Christian Kramme was working at his desk in the Church Lab at Harvard Medical School when a colleague sent him a blown-up image from a microscope that “literally made my jaw drop,” he recalls.
The image showed a series of nested circles, each one a fabric of intertwined fibers and cells, illuminated by imaging technology in hues of green and purple, centered around an open cavity. It was like gazing into a galaxy.
The scientists in the lab had grown an “ovaroid,” an assembly of cells designed to mimic the structure and function of a crucial part of a human ovary: the follicle. Follicles are the pockets within the ovary that support and nourish eggs as they prepare to be released for fertilization.
Kramme and his colleagues at the Church Lab and elsewhere had been working toward this for years, honing biochemical and computational tools to build a follicle piece by piece out of multiple different kinds of cells. The ovaroid was a combination of all these cells in one organized structure. And to Kramme’s amazement, this lab-grown version looked exactly like a microscopic image of a real human follicle.
“To see them all come together and self-organize into something that beautiful and complicated was priceless,” he says.
The ovaroid, which was unveiled earlier this year, doesn’t yet do the whole job of growing an egg. But it’s a huge step toward developing a suite of biotechnologies that could make the previously impossible possible in baby-making. These technologies could enable women who have lost their fertility to age or illness to conceive with their own eggs — and to do so with far less suffering than in vitro fertilization (IVF) currently exacts. Or enable men with infertility problems to generate healthy sperm from other kinds of cells. Or even same-sex couples to create sperm from biological females or eggs from biological males and conceive children who are genetically related to both parents. In short, these tools could help bring more equity to the highly inequitable realm of reproduction. (This article uses the terms “woman” and “man,” but the author recognizes that the experiences described here may apply to trans men and trans women.)
Today, the boundaries of gender and reproductive freedoms are being contested — with more than 20 states banning or restricting gender-transition care, efforts to remove LGBTQ-themed books from libraries at record highs, and the Supreme Court’s overturning of Roe v. Wade. But in the coming years, technologies like these could create new reproductive possibilities — and perhaps new social conflicts too.
“The technology keeps pushing the envelope, not just biologically but conceptually,” says Vardit Ravitsky, president of the bioethics research institute the Hastings Center and bioethicist at Harvard Medical School. This research “links technology development with the most profound concepts of humanity,” expanding the concept of how families can be made.
Step one: boosting fertility
As the lab-grown ovaroid is further refined to function reliably like a human follicle, its first and most obvious clinical use is probably to make IVF work a lot better for women.
Currently, women undergoing IVF must take a series of extremely expensive hormone injections to stimulate their ovaries to mature eggs, which can cause cramping, bloating, headaches, mood disruptions, and painful ovarian swelling. IVF typically costs tens of thousands of dollars. And it’s a process that the female partner may suffer through even when a couple’s infertility problems are caused by the male partner.
“The burden between men and women is so astronomically far apart,” says Kramme, who is now vice president of cell engineering at biotech company Gameto, which has licensed the ovaroid technology from the Church Lab. “We’re trying to even out the burden.”
How? First, the cells derived from an ovaroid could be used to enable in vitro maturation (IVM), moving the biologically intensive process of readying an egg for fertilization out of the female body and into the lab. In this scenario, a woman could skip most of the hormone injections required for IVF. Her eggs would be extracted and their maturation process finished in a dish. Women could also potentially use more of the eggs extracted from them, rather than having to toss out the immature ones.
Researchers expect that having a larger pool of eggs to choose from could improve the often heartbreakingly low success rate of IVF: 40 percent for women ages 35-37, dwindling to 4 percent for women over 42.
Such advancements could ease some of the stress caused by the natural age limit on women’s fertility, which pressures women to sacrifice career progress for motherhood and/or have children before they or their relationships are ready. With scant public support for working parents in the form of child care and paid parental leave, says Ravitsky, “The equity issue here is that we created a systemic societal problem and we’re trying to solve it individually on the shoulders of women.”
Dina Radenkovic, the CEO of Gameto, envisions lab-grown ovaroids helping younger women who want to freeze their eggs to preserve their fertility by making the process easier and cheaper. “If your egg freezing experience becomes something you can do over a weekend, you don’t need to spend a lot of money,” she says. “You then have your eggs frozen in your late 20s or early 30s and give yourself a little bit more control over your reproductive timeline,” coming closer to the flexibility that men have.
Step two: making sex cells from scratch
At first, ovaroids could be used to nurture a woman’s existing eggs, but researchers are also pursuing a step that sounds even more fantastical: creating new egg cells where none existed. These new cells could be derived from other kinds of cells in the body of a woman who has lost her viable eggs to age or illness. Or these cells could even, a bit further into the scientific future, come from a man.
The process for creating these eggs shares scientific roots with the process of creating the ovaroid. Both technologies are based on the knowledge that all of our many cell types, from skin to blood to bone to eggs, arise from one kind of cell that serves as a kind of blank slate — a stem cell. Creating eggs, like creating the ovaroid, involves reprogramming a cell back into a stem cell and then finding the right chemical recipe to direct it to become a different cell.
