Oocyte gene mutations increase rates of total fertilization failure: a systematic review and meta-analysis

Total fertilization failure (TFF) remains a critical barrier in assisted reproductive technology (ART), occurring in 5–10% of treatment cycles. While TFF can result from both male and female gamete factors, emerging evidence suggests that oocyte gene mutations may play a significant role. This study systematically reviews and meta-analyzes the influence of specific oocyte gene mutations (OGMs) on fertilization outcomes, focusing on their association with TFF and fertilization rates (FRs). This study has a preregistered protocol (CRD42024608566). A comprehensive search was conducted in PubMed, EMBASE, and Cochrane Library on December 10, 2024 and updated on February 5, 2026. Studies involving women undergoing ART with known oocyte gene mutations—including WEE2, PATL2, TUBB8, and others—were evaluated alongside studies of women without identified mutations. TFF and FR were the primary and secondary outcomes, respectively. Data synthesis included pooled proportions with confidence intervals (CIs) using random-effects models. Of the 11,966 records identified, 105 studies were included. A total of 74 studies reported on women with 19 different OGMs, with 31 studies serving as indirect comparators. TFF rates were higher in women with specific mutations including WEE2, PATL2, and TUBB8, when analyzed alongside the indirect comparison patients; which were 66% (95% CI: 44–82%), 67% (95% CI: 50–81%) and 18% (95% CI: 8–38%) respectively. FRs were lower among carriers of these mutations: 3% (95% CI: 1–10%), 2% (95% CI: 0–10%) and 20% (95% CI: 10–38%) respectively. In contrast, the indirect comparator group had a low TFF rate, which was 9% (95% CI: 6%; 14%) and high FR, which was 67% (95% CI: 62%; 71%). Our findings suggest that specific OGMs may be associated with increased TFF rates and decreased FRs in ART. These results highlight the potential clinical value of genetic screening in women with unexplained infertility or repeated ART failures. 1. The presence of several oocyte gene mutations (OGMs) results in higher rates of total fertilization failure (TFF) and lower fertilization rates (FRs). 2. WEE2 and PATL2 mutations showed increased TFF rates up to 67% in assisted reproduction. 3. Physicians should consider genetic testing for OGM for women undergoing ART with a diagnosis of unexplained infertility.