A New Hope for Male Fertility After

Cancer Treatment
An experimental procedure that regenerates sperm could ensure that men are able to
have kids following chemotherapy.

When Branden Lischner was 18, he got testicular cancer. Between surgery and
radiation, which can cause infertility, he saved a sperm sample. But he was so removed
from the idea of fatherhood that he soon stopped paying for his banked sperm. Then, in
2013, shortly after he got married, his cancer came back. Lischner only wanted to worry
about the surgery to remove his second testicle, but his urologist pushed him to take the
time to store sperm.

Lischner saved three samples. On the way into the operating room, the urologist asked
if maybe hed try once more. By then, the insistence was annoying. But four years later,
Lischner and his wife credit the doctor with giving them the family they didnt know
they wanted.

On average, men produce between 200 and 500 million sperm per ejaculate, although
only a fraction of them reach the uterus. Lischner had only 13 sperm to work with.
Joseph Sanfilippo, the director of reproductive endocrinology and infertility at Magee
Womens Hospital in Pittsburgh, estimates Lischners wife had about a one in 100,000
chance of getting pregnant. It really shouldnt have worked. But it did.

While the Lischners got extremely lucky, researchers are now working on a new
treatment that could help men like Lischner who didnt save a sample before radiation,
or even prepubescent boys who develop cancer and have no sperm to save. This
experimental technique takes a sample of testicular tissue and turns sperm precursor
cells into actual sperm cells. Put back in the testes, these sperm multiply, repairing
normal sperm production. This holds the promise of allowing men who lose fertility
through cancer treatment to have biological children not just in a lab, but the old-
fashioned way.

***

Dylan Hanlon was diagnosed with Ewings sarcoma when he was 9. At first, the news
overwhelmed his mother, Christine Hanlon. A busy lawyer and single mom near
Tampa, Florida, she put his care entirely in the hands of his doctors. But after the
treatment succeeded in preventing Dylans cancer from spreading, she started
researching its short- and long-term effects. Furious that none of the doctors had
mentioned a high risk of infertility, she did more research, and learned of Magee-
Womens Hospitals experimental procedure.

The doctors insist theyd never suggest the procedure to patients if they didnt foresee
progress.

Hanlon was worried it was too late for Dylan after 12 weeks of chemo. Kyle Orwig, the
head of the Fertility-Preservation Program at Magee, told her there was still a good
chance Dylan had some spermatogonial stem cells. Theyd do the procedure and check,
and if they werent there, they wouldnt save the sample.

Pioneered at the University of Pennsylvania School of Veterinary Medicine,

spermatogonial stem-cell transplantation, as the procedure is called, was successfully
performed on mice in 1994. Sperm are continuously created in adult men by turning
spermatogonial stem cells into sperm. Prepubescent boys already have the stem cells,
too; they just lack the ability to turn them into sperm. The technique collects a sample of
stem cells, freezes it, and returns it to the testes. Although sperm precursor cells are
damaged by radiation and chemotherapy, other cells in the testes seem to function
normally after therapy. So putting the healthy, undamaged stem cells into the testis
environment recreates the normal situation and promotes the nurturing of
spermatogonial stem cells until they become actual sperm.

The procedure has since been done on rats, pigs, goats, sheep, and in 2012, nonhuman
primates. Now, some fertility specialists are freezing testicular samples in the
expectation of imminent human trials. At Magee Fertility-Preservation Program, doctors
started freezing testicular samples in 2011. Although the exact amount of time these
tissues can be frozen is uncertain, Orwig says there is evidence in mice that stem cells
can be thawed and transplanted to regenerate spermatogenesis after 14 years of
storage. Frozen eggs and sperm have been used to produce babies after decades of
storage.

After consulting with Orwig, Hanlon talked to Dylanalert and intelligent, it seemed to
her, beyond his nine years. Dylan hated the chemo; he screamed and cried every time
they tried to access his portal. He said more than once, I dont care if I die, just make
them stop. But he was enthusiastic about the experimental idea, according to Hanlon.
So Id be a guinea pig? he joked. She laughed and said yes.

Dylans doctors in Florida were not excited about the idea. Oncologists are concerned
with saving the lives of their patients, and generally dont want time and resources
diverted from cancer treatment. If there isnt a living patient, then fertility wont ever be
an issue. But Orwig contends that it was the right choice if Dylan was to have any
chance of becoming a biological father one day.

***

Orwig sees it as his mission to disabuse doctors of the idea that thinking about fertility
has to be a burden. Recently, he stood in front of a hospital conference room full of
oncologists working within the University of Pittsburgh Medical Center health-care
company system at their quarterly meeting, and explained a gap in care: His team
estimates that they could do 1,119 fertility procedures a year, but they expect to do only
144 this year. Harvesting tissue need not delay treatment, he maintains; it can be
scheduled to coincide with treatment-related procedures. And oncologists need not help
patients decide whether or not to participate. They could merely present the option, give
the Fertility-Preservation Programs hotline number, and step back.

Orwig and his team give patients the option of saving a whole testicle or 20 percent of
testicular tissue. The benefit of a whole testicle is that the team has more to work with,
but the effects are more obvious. Taking 20 percent only appears as an indentation. In
either case, the team keeps a quarter of each sample for future research.

A testis sample from a patient, with therapeutic

germ cells highlighted (Fertility-Preservation
Program)

What are the chances a successful procedure for restoring fertility will be available by
the time Dylan, whos now 16, is ready to have children? Sanfilippo and Orwig insist
theyd never suggest the procedure to patients if they didnt foresee progress. Orwig
uses egg freezing as a comparable example: In 2011, it was experimental. Now its a
standard of care. With childhood-cancer survival rates up to 85 percent, they see it as
their responsibility to advance treatment.

Orwig also considers it his duty to educate doctors and to push men to think about
infertility more generally. According to him, although a roughly equal number of men
and women struggle with infertilityabout 12 percentfewer men think about fertility
preservation. Their doctors talk less about it, too. Female fertility preservation is more
complicated and costs more, both in the moment and in long-term storage fees.

Word is slowly spreading. In July, Donald and Jacqueline Renk took their son Paxton,
not quite 2 years old, to the ER because he hadnt urinated in 24 hours, and a tumor was
found in his bladder. When they later sat with Paxton on a hospital bed waiting for his
chemowhich his doctors are using to shrink the tumor because its too big to be
removedthey told his doctor that fertility was the last thing on their minds. The doctor
mentioned the procedure, but they were doubtful. He advised them to think about
whether it might be worthwhile for Paxton to have the option in the future.

And Paxton has a future for his parents to consider. His cancer is predicted to be gone
within a year. The oldest of Donald and Jacquelines four other children asked, So he
wont be able to adopt kids? When they said he would, he replied, Well, then whats
the big deal? Donald and Jacqueline loved that this is how their children think. And
they decided that if Paxton might have the opportunity to have a biological child in the
future and it wouldnt delay his treatment, then there was really no reason not to do it.
At the very least, they reasoned, his sample could help others.