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The Inefficient Embryonic Development Process That May Be Affecting Your Fertility

Only one in three fertilizations leads to a successful pregnancy. Where do things go wrong?

June 30, 2021
Alexandra Ross

Not many people are aware of how common unsuccessful embryonic development is, but in fact, two-thirds of fertilizations fail to develop successfully. For a long time, scientists have struggled to determine precisely why, how, and when certain embryos are successful while others are not. 

Now, scientists across the world have teamed up to develop a new kind of model system for studying early embryonic development. With this advancement, they have been able to pinpoint how one phase of embryonic development leads to so many unsuccessful fertilizations.

Blue and white pregnancy test that reads "Not Pregnant"
Many people who have issues with infertility feel that they are alone or abnormal in their struggle. In reality, fertility struggles are far from abnormal — only one in three fertilizations leads to a successful pregnancy.

Errors at the start of life

When fertilization occurs, 23 chromosomes from the father’s sperm and 23 chromosomes from the mother’s egg come together to create a 46-chromosome embryo. For a little while after fertilization, the two sets of chromosomes are separated into two pronuclei, but eventually they move towards one another until they combine.

Often, even the majority of the time, errors in this process cause human embryos to end up with an incorrect number of chromosomes. This doesn’t always lead to unsuccessful pregnancies — individuals with Down Syndrome are born with three copies of chromosome 21, for example. However, erroneous genome unification is one of the leading causes of infertility and miscarriages.

“About 10 to 20 percent of embryos that have an incorrect number of chromosomes result from the egg already containing too few or too many chromosomes prior to fertilization. This we already knew,” said Melina Schuh, director of Biophysical Chemistry at the Max Planck Institute (MPI) in Germany. “But how does this problem arise in so many more embryos? The time immediately after the sperm and egg unite — the so-called zygote stage — seemed to be an extremely critical phase for the embryo's development. We wanted to find out why this is the case.”

Scientist wearing PPE inspects unidentified object through microscope
Because embryonic development happens on such a tiny scale, the use of  microscope technology was essential in this research. Scientists analyzed microscopy videos of human embryos and  live-cell microscopy of bovine embryos.

A new model organism

In order to get a better look at the human reproductive system and better study early embryonic development, cell biologists working in Shuh’s laboratory at the MPI in Göttingen, Germany teamed up with other researchers from the Institute of Farm Animal Genetics in Mariensee and other scientists from around the world. 

Together, this team developed a new model system for studying early embryonic development. Microscopy videos of human zygotes, recorded by an English laboratory, were first analyzed. Then, the scientists set out to find a new kind of model organism that could help them to study early embryonic development in closer detail. 

This is why collaboration with researchers at the Institute of Farm Animal Genetics was so crucial to the project. Together with their collaboration partners at the Institute of Farm Animal Genetics, Shuh’s scientists at the MPI developed methods for studying live bovine embryos. 

Bovine, or cattle, embryos closely resemble human embryos in many ways, including the timing of the first cell divisions and the frequency of chromosomes distributing incorrectly. The use of bovine embryos also helped to reduce ethical concerns, as these embryos were developed from slaughterhouse waste, eliminating the need to sacrifice additional animals.

In vitro fertilization and live-cell microscopy were used to create and track the bovine embryos. The scientists were interested in investigating how the parental genetic material unites in the process of early embryonic development, which led them to find that the parental chromosomes cluster at the interface between the two pronuclei. This is when errors occur that result in developmental issues. 

“The clustering of chromosomes at the pronuclear interface seems to be an extremely important step," said Tomaso Cavazza, one of the researchers at the MPI. "If clustering fails, the zygotes often make errors that are incompatible with healthy embryo development.”

A man in the forest smiles next to a brown dog and a brown cow
Though dogs may be man’s best friend, it is actually the embryo of a cattle that more closely resembles the embryo of a human. MPI researchers used bovine embryos to make these groundbreaking discoveries about human fertility. 

Clustering and lost chromosomes

The scientists who collaborated on these investigations into early embryonic development came to the conclusion that the errors occur when individual chromosomes failed to cluster with the others between the pronuclei. 

These chromosomes are therefore lost when the mother’s and father’s genomes unite, and the resulting embryo does not have enough chromosomes to continue healthy development. 

Once they had discovered this, the researchers at the MPI turned to the question of why chromosomes fail to cluster correctly so often. Through further analysis of the bovine embryos, they found an answer.

“Components of the cytoskeleton and the nuclear envelope control chromosome movement within the pronuclei,” said Cavazza. “Intriguingly, these elements also steer the two pronuclei towards each other. So we are dealing with two closely linked processes that are essential, but often go wrong. Thus, whether an embryo will develop healthily or not depends on a remarkably inefficient process.”

A couple, faces unseen, together holding ultrasound pictures
If you are worried about your ability to get pregnant, talk to your doctor about what options are available to you. With the help of fertility treatments like IVF, you could become a parent in less than a year.

Are clustering errors preventable?

Researchers have not yet found a link between behavior and the success of the clustering process, so there is not a known way for prospective parents to decrease the likelihood of this early embryonic development error. However, if you are struggling with infertility, there are many options available to you to generally improve your chances at a successful pregnancy.

On your own, there are many methods for increasing fertility that are supported by scientists. For example, decreasing stress through exercise, meditation, and other methods may increase your likelihood of getting pregnant. Additionally, tracking your menstrual and ovulation cycle ensures that you won’t miss your window of opportunity for fertilization. 

If these methods aren’t working for you, you may want to consider utilizing a fertility treatment such as in vitro fertilization (IVF). In fact, the research done by Shuh’s laboratory could help to make IVF treatment even more effective, as the proper clumping of chromosomes between the pronuclei can be used as selection criteria for viable embryos. Ask your doctor about the risks and benefits of IVF to see if it could be the right path to pregnancy for you. 

A mother holds her baby to her torso. She is in a white sweater and the baby is in a beige blanket. Their faces are unseen

While chromosome clustering errors may be out of your control, there are still many treatment options to overcome your fertility struggles. One of the most successful of these treatments is in vitro fertilization, or IVF.

Thanks to the research of the Max Planck Institute, we now know that the clustering phase of early embryonic development is one of the most influential in determining the future course of a pregnancy. If chromosomes fail to cluster, it is unlikely that a fetus will healthily develop.

While it is unfortunate that MPI researchers did not determine any link between behavior and clustering that could help eliminate these errors, this is a promising step forward in fertility research that will serve to improve fertility treatments in the future.


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