In IVF treatments, couples are given a report regarding the embryo quality and/or pictures of the transferred embryos by the centre they completed their treatment. If they have not been given a detailed embryo breakdown report prior to or after the transfer, couples can not get reliable/scientific information on the status just by the pictures. However, in most cases these reports/pictures can be useful for the next treatment stage, since the information found will be used for analyzing reasons behind negative result.
Embryo transfer procedure can be performed on different embryo development days (from the 2nd day of embryo development until the 5th or 6th day) depending on the course of IVF treatment. Second day of embryo transfer may be preferred in couples with low number of developed embryos (1 or 2 embryos) by considering that these embryos could develop better in their natural environment (uterus). However, in cases the number of embryos appearing to develop healthily is a higher amount, which means embryos can be kept and observed in the laboratory environment a few more days in order to select the embryo considered to have the highest chance of implantation to the uterus. The probability of implantation of the embryo(s) can be selected by monitoring the embryos on a daily basis and assessing their cell quality.
These selection methods and criteria, which are called “embryo quality” among treated couples, are actually evaluated in the laboratory on a daily basis and by using specially designed criteria to grade embryos. According to this criterion, whose most important objective is to select the embryo with a high chance of success of implantation after transfer as well as to make a realistic estimation of the differentiating embryo quality and which has a good chance to create pregnancy, whether it is of a low or high quality; Couples can be quite anxious when the specialists providing the embryo quality start to give detailed information on this subject before the procedure. The most important point that should not be forgotten is that quality evaluation is only an estimation, which cannot determine the result and treatment outcome. This criteria is only important in terms of the selection of the embryo(s) to be transferred, the person that can help determine your success in your treatment and in the most accurate and realistic way, is your physician.
There are many different criteria used in embryo selection differently in each development day. Usually, indicators such as the number of cells that an embryo has (division rate), equality of the cells with each other, the condition of the intracellular cytoplasm as well as the zona of the embryo are some of the criteria taken into consideration when expressing the embryo quality in the early development period (day 2 or 3). On the other hand, the embryo evaluation criteria used on day 3 and before are insufficient for day 4 and later. This is because; the embryo starts to change in shape and volume by passing a different stage on day 4 and later. At this stage, the embryo is now called blastocyst and evaluated in a different way with its unique structure. It is impossible to count the cells in the blastocyst stage, as there are a large number of them. Therefore, features such as placement and appearance of the cells, the status of the opening called cavity, the presence of the region called Inner Cell Mass and its physical condition are analysed and the decision about the quality of the embryo is given.
Embryonic development and quality evaluation on day 4 and later are as follows:
Morula (CM): is the stage before the blastocyst stage. The region that we call cavity is not formed in the embryo yet however, the cells started to prepare the structure before cavity is formed by coming together. It is impossible to count number of the cells forming the embryo in this stage as seen.
Early Blastocyst (1): The embryo at this stage, which is also called as early blastocyst, is classified as 1. As seen in the picture, the cavity started to be formed however; the inner and outer cell separation cannot be made yet. The embryo in this situation can now be called as blastocyst. It is better than the morula in terms of quality and its chance of pregnancy is higher.
Early Blastocyst (2): A blastocyst, as seen in the picture, with enlarged cavity however, the inner and outer cells are not completely separated yet are classified as 2. This stage shows that the embryo maintains its viability and that it passed a lot of controls before and during blastocyst formation. The embryo will now start to expand and the cells will start to disintegrate among themselves.
Blastocyst (3): When the embryos reach the 3rd blastocyst stage, then the status of the cells can be observed better. The features such as placement and layout of inner cell mass and outer cells (trophoblast), thickness of the zona of the embryo can be classified. At this stage and later, the embryos are not named with only stage numbers but also by adding letters showing the status of the inner and outer cells. After the stage number, one letter is added first for the quality of the inner cells and then one for the quality of the outer cells. For example, we can say 3AB for the embryo in the picture. The open writing of this is an embryo at 3rd stage with grading A quality inner cells and B quality outer cells.
Blastocyst (4): The blastocyst at 4th stage is now started to demonstrate its potential completely. As also can be seen in the picture, the egg is enlarged and the zona of the embryo is thoroughly thinned. Inner cell mass can be observed very clearly; the placement of the outer cells and their relationship with each other is very clear. If we make an evaluation as in the previous embryo, we can say 4AA for this embryo. So, the embryo is enlarged and with thinned zona (4), in addition the quality of the inner cells and outer cells is A.
