Advance offers new hope for fertility preservation in young boys with cancer

Henrietta Strickland
March 23, 2019

More and more people are surviving childhood cancer, but almost 1 in 3 will be left infertile from the chemotherapy or radiation that helped save their life.

Although babies have previously been born from testicular tissue in mice and pigs, a monkey birth from frozen tissue is the best hope yet that the technique could work in humans.

"It's a huge step forward" that should give hope to families, said Susan Taymans of the National Institute of Child Health and Human Development, which helped fund the research published in the journal Science.

Chemotherapy and radiotherapy can destroy someone's ability to have children. For that reason, the procedure might not be recommended for patients who survived childhood leukemia, lymphoma, or testicular cancer.

Adult men can freeze their sperm and store to later have a biological child, but "sperm freezing is not an option for prepubertal boys, who are not yet producing sperm", researchers said in the paper.

The animals had not started puberty so their testes were not yet sperm-making factories.

Around half a year later the monkeys were made infertile.

Then fragments of their preserved testes were thawed and were grafted underneath the monkey's skin.

"We know that chemotherapy and radiation therapy can cause permanent infertility, and we know that cancer survivors say fertility has an important impact on their quality of life", Kyle Orwig, from the University of Pittsburgh School of Medicine, said.

Image copyright Oregon Health and Science University Image caption Baby Grady aged 12 weeks old How effective was it? "In this study, we demonstrated that frozen and thawed prepubertal testicular tissue could be matured in vivio by grafting under the back skin or scrotal skin of the same animal to produce functional sperm and a healthy baby".

The researchers then fertilised 138 eggs using a technique called intracytoplasmic sperm injection or ICSI. About 40 percent grew into early-stage embryos.

Grady, a rhesus macaque whose name derives from "graft-derived" and "baby", was born from sperm harvested from frozen tissue.

The study was welcomed by stem cell scientists Nina Neuhaus and Stefan Schlatt, who in an accompanying editorial said it "brings this as yet experimental approach close to clinical application".

This sperm was used to fertilise eggs, using a technique from IVF, and was able to produce a live monkey baby a year ago.

The need for such an advancement is mounting as childhood cancer survival rates climb.

If any cancerous material was hidden inside the testes, then it too would be frozen and reintroduced to the child's body along with the graft.

However it may be problematic for children with leukaemia and similar blood cancers, as well as those with testicular cancer, as traces of the cancer may linger in their tissue.

Sex hormone levels in the body are also influenced by the pituitary gland, so radiation therapy to the head area can affect sexual development and sperm production as well.

"This is one live healthy baby, which is fantastic, but I think we'd like to see a couple more". The researchers chose to use sperm made from tissue that had once been frozen, given that's how the process would nearly certainly work with people.

For the study, the researchers first removed testicular tissue from five rhesus macaques who had not yet begun puberty.

"I believe we will have this technology in the clinic in the next two to five years", he continued, adding that discussions were already underway with regulators.

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