This egg creation process is called in vitro gametogenesis (IVG). In principle, related methods could be used to create sperm. Think of it as the next step up in complexity as science tries to mimic the magic of human reproduction.
The starter cells that could currently be used to achieve this are skin and blood cells. In a milestone study in March 2023, researchers from Japan announced that they had reengineered stem cells from the tail skin of male mice into eggs, fertilized them with mouse sperm, and implanted the embryos in female mice, resulting in the births of live pups — effectively generating offspring conceived by two males.
Writing in the journal Nature, reproductive scientists Diana Laird and Jonathan Bayerl of the University of California, San Francisco, noted that this method “might even provide a template for enabling more people — including male same-sex couples, and transgender and XXY individuals — to have biological children, while circumventing the ethical and legal issues of donor eggs.” (Currently, male-male couples need both an egg donor and a pregnancy surrogate to create a baby with one of their sperm, and in doing so must confront both staggering financial costs and ethical questions about who is paid to provide those and the medical risks women take to do so.)
Could scientists eventually even reprogram cells to produce a functioning uterus that could grow a baby outside the body? George Church, the geneticist who leads the Church Lab, thinks it’s possible. In fact, he hopes to do it to help propagate endangered species such as elephants. Scientists still haven’t worked out how to nourish such an organ well enough for it to survive long outside the body, Church says, “But there’s no basic law of physics or biology that prevents it; it’s just a matter of funding and creativity and persistence.”
Church even imagines that, in a distant future, if synthetic uteruses can be made to work for humans, “You could consider it primitive that women had to risk their lives and pain and so forth to give birth.”
Taken together, these emerging technologies could increase equity for anyone trying to build a biological family missing a component, be that an egg, a sperm, or a uterus, says Ravitsky, the bioethicist. While critics contend that people can build a family just as well through adoption, without shared DNA, Ravitsky counters that genetic links feel profoundly important to many hopeful parents, and that makes reproduction a matter of equity.
“Any technology that allows us to do things we couldn’t do before, my impulse says, if we manage to do this responsibly and wisely, who gets to join the party of reproduction?” she says.
Step three: sorting out the ethics
Between here and the potential fertility technologies that the ovaroid researchers envision, years of scientific, ethical, and legal hurdles remain.
Maturing eggs in a dish to ease the IVF process is within reach. This month, Gameto released study results showing that, in women given just a fraction of the usual hormone treatments before egg extraction, using stem cell-derived cells to mature eggs worked significantly better than other methods of maturing eggs. But growing eggs or sperm from other kinds of cells is much further away. Predictions of its timeline vary among researchers.
In their Nature commentary, Laird and Bayerl laid out some of the limitations of the male-male mouse study. For one, the method for reprogramming stem cells into egg cells is not yet reliable for humans. Plus, only seven of the 630 implanted mouse embryos grew into live pups — about a 1 percent success rate (though these new mice grew up to have pups of their own).
“If the public takeaway is that we’re capable of doing amazing things in a lab model like a mouse, that’s great, it is incredible,” Laird says. “But it’s very different than deciding it’s OK to do in humans.”
Laird added that skin cells may not be the optimal starting point for humans trying to create eggs or sperm from scratch. “How many sunburns has [the donor] had in their lifetime?” she says. “You’re taking probably one of the most abused cells that’s acquired the most mutations … and you’re turning it into the most important cell in development.” Certain kinds of blood cells might work better, she said, but they’re harder to reprogram.
Beyond effectiveness, researchers will need to resolve significant safety questions, particularly for a baby born through these methods. Laird cautions that, before making an option like same-sex-couple-created offspring widely available to humans, we’d have to know the impacts on a baby with a life expectancy of 80-plus years and the impact on their own fertility, seeing the process work for multiple generations in primates first.
We’d also need robust laws to ensure that a Beyoncé or Brad Pitt fan couldn’t brush up against the star on the red carpet, scrape off some skin cells and pay to make a little Bey or Brad baby. Or that an obsessed ex couldn’t do the same to any of us.
And we’d need substantial investment in the technologies to bring the cost within reach for everyone, not just the uber-rich. Without equitable access, says Laird, “The field of reproductive biology is gatekeeping in who gets to propagate their genes.”
So what are the chances that these scenarios will come to pass? Scientifically, the researchers consider this more likely a question of when than if. Politically and economically, it could be more if than when.
Ravitsky expects that some people will decry these new methods as unnatural or immoral. But she anticipates that, provided we set laws to prevent abuse of the technology, over time creating families this way will become normal. In the early days of IVF, “we called them test-tube babies and we thought they were artificial children,” she recalls. Now we simply call them babies.
Kramme comes from a family of seven children and hopes to create a family of his own someday. But he’s 26, his partner is working on her PhD, and it’s not the right time for either of them to become parents. He worries about their fertility as they push baby-making into their 30s, and he hopes to ease that fear for future generations.
“I really do believe that within my lifetime and my partner’s lifetime, we will cure infertility,” he says. “‘Cure’ means not just can it be done, but can I access it.”
Grace Rubenstein is a health and science writer and cofounder of the podcasting company SeedPod Media.