Blastocyst (5): Embryos after a certain stage, after the zona is thoroughly thinned, starts to hatch in order to implant to the uterus. Hatching embryo is now evaluated as a blastocyst in the 5th stage. Other evaluations are the same as the previous stage. Embryos reaching this level are also eligible to perform biopsy for genetic diagnosis. Samples from the hatching cells seen in the picture can be obtained and analysed.
Blastocyst (6): A blastocyst can live in vitro up to this stage. As seen in the picture, whole embryo is hatched from the zona and has to implant to the mother’s uterus. After this stage, the embryo cannot survive if the implantation does not take place. In general, the embryos in IVF centres are not waited to come to this stage. Because, a fully hatched embryo is very sensitive and it can be damaged very quickly. We should be very careful during carrying over and transfer of embryos at this stage. The disintegration of the cells or deterioration of the structure of the blastocyst is likely with the smallest compulsion.
By Jessica Hamzelou
WILL it be a boy or a girl? For people undergoing IVF, the nutrient-rich liquid their embryos grow in could tip the balance. The finding adds to mounting evidence that the culture medium is playing a role in an embryo’s development and future health.
Women undergoing IVF are treated with hormones that stimulate the release of eggs. The eggs are collected and fertilised with sperm in a dish. Sperm can either be left to do the job or, if the male partner has fertility problems, they can be injected directly into the eggs. The resulting embryos are then grown in the culture medium for between three and five days. At that point, the healthiest looking embryo is selected and implanted into the woman’s uterus.
Research in cattle has shown that the type of culture medium can influence how well male and female embryos develop. A glucose-rich medium, say, seems to favour the development of male embryos and the loss of female ones.
To find out if a similar effect was seen with human IVF embryos, Jinliang Zhu and his colleagues at Peking University Third Hospital in Beijing, China, analysed more than 4400 IVF procedures that had resulted in births between 2011 and 2013. The procedures used one of four common types of culture media made by different companies, the exact content of which is a closely guarded secret.
Four commonly used culture liquids result in different proportions of boy and girl babies
For people that had sperm injected into eggs, the sex of their healthiest embryo – and therefore their baby – was associated with the type of culture media that had been used. For example, the proportion of males at birth was 56 per cent for one type of medium, but just 45 per cent for another. The equivalent figure for natural births in the UK and US is 51 per cent. The association remained even after Zhu’s team had accounted for possible confounding factors such as the parents’ age, body mass index and the type of infertility they were experiencing (Human Reproduction, doi.org/2t4). The effect wasn’t seen in embryos not fertilised by sperm injection. “It’s a highly significant finding,” says Roger Sturmey at Hull York Medical School, UK.
Zhu’s team think that the male and female embryos respond differently to the mix of ingredients the different manufacturers use. It is already known that there are metabolic differences between male and female embryos – male embryos develop faster than female embryos, for example. These differences are probably down to the action of proteins coded for by DNA on the sex chromosomes.
Beyond that, it is difficult to tell what is going on or why the culture medium did not affect more naturally fertilised embryos. “It could be down to the selection of sperm, embryo development rates, how the embryos implant, or another mechanism related to miscarriage,” says Allan Pacey at the University of Sheffield, UK, who studies male fertility. The picture is further clouded by the fact that the industry doesn’t reveal the composition of culture media, he says.
In Canada, New Zealand, the UK and a number of other western European countries, it is illegal to genetically select a male or female embryo during IVF, unless there is a medical reason. But clinicians are free to choose whichever culture medium they like. “A couple reading this paper who have already got a girl might well say ‘hmm, perhaps I should be using the [male-favouring] medium’,” says Daniel Brison, a consultant embryologist at the University of Manchester, UK. “But it’s not really a very effective method of choosing a gender.”
Brison is more concerned about the other potential effects of culture medium on developing embryos. Last year, researchers at Maastricht University Medical Centre in the Netherlands found that the culture medium can affect the birth weight of the resulting babies, and that the effect lasts for at least two years (Human Reproduction, doi.org/2t5). The finding is important given that a low birth weight is known to predispose individuals to chronic conditions like diabetes and heart disease later in life, says Brison.
The period of development that comes just after the egg has been fertilised is thought to be critical, genetically. Not only is it the time when the parents’ genomes are shuffled together, it is also when a number of epigenetic changes – chemical modifications to DNA – are thought to take place. This might explain why slight changes to the embryo’s environment during IVF can have an impact on its development.
This article appeared in print under the headline “IVF nutrients may dictate sex of baby”
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