Some approaches to in vitro fertilization involve mixing sperm and egg in a test tube and letting nature take its course. But in about half of all infertility cases, a problem with the man’s sperm may require a more direct method. In these cases, a different process, called intracytoplasmic sperm injection (ICSI), in which a single sperm cell is injected directly into an egg, is sometimes used. With this one-shot opportunity, it’s important to choose a sperm cell with the best potential for success. A team at the University of Edinburgh, Scotland, has now announced a new technique to ensure that the best sperm win: analyzing their DNA for potential damage beforehand, and choosing those that are structurally sound.
“It’s a new development that could be very promising,” says Alan Penzias, a reproductive endocrinologist at Boston IVF and Harvard Medical School, who was not involved in the research. Penzias explains that current standards for choosing a single sperm cell for an ICSI procedure usually depend on assessing how well the sperm swims; if none of the sperm can swim, a chemical test can find those that are intact and alive. “It’s been really pretty crude,” he says.
Alistair Elfick, lead scientist for the Edinburgh team, explains that by choosing a single sperm rather than allowing many sperm to swim to and compete for a place in the egg, “you have very much become the arbiter of the quality of that sperm. So clearly, there’s a motivation to have a more rigorous selection procedure.” With this new technique, the researchers can rank different sperm and choose the one with the most intact DNA. “The endpoint we’re moving towards is having a score of DNA quality,” Elfick says. But he adds that the approach is an overall measure of the sperm’s health; it’s not sensitive enough to pick and choose traits.
The method that Elfick and his colleagues developed relies on Raman spectroscopy, a technique that measures the way that molecules scatter photons from a beam of laser light, revealing the molecules’ vibrational properties. In order to probe a single sperm cell with Raman spectroscopy, the researchers first pin it down with optical tweezers–a focused laser beam that is able to “trap” a small object like a living cell. The unique scattering produced by each molecule creates a fingerprint of the contents in a sample, allowing scientists to analyze its chemical makeup. In this application, the researchers use Raman spectroscopy to look at the structure of a sperm cell’s DNA and determine whether that DNA is broken or intact. Elfick explains that when DNA breaks, a chemical group forms at the ends of the breaks, and they can be detected with Raman spectroscopy.
DNA damage has been associated with cases of male infertility and a loss of sperm’s ability to swim. Although the association between DNA breaks and infertility requires more research, Elfick says that “it’s highly likely that the better the DNA, the better off the sperm will be.”
Preliminary tests suggest that the technique does not harm the cells, although Elfick says that more rigorous testing must be done in order to bring the technique into clinical use. His team is hoping to commercialize this and other applications for Raman spectroscopy, including analyzing breast-cancer cells for specific proteins in order to tailor chemotherapy to individual patients.
Michael Morris, a chemist at University of Michigan who uses Raman spectroscopy to analyze bone, says that many investigators are working on clinical applications for the technique. At the level of individual cells, scientists are using Raman spectroscopy to distinguish normal cells from cancerous ones, and to identify specific strains of bacteria, such as those that cause treatment-resistant infections in hospitals. Raman spectroscopy also holds promise as a way of studying disease directly in patients. Researchers such as MIT’s Michael Feld are investigating the possibility of using it in conjunction with minimally invasive probes to look for cancer or other disease processes inside patients’ tissues. Denny Sakkas, a scientist at Yale University and Molecular Biometrics, has developed a similar technology called spectrophotometry to evaluate the viability of embryos, and is working to expand it to analyze human eggs. Morris suspects that many new applications will emerge, as the technology has a great deal of power for detecting chemical change in small samples.
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