Mosaic Embryos: ‘Who’ or ‘What’ are They? Is It Possible to Transfer Them?

The interpretation of mosaicism among tiny preimplantation embryo–babies is complicated both for doctors and patients. Mosaic Embryo is an embryo with both types of cells: normal and abnormal ones. Therefore mosaic embryos represent a third category between normal (euploid) and abnormal (aneuploid) embryos. Some of the mosaic embryos have perfect chances to turn into the wonderful healthy fetuses. The others may cause the early or late pregnancy loss or even more complexities. This category of Mosaic Embryos may be characterized by decreased implantation and pregnancy potential with increased risk of genetic abnormalities to the fetus and adverse pregnancy outcomes. But every case of Embryonic Mosaicism is unique and should be investigated prior to embryo implantation.

1. What is an ‘EMBRYO’?

The assembly of a new life first depends on the union between a spermatozoon and an oocyte culminating in fertilization. If the fertilization occurs, the embryo appears. Fertilization is a mysterious phenomenon that turns two cells into a tiny embryo–dude or a tiny embryo–lady, or if two oocytes are fertilized than…two tiny embryo–dudes. Or two tiny embryo–ladies. Or if three oocytes are fertilized than three tiny embryo–babies: two tiny embryos male or female. Many versions can be inserted here.

2. How does the embryo appear in a natural way?

Wondering how does fertilization happen? Usually, a spermatozoon and an oocyte ‘meet’ in one of the two Fallopian tubes that connect the ovaries to the womb (uterus). Wondering how does the embryo–baby normally ‘appears’ and implants in the uterus? The tiny embryo–dude or the tiny embryo–lady (fertilized oocyte) then moves down the Fallopian tube by being wafted by fine hairs inside the tubes until it reaches the womb (uterus) two, three or four days later. Once there, this tiny embryo–bundle wonders where it should cuddle up itself in this new place. And it implants, attaching itself to the womb lining and that is where it usually continues to grow and develop.

The ability of the Fallopian tube to transfer the early embryo into the uterus is an excessive modality for a successful pregnancy. Apparently, structural abnormalities and functional abnormalities of the Fallopian tube will interfere with the Embryo Transfer process that can lead to tubal pregnancy.

3. How does the EMBRYO appear in case if it is IVF Treatment cycle? 

In Vitro Fertilization Treatment cycle is designed to create the embryos in the laboratory and after that to transfer them to the mother’s uterus. In other words, fertilization [or EMBRYO ‘CREATION’] happens in the laboratory.

Embryologists will ‘design’ your tiny embryo–ladies and embryo–dudes in the laboratory. They will take the retrieved oocytes and toss them in a Petri dish with your husband’s sperm and let them do their thing. Another option is called Intracytoplasmic Sperm Injection (ICSI), where the Embryologists manually fertilize the oocytes with the sperm individually, but it is for extreme cases only.

The embryo will appear inside your uterus via the catheter. Your tiny scared embryo–lady or embryo–dude is taken out of the Petri–dish and waits for a ‘BIG TRANSFER’. If it is the time to replace this small embryo–bundle from the tube inside your uterus, it is placed inside a flexible catheter. The procedure of Embryo Transfer takes only several minutes. It takes all of three minutes to insert a weird kind of catheter, get it to where it needs to be, accurately place your little embryo inside your uterus, and that is all. Yes, and it has to ‘LEARN’ so many things inside. It wonders: ‘Where am I?’ ‘What has happened?’ ‘Everything is pulsating around me…’ ‘Should I curl up here or there?’ ‘Oh, it is better on the left side?’ ‘I am scared. I will just cuddle up to that warm place and sleep there.’

4. Embryo Classification [Classifying mosaicism in embryos]

Most Fertility Clinics and labs have the strong exclusion/inclusion criteria for the embryo classification. They classify embryos as “normal” (euploid) or “abnormal” (aneuploid). Normal embryos should implant without complications. They (euploid embryos) should be preferentially transferred over mosaic embryos. Abnormal embryos may implant, but even in this case, the miscarriage will occur. And mosaic embryos are the most mysterious ones. They not only have both normal and abnormal cells. That means that they may correct themselves and become the viable healthy fetuses or may cause the miscarriages and variable abnormalities.

Embryonic Mosaicism occurs when the embryo has multiple genotype content. That means that two or more cell populations with different genotypes are present within the same embryo.

New diagnostic techniques for Preimplantation Genetic Screening (PGS), such as Next–Generation Sequencing, have led to increased revealing and reporting of mosaicism. Most experts do not recommend transferring the mosaic embryos because of the lower implantation rates, increased risks of miscarriages, and increased risks of genetic abnormalities. But there is still one but. The interpretation of mosaicism is complicated because the transfer of some mosaic embryos has resulted in healthy fetuses and births of the healthy babies. Do you remember that sometimes the mosaic embryos can correct themselves?

