Can In Vitro Fertilization (IVF) with Preimplantation Genetic Testing (PGT) prevent passing multiple hereditary osteochondromas to the offspring if one parent has the condition?

Preimplantation Genetic Testing for Multiple Hereditary Osteochondromas

Yes, IVF with Preimplantation Genetic Testing for Monogenic disorders (PGT-M) can effectively prevent the transmission of multiple hereditary osteochondromas from an affected parent to their offspring.

Understanding Multiple Hereditary Osteochondromas and PGT-M

Multiple hereditary osteochondromas (MHO) is a monogenic disorder that follows autosomal dominant inheritance, meaning each child of an affected parent has a 50% chance of inheriting the condition. PGT-M offers a solution by allowing genetic testing of embryos created through IVF before implantation.

How PGT-M Works for Monogenic Disorders:

1. IVF Procedure: The couple undergoes standard IVF to create embryos
2. Embryo Biopsy: Cells are removed from each embryo at the blastocyst stage
3. Genetic Analysis: The cells are tested specifically for the pathogenic variant causing MHO
4. Embryo Selection: Only embryos without the pathogenic variant are selected for transfer
5. Pregnancy: Unaffected embryos are transferred to the uterus to establish pregnancy

Clinical Evidence and Guidelines

Current guidelines support the use of PGT-M for monogenic disorders like multiple hereditary osteochondromas. According to the Chinese experts' consensus guideline, PGT-M is specifically indicated to "diagnose pathogenic gene variants in preimplantation embryos, select unaffected embryos for transfer, and block disease transmission to the offspring" 1.

The American College of Medical Genetics and Genomics (ACMG) recognizes the clinical utility of genetic testing for embryo selection, particularly for monogenic disorders with clear inheritance patterns 1. Unlike polygenic conditions where risk prediction is more complex, monogenic disorders like MHO have a clear genetic basis that can be reliably detected through PGT-M.

Effectiveness and Success Rates

PGT-M has demonstrated high accuracy rates for monogenic disorders. Recent studies show accuracy rates of 97% to >99% for PGT-M 2. A retrospective study of PGT-M for various hereditary conditions reported a transferable embryo rate of 12.45%, clinical pregnancy rate of 74.19%, and live birth rate of 89.47% 3. This indicates that while not all embryos will be suitable for transfer, the success rate for achieving pregnancy with unaffected embryos is relatively high.

Important Considerations

Benefits:

• Prevention of Disease Transmission: PGT-M can effectively prevent the transmission of MHO to offspring
• High Accuracy: Current techniques offer high accuracy in detecting monogenic variants
• Avoidance of Termination Decisions: Allows selection of unaffected embryos before pregnancy, avoiding potential difficult decisions about pregnancy termination

Limitations:

• Physical and Psychological Burden: The IVF process can be physically demanding for women and emotionally challenging for couples
• Success Rates: Not all IVF cycles result in pregnancy (approximately 50-60% success rate) 1
• Cost Implications: The procedure may be expensive and not always covered by insurance
• Limited Embryos: Only a portion of embryos will be genetically suitable for transfer

The PGT-M Process for MHO

1. Genetic Counseling: Identification of the specific pathogenic variant in the affected parent
2. IVF Procedure: Ovarian stimulation, egg retrieval, and fertilization
3. Embryo Development: Embryos are cultured to blastocyst stage
4. Biopsy and Testing: Cells are removed and tested for the MHO-causing variant
5. Embryo Selection: Unaffected embryos are identified
6. Transfer: Selected embryos are transferred to establish pregnancy
7. Confirmation: Prenatal or postnatal confirmation testing is recommended

Emerging Technologies

Recent advances in PGT technology include comprehensive platforms that allow simultaneous testing for monogenic disorders, structural rearrangements, and chromosomal abnormalities using a single universal platform 4. Additionally, research into non-invasive PGT methods using cell-free DNA from spent embryo culture medium may offer less invasive options in the future 5.

Conclusion

PGT-M through IVF offers an effective method to prevent the transmission of multiple hereditary osteochondromas from an affected parent to their offspring. With high accuracy rates and established clinical protocols, this approach provides a viable reproductive option for families affected by this condition, though the physical, emotional, and financial aspects of the process should be considered.