Abstract
Background: Mitochondrial dysfunction has been suggested as a major cause of age-induced decline in oocyte quality. In the past, donor oocyte cytoplasmic transfer showed some success but was abandoned due to the concerns with heteroplasmy. Recent studies indicated presence of oogonial precursor cells (OPCs) in the human ovary, which could be an autologous source of 『『healthy mitochondria.』』 We sought to investigate the clinical efficacy of OPC-derived autologous mitochondrial injection (AMI) to improve oocyte quality in women with multiple in vitro fertilization (IVF) failures. Methods: The OPCs were isolated from laparoscopically obtained ovarian cortical pieces by cell sorting using a monoclonal anti-vasa homolog (anti-DDX) antibody. They were then disrupted and mitochondria were isolated. Reconstituted mitochondria were injected into each oocyte during intracytoplasmic sperm injection. Paired comparisons were made between the first failed cycles and the post-AMI cycles. Results:Of the 15 women undergoing ovarian stimulation, 2 were canceled and 3 decided to pool oocytes for later AMI. In remaining 10 (mean age 34.7 + 4.1), AMI significantly improved fertilization rates (49.7 + 31.3 vs 78.3 + 18.9; P ¼ .03) with a trend for better embryo grades (2.3 + 0.3 vs 3.1 + 0.7; P ¼ .08). Four of 10 women conceived after single frozen embryo transfer and 3 after confirmation of diploidy via array comparative genomic hybridization (aCGH) (clinical pregnancy/embryo transfer ¼ 4/10).
Conclusion: These data show encouraging results for AMI in comparison to previous failed IVF cycles.
Keywords
oogonial precursor cells, mitochondria, embryo transfer, pregnancy, oocyte quality, IVF
背景：線粒體功能障礙是高齡女性卵子質量差的主要原因。過去，供體卵母細胞胞質移植提高了IVF成功率，但是由於異質性而被忽略。最近的研究發現在人卵巢存在卵原前體細胞，並且此細胞可以是自體 「健康線粒體」的來源。在此，我們以源於卵原前體細胞的自體線粒體注射（(AMI)）來提高卵母細胞質量，研究它對IVF反覆失敗患者的臨床治療效果。方式：通過腹腔鏡獲得卵巢皮質，然後經單克隆抗體（anti-DDX）篩選得到卵原前體細胞（OPCs）。裂解卵原前體細胞後分離得到線粒體，然後通過胞漿內單精子注射技術把線粒體注射入卵母細胞中。以第一次失敗周期為對照，比較AMI後的臨床效果。結果：共15位患者經歷促排卵，其中2位不決定AMI，3位決定儲存卵子為以後的AMI。剩餘的10位（平均年齡34.7 + 4.1），進行AMI後其妊娠率（49.7 + 31.3 vs 78.3 + 18.9; P ¼ .03）顯著提高，並且胚胎評分（2.3 + 0.3 vs 3.1 + 0.7; P ¼ .08）有更好的趨勢。10位患者中的4位經冷凍單胚移植後成功妊娠，其中3位經基因組雜交檢測後確定是二倍體（臨床妊娠/胚胎移植¼ 4/10）。
關鍵詞：卵原前體細胞，線粒體，胚胎移植，懷孕，卵母細胞質量