Ovaries contain hundreds of thousands of underdeveloped eggs, held in a kind of suspended animation. Each month, one matures and is released—potentially to be fertilized by sperm and create an embryo. For the first time, scientists say they have managed to take eggs from the ovaries of transgender men and get them ready for fertilization in a process completed entirely outside the body.
The achievement, carried out by a team led by Evelyn Telfer, a reproductive biologist at the University of Edinburgh, suggests that viable eggs can be obtained from transgender men even after years of testosterone therapy, which can stop ovulation.
This would allow transgender men who want children to avoid having to pause gender-affirming medical care and avoid vaginal probes, women’s health clinics, and female-hormone-based treatments, all of which can be physically or emotionally distressing. Telfer discussed her findings, which have not yet been peer-reviewed, in a virtual presentation to the Society for Reproductive Investigation at its annual meeting, which was held in Denver, Colorado, last month.
“It’s very exciting, very important work … and is going to be an important advancement that will potentially help a lot of patients,” says Samir Babayev, a reproductive endocrinologist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the research but attended the meeting where Telfer presented her work.
Limited options
Transgender men were assigned female at birth, but identify as male. Some trans men undergo treatment with the hormone testosterone to develop more masculine traits, such as facial and body hair and a deeper voice. The course of treatment varies and depends on the individual’s own preferences, as well as the age at which they began gender-affirming medical care.
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There are a handful of options for people who choose such treatment but want the option of having biological children someday. Adults can freeze their eggs, for instance. But this typically involves stopping testosterone treatment and allowing a menstrual cycle to return, which can take months. Hormone-based drugs are used to stimulate the ovaries to release multiple mature eggs, which are then collected in a surgical procedure that involves vaginal probes. The procedure can be particularly distressing for transgender men, says Babayev. In addition, pausing testosterone therapy for months can cause fatigue, mood changes, and sleep problems.
Many transgender men would want to be able to create their own families without such disruptions, says D. Ojeda, senior national organizer at the National Center for Transgender Equality in Washington, DC.
The options are even more limited for young people who want to begin gender-affirming medical care before they reach puberty—which means they can’t freeze their eggs because they won’t have started ovulating. They might choose to have part or all of their ovaries removed and frozen, in which case the tissue could theoretically be reimplanted later—but few trans men would opt for that procedure, because it would increase estrogen levels in the body, says Kenny Rodriguez-Wallberg, a reproductive oncologist at the Karolinska Institute in Sweden, who also saw Telfer present her work.
The alternative that Telfer and her colleagues are working on involves taking eggs from the ovaries and maturing them outside the body, in the lab. The team has already had some success in doing this with eggs taken from women’s ovaries, but they didn’t know if they’d be able to mature eggs from the ovaries of people who had already begun gender-affirming medical care.
Stiff ovaries
Telfer’s first task was to find out what testosterone therapy does to ovaries, which is a matter of disagreement among clinicians.
To get a clearer idea, Telfer teamed up with two gender affirmation clinics in the UK. Transgender men who had been taking testosterone and were undergoing surgery that included the removal of their ovaries were asked if they wanted to donate them for research. In total, four people donated eight ovaries. The team compared pieces of the ovaries with eight slivers donated by women undergoing cesarean sections, who were of similar ages.
The ovaries from transgender men were indeed different—they had more collagen and less elastin, making the tissue more rigid. This stiffness might make it harder for follicles to grow and release mature, ready-to-fertilize eggs.
The more options [to start a family] we have as trans people, the better.
D Ojeda, senior national organizer at the National Center for Transgender Equality in Washington, DC
Telfer and her colleagues also assessed 4,526 follicles from pieces of the eight testosterone-exposed ovaries. Around 94% of the follicles weren’t growing, versus 85% in pieces of ovary from women who had not taken testosterone.
The team then tried to mature eggs from the trans men’s ovaries. Their method involves cutting up the tissue surrounding each follicle and then stretching it out in a dish. This seems to trigger signaling pathways within the tissues that allow follicles to release mature eggs.
It worked—the researchers were able to mature a small number of eggs to a point where they are ready to be fertilized by sperm.
In theory, the team could use IVF techniques to create embryos with the eggs, and those embryos could be transferred to the uterus of a partner or surrogate. To do this in the UK, the team needs to obtain a license from the Human Fertilisation and Embryology Authority. No such license is required in the US.
The technique will appeal to some transgender men, says Ojeda: “The more options [to start a family] we have as trans people, the better.”
Telfer and her colleagues haven’t gone this far yet, though. The first eggs that the team matured in the lab didn’t look entirely normal. When eggs mature, they typically undergo a special type of cell division that halves the number of chromosomes, readying them for fertilization. The chromosomes that aren’t used are separated off into a small cell called a polar body. The polar bodies of the eggs matured in the lab looked unusually large.
A large polar body is likely to be totally harmless. But the team is tweaking the contents of the fluid in which the eggs are matured, just in case. More recent attempts have resulted in more typical-looking eggs, cells Telfer. The team has matured around 10 eggs so far, but the project is ongoing. “I would like to have our culture system be more robust before attempting fertilization,” says Telfer.
She wants to trial the procedure in sheep before she attempts it in people. Those experiments are scheduled to take place later this year. If they’re successful, Babayev predicts that the technique will take off among clinics. Most fertility treatments bypass clinical trials before becoming widely offered by clinics.
“Clearly the kinks will have to be worked out, but if she’s successful, I don’t think it will take a long time for others … to implement it very, very quickly,” says Babayev. But he is waiting for more evidence to be convinced the technique will work clinically. “I would have to see a baby,” he says.
If it can be used to help transgender men conceive healthy babies, the technique could be useful in plenty of other circumstances, too, says Rodriguez-Wallberg. Children facing cancer treatments that might damage their ovaries could have parts of them frozen first, offering them a way to have their own biological children when they’re older.
The method could also help others struggling to conceive, says Kutluk Oktay, a reproductive endocrinologist and fertility preservation specialist at Yale School of Medicine. Ovarian freezing could be an alternative to egg freezing: taking a single biopsy from an ovary might be preferable to the many steps involved in egg retrieval.
And while egg retrieval tends to result in around 10 eggs each time, a tiny piece of ovary could be used to produce 100 eggs. “A little biopsy from the ovaries … might be enough for a lot of babies,” says Oktay. “If we can figure out how to efficiently do this, it could be widely used.”
