Infertility affects a significant number of couples worldwide and its incidence is increasing. While assisted reproductive technologies (ART) have revolutionized the treatment landscape of infertility, a significant number of couples present with an idiopathic cause for their infertility, hindering effective management. Profiling the genome and transcriptome of infertile men and women has revealed abnormal gene expression. Epigenetic modifications, which comprise dynamic processes that can transduce environmental signals into gene expression changes, may explain these findings. Indeed, aberrant DNA methylation has been widely characterized as a cause of abnormal sperm and oocyte gene expression with potentially deleterious consequences on fertilization and pregnancy outcomes. This review aims to provide a concise overview of male and female infertility through the lens of DNA methylation alterations.

Antibody-drug conjugates (ADCs) have transitioned from clinically marginal agents into a defining therapeutic class for solid tumor oncology. In DESTINY-Breast03, trastuzumab deruxtecan achieved a four-fold progression-free survival advantage over trastuzumab emtansine, attributable not to antibody engineering but to the linker-payload axis: a cleavable peptide linker and a topoisomerase I payload with bystander activity. Sacituzumab govitecan extends the same logic to Trop-2-positive disease via extracellular payload release, and the framework now spans breast, urothelial, gynecologic, lung, gastric, and colorectal cancers, with enfortumab vedotin plus pembrolizumab displacing platinum chemotherapy as first-line therapy for urothelial cancer in EV-302 (median overall survival 31.5 versus 16.1 months). This review synthesizes ADC biology along three analytical axes. The mechanistic axis links each linker-payload-DAR configuration to a specific tumor-biology barrier: vascular limitation, which delivers approximately 0.1% of the administered dose to tumor tissue; the binding-site barrier, which concentrates exposure at the perivascular margin; and antigen mosaicism, which defeats internalization-dependent killing. The translational axis examines resistance as a coordinated failure across antigen modulation, trafficking, efflux, apoptotic execution, and lysosomal processing. The clinical axis traces the platform’s migration toward earlier-line and curative-intent settings. We close by examining whether the ADC delivery architecture translates to precision immunosuppression in autoimmune disease, where the glucocorticoid receptor modulator ADC ABBV-154 met placebo-controlled efficacy endpoints in rheumatoid arthritis but was discontinued because its benefit-risk profile did not differentiate it from existing biologic therapies.