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Faster, cheaper and less damaging to DNA, a microchip device that pits sperm racing against one another is being developed by Afrouz Ataei from Florida Atlantic University and may help to improve IVF success rates in the future.

Ataei is presenting the fitness stats on the sperm sorted by her device this week at the American Physical Society March Meeting in Boston, and she will also participate in a press conference describing the work. Information for logging on to watch and ask questions remotely is included at the end of this news release.

“An integral part of in vitro clinical procedures is the isolation of motile and morphologically normal viable sperm from the semen,” said Ataei, who explained that this step increases the chances of successful egg fertilization in plastic dishes outside the body (in vitro).

However, the conventional method used to sort the speediest sperm involves centrifugation and several high-speed, G-force inducing spinning steps, which can damage the delicate DNA encased within a sperm’s head. And an egg fertilized with sperm damaged in this manner is unlikely to progress to a viable embryo for implantation into the womb.

In women under 35 there is only a 21.5 percent chance of a single round of in vitro fertilization, or IVF, resulting in a full-term live birth. And with each round of IVF in the U.S. costing an average of $10,000-$15,000, this makes improving the odds of IVF success key for the financial and emotional well-being of many of the couples who experience fertility problems.

Ataei’s device manages to select the faster swimmers without any damaging centrifugation steps. Instead, her device exploits the observation that sperm swim against an opposing flow of liquid at certain flow rates. The microchip is designed to induce hydrostatic pressure, which generates liquid flow without the use of other equipment.

“No other devices generate the flow in this way, and our device is much easier to use,” said Ataei.

An unprocessed semen sample is injected into the chip’s inlet until it fills the lower microchamber, and the sperm gradually swim upstream against the flow. If fit and fast enough, the sperm make it past the ultrathin membrane filter, which acts as the finish line, and into the top chamber. Ataei has analyzed the winner’s fitness stats.

“After 45 minutes we collect the sample from the top retrieval chamber and start observing and analysing the sperm’s velocity, whether they have DNA fragmentation, and what’s the percentage of this compared with current methods like centrifugation,” said Ataei. “We found that at a specific flow rate, we get the most motile sperm with highest motility.”

“I think this device has potential for clinical use,” Ataei added.

The team at Florida Atlantic University is continuing to optimize the microfluidic device, hoping to increase the concentration of sperm collected in the top chamber before they file a patent on their design.

Date: March 4, 2019

Source: American Physical Society Source: https://www.sciencedaily.com/releases/2019/03/190304095727.htm

Reviewed by James Ives, M.Psych. (Editor)Apr 13 2020

Scientists have created a mathematical model that can help explain why so many pregnancies and in vitro fertilization attempts fail.

The Rutgers-led study, which may help to improve fertility, is published in the journal Proceedings of the National Academy of Sciences.

Mistakes in female meiosis, the cell division process that creates egg cells, result in eggs with an abnormal number of chromosomes (too many or too few). This phenomenon is strongly associated with the repeated loss of pregnancies and the failure of in vitro fertilization (IVF) procedures, as well as developmental disorders such as Down syndrome.

Our study demonstrates that in the future, mathematical models can be powerful tools for predicting the outcomes of in vitro fertilization for infertility patients and/or provide the basis for considering alternative family planning options, such as adoption.”

Jinchuan Xing, senior author, associate professor in the Department of Genetics in the School of Arts and Sciences and at the Human Genetics Institute of New Jersey at Rutgers University–New Brunswick

“Modeling efforts such as ours can provide guidelines on, for instance, how many eggs must be collected during a single IVF cycle to ensure there will be at least one chromosomally normal conception,” said co-author Karen Schindler, an associate professor in the Department of Genetics and at the Human Genetics Institute of New Jersey.

Pregnancy loss is extremely common, with nearly 20 percent of clinically recognized pregnancies resulting in miscarriage, and many more unrecognized pregnancies end earlier, the study notes.

A leading cause of early miscarriage is called aneuploidy, when eggs have the wrong number of chromosomes, and it’s also the main cause of IVF failure. The vast majority of eggs with chromosome problems are linked to errors in female cell division that increase as women age. Understanding how that happens is crucial because the average age at conception is rising in developed countries.

“Such basic knowledge is required to pave the way for future diagnostic and therapeutic innovations to improve human fertility,” the study says.

The scientists developed a mathematical model describing all possible abnormal chromosome count issues in eggs due to cell division errors. Using data on 11,157 early stage human embryos (blastocysts), the model revealed previously unknown patterns of errors.

