Polar Body Diagnostics (PBD)

Our team at IMMG has more than 11 years of experience in polar body diagnostics of monogenic (Mendelian) human diseases. We added PBD to our diagnostic portfolio in 2006 and the first child in Switzerland, after PBD of a monogenic disease (myotonic dystrophy) in our institute, was born in 2008.

Today, the list of diseases includes: Cystic fibrosis, myotonic dystrophy Curschmann Steinert (DM1), Adrenoleukodystrophy, Bruton disease, Osteogenesis imperfecta type VII, Peutz-Jeghers syndrome, and pyridoxin-dependent epilepsy. Additional 13 indications are currently in progress.

What is a polar body?

Polar bodies (PBs) are byproducts of the oocyte maturation. The female gametes are created in a process called oogenesis. During this process, the primordial oocytes undergo mitosis to produce the primary oocytes. These cells enter meiosis 1 and stay arrested in prophase 1 until puberty. At puberty, due to hormonal influence, meiosis 1 will complete with the outcome of the secondary oocyte and the first polar body (PB1). If fertilization occurs, meiosis 2 will be completed and an ootid with the second polar body (PB2) is created.

Meiosis

Formation of the polar bodies 1 and 2 (PB1 and PB2) during the female Meiosis 1 and 2. The circles filled in red and blue represent the female and male pronuclei, respectively.

Background

Genetic analysis of the first and second polar bodies (PBs) is the only technique of choice in countries where embryo biopsy procedures are restricted by law. It has been used for the diagnosis of various single gene disorders of maternal origin during the last two decades.

The procedures in PBD comprise a nondirective counseling interview with the couple, an initial genetic analysis, followed by testing of the polar bodies. The initial genetic analysis includes the validation of the disease causing mutation in the family and the identification of additional informative genetic markers, which co-segregate with the mutation and minimize the risk of misdiagnosis. Polar body testing includes its lysis, amplification of the genetic material (genomic DNA), followed by marker analysis. Finally, the results are reported  to the IVF laboratory.

Prerequisites for PBD

Pedigree

PBD requires an index patient with a known mutation as well as additional unaffected and/or affected family members for segregation analysis. The figure shows a pedigree with autosomal dominant inheritance. The arrow indicates the consulter, who is affected and asked for PBD.
A counseling interview is the first step to determine whether or not PBD is an appropriate alternative for the couple. Moreover, the couple is informed about the disorder, genetic risk assessment and recurrence risk, the genetic testing procedures, reliability of the test and possible reasons for misdiagnosis. Additionally, alternatives to PBD, the time line and the costs are communicated. Usually, PBD is not covered by the regular heath insurance.

Limitations

The two most significant limitations of PBD represent the fact that (i) only the maternal contribution to disease can be detected, and (ii) the diagnosis is indirect (the result of the polar body is used to conclude what is left in the oocyte).
For these and other reasons, a conventional prenatal testing in week 10-12 of gestation is recommended in order to confirm PBD results.

Perspectives

So far, genetic testing of in vitro fertilized embryos is not possible in Switzerland. However, revision of the Swiss law is in progress. The revised law for human reproductive medicine will allow genetic testing of embryos at risk for a severe genetic disorder before reimplantation of the fertilized oocyte. In contrast to PBD, both the maternal and paternal contributions to a disease can be diagnosed.  

Collaboration

Prof. Dr. Bruno Imthurn and PD Dr. Min Xie (Department of Reproductive Endocrinology, University Hospital Zurich)