Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice.

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.

The PARP inhibitor, olaparib, depletes the ovarian reserve in mice: implications for fertility preservation.

Study Question: What is the impact of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, alone or in combination with chemotherapy on the ovary in mice?

Summary Answer: Olaparib treatment, when administered alone, depletes primordial follicle oocytes, but olaparib does not exacerbate chemotherapy-mediated ovarian follicle loss in mice.

What Is Known Already: The ovary contains a finite number of oocytes stored within primordial follicles, which give rise to all mature ovulatory oocytes. Unfortunately, they are highly sensitive to exogenous DNA damaging insults, such as cytotoxic cancer treatments.