Evaluating the Reproductive Impact of Pembrolizumab in Mice: Ovarian Function and Hormonal Changes

Background/Aim: Pembrolizumab, an immune checkpoint inhibitor used in cancer therapy, is associated with immune-related adverse effects, yet its impact on female reproductive health remains unclear. This study aimed to evaluate the effects of pembrolizumab on ovarian function and hormonal balance in a mouse model. Materials and Methods: Twenty-four Swiss albino mice were divided into acute and chronic groups, each comprising a pembrolizumab-treated and a saline-control subgroup (n=6 per subgroup). All mice underwent a superovulation protocol, and serum levels of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) were measured using enzyme-linked immunosorbent assay kits. Ovarian tissues were evaluated histologically for follicular counts, including primordial, preantral, and secondary follicles. Results: Estradiol levels were significantly reduced in pembrolizumab-treated mice compared with controls (p=0.007). Significantly higher levels of LH were observed in the chronic control group compared to the chronic pembrolizumab-treated group (p=0.023), while FSH and AMH levels did not differ significantly (p=0.461 and p=0.460, respectively). Primordial follicle counts were significantly higher in control groups than in pembrolizumab-treated groups (p=0.009). Conclusion: Pembrolizumab administration in mice led to reduced estradiol levels and diminished primordial follicle counts, indicating potential adverse effects on ovarian reserve. These findings highlight the importance of evaluating reproductive risks in female patients receiving immunotherapy.