Prepregnancy testing for single-gene disorders by polar body analysis

Area of Science:

• Reproductive genetics
• Preimplantation genetic diagnosis
• Molecular biology

Background:

• Current methods for preventing single-gene disorders rely on prenatal diagnosis, often resulting in pregnancy termination.
• A significant limitation is the termination of 25% of wanted pregnancies when affected fetuses are detected.
• There is a need for methods that allow for genetic screening before pregnancy is established.

Purpose of the Study:

• To develop and evaluate a prepregnancy genetic testing method using polar body analysis.
• To enable couples at risk of single-gene disorders to select unaffected embryos for in vitro fertilization (IVF).
• To reduce the incidence of genetic disorders through preimplantation genetic screening.

Main Methods:

• DNA analysis of the first and second polar bodies extruded during oocyte maturation and fertilization.
• Sequential multiplex nested PCR analysis of polar bodies to detect specific gene mutations and linked polymorphic markers.
• In vitro fertilization (IVF) procedures followed by polar body genetic testing for preselection of mutation-free oocytes.

Main Results:

• 191 out of 399 tested oocytes were predicted to be mutation-free and preselected for IVF.
• 20 pregnancies resulted from the transfer of unaffected embryos, leading to 19 healthy births.
• Follow-up analysis confirmed the diagnosis in 97% of cases, demonstrating high reliability.

Conclusions:

• Prepregnancy genetic testing via polar body analysis is a reliable method for preventing single-gene disorders.
• This technique offers a viable alternative to prenatal diagnosis, reducing the need for pregnancy termination.
• The study successfully demonstrated the effectiveness of polar body analysis in selecting healthy embryos for conception.