A 36-year-old man born without testicles received one transplanted from his identical twin brother in a six-hour operation performed on Tuesday in Belgrade, Serbia, by an international team of surgeons.
The surgery was intended to give the recipient more stable levels of the male hormone testosterone than injections could provide, to make his genitals more natural and more comfortable, and to enable him to father children, said Dr. Dicken Ko, a urologist and transplant surgeon at Tufts University School of Medicine in Boston, who flew to Belgrade to help with the procedure.
The operation was only the third known transplant of this type. The first two were performed 40 years ago in St. Louis, also for identical twins, each pair with a brother lacking testicles.
The absence of testicles is an exceedingly rare condition, but doctors say that the surgery may have broader applications for transgender people, accident victims, wounded soldiers and cancer patients. But the procedure raises questions about the ethics of transplants that are not lifesaving, and about the possibility of recipients’ someday fathering children with sperm from donors who may not even be related to them.
The surgery was performed at the University Children’s Clinic in Tirsova, a section of Belgrade. The Serbian brothers are doing well, doctors said. By Friday, the recipient already had normal testosterone levels.
“He’s good, he looks good, his brother looks good,” Dr. Ko said in a telephone interview on Friday. The donor, who already has children, should remain as fertile as he was before, despite giving up a testicle.
Dr. Ko said the brothers, who have been sharing a hospital room, were expected to go home this weekend. They preferred not to be identified or interviewed, the doctors said.
Because the patients are identical twins with the same genetic makeup, there is no concern that the recipient’s body will reject the transplant, so he does not have to take the immune-suppressing drugs that most transplant patients need.
Surgeons operated on the brothers simultaneously, in adjoining rooms. The procedure was challenging because it required sewing together two arteries and two veins that were less than 2 millimeters wide.
“Once you remove the testicle from the donor, the clock starts ticking very fast,” said Dr. Branko Bojovic, an expert in microsurgery at Harvard Medical School and part of the team in Belgrade.
“Within two to four hours, you have to have it re-perfused and working again,” Dr. Bojovic said. Without a blood supply, a testicle is viable for only four to six hours.
It can take 30 to 60 minutes to make each of the four blood-vessel connections. But the team managed to complete them all in less than two hours, he said.
The team did not connect a structure called the vas deferens, which carries sperm out of the testicles. The surgeons could not find the tissue in the recipient needed for the connection, which means that for now, he cannot father children in the usual way.
Another operation to make the connection may be possible. Otherwise, if the recipient wants children, he might undergo a procedure to extract sperm from the testicle for in vitro fertilization. Or his twin brother’s sperm could be used.
Dr. Ko and Dr. Bojovic were both part of the surgical team that performed the first penis transplant in the United States, in 2016, on a man whose penis had been removed because of cancer.
Dr. Miroslav Djordjevic, who led the team in Belgrade, specializes in urologic reconstruction and sex reassignment surgery at Mount Sinai Hospital in New York and at the University of Belgrade. He said the brothers approached him after learning that he had performed a successful uterus transplant between twins sisters, which enabled the recipient to give birth.
Dr. Bojovic said that after the penis transplant, the surgical team received inquiries from people undergoing female-to-male sex reassignment who wondered if they might receive transplants instead of the usual surgery, which creates a penis from the patient’s own tissue.
But a transplant from any donor other than an identical twin would require immune-suppressing drugs to prevent rejection. The drugs have side effects that lead some experts to argue that the bar for such transplants must be very high.
“It’s becoming more of a popular topic for these patients,” Dr. Bojovic said. “They say, ‘If immunosuppression is getting safer, I don’t want to use a big piece of tissue from my forearm or thigh or back for something that looks like phallus but isn’t.’”
He added that in patients having male-to-female reassignment surgery, the penis and testicles that were surgically removed are discarded, but in theory could be used for transplants.
The lead surgeon, Dr. Djordjevic, said that he had developed a surgical plan for transplanting a penis onto a body that is anatomically female, and that he hoped to begin performing that surgery within the next year or so.
“We have to do this as soon as possible, to stop putting healthy organs in the garbage,” he said.
But he would not transplant testicles as part of transgender surgery, he said. Doing so would open up the thorny possibility that the recipient could have children produced by the donor’s sperm. If the idea were extended to deceased organ donors, special permission would be required from them before death, or from their families.
“Then the offspring is technically whose child?” Dr. Ko asked. “It raises much debate in the literature of medical ethics.”
Last year, when surgeons at Johns Hopkins Hospital transplanted a penis, scrotum and other tissue to a young soldier who had been maimed in combat, they deliberately left out the testicles. The idea that he might father children who were genetically someone else’s was considered unacceptable.
The first report of a testicle transplant, by Dr. Sherman J. Silber, a fertility specialist in St. Louis, was published in a medical journal in 1978. In that case, the twin brothers were 30 when they consulted Dr. Silber.
The brother without testicles had not reached puberty until he was given testosterone at age 18, which caused a growth spurt that left him four inches taller than his brother. He needed regular testosterone injections to maintain his masculine characteristics, but the hormone levels fluctuated and sometimes caused mood swings.
He spent five years searching for a doctor who could perform a testicle transplant before he found Dr. Silber, after reading a New York Times article about his work published in 1975.
Dr. Silber said that he had performed more than 2,000 kidney transplants in rats, which required microsurgical techniques to sew together minute blood vessels the same size as those in human testicles.
“So doing a testicle transplant was not a big deal,” he recalled in an interview on Thursday. “It was like just another kidney transplant in a rat.” He said the operation took two hours.
Dr. Silber said that the donor was gay and the recipient straight, and that the brothers told him they wondered if the transplanted testicle might somehow alter the recipient’s sexual orientation. There is no scientific reason for such an effect, and none occurred.
The transplant was a success, and the recipient eventually had five children, Dr. Silber said. A year or so later, he performed the surgery again for another pair of identical twin brothers, though he did not write up their case in a journal.
Regarding the operation in Belgrade, Dr. Silber said, “I imagine these surgeons must be pretty good, because most people wouldn’t dare to try this.”