The model can be used to identify IVF patients who produce an extreme number of abnormal embryos. It’s also a powerful tool for understanding why abnormal numbers of chromosomes arise when cells divide and for predicting the outcomes of IVF reproduction. The model potentially could provide guidance for clinicians on the expected number of IVF cycles needed to get a normal conception for each patient. The modeling framework can also be expanded and adapted to address other processes, such as predicting errors in sperm.

Source: https://www.news-medical.net/news/20200413/New-mathematical-model-can-help-explain-why-so-many-pregnancies-and-IVF-attempts-fail.aspx

Tel Aviv University (TAU) researchers have developed a safe and accurate 3D imaging method to identify sperm cells moving at a high speed.

The research, a study of which was published in Science Advances on April 10, was led by Prof. Natan Shaked of the Department of Biomedical Engineering at TAU’s Faculty of Engineering together with TAU doctoral student Gili Dardikman-Yoffe.

The new technology could provide doctors with the ability to select the highest-quality sperm for injection into an egg during IVF treatment, potentially increasing a woman’s chance of becoming pregnant and giving birth to a healthy baby.

The IVF procedure was invented to help fertility problems. The most common type of IVF today is intra-cytoplasmic sperm injection (ICSI), which involves sperm selection by a clinical embryologist and injection into the woman’s egg. To that end, an effort is made to select the sperm cell that is most likely to create a healthy embryo.”

Natan Shaked, Professor, Department of Biomedical Engineering, Faculty of Engineering, TAU

Under natural fertilization in the woman’s body, the fastest sperm to reach an egg is supposed to bear high-quality genetic material. Progressive movement allows this “best” sperm to overcome the veritable obstacle course of a woman’s reproductive system.

“But this ‘natural selection’ is not available to the embryologist, who selects a sperm and injects it into the egg,” Prof. Shaked says. “Sperm cells not only move fast, they are also mostly transparent under regular light microscopy, and cell staining is not allowed in human IVF.

“Existing imaging technology that can examine the quality of the sperm’s genetic material may cause embryonic damage, so that too is prohibited. In the absence of more precise criteria, sperm cells are selected primarily according to external characteristics and their motility while swimming in water in a dish, which is very different from the natural environment of a woman’s body.

“In our study, we sought to develop an entirely new type of imaging technology that would provide as much information as possible about individual sperm cells, does not require cell staining to enhance contrast, and has the potential for enabling the selection of optimal sperm in fertilization treatments.”

The researchers chose light computed tomography (CT) technology for the unique task of sperm cell imaging.

“In a standard medical CT scan, the device rotates around the subject and sends out X-rays that produce multiple projections, ultimately creating a 3D image of the body,” says Prof. Shaked. “In the case of the sperm, instead of rotating the device around this tiny subject, we relied on a natural feature of the sperm itself: Its head is constantly rotating during the forward movement.

“We used weak light (and not X-rays), which does not damage the cell. We recorded a hologram of the sperm cell during ultrafast movement and identified various internal components according to their refractive index. This creates an accurate, highly dynamic 3D map of its contents without using cell staining.”

Using this technique, the researchers obtained a clear and accurate CT image of the sperm at very high resolution in four dimensions: three dimensions in the space at resolution of less than half a micron (one micron equals one millionth of a meter) and the exact time (motion) dimension of the second sub-millisecond.

“Our new development provides a comprehensive solution to many known problems of sperm imaging,” Prof. Shaked says. “We were able to create high-resolution imaging of the sperm head while it was moving fast, without the need for stains that could harm the embryo. The new technology can greatly improve the selection of sperm cells in vitro, potentially increasing the chance of pregnancy and the birth of a healthy baby.

“To help diagnose male fertility problems, we intend to use our new technique to shed light on the relationship between the 3D movement, structure and contents of sperm and its ability to fertilize an egg and produce a viable pregnancy,” Prof. Shaked concludes. “We believe that such imaging capabilities will contribute to other medical applications, such as developing efficient biomimetic micro-robots to carry drugs within the body.”

Source:

American Friends of Tel Aviv University

Journal reference:

Dardikman-Yoffe, G. et al. (2020) High-resolution 4-D acquisition of freely swimming human sperm cells without staining Science Advances. doi.org/10.1126/sciadv.aay7619.

(Source: https://www.news-medical.net/news/20200508/Researchers-develop-safe-accurate-3D-imaging-method-to-improve-IVF-treatments.aspx)