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Sequencing the RNA of sperm may better diagnose a man's infertility

The method could greatly benefit couples who are having trouble getting pregnant

There’s a new, more reliable method for figuring out if a man’s infertile. The discovery could help couples struggling to conceive to spend less time and money on fertility treatments that don’t work.

In a new study published today in Science Translational Medicine, researchers detail how sequencing genetic information in sperm can show whether a man is infertile. The scientists looked at the sperm’s RNA, a cornerstone in any cell — it helps cells to "read" DNA, and it plays a role in regulating genes’ activities. Men who are missing certain RNA sequences from their semen have a much lower likelihood of conceiving than men whose sperm contain these sequences. The findings suggest that sperm RNA could serve as a fingerprint for male fertility.

Sperm RNA could serve as a fingerprint for male fertility

Around 12 percent of couples are infertile, and in about 40 percent of these cases, the male partner is either the sole cause or partially contributing, according to the American Society for Reproductive Medicine. Fertility treatments are often expensive; the average price of in vitro fertilization hovers around $12,400. If clinics could tell patients whether they should save their money — or go directly to high-cost interventions, skipping the cheaper ones that won’t work — that may be reason enough to justify RNA sequencing of sperm.

Current methods for diagnosing male infertility involve looking at the shape, number, and movement of a man’s sperm. But sometimes this isn’t enough to tell which men are infertile; in many cases, there’s no obvious reason that a man should have difficulty with fertility, a condition known as idiopathic infertility. "It’s difficult to say why they pass all the fertility tests, and we can’t ascertain the underlying cause of the infertility," study author Stephen Krawetz, a professor at Wayne State University in Detroit, tells The Verge.

"Current methods don’t really provide great information on the chance of natural pregnancy or what may be causing abnormal sperm production," says Peter Schlegel, a professor of urology at Cornell University who was not involved with this study. "There certainly is a potential need for this method."

Sperm harbors a rich population of RNA (C. Bickel/Science Translational Medicine)

Krawetz has long suspected that sperm RNA might play a role in infertility. Researchers have known that sperm contains important DNA, which carries essential genetic information. But around 20 years ago, Krawetz and his research team discovered that sperm also house RNA — but its exact function within sperm remains unknown. It’s possible this RNA is passed onto the egg during fertilization, but scientists also suspect it plays a role in the development and production of sperm. Since this discovery, researchers have been working to determine how sperm microRNA may be related to a man’s fecundity.

Scientists identified 648 sperm RNA elements linked with male fertility

So Krawetz and his team collected sperm from 96 men who were receiving different types of treatments at a fertility clinic. Some of these men did not actually have infertility and were able to conceive with their partners after adjusting the timing of their intercourse. This group served as the control group, in contrast to the men who still struggled to conceive despite minimal intervention. The scientists sequenced the RNA of both groups’ sperm.

That let scientists identify 648 sperm RNA elements — known as exons — linked with male fertility. Men in the group who had trouble conceiving all had at least one of these RNA sequences missing in their sperm. Men who lacked more than one of the sequences had a 27 percent chance of conceiving naturally compared to a 73 percent chance among those in the control group. What’s more, these RNA elements correspond to genes that matter for sperm development, movement fertilization and other key functions.

Krawetz suggests that sperm RNA could help to chart the course of treatment for couples hoping to conceive. Along with examining sperm shape and size, fertility clinics could also look to see if these 648 RNA elements are present in the semen.

"If they are present, that would suggest they could use a minimal intervention treatment that would lead to a successful pregnancy," says Krawetz. "If they’re not present, that would suggest they should immediately proceed to assistive reproductive technology. It gives us more of a rationale for making a decision."

"We still need a clear understanding of what the critical RNAs are and how they interact with the causes of male infertility," he says.

This study is only the beginning, cautions Cornell’s Schlegel. "We still need a clear understanding of what the critical RNAs are and how they interact with the causes of male infertility, but they’re clearly an important component of sperm development."

Krawetz says the benefits of this study may extend beyond just aiding infertility diagnoses, though. Since sperm RNA correspond to genes in a child’s genome, the researchers may be able to study these sequences to see if any are linked with potential genetic disorders. But until then Krawetz says the main goal is to automate RNA sequencing of sperm so that it can be a routine procedure for men. Otherwise, the value of this research holds little real world benefit.