11/24/2025
ZP3 and Genuine Empty Follicle Syndrome
Empty Follicle Syndrome (EFS) occurs when you do IVF but the follicles are empty with no eggs in side of them. Usually EFS happens when there are errors with trigger medication but when this isn't the cause, it can sometimes be referred to as 'Genuine' EFS. There can be many different causes but sometimes it can be genetic.
The ZP3 gene plays a role in the formation of the zona pellucida, the shell that protects the egg. People with a harmful change in this gene have abnormalities in the zona pellucida and may experience Genuine EFS because the egg is not protected, so it degenerates within the follicle. Others may have oocyte death observed after egg retrieval, or fertilization failure.
Interested in exploring genetic causes for your infertility? The waitlist for DNAide's Advanced Genetic Testing Program is open! The link is in our bio.
Video description: Meaghan, a woman with curly brown hair speaks to the camera. Part way through the video she shows an image of a normal egg, with a dark purple zona pellucida around it. Then she compares this to an abnormal egg from a person with a genetic change in ZP3. The egg has no zona pellucida, isn't round, and has started to degenerate
Chen T, Bian Y, Liu X, et al. A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility. Am J Hum Genet. 2017;101(3):459-465. doi:10.1016/j.ajhg.2017.08.001
Yang P, Chen T, Liu Y, et al. The critical role of ZP genes in female infertility characterized by empty follicle syndrome and oocyte degeneration. Fertil Steril. 2021;115(5):1259-1269. doi:10.1016/j.fertnstert.2020.11.003
Zhang D, Zhu L, Liu Z, et al. A novel mutation in ZP3 causes empty follicle syndrome and abnormal zona pellucida formation. J Assist Reprod Genet. 2021;38(1):251-259. doi:10.1007/s10815-020-01995-0
