Is the test – tube conception dangerous?

But how safe are the auxiliary reproductive technologies (ART)? Having summarized the data accumulated by the world science, specialists of the Research Institute of Medical Genetics (Tomsk Scientific Center, Siberian Branch, Russian Academy of Medical Sciences) tried to look into only one aspect of the ART safety – risk of genomic imprinting diseases.

What kind of diseases are they? Normal mammal development requires that maternal and paternal gene sets differed functionally. In certain genes, only the maternal copy should work. And in others – only the paternal copy should. The mechanism regulating functional differences of parental genomes is called genomic imprinting. This is a complicated and multi-step process, which starts in the parental gametal cells, where special enzymes mark and disconnect the required genes (a human being has about 70 of them), and continues after impregnation. Heavy pathologies can be caused by failure of such marking at some stage, and several genomic imprinting diseases are known with human beings.

Genomic imprinting reacts to external factors, and the researchers expected that the auxiliary reproductive technologies could influence it. The first example of such influence was discovered in experiments on animals’ artificial impregnation. The “large posterity syndrome” sometimes develops with big horned cattle and sheep after embryo cultivation, the posterity weight often by twice exceeding the norm. Another important indication is increased fetus mortality in the course of pregnancy and in labour, at that the pregnancy is long and the delivery is difficult. The deceased fetus and new-borns have internal pathologies. The “large posterity syndrome” caused by derangements of genomic imprinting is very similar on the surface to the Wideman-Beckwith human syndrome arising for the same reason. In case of the Wideman-Beckwith syndrome, infants are born very big and with multiple pathologies. The syndrome frequency is normally one case per 12 to 15 thousand of new-borns, but it is several times higher with the children born with the help of the ART.

The researchers suggest several hypotheses explaining why genomic imprinting diseases occur more often in case of the ART than in case of traditional conception. Firstly, the process may be influenced by methodical peculiarities of artificial impregnation. In case of extracorporal fertilization, women are injected hormones to stimulate the ovulation. Possibly, gonadotropins accelerate maturation of ovums, which have not finished yet the genomic imprinting process. In some cases ovums have to be cultivated in nutrient medium prior to fertilization, and after fertilization embryos are bred on it before transplanting in the maternal organism. The nutrient medium composition and the lack of signals coming from the maternal organism in a normal case can also impact genomic imprinting, which takes place both in maturing ovums and in the developing embryo. It is not improbable that the genome marking can be influenced by cryopreservation of gametal cells and embryos, which is often practiced.

Secondly, the ART enables the events that would have never happen in a natural way. Thus, “anomalous” ovums can mature in case of hormone stimulation, such ovums would have scarcely mature during a natural cycle. Spermatozoa also can have imprinting defects. Normally, their fertility is low but they can be used for artificial impregnation, and then trouble is inevitable. Finally, artificial impregnation makes it possible that ill children are born with infertile married couples who have predisposition to genomic imprinting diseases.

Now, there is no unanimous opinion among the researchers as regards to the ART and genomic imprinting diseases. Some assume that the birth “the test-tube” children is an extremely rare event and it cannot be the reason for rejection of artificial impregnation. Their opponents believe that the genomic imprinting abnormalities cases known to us make only the visible part of the iceberg. We do not know too many things, and the risk of giving birth to infants with imprinting defects is although little, but important. Therefore, it is necessary to investigate the problem and to make extracorporal fertilization safe in every respect.