As cancer survival rates continue to improve, long-term outcomes have become a central concern for adolescents and young adults treated for the disease. For many patients diagnosed during their reproductive years, parenthood is a major public health concern. Clinicians are increasingly required to address the risk for infertility before treatment begins and to support patients through complex reproductive decisions after treatment.

Researchers at the Research Laboratory on Human Reproduction (RLHR) at the Université Libre de Bruxelles (ULB), Brussels, Belgium, are advancing fertility preservation approaches prior to chemotherapy.

Preservation Strategies

Laboratory work focuses on fertility preservation prior to chemotherapy. The program is led by Isabelle Demeestere, MD, PhD, research director at ULB, and is embedded in a multidisciplinary framework developed in collaboration with oncology centers in Belgium and across Europe. Ongoing clinical research examines how newer anticancer therapies affect ovarian function and evaluates pharmacologic strategies designed to reduce treatment-related gonadotoxicity.

Speaking with MediQuality, a Medscape Network platform, Margherita Condorelli, MD, gynecologist specializing in oncofertility at the Hôpital Erasme Fertility Clinic of Brussels University Hospital (H.U.B.), said, “Our laboratory has been involved in several oncofertility studies, including CHANCE, BROVALE, and FAMHOPE. Some of these are ongoing; others we’ve completed.”

She is currently pursuing her PhD in breast cancer (BC) oncofertility management at the ULB’s RLHR, working under the supervision of Demeestere. Her research focuses on the critical question of how assisted reproductive technologies and newer cancer treatments affect fertility in young patients with BC. What is their impact on cancer outcomes?

“This involves enrolling patients from Erasmus Hospital and Queen Fabiola Children’s University Hospital, both of which are part of the Brussels University Hospital (H.U.B.) network affiliated with the ULB.”

The CHANCE study examined anti-Müllerian hormone (AMH) as a predictive factor for the risk for future infertility in prepubertal and pubertal patients treated for cancer. The BROVALE study evaluated the efficacy and safety of controlled ovarian stimulation (COS) combined with the aromatase inhibitor letrozole for fertility preservation in patients with BC. fAMHOPE was a prospective multicenter cohort study assessing COS in patients newly diagnosed with BC; however, the study was discontinued following the implementation of new European clinical trial regulations.

Pregnancy Considerations

The ULB team has also contributed to major international trials, including the POSITIVE study, which has influenced clinical decision-making regarding pregnancy planning in patients receiving endocrine therapy for hormone receptor-positive BC.

“This study allowed us to assess ovarian reserve through hormone analysis, particularly AMH,” Condorelli said.

Patients treated for BC face an increased risk for infertility related to anticancer therapy and age at diagnosis. As a result, some patients interrupt adjuvant endocrine therapy earlier than the recommended minimum of 5 years to attempt pregnancy.

The multicenter POSITIVE trial, conducted by the International Breast Cancer Study Group, evaluated whether temporarily interrupting adjuvant endocrine therapy to attempt pregnancy was feasible and safe in young women with hormone receptor-positive early BC at sufficient risk for recurrence. This study also assessed fertility-related outcomes, pregnancy parameters, and cancer biology in young women. A complementary psycho-oncological study examined fertility concerns, psychological well-being, and decisional conflicts.

Treatment Effects

The RLHR also serves as a sponsor center for several academic studies. It was awarded a prestigious Horizon Europe grant to lead the PredictAYA project.

This 5-year initiative focuses on fertility-related outcomes in adolescent and young adult patients aged 15-39 years who have been treated for cancer. PredictAYA brings together 18 partners from 10 European countries and is funded through Horizon Europe with a total budget of €6,329,134.26.

Despite their high survival rates, many young adults experience late effects of cancer treatment, including infertility and toxicity to other organs. These long-term consequences remain poorly characterized and are rarely addressed in current clinical guidelines.

Running until May 2030, PredictAYA integrates clinical research, epidemiology, pharmacogenetics, and experimental science to identify patients at the highest risk for late treatment-related toxicity and to clarify the underlying biological mechanisms. Demeestere leads the project on reproductive health, sexuality, and post-cancer quality of life.

The PredictAYA team will also collect data on patient-reported care preferences and psychosocial outcomes. Researchers are developing biomarkers to identify individuals at an increased risk for organ toxicity, support targeted screening and personalized counseling, and explore the genetic factors associated with treatment-induced toxicity.

The findings of PredictAYA will be disseminated to patients, healthcare professionals, caregivers, researchers, policymakers, and the public. This project aimed to provide clinical recommendations and support policies that prioritize long-term outcomes for young cancer survivors and their families in Europe.

“We are part of the teams that contribute to the drafting of guidelines, and we participate in the collection of data,” said Condorelli. “Our laboratory evaluates medically assisted reproduction in these young patients, the likelihood of success, and the associated oncologic risk for recurrence.”

Gonadotoxicity Protection

Additional studies on RLHR have focused on preserving ovarian function during chemotherapy. Early studies examined the protective effect of gonadotropin-releasing hormone agonists administered during chemotherapy in patients with lymphoma, helping to establish international collaborations and confirming the laboratory’s expertise in evaluating chemotherapy-induced gonadotoxicity.

The laboratory now serves as a reference center for several national and international studies.

“We evaluate all gonadotoxic anticancer treatments, but our primary focus is cyclophosphamide,” said Condorelli. “Its toxicity profile is well established, which allows detailed analysis of treatment-related ovarian damage.”

This story was translated from MediQuality.