5. What Are the Mosaic Embryos?

The ‘Mosaic Embryo’ is the term that is assigned to that embryo that has both normal and abnormal cells, that are revealed during Preimplantation Genetic Screening (PGS) Testing. In the case of Embryonic Mosaicism, the testing discloses the percentage of the cells with different genetic complements and shows the potential embryonic viability.

Not only IVF embryos’ may have mixed chromosomal contents, one embryo can be normal, another embryo can be abnormal, and the third embryo can be mosaic, but also those tiny embryo–dudes and embryo–ladies that appeared naturally. Wondering what does that mean ‘mosaic embryo has mixed chromosomal content’? The mosaic embryo contains some cells with a normal number of chromosomes and others with an abnormal number of chromosomes.

Mosaic embryos may represent a third category of embryos being between normal and abnormal ones. Wondering why do they represent the third category? They represent the third category because of the mysterious self–correction phenomenon. The experts say that mosaic cleavage stage embryos left in extended culture have been shown to self–correct to euploid blastocysts (normal embryos) in nearly 50% of cases.

Therefore, this pattern of mysterious Embryonic Mosaicism, which is characterized by the presence of two or more genetically distinct cell lineages, typically one with a chromosome abnormality and the other with a normal chromosome composition, has become a controversial topic with the spirited debate over their potential viability.

6. Why does the mosaicism happen? 

You won’t believe but the embryos are prone to mosaicism. Embryonic Mosaicism was found to result from mitotic errors occurring after fertilization (after the embryo is created). As an early embryo (the fertilized oocyte) develops into a fetus, cells that initially acquired the extra chromosome give rise to new and larger populations of cells with the extra chromosome. All cells produced from the initial abnormal cell have the trisomy, but cells produced from the normal cells have the usual 46 chromosomes.

Or, there is another version of the mosaicism. The Embryonic Mosaicism happens because the sperm or oocyte itself had an extra copy of the chromosome. Normally, an early embryo (fertilized oocyte) contains 46 chromosomes. Mosaicism occurs in case if an early embryo (fertilized oocyte) contains 47 chromosomes. This occurs as a result of trisomy, in which there is an extra copy of a chromosome appears in an embryonic cell. In some cases, only some of the embryonic cells have the extra chromosome. Why does an extra copy of a chromosome appear in some embryonic cells? This happens in case if the sperm or oocyte itself had an extra copy of the chromosome, and the extra copy was not passed on to all cells after fertilization.

And the most wonderful thing is that the mosaic embryos may correct themselves. Isn’t it amusing?

7. Is it possible to reveal the mosaicism in an early embryo? 

Yes, it is possible to reveal the mosaicism in an embryo. Preimplantation Genetic Screening (PGS) was exclusively designed for the detection of the Embryonic Mosaicism in a single biopsy. The testing, usually performed on day 5 of embryo development, is completed by taking a tiny biopsy of the embryonic cells and examining the genetic makeup of the cell. During the examination, embryologists can detect, and often diagnose, potential chromosomal abnormalities.

8. Embryo Selection: which Mosaic Embryos are better to transfer?

Chromosomal abnormalities that occur in Mosaic Embryos can be categorized as ‘monosomies’ and ‘trisomies’ Normally, there are 46 chromosomes arranged in 23 pairs. Twenty–two chromosomal pairs are called ‘autosomes’, and one pair, number 23, is the sex chromosomes. Any variation from this gold pattern causes chromosomal abnormalities.

A chromosome from any of the pairs may be duplicated (trisomy) or absent (monosomy); an entire set of 23 chromosome pairs can be duplicated three (triploidy) or more (polyploidy) times; or one arm or part of one arm of a single chromosome may be missing (deletion).

The experts recommend that the percentage of mosaicism be considered in Embryo Selection decisions. It must be also noted that the proportion of aneuploidy should be less than 20 percent because the higher percentage of aneuploidy is associated with the adverse outcomes. The higher percentage of aneuploidy not only disturbs but also may disrupt the delicate balance of genetic content.

They also recommend the preferential transfer of embryos showing mosaic monosomies over mosaic trisomies. It should be also noted that if the mosaic embryo doesn’t correct itself, the consequences can be fatal, including the early or late pregnancy loss, physical and cognitive defects, morbidity and mortality.

CONCLUSIVE REMARKS

Because mosaic embryos are less likely to produce a viable pregnancy your doctor may recommend you not to transfer them. Normal embryos should be preferentially transferred over mosaic embryos. In case if you would decide to transfer the tiny mosaic embryo–dude or gorgeous mosaic embryo–lady, you should know that this small bundle of nerves has the chances as it may correct itself. If transfer of a Mosaic Embryo is being considered, you should have also the genetic counseling about potential benefits and risks that are closely associated with this issue.

Readibility rating: ‘C’ [the text can be read by the general public]. ‘C’ because this is embryology and embryology has its terms without which it is impossible to describe the issues.