Better Outcomes for Young Women Surviving Cancer

Newswise — Reproductive health is not the same as sex ed,” Teresa K. Woodruff, PhD, from the Feinberg School of Medicine, Northwestern University, reminded us in yesterday’s plenary session, “Oncofertility: From Bench to Bedside to Babies.” The war on cancer has been hard fought, with more young women than ever now surviving cancer but being faced with the possibility of infertility.

We often think of fertility management as an elective treatment for those with the means to seek it, rather than understanding the health risks associated with loss of this important endocrine function. Infertility sometimes leads to premature menopause, which is associated with many long-term health risks including premature death, cardiovascular disease, osteoporosis, neurologic disease, and other disorders. Estrogen treatment doesn’t completely mitigate these outcomes. Children with damaged ovaries that don’t allow for a normal pubertal transition face compounded risks. 

Woodruff reminded the audience that clinical research is integral to improving fertility management for cancer survivors. Emerging assays provide more options for young women to manage their fertility after cancer treatment. For example, a blot-spot assay for anti-Mullerian hormone (AMH) enables patients to send in a blood spot from home to assess their ovarian reserve, facilitating an estimate of the reserve of growing follicles each month. This knowledge enables physicians and patients to make timely, educated decisions about fertility options that can include embryo or egg banking, surrogacy, and ovarian cryopreservation. 

Beyond assessing fertility status, Woodruff’s laboratory is working to provide solutions for endocrine and fertility loss in cancer survivors. With a complete understanding of what makes a healthy egg and microenvironment, and how somatic cells and oocytes communicate, the aim of these efforts is to better inform testing, treatment, and functional restoration—and Woodruff and her colleagues are closer to doing so than we might have imagined. She described an in vitro microfluidic system that produced a 28-day menstrual cycle hormone profile in murine ovarian follicles. This technology, named EVATAR, mimics the complex endocrine loops between ovary, fallopian tube, uterus, cervix, and liver by circulating fluidics between each of these tissues. This phenocopy of the female reproductive system provides an accessible system for evaluating the effects of certain treatments on the reproductive system at a personal level. 

The introduction of the EVATAR is also opening a new era in reproductive health research where microfluidics carry signals between organs, bring fresh nutrients, and remove metabolic waste products. This seemingly small difference allows researchers to study cycling hormones and tease out nuances in signaling that are lost in static culture models.

Woodruff and her colleagues are pursuing possible interventions, including engineering an ovarian bioprosthetic, that will maintain and restore normal autonomous function to follicles. Already, her lab has restored ovarian function in sterilized mice using 3D printed microporous scaffolds to create a bioprosthetic ovary that allowed for pups born through natural mating. This important breakthrough provides new treatment possibilities for endocrine support and infertility in the many premenopausal and prepubertal cancer survivors. 

In Woodruff’s experience, many oncologists tend to be uninformed about reproductive health. This is an area in which more education about the role of hormones in fertility and endocrine support could produce healthier lives. This rapidly advancing frontier will require our close attention to ensure that cancer survivors achieve the best possible long-term health outcomes. Woodruff closed with a reminder that “when grants and papers meet clinical problems, patient needs are met and we can change a devastating diagnosis into hope for the future.”