Personalized cervical plug combines mechanical and biological regulation for enhanced embryo implantation and live births

Abstract

Declining birth rates and widespread infertility highlight the urgency of addressing the global population crisis. Despite advancements in in vitro fertilization (IVF) embryo transfer, low implantation rates due to uterine peristalsis and insufficient embryo-endometrium interaction leads to low pregnancy rate and live births. We introduce a personalized, 3D-printed cervical plugging device (CervPlug), tailored to individual cervical dimensions. This non-invasive, patient-friendly intervention effectively improves embryo residence time in the uterus, enhancing embryo-endometrium contact and achieving efficient live births. Moreover, CervPlug also facilitates biological regulation by integrating a supramolecular phenolic nanocomplex composed of green tea polyphenol and Zn²⁺ ions. This enables controlled release of progesterone, reduces cervical inflammation, and lowers intra-embryonic reactive oxygen species (ROS). In vivo experiments demonstrate that CervPlug significantly increases implantation rates from 45% to 65% and live births, with no significant adverse effects on the reproductive system. This biomaterial-driven strategy offers a safer, less intrusive alternative in reproductive medicine.