Birth rates continue to decline as more women experience fertility issues. Assisted reproductive technologies are available for patients seeking fertility treatment, including cryopreservation techniques. Cryopreservation can be performed on gametes, embryos, or gonadal tissue and can be used for patients who desire to delay in vitro fertilization treatment. This review focuses on ovarian tissue cryopreservation, the freezing of ovarian cortex containing immature follicles. Ovarian tissue cryopreservation is the only available treatment for the restoration of ovarian function in patients who undergo gonadotoxic treatments, and its wide adoption has led to its recent designation as “no longer experimental” by the American Society for Reproductive Medicine. Ovarian tissue cryopreservation and subsequent transplantation can restore native endocrine function and can support the possibility of pregnancy and live birth for the patient. Importantly, there are multiple steps in the procedure that put the ovarian reserve at risk of damage. The graft is highly susceptible to ischemic reperfusion injury and mass primordial follicle growth activation, resulting in a “burnout” phenomenon. In this review, we summarize current efforts to combat the loss of primordial follicles in grafts through improvements in freeze and thaw protocols, transplantation techniques, and pharmacologic adjuvant treatments. We conducted a review of the literature, with emphasis on emergent research in the last 5 years. Regarding freeze and thaw protocols, we discuss the widely accepted slow freezing approach and newer vitrification protocols. Discussion of improved transplantation techniques includes consideration of the transplantation location of the ovarian tissue and the importance of graft sites in promoting neovascularization. Finally, we discuss pharmacologic treatments being studied to improve tissue performance postgraft. Of note, there is significant research into the efficacy of adjuvants used to reduce ischemic injury, improve neovascularization, and inhibit hyperactivation of primordial follicle growth activations. Although the “experimental” label has been removed from ovarian tissue cryopreservation and subsequent transplantation, there is a significant need for further research to better understand sources of ovarian reserve damage to improve outcomes. Future research directions are provided as we consider how to reach the most hopeful results for women globally.

中文翻译：

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卵巢组织冷冻保存和移植过程中卵巢储备功能损伤的前瞻性解决方