P-138 Effects of caffeine supplementation prior to fertilization on oocyte quality and euploidy rates in aged women

Abstract Study question Could caffeine supplementation before fertilization improve the clinical outcomes in women over 40? Summary answer Caffeine supplementation significantly improved the rates of oocytes with normal spindle location, top-quality blastocyst and euploidy in women over 40. What is known already In aged oocytes, caffeine could inhibit Myt1/Wee1 activity, leading to a reversible switch from inactive to active MPF. Consequently, caffeine increases MPF activity which inhibits oocyte aging. Subsequently, many studies have reported that caffeine treatment can inhibit oocyte aging in several species. However, the effect of caffeine on human oocytes has not been studied. We investigated the effect of caffeine supplementation prior to fertilization on clinical outcomes in aged human oocytes. Study design, size, duration The retrospective data collected from June 2022 to December 2024 on 10474 oocytes from 783 patients were analyzed. To eliminate the influence of genetic background factors, the same patients were divided into a group of previous cycles without caffeine (previous group; 5313 oocytes) and a group of cycles with caffeine (caffeine group; 5161 oocytes). Participants/materials, setting, methods The inclusion criteria were the patients aged over 40 years, with a history of previous IVF. The caffeine group had 1.25mM caffeine added to fertilization medium for 4 hours following ovum pick up. Oocytes were washed and transferred to a new fertilization medium. Subsequently, mature oocytes were fertilized by ICSI and cultured. Spindles were imaged using the Polscope and biopsy was conducted on blastocyst stage embryos (PGT-A). Main results and the role of chance A total of 783 patients were divided into caffeine group and previous group, and the two groups were similar in age (41.8 vs 41.3, p = 0.2780) and number of previous IVF procedures (6.1 vs 6.0, p > 0.05, p = 0.4788). In 205 out of 783 patients, the meiotic spindle was visualised and examined using the Polscope prior to ICSI in both groups. The normal localization of spindle (under 30 degrees angle) in oocytes was significantly higher in caffeine group compared to previous group (79.2% vs. 58.6%, p < 0.0001). Also, the incidence of spindles with an angle over 30 degrees and the absence of visible spindle was significantly lower in caffeine group (20.8% vs. 41.4%, p < 0.0001). The caffeine group had significantly higher incidence of fertilization, top-quality cleavage rate on day 3 and blastocyst utilization rate than previous group (77.5% vs. 71.8%, 64.0% vs. 57.7%, 39.5% vs. 32.8%, p < 0.0001). In particular, the rate of top-quality blastocysts was 10.2% higher in caffeine group than in previous group (40.4% vs. 30.2%, p < 0.0001). The rate of euploidy was significantly higher in caffeine group than in previous group (23.5% vs. 15.6%, p = 0.02) and the rate of mosaicism was significantly lower in caffeine group than in previous group (18.6% vs. 29.4%, p = 0.0048). Limitations, reasons for caution This study is the first investigation regarding the effects of caffeine on human oocytes. Further investigation is needed to confirm the specific mechanism of caffeine in oocytes. Wider implications of the findings These results demonstrate that caffeine has a positive effect on embryo development. Therefore, caffeine supplementation prior to fertilization has the potential as a novel strategy for aged women who experienced poor results in previous IVF cycles. Trial registration number No