While assisted reproductive technology has advanced significantly in recent years, there are cases where egg maturation, fertilization, or early embryonic development repeatedly ceases even after repeated in vitro fertilization. This condition is called OZEMA (Oocyte/Zygote/Embryo Maturation Arrest), and the involvement of certain gene variants (differences in DNA base sequences) has been suspected. However, until now, the genetic background of OZEMA in Japanese patients has not been fully understood.
Therefore, a research group at Fujita Health University, in collaboration with 34 infertility treatment facilities nationwide, conducted a comprehensive genetic analysis using whole-exome sequencing on 50 Japanese women who had tested positive for OZEMA. As a result, gene variants that were judged to be the cause of disease or pathological conditions, or highly likely to be the cause (pathogenic/highly pathogenic) were identified in 10 patients (20%) based on international standards. The most common causative gene was "TUBB8," a gene for a protein that makes up microtubules, which are important for egg maturation and early development after fertilization, with 6 patients, followed by "PATL2," "ZP2," "ZP3," and "CHEK1," with 1 patient each.
Furthermore, in all patients identified with pathogenic or highly pathogenic variants in this study, no Day 3 embryos were ever obtained. This result suggests that the clinical finding of "inability to obtain Day 3 embryos" may be a practical clue for prioritizing genetic testing and identifying the genetic cause early. This finding is expected to lead to the consideration and development of patient-specific treatment strategies and appropriate genetic counseling for patients and their families.
In the future, the researchers plan to validate these findings in a larger patient population and to identify new causative genes and other pathological mechanisms for cases where the cause could not be identified in this analysis.
Paper information: [Scientific Reports] Gene panel analysis for oocyte/zygote/embryo maturation arrest in female infertility: a multicenter study in Japan
