Around 1% of men have azoospermia, a condition in which there is no sperm in their ejaculate. While 1% may not sound like a large number, that equates to roughly 1.7 million males in the US alone. “It’s possible to retrieve sperm from the testes of about half of those people,” said Kyle E. Orwig, PhD, director of the Fertility Preservation Program at the University of Pittsburgh in Pittsburgh. “For the other half where sperm aren’t retrieved, there’s no option to have a biologically related child.”

Scientists have been working on a way to help men in this situation, with the goal of creating viable sperm out of their own stem cells. But the research has proven to be incredibly complex and the progress slow. A new study published online in Cell Stem Cell in July 2026 shows that scientists are one step closer to making stem cell sperm a reality.

Theory vs Reality

The goal: Create functional sperm starting with cells taken from a man’s body. “In theory, you should be able to derive a pluripotent stem cell from any man, any tissue in his body basically, skin biopsy or blood sample,” said Orwig. Induced pluripotent stem cells, or iPSCs, can develop into many different types of cells. Scientists could then use these iPSCs to recreate the stages of sperm development until you have mature sperm.

In vitro gametogenesis (IVG), the process of growing sperm and eggs from stem cells in a dish, has been something scientists have been working on for years. Mouse sperm and eggs have already been generated this way, resulting in live offspring. But human sperm cells have proven to be far more stubborn.

“Only very recently have people started to generate something really authentic,” said Kotaro Sasaki, MD, PhD, associate professor at the University of Pennsylvania in Philadelphia, and senior author of the new study. Sasaki, who previously worked in a Japanese lab that accomplished this in mice, began working on the human side of the problem about a decade ago. His approach has been to recreate the normal developmental pathway of sperm one stage at a time, taking stem cells to primordial germ cell-like cells to prospermatogonia. With this new study, his team has taken the process one step further to spermatogonia-like cells, which resemble the stem and progenitor cells inside the testes responsible for lifelong sperm production.

If stem cell-derived mature sperm were found to be safe and functional, they could then be used to fertilize eggs via in vitro fertilization. “Then in theory, a man who had absolutely no chance of having a biologically related child now would have the potential to have a biologically related child because you did it from his own cells,” said Orwig. This could include men who have lost the ability to produce sperm after treatments such as chemotherapy. “That’s going to transform human reproductive medicine completely,” said Sasaki.

How the New Study Unfolded

Since human fetal testicular tissue is difficult to access, Sasaki and his team used fetal testicular cells from mice. They then combined them with the human germ cell precursors to create what Sasaki calls a “tiny mini testis.” The initial plan was to grow these in a dish, but after 2 months, the researchers found that the cells started to die, which they attributed to problems getting enough oxygen and nutrients to the cells.

In this study, they tried something different. The team transplanted the mini testes under the kidney capsules of immunodeficient mice. This gave the cells an environment where they could survive longer and continue developing. “They continuously survive, and then they mature. They form nice 3D [three-dimensional] structures,” Sasaki said. “And then inside this 3D structure, we found the germ cell getting more and more mature and eventually becoming spermatogonia.”

The researchers harvested the structures after periods of 1, 2, 4, and 6 months. And even though the human germ cells were developing alongside mouse testicular cells, the process resulted in spermatogonia-like cells that were remarkably similar to spermatogonia that naturally occur in humans. “The surprise really was that it worked as well as it did,” said Eoin Whelan, PhD, the study’s first author. “These spermatogonia are sitting in a mouse environment, and when we compared them to normal human, which we did, we looked at all of their RNA; we’ve also looked at their DNA, and they’re exceedingly similar.”

The Next Big Hurdle, Roadblock, and Bottleneck (All in One Thing)

While this is exciting progress, there are still several steps to go before scientists can make functional human stem cell sperm. The next big hurdle: getting the cells through meiosis.

This process of cell division reduces the number of chromosomes by half, which is necessary to make sperm. “The big bottleneck is going through meiosis to produce haploid either spermatid or sperm,” said Orwig. “That process of going through meiosis in vitro is a huge hurdle, and nobody’s accomplished that yet really, as far as I’m aware, in any species except for mouse.”

During the study, the researchers did see a small number of cells reach the preleptotene spermatocyte stage, which occurs just before or at the beginning of meiosis, but the cells didn’t appear to progress any further. “It may not seem like we have much further to go from spermatogonia to sperm, but that bottleneck of going through meiosis is a really tough one,” said Orwig.

One possibility is the environment they were growing in. “The mouse and the human are not quite perfectly compatible, so we are trying to mix them with human cells and see if that will improve the progression,” said Whelan. Temperature may also be a factor, as the mini testes were transplanted inside the mice, where they were exposed to the animals’ core body temperature. This could be an issue since testes are normally cooler than the rest of the body, which is important for sperm development. The team is now working toward replacing the mouse testicular cells with human cells.

