Miyazaki Kotaro, Yamada Mitsutoshi, Akashi Kazuhiro, Jwa Seung Chik, Utsuno Hiroki, Kamijo Shintaro, Arimitsu Takeshi, Hida Mariko, Sato Yasunori, Hirota Yasushi, Narumi Satoshi, Tanaka Mamoru, Osuga Yutaka, Kuji Naoaki
Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Obstetrics and Gynecology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Sci Rep. 2025 Jul 29;15(1):27547. doi: 10.1038/s41598-025-12445-1.
The potential effect of artificial oocyte activation (AOA) following intracytoplasmic sperm injection (ICSI) on neurodevelopment remains uncertain. Since AOA does not fully replicate the physiological Ca²⁺ oscillations essential for fertilization, concerns persist regarding its safety. This study evaluates neurodevelopmental outcomes in children conceived via ICSI-AOA compared to conventional ICSI. A multicentre, cross-sectional study was conducted at Keio University Hospital and eight affiliated institutions, assessing 158 children (ICSI: n = 81, ICSI-AOA: n = 77) aged 12-60 months using the Japanese Ages and Stages Questionnaire, 3rd Edition (J-ASQ-3), covering communication, gross motor, fine motor, problem-solving, and personal-social skills. No significant differences were found in J-ASQ-3 subdomain scores across age groups, and fully adjusted models showed no significant differences in children scoring below the monitoring zone. Subgroup analyses compared differences between AOA protocols (A23187: n = 59; ionomycin: n = 15). AOA protocols were not significantly associated with score variations. Neurodevelopmental outcomes in children conceived via ICSI-AOA were comparable to those conceived via conventional ICSI, suggesting that AOA does not adversely affect early childhood neurodevelopment. These findings support the safety of AOA in assisted reproduction, though further longitudinal research is needed to assess long-term outcomes.
卵胞浆内单精子注射（ICSI）后进行人工卵母细胞激活（AOA）对神经发育的潜在影响仍不确定。由于AOA不能完全复制受精所必需的生理性Ca²⁺振荡，其安全性仍受关注。本研究评估了通过ICSI-AOA受孕的儿童与传统ICSI受孕儿童的神经发育结局。在庆应义塾大学医院和八个附属医院进行了一项多中心横断面研究，使用日本版第三版年龄与发育进程问卷（J-ASQ-3）对158名年龄在12至60个月的儿童（ICSI组：n = 81；ICSI-AOA组：n = 77）进行评估，该问卷涵盖沟通、大运动、精细运动、解决问题和个人社交技能。各年龄组的J-ASQ-3子领域得分无显著差异，完全调整模型显示，得分低于监测区间的儿童之间也无显著差异。亚组分析比较了不同AOA方案（A23187：n = 59；离子霉素：n = 15）之间的差异。AOA方案与得分变化无显著相关性。通过ICSI-AOA受孕的儿童的神经发育结局与通过传统ICSI受孕的儿童相当，这表明AOA不会对幼儿神经发育产生不利影响。这些发现支持了AOA在辅助生殖中的安全性，不过仍需要进一步的纵向研究来评估长期结局。
