# Oncofertility in Women with Renal Cell Carcinoma in the Immune Checkpoint Inhibitors Era: A Multidisciplinary Perspective

**Authors:** Michele Miscia, Antonio Raffone, Veronica Mollica, Pietro Piazza, Linda Cipriani, Manuela Maletta, Stefano Ferla, Maria Perucci, Federica Cortese, Irene Pesaresi, Enrico Pazzaglia, Luigi Cobellis, Renato Seracchioli, Diego Raimondo

PMC · DOI: 10.3390/jcm15062452 · Journal of Clinical Medicine · 2026-03-23

## TL;DR

This review discusses fertility preservation and reproductive counseling for women with kidney cancer treated with immune checkpoint inhibitors, emphasizing the need for multidisciplinary care.

## Contribution

The paper provides a multidisciplinary counseling framework for oncofertility in RCC patients treated with ICIs, distinguishing evidence-based and extrapolative domains.

## Key findings

- Contemporary RCC treatment allows feasible timepoints for fertility preservation discussions.
- Evidence-secure recommendations include pregnancy avoidance during therapy and agent-specific washout.
- Long-term ovarian reserve effects and post-ICI periconception safety remain extrapolative domains.

## Abstract

Background/Objectives: Renal cell carcinoma (RCC) care has been reshaped by immune checkpoint inhibitors (ICIs), now used across adjuvant and metastatic settings as PD-1/PD-L1 blockade alone, combined with anti-CTLA-4 agents, or in combination with vascular endothelial growth factor (VEGF)-targeting tyrosine kinase inhibitors (TKIs). As survival improves and systemic therapy courses extend, survivorship priorities—including fertility preservation, reproductive endocrine health, contraception, and pregnancy counselling—become increasingly relevant, even though RCC-specific oncofertility evidence remains sparse. This review examines the biological rationale and clinical considerations underpinning reproductive counselling for women of reproductive age exposed to ICIs (alone or with TKIs) in RCC. Methods: A narrative review was conducted in accordance with the SANRA framework, integrating targeted PubMed/MEDLINE searches up to 20 February 2026 and consultation of regulatory product labels to synthesize mechanistic, clinical, and safety data relevant to fertility, endocrine function, contraception, pregnancy, and breastfeeding in RCC. Results: We delineate the contemporary RCC treatment landscape to identify feasible timepoints for fertility preservation discussions and propose a pragmatic, implementation-oriented counselling framework that distinguishes evidence-secure recommendations (pregnancy avoidance during therapy, endocrine monitoring, agent-specific washout) from extrapolative domains (long-term ovarian reserve effects and post-ICI periconception safety beyond label intervals). Conclusions: By integrating a ‘multi-hit’ biological rationale, treatment context, and available human data, this review highlights RCC-specific research priorities while supporting transparent, evidence-aligned, and multidisciplinary counselling for both fertility preservation and pregnancy safety in the ICI era.

## Linked entities

- **Proteins:** PDCD1 (programmed cell death 1), CD274 (CD274 molecule), CTLA4 (cytotoxic T-lymphocyte associated protein 4), VEGFA (vascular endothelial growth factor A)
- **Diseases:** renal cell carcinoma (MONDO:0005086), RCC (MONDO:0005086)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}
- **Diseases:** RCC (MESH:D002292)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

63 references — full list in the complete paper: https://tomesphere.com/paper/PMC13026637/full.md

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Source: https://tomesphere.com/paper/PMC13026637