“So germ cell from stem cell, somatic cell from both stem cells, and then mix them together, make mini testes, and then culture and then make a sperm,” said Sasaki. “That’s the long-term goal.”

Looking Like a Thing Doesn’t Make It a Thing

Researchers were surprised by how closely spermatogonia-like cells that were created in the study resembled naturally occurring human spermatogonia. But looking like the real thing doesn’t necessarily mean they will work like it. “It looks normal, like gene expression, RNA level, they’re very normal. It’s almost indistinguishable from the normal spermatogonia. But functionally, we don’t know,” said Sasaki.

To put this to the test, scientists are also studying the process in monkeys, specifically macaques. They were able to create spermatogonia-like cells from macaque stem cells, but getting there came with another challenge. When they initially tried using the same process that had worked with the human cells, the macaque cells repeatedly formed tumors after being transplanted into mice. “Every time you transplanted, you got a tumor,” said Whelen.

The tumors were teratomas, tumors that can contain multiple types of tissue, that appeared to form because some of the early germ cells developed into other types of tissue instead of continuing down the path toward sperm. But by keeping the early germ cells in a Petri dish longer before transplantation, the team was able to reduce the chances of the tumors forming. This took nearly a year to figure out but got the researchers back on track (and illustrates just how long and arduous a quest this has become).

After adjusting the process, they were able to produce macaque spermatogonia-like cells. The next step will be to transplant those cells into monkey testes to see whether they can continue developing into sperm. If this occurs, researchers plan to retrieve the sperm from the monkeys and use in vitro fertilization to see whether the sperm can fertilize an egg and ultimately result in offspring.

A Use for the Technology Right Now

The technology developed in this study could have immediate uses, such as reproductive toxicology. It may, for instance, be able to help scientists study how drugs, chemicals, pesticides, and other environmental exposures affect the development of human germ cells. “It could be a valuable tool to use in toxicology or in the pharmaceutical industry,” said Orwig. “This is a good one and an important one.”

Sasaki also sees the system as a new way to study human sperm development itself. With this process, researchers will be able to observe the cells as they move through different developmental stages and manipulate genes to better understand their role in the process. “This is the first platform that in humans we established to understand the molecular mechanism of human germ cell development,” said Sasaki.

Ethical Concerns and ‘Designer Babies’

No stem cell-derived sperm can be used for fertility treatments until researchers determine they’re safe. That means looking for abnormalities in the cells’ DNA and examining whether genes are being regulated as they should be. “It has to be safe,” said Sasaki. “So we need to analyze their RNA, we need to analyze their small RNAs, piRNAs [piwi-interacting RNAs], we need to analyze their genome, make sure the genome is intact.” Researchers would also need to ensure that the sperm and resulting embryos have normal epigenomes.

Then there are the ethical questions that come with being able to create reproductive cells from a person’s ordinary cells. “It’s really good to think about these things while the technology is still developing so that guardrails can be put in place before the technology is deployed,” Sasaki said.

Another interesting factor: This technology may be able to fundamentally change who is able to have a genetically related child. Sasaki said that, at least theoretically, IVG could someday make it possible to create sperm from a woman’s cells or eggs from a man’s cells, potentially allowing same-sex couples to have children genetically related to both partners. While this is not currently possible, IVG could potentially make it possible.

Gene editing is another possibility. Whelan said scientists could potentially edit a patient’s iPSCs before turning them into sperm. If infertility is caused by a genetic mutation, researchers may be able to correct that mutation first. The same approach could potentially be used to prevent a parent from passing a disease-causing mutation to a child.

“This approach has significant therapeutic potential, both for treating infertility and preventing diseases that would otherwise be incurable,” said Whelan. But he also stresses that these changes could also be passed down to future generations, which may raise questions about where to draw the line between treating disease and genetic enhancement, or what Whelan calls “designer babies.”

How Close Are We?

These new developments have researchers excited, but they are quick to remind us that it’s not easy to predict exactly when stem cell-derived sperm could become a viable fertility treatment. Their best guess? Years.

Producing the sperm in the lab would be the first step, but the testing and approvals that would impact the world would take much longer. Progress has moved faster than Orwig once expected. But he also agrees that it will likely take longer before those sperm could be used to help people have children. “While I think the technology might be there in 5 years in humans, the application in humans for reproduction, I would say, is probably 10 plus years out,” he said.

Researchers remain determined to keep moving the science forward. Sasaki said he believed from the beginning that creating human sperm and eggs from stem cells would eventually be possible.

“When I started this IVG research 16 years ago, I already thought this was possible,” he says. “I mean, why not? We can make other different kinds of cells from stem cells, like liver cells, skin cells, intestinal cells. We can create all these cells from stem cells, so why not sperm cells?”

Disclosure information for study authors is available in the original study publication.