Chromosomal maldistribution contributes significantly to the loss of embryos before and after implantation.
Numerous studies show that the implantation failure of embryos both after natural conception and after IVF or ICSI therapy, as well as the occurrence of abortions in the first third of pregnancy, is to a considerable extent due to spontaneously occurring chromosomal maldistribution. For the IVF/ICSI treatment, the idea is therefore obvious to exclude oocytes with possible chromosomal maldistribution from the fertilisation process by polar body diagnostics and thus to significantly increase the proportion of transferred embryos with a normal set of chromosomes.
It is possible to have an additional examination of your eggs as part of your planned IVF - or IVF /ICSI - treatment, called polar body diagnosis. This examination can provide information about the quality of your eggs and improve the chances of success of your treatment.
Polar body diagnostics currently offers the only possibility for chromosomal/genetic examination of unfertilised eggs in compliance with the legal framework in Germany. The following information will give you an overview of this special diagnostic procedure and explain what it means for you if you decide to undergo this additional examination.
During its maturation, the oocyte must undergo 2 divisions. An initially duplicated set of chromosomes is distributed evenly over the egg cell and the first polar body during the 1st division, which is discharged into the perivitelline space, i.e. the area between the egg cell and the envelope surrounding the egg cell (zona pellucida). The egg is then in a mature stage and ready to be fertilised by the penetration of a sperm cell. This is followed by the 2nd maturation division, in which each chromosome is split into two chromatids. The chromatids are now once again distributed evenly over the egg cell and the 2nd polar body, which is then also discharged.
Normally, the number of chromosomes in the egg cells and in the corresponding polar bodies is the same. However, it is known that chromosomal distribution errors can occur during maturation division, leading to numerical chromosomal anomalies (aneuploidies) in the affected oocytes. When such chromosomal misalignment occurs, the number of chromosomes in the eggs and in the corresponding polar bodies is unequal. Recent scientific studies have shown that oocytes from patients aged > 35 years have a chromosomal misalignment rate of over 50% (Pellestor et al., Hum Genet 112, 2003). This means that from the outset, more than half of the eggs are not capable of producing a healthy pregnancy. This can be seen as one of the reasons why the chance of pregnancy decreases in women with increasing age, while at the same time the risk of chromosomal miscarriage increases until the birth of a child affected by a chromosomal disorder (e.g. Down's syndrome). Relevant here are especially aneuploidies ( maldistribution ) of chromosomes 13, 15, 16, 18, 21 and 22 (Wieacker et al., Reproductive Medicine 18, 2002). These anomalies are mainly attributed to chromosomal maldistribution, which occurs in the oocytes mainly during the 1st division of maturity (Abruzzo and Hassold, Environ Mol Mutagen 25, 1995).
Both polar bodies can be removed from the egg cell after opening the egg cell envelope by means of a special laser, which is harmless to the egg cell, through a biopsy and subjected to a FISH analysis (fluorescence in situ hybridisation). With this examination method, the chromosome or chromatid sets in the polar bodies can be checked and conclusions can be drawn about the chromosome set remaining in the egg cell. Oocytes with chromosomal abnormalities can thus be identified. This information is very valuable, as the chromosomes may be maldistributed (aneuploidy) during maturation divisions. Approximately 95% of all distribution errors occur during the 1st mature division, i.e. during the formation of the 1st polar body, and only a few (approx. 5%) during the formation of the 2nd polar body (2nd mature division).
Embryos created from aneuploid oocytes often die before or shortly after implantation in the uterus. In some cases, however, pronounced malformations can be the result. For example, mongolism (Down syndrome) is caused by the triple presence of chromosome 21. Chromosomal defects in embryos are 80% oocyte-related, while 20% are due to maldistribution in the sperm cells. The proportion of aneuploid mature oocytes increases sharply in women after the age of 35. In women over 40, the proportion of these eggs is already 50 to 70%. For these women, the chances of achieving and carrying out a pregnancy without complications are significantly reduced.
Polar body diagnostics (PKD) is an internationally established, successfully applied diagnostic procedure to avoid the transfer of genetically not intact embryos. The removal of the two polar bodies is not dangerous for the egg cell and its further development if carried out properly and takes place a few hours after IVF or ICSI. However, we would like to point out that the removal of the second polar body is not always possible, as this is often still firmly attached to the egg cell membrane and cannot then be removed without damaging the egg cell. The evaluation of the examination of the removed polar bodies is only carried out on the following day. In the laboratory, the genetically perfect oocytes are then further cultivated for transfer.
Statistically significant are mainly maldistributions of chromosomes 13, 16, 18, 21 and 22, which are recorded in a routinely performed FISH examination in the context of PKD. However, depending on the initial genetic situation of the couple, various other chromosomes can also be analysed.
Numerous studies in animal models and also in humans have shown that no damage to embryos resulting from biopsied oocytes was observed. As mentioned above, the investigations using the FISH technique usually only include chromosomes 13, 16, 18, 21 and 22. A maldistribution of the remaining chromosomes cannot therefore be ruled out. If the 2nd polar body cannot be removed for the reasons already mentioned, there is a methodically determined residual risk of further undetected maldistribution of about 5 %. Irrespective of how a pregnancy is achieved, i.e. even if it occurs in the normal way, there is always a basic genetic risk of approx. 3 - 5 % for the occurrence of fetal malformations.
For this reason we recommend that, despite carrying out polar body diagnostics in the case of pregnancy, you have the various prenatal examinations such as ultrasound examinations, blood tests and, if necessary, genetic examinations such as an amniocentesis carried out.
Avoidance of the transfer of embryos with chromosomal maldistributions that do not lead to pregnancy or, in the case of pregnancy, end in miscarriage, which may require scraping and may be associated with great mental and physical pain.
Prognosis for the further course of treatment. From the experience of international science we know that women who only produce oocytes with chromosome maldistribution are very unlikely to produce healthy oocytes in future treatment cycles. Although this is a bitter truth, it can lead to a decision not to try treatment and to incur costs that are disproportionate to the chances of having a healthy child.
In our fertility centre we carry out polar body analysis using the FISH technique in cooperation with the University Women's Hospital in Bonn.
The genetic diagnosis of oocytes is not covered by the statutory health insurance (GKV) and only occasionally by private health insurance (PKV). Therefore, this service cannot usually be provided at the expense of the health insurance companies. Before the polar body diagnosis is carried out, a consultation with one of the attending doctors is necessary. If you decide to have the polar body diagnostics carried out, a declaration of consent signed by you and the doctor must be available.