Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice

Nat Cancer. 2022 Aug;3(8):1-13. doi: 10.1038/s43018-022-00413-x. Epub 2022 Aug 25.


Loss of fertility is a major concern for female reproductive-age cancer survivors, since a common side-effect of conventional cytotoxic cancer therapies is permanent damage to the ovary. While immunotherapies are increasingly becoming a standard of care for many cancers-including in the curative setting-their impacts on ovarian function and fertility are unknown. We evaluated the effect of immune checkpoint inhibitors blocking programmed cell death protein ligand 1 and cytotoxic T lymphocyte-associated antigen 4 on the ovary using tumor-bearing and tumor-free mouse models. We find that immune checkpoint inhibition increases immune cell infiltration and tumor necrosis factor-α expression within the ovary, diminishes the ovarian follicular reserve and impairs the ability of oocytes to mature and ovulate. These data demonstrate that immune checkpoint inhibitors have the potential to impair both immediate and future fertility, and studies in women should be prioritized. Additionally, fertility preservation should be strongly considered for women receiving these immunotherapies, and preventative strategies should be investigated in future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fertility Preservation*
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunotherapy / adverse effects
  • Mice
  • Neoplasms*
  • Oocytes / pathology


  • Immune Checkpoint Inhibitors