Certain Cancer Immunotherapy Treatments Impair Fertility: Study

Studies are needed to determine if the adverse affects of immune checkpoint inhibitors on fertility in mice are replicated in humans. Pro-stock studio/Adobe Stock

Australian researchers have found that some immunotherapy treatments for cancer can damage fertility, prompting a call for further research and preventative measures such as freezing eggs.

A pre-clinical trial, led by experts from Monash University’s Biomedicine Discovery Institute and the Peter MacCallum Cancer Centre, demonstrated that a common type of immunotherapy drug known as immune checkpoint inhibitors led to the permanent damage of mouse ovaries and the eggs within.

While traditional cancer therapies such as chemotherapy and radiotherapy are already known to adversely affect the ovaries, leading to infertility and premature menopause in young girls and women, the potential side effects of immunotherapy cancer drugs on fertility had been previously unknown.

The study found that checkpoint inhibitors, which enhance the body’s ability to fight cancer, can impair both immediate and future fertility by reducing the number and quality of eggs, interfering with ovulation, and disrupting the fertility cycle.

Co-lead author and PhD candidate in the Monash Biomedicine Discovery Institute, Lauren Alesi, said in a media release on Friday that human studies must now be prioritised.

“Initially, these treatments were thought to be less damaging (than chemo and radiotherapy) in the context of off-target effects to the body in general,” she said.

“However, it is now clear that inflammatory side effects in other organ systems are quite common with these drugs.

“Our study highlights that caution should be exercised by clinicians and their patients, for whom fertility may be a concern.”

Appropriate Interventions Needed

Specialist Medical Oncologist Professor in breast cancer and a senior author of the study, Sherene Loi, said appropriate interventions that can preserve fertility and ovarian function could be implemented before cancer treatment to facilitate pregnancies post-treatment.

“These interventions need to be implemented in a timely manner so as not to delay anti-cancer treatment,” she said.

“Immunotherapy is now becoming a standard of care for many women with curable early stage breast cancer, due to impressive results in reducing breast cancer recurrences, but further research into the long-term effects of immunotherapy is needed.”

Embryos are frozen and stored in the cryo store at Birmingham Women's Hospital fertility clinic in Birmingham, England on January 22, 2015. Photo by Christopher Furlong/Getty Images

Alesi said that apart from drugs that block hormone production during chemotherapy and strategies to prevent premature menopause in younger women, egg and embyo freezing were the only fertility preservation measures currently available.

However, she noted that embryo freezing was expensive, invasive, and did not prevent ovarian damage, meaning premature menopause could still pose a risk for these women.

“Therefore, we are now prioritising investigation of targeted ovarian preservation strategies that aim to prevent the damage to the ovary from occurring in the first place, without interfering with the drug’s ability to fight the cancer,” she said.

Alesi added that the study findings demonstrate the need to also assess other immunotherapy classes.

“Our results may have implications for other immunotherapies since our results have revealed a close relationship between immune cells, the communication molecules (cytokines) they release, and regulating many aspects of fertility,” she said.