New research has shed light on our understanding of male infertility and how we may better treat it in the near future.
A U.K. study presented recently at the European Association of Urology Congress in Barcelona showed that sperm DNA extracted from the testicles of infertile men was just as healthy as the ejaculated sperm of fertile men.
The research team led by Dr. Jonathan Ramsay, a consultant urologist at Imperial College Healthcare, London, took sperm directly from the testicles of 63 men who were infertile, and then compared these samples with ejaculated sperm from the same men.
All of these men had experienced failed fertility treatments of intracytoplasmic sperm injections (ICSI). ICSI is an in vitro fertilization technique in which sperm is inserted directly into an egg’s cytoplasm.
Both the ejaculated and extracted testicular sperm from these men were examined for single and double DNA strand breaks. The researchers compared these samples to the ejaculated sperm of 76 fertile men who participated in the study.
What were the results?
The researchers found that when they looked at ejaculated sperm, the extent of sperm DNA damage was much higher in infertile men (40 percent) than in fertile men (roughly 15 percent).
“It wasn’t a surprise to see greater DNA damage in ejaculates of infertile men. What we didn’t expect was the consistency in these results when we looked at sperm taken directly from the testicles of infertile men, we found that it was of similar quality to that of ejaculated, fertile sperm,” Ramsay said in a press release.
Essentially, the DNA taken from the infertile men’s testicles was as healthy as that in the ejaculate of their more fertile counterparts.
Ramsay added that the majority of DNA damage in sperm is caused when it’s in transit from testicle to ejaculation. This damage is spurred by oxidative stress, which can cause DNA single-strand breaks.
Men who lead unhealthy lifestyle habits might want to listen up.
Ramsay said that this oxidative damage could occur from poor diets, smoking, or remaining sedentary all day.
People with conditions like type 2 diabetes and Crohn’s disease may also have a higher chance of this oxidative stress on sperm DNA.
If you’re confused about the way DNA is studied, Dr. Bobby Najari, director of the Male Infertility Program at NYU Langone Health, explained that assays (the laboratory testing method) used to assess sperm DNA damage is not evaluating genetic content or DNA code, but instead “how well the DNA is packaged.”
Think of sperm as “vessels” for transporting DNA content to an egg. There is no evidence right now to suggest that DNA damage leads to any abnormalities in offspring, but it “may play a role in poor fertilization and pregnancy rates,” Najari said.
“DNA damage assays are not considered standard of care by the American Urological Association or the American Society of Reproductive Medicine. However, many reproductive specialists find them useful in certain circumstances,” Najari, who was not affiliated with this study, told Healthline.
Najari said he offers the assay when “patients have normal semen analyses parameters but recurrent miscarriage,” when a man has a varicocele (an enlargement of the veins within the scrotum) and more data is needed before a decision can be made about removing it, or “when patients have had recurrent IVF or ICSI failure.”
He said the findings of this particular study weren’t necessarily surprising, stressing that this work adds to the current body of literature that suggests “when sperm DNA damage is elevated, it tends to accumulate as sperm progress through the male reproductive tract.”
Najari added that while there are other studies of similar populations of men that show improved fertilization and pregnancy rates when using testicular sperm compared to ejaculated sperm, a lot of this research is limited by the fact that there weren’t appropriate control groups.
“What needs to be done is a study where couples split the embryos between receiving testicular and ejaculated sperm and compare the outcomes between the two groups,” he said.
“Still, the evidence that we do have does suggest that in certain populations, it may be helpful to use testicular sperm as opposed to ejaculated sperm.”
Dr. Jesse Mills, director at The Men’s Clinic at University of California, Los Angeles (UCLA), echoed Najari, saying that it’s been known for the last few years that men with “high DNA fragmentation rates have more difficulty initiating pregnancy” as well as experience “higher rates of early term pregnancy loss.”
Mills, who was also not part of the new research, explained, “What this study shows is that extracting testicular sperm from ‘subfertile’ men will yield a higher number of viable sperm that can be used in in vitro fertilization.
“Right now, when embryologists select sperm from an ejaculated sample, they go after the fastest moving, best-shaped sperm in hopes that that will be a good sperm. But even a fast, good-looking sperm in an ejaculated sample can have oxidative damage and not be a good fertilizer.”
He added, “As a male reproductive specialist, this study gives me more evidence that couples whose male partner has a high DNA damage rate in his semen may benefit from a minor surgical procedure to extract sperm directly from the testicle, and this may increase that couple’s odds of a viable pregnancy.”
Mills said that the current cost of IVF in the United States is often “tens of thousands of dollars,” while the cost of a sperm extraction procedure is “a fraction of that.”
He said that many couples will take the extra step when he tells them that “having the man go through a minor procedure that adds about 10 percent to the IVF bill” will significantly increase their chances.
However, as promising as these findings are, Najari noted that it’s important to emphasize that they are only “applicable to the population of men who have abnormal ejaculated sperm DNA damage.”
So what impact could this research have on future treatment?
Najari said we may see a future where DNA damage assays may be applied earlier when it comes to the care of infertile couples.
“If research accumulates that testicular sperm has improved assisted reproductive outcomes in men with DNA damage in ejaculated sperm, it may be more effective to screen men for sperm DNA damage earlier in their evaluation,” he said.
“Screening for sperm DNA damage earlier may also give us an opportunity to address the underlying cause of DNA damage, such as varicocele, before a couple spends their time and resources on IVF cycles that are less likely to be successful.”
Mills also pointed out that this study might indicate that male infertility could be responsible for “a lot more pregnancy loss and difficulties” than we may already know.
He added that future studies need to look at whether lifestyle or hormonal changes can improve the rates of DNA fragmentation in sperm “to the point where couples can still use ejaculated sperm.”
Research presented at the 2019 European Association of Urology Congress in Barcelona revealed that the DNA of sperm extracted from the testicles of infertile men might be just as healthy as the sperm found in the ejaculate of fertile men.
The research could have implications for improved treatment of male infertility down the line.
Urologists say that this research isn’t surprising. It supports past understanding of the role DNA fragmentation in sperm plays in male infertility, as well as how lifestyle risks from poor diets to smoking can affect infertility.
More still needs to be learned, but the research suggests that looking into yet-to-be-damaged sperm in the testicles could offer a solution to couples working to overcome infertility challenges.