Research progress on mechanism of follicle injury after frozen ovarian tissue transplantation and protective strategies.

The iatrogenic ovarian dysfunction caused by cancer treatment have been increasing, along with the age at onset of malignant tumors getting younger, the survival of cancer patients being longer, as well as the delayed childbearing age for females; therefore it becomes a major clinical challenge to preserve the fertility of these patients. Ovarian tissue cryopreservation is the only solution for female cancer patients in prepubertal ages and those who cannot delay gonadotoxic therapy. However, the successful rate of cryopreservation and transplantation of ovarian tissue is still low at present due to the risk of ischemia and hypoxia of grafted tissues. Abnormal activation of primordial follicle and ischemia-reperfusion injury after blood supply recovery also cause massive loss of follicles in grafted ovarian tissues. It has been tried in various studies to reduce the damage of follicles during freezing and transplantation by adding certain drugs, and extend the duration of endocrine and reproductive function in patients with ovarian transplantation. For example, melatonin, N-acetylcysteine, erythropoietin or other antioxidants are used to reduce oxidative stress; mesenchymal stem cells derived from different tissues, basic fibroblast growth factor, vascular endothelial growth factor, angiopoietin 2 and gonadotropin are used to promote revascularization; anti-Müllerian hormone and rapamycin are used to reduce abnormal activation of primordial follicles. This article reviews the research progress on the main mechanisms of follicle loss after ovarian tissue transplantation, including hypoxia, ischemia-reperfusion injury and associated cell death, and abnormal activation of follicles; and explores the methods of reducing graft follicle loss to provide reference for improving the efficiency of ovarian tissue cryopreservation and transplantation.移植冷冻卵巢组织是青春期前女性及不能推迟性腺毒性治疗患者唯一的生育力保存手段。目前，卵巢组织冷冻保存及移植效率仍低，卵巢组织移植后面临缺血缺氧风险，始基卵泡的异常激活和血供恢复后的缺血-再灌注损伤也造成移植物卵泡大量损失。大量研究尝试通过添加某些药物，减少卵泡在冷冻及移植过程中所受的损伤，延长卵巢移植患者内分泌功能及生殖功能持续的时间：如添加褪黑素、N-乙酰半胱氨酸、促红细胞生成素或其他抗氧化剂以减轻氧化应激，添加不同来源的间充质干细胞、碱性成纤维细胞生长因子、血管内皮生长因子、血管生成素2、促性腺激素以促进血运重建，添加抗米勒管激素、雷帕霉素以减少始基卵泡异常激活。本文重点阐述了卵巢组织移植后卵泡损伤的主要机制及减少移植卵巢卵泡损伤的方法，以期为提高冷冻卵巢组织复苏效率提供参考。.