Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology

Area of Science:

• Oncology and Immunology
• Reproductive Medicine

Background:

• Immune checkpoint inhibitors (ICIs) demonstrate significant efficacy in treating various cancers, including melanoma.
• Melanoma is a prevalent cancer among reproductive-aged individuals, yet the reproductive toxicities associated with adjuvant and first-line immunotherapies remain largely uncharacterized.
• The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway plays a crucial role in reproductive homeostasis, fertility, and successful pregnancy.

Approach:

• This review presents a case study of a reproductive-aged female with stage IIIC melanoma seeking family planning advice post-pembrolizumab therapy.
• It synthesizes current knowledge on fertility-related toxicities of ICIs.
• The review examines potential reproductive toxicity targets in both males and non-pregnant females, alongside the implications of anti-PD-1 therapy on fetomaternal tolerance.

Key Points:

• The PD-1/PD-L1 pathway is critical for maintaining fetomaternal tolerance and ensuring a healthy pregnancy.
• Understanding the impact of ICIs on fertility is essential for reproductive-aged cancer patients.
• Data and consensus are needed to support informed family planning decisions for patients undergoing immunotherapy.

Conclusions:

• Adjuvant and first-line immunotherapies, particularly anti-PD-1 agents, may pose risks to male and female reproductive health.
• Further research is required to fully elucidate the reproductive toxicities of ICIs and their effects on fertility and pregnancy.
• Establishing clear guidelines and sharing data will empower patients and clinicians in making informed family planning choices.