Reproductive Genetics and Preimplantation Genetic Testing
Fundamentals
Understand inheritance patterns: autosomal dominant, autosomal recessive, X-linked, and mitochondrial. Carrier screening is offered to couples, with expanded panels now common. Balanced translocations cause recurrent loss and can be addressed with PGT.
PGT types
- PGT-A: aneuploidy screening; benefit is debated and greatest in advanced maternal age or recurrent loss.
- PGT-M: monogenic disorders.
- PGT-SR: structural rearrangements.
PGT requires biopsy (blastocyst trophectoderm) and is reported as euploid, aneuploid, mosaic, or inconclusive. Mosaicism complicates counseling; transfer of mosaic embryos may be considered with counseling.
Traps
- Assuming PGT-A guarantees a live birth or eliminates miscarriage.
- Confusing PGT-M (single gene) with PGT-A (chromosome number).
- Forgetting that a balanced translocation carrier is phenotypically normal but at risk for unbalanced offspring.
- Missing that mitochondrial disorders have unique inheritance and limited reproductive options.
Worked example
A couple with a child with cystic fibrosis: both are carriers (autosomal recessive). PGT-M can identify unaffected embryos; each embryo has a 25% affected, 50% carrier, 25% unaffected chance.