Polar body biopsy is the sampling of a

polar body A polar body is a small haploid cell that is formed at the same time as an egg cell during oogenesis, but generally does not have the ability to be fertilized. It is named from its polar position in the egg. When certain diploid cells in animals ...

of an

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...

. It was first applied clinically in humans in 1987 after extensive animal studies. A ''polar body'' is a small

haploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...

cell that is formed concomitantly as an

egg cell The egg cell, or ovum (plural ova), is the female reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female gamete is ...

during

oogenesis Oogenesis, ovogenesis, or oögenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage. O ...

, but which generally does not have the ability to be

fertilized Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

. After sampling of a polar body, subsequent analysis can be used to predict viability and

pregnancy chance Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...

of the oocyte, as well as the future health of a person resulting from such a pregnancy. The latter use makes it a form of

preimplantation genetic screening Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...

(PGS). Compared to a

blastocyst biopsy Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...

, a polar body biopsy can potentially be of lower costs, less harmful side-effects, and more sensitive in detecting abnormalities."Delivery of a chromosomally normal child from an oocyte with reciprocal aneuploid polar bodies". Scott Jr, Richard T., Nathan R. Treff, John Stevens, Eric J. Forman, Kathleen H. Hong, Mandy G. Katz-Jaffe, William B. Schoolcraft. Journal of Assisted Reproductive Genetics Vol. 29 pp. 533-537. 2012.

Techniques

The first polar body is removed from the unfertilised oocyte, and the second PB from the

zygote A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicellula ...

, shortly after fertilization. The biopsy and analysis of the first and second polar bodies can be completed before

fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

, which is the moment from which the zygote is generally considered an embryo and may become protected by law. By screening the first polar body for chromosomal anomalies, non-viable eggs can be reliably identified, though eggs with normal first polar bodies can still be affected by errors. This method was initially performed with

fluorescence in situ hybridization Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed b ...

(FISH), then by hybridizing a sample into

lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...

to observe it in

metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, align ...

, and more recently by

microarrays A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...

, which are fully automated and make it easier to distinguish between chromosome vs. chromatid abnormalities."Is the polar body approach best for pre-implantation genetic screening?" Delhanty, Joy. Placenta Vol. 32, pp. 268-270. 2011. The main advantage of the use of polar bodies in PGD is that they are not necessary for successful fertilisation or normal embryonic development, thus ensuring no deleterious effect for the embryo. One of the disadvantages of PB biopsy is that it only provides information about the maternal contribution to the embryo, which is why cases of autosomal dominant and X-linked disorders that are maternally transmitted can be diagnosed, and autosomal recessive disorders can only partially be diagnosed. Another drawback is the increased risk of diagnostic error, for instance due to the degradation of the genetic material or events of recombination that lead to heterozygous first polar bodies. It is generally agreed that it is best to analyse both polar bodies in order to minimize the risk of misdiagnosis. This can be achieved by sequential biopsy, necessary if monogenic diseases are diagnosed, to be able to differentiate the first from the second polar body, or simultaneous biopsy if FISH is to be performed. In theory, molecular analysis of polar bodies may include

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

profiling in the near future.

Target diseases

Aneuploidy

Several studies have suggested that

screening for

aneuploidy Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...

may not be optimal. When the majority of errors occur in

chromatids A chromatid (Greek ''khrōmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chro ...

rather than entire

chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

(a condition correlated with the age of the mother), screening only the first polar body will fail to detect a large percentage of defective eggs. As mentioned earlier, chromosomal abnormality in the first polar body can result in a healthy embryo, meaning that eggs may in fact be wasted as a result of the screening. Polar body testing will also be unable to detect post-zygotic errors in an

. Because

euploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...

polar bodies contain the same chromosomes as the oocyte, they can be used as a source of genetic material that is easily accessed without destroying the egg. This presents a research advantage by minimizing damage to the oocytes under investigation.

Usage

Polar body biopsy is used mainly by two PGD groups in the USA and by groups in countries where cleavage-stage embryo selection is banned.

References

{{reflist Medical genetics 1987 introductions