Oktay Kutluk, Baltaci Volkan, Sonmezer Murat, Turan Volkan, Unsal Evrim, Baltaci Aysun, Aktuna Suleyman, Moy Fred
Laboratory of Molecular Reproduction and Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College, New York, NY, USA Innovation Institute for Fertility Preservation and IVF, New York, NY, USA GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey
GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey.
Reprod Sci. 2015 Dec;22(12):1612-7. doi: 10.1177/1933719115612137.
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.
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.
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 = .03) with a trend for better embryo grades (2.3 ± 0.3 vs 3.1 ± 0.7; P = .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 = 4/10).
These data show encouraging results for AMI in comparison to previous failed IVF cycles.
线粒体功能障碍被认为是年龄导致卵母细胞质量下降的主要原因。过去，供体卵母细胞胞质移植曾取得一些成功，但由于对异质性的担忧而被放弃。最近的研究表明，人类卵巢中存在卵原细胞前体（OPC），这可能是“健康线粒体”的自体来源。我们试图研究OPC来源的自体线粒体注射（AMI）改善多次体外受精（IVF）失败女性卵母细胞质量的临床疗效。
通过使用单克隆抗血管同源物（抗DDX）抗体进行细胞分选，从腹腔镜获取的卵巢皮质碎片中分离出OPC。然后将其破坏并分离出线粒体。在卵胞浆内单精子注射期间，将重组线粒体注入每个卵母细胞。对第一个失败周期和AMI后周期进行配对比较。
在接受卵巢刺激的15名女性中，2名被取消，3名决定将卵母细胞集中起来用于以后的AMI。在其余10名（平均年龄34.7±4.1岁）女性中，AMI显著提高了受精率（49.7±31.3 vs 78.3±18.9；P = 0.03），胚胎等级有改善趋势（2.3±0.3 vs 3.1±0.7；P = 0.08）。10名女性中有4名在单次冷冻胚胎移植后受孕，3名在通过阵列比较基因组杂交（aCGH）确认二倍体后受孕（临床妊娠/胚胎移植 = 4/10）。
与之前失败的IVF周期相比，这些数据显示AMI取得了令人鼓舞的结果。
