10 cells from the trophectoderm of the blastocyst and send them to the genetics laboratory for testing.
6. Genetic Testing: Use NGS or aCGH platforms for chromosomal copy number analysis or gene mutation detection.
7. Embryo Selection and Transfer: Based on test results, select embryos with normal chromosomes or those not carrying the pathogenic gene for transfer.
8. Prenatal Diagnosis: Perform amniocentesis at 12-18 weeks of pregnancy to verify the fetal genetic status.

The entire cycle takes about 2-3 months (excluding family verification time). Costs vary depending on the type of testing and the hospital, with PGT-A costing approximately 30,000-50,000 RMB and PGT-M costing approximately 40,000-60,000 RMB (including family verification costs).

Technical Differences Across Countries

In China, conducting PGT requires strict qualification approval. Currently, about 80 reproductive centers nationwide have obtained trial or formal operation qualifications for PGT. The testing platform is mainly NGS, covering chromosomal aneuploidy, microdeletions/microduplications, and some single-gene disorders. Some European countries (e.g., the UK, Spain) have broader coverage of gene panels for PGT-M, allowing simultaneous testing for hundreds of single-gene disorders. The United States focuses more on individualized testing protocols, allowing customization of testing content based on patient needs. Technically, there is little difference between China and other countries; the main differences lie in the scope of testing, cost structure, and ethical approval processes.

Conclusion: Doctor's Advice

— This article was reviewed by a reproductive medicine clinician and written based on Chinese assisted reproductive technology standards and international PGT consensus. The content is for科普 reference only. For specific diagnosis and treatment plans, please refer to the evaluation of the reproductive center doctor.