Chromosomal analysis in IVF: just how useful is it?

Area of Science:

• Reproductive Medicine and Genetics
• Embryology
• Genomic Technologies

Background:

• Preimplantation genetic diagnosis (PGD) and preimplantation genetic testing for aneuploidy (PGT-A) are crucial for minimizing genetically abnormal embryos in assisted reproduction.
• PGT-A aims to reduce miscarriage rates, prevent live births of children with trisomy, and enhance the success of in vitro fertilization (IVF).
• Various diagnostic methods, including FISH, aCGH, PCR, NGS, and karyomapping, are employed for comprehensive chromosome screening (CCS).

Purpose of the Study:

• To review the current state-of-the-art in PGT-A, encompassing diagnostic techniques and controversial aspects.
• To explore the mechanisms and implications of mosaicism in human embryos during PGT-A.
• To propose a practical path forward for future PGT-A diagnosis and applied research, addressing the need for increased funding.

Main Methods:

• Review of contemporary diagnostic approaches for PGT-A, including next-generation sequencing (NGS) and karyomapping.
• Analysis of different embryo biopsy techniques: polar body (PB), cleavage-stage (blastomere), and blastocyst (trophectoderm - TE) biopsy.
• Evaluation of combined strategies involving improved biopsy, diagnosis, and freeze-all protocols.

Main Results:

• Next-generation sequencing (NGS) offers an improved dynamic range, while karyomapping can simultaneously detect chromosomal and monogenic disorders.
• Blastocyst (TE) biopsy is increasingly preferred over cleavage-stage (blastomere) biopsy due to higher abnormality detection and reduced embryo damage.
• Mosaicism presents complex challenges, with varying outcomes depending on its origin (meiotic vs. post-zygotic).

Conclusions:

• Improved PGT-A techniques and strategies show potential to revolutionize IVF outcomes.
• Unanswered questions regarding human embryo chromosome complements necessitate further basic biological research and funding.
• The evidence base for routine PGT-A requires further strengthening to address ongoing criticisms and guide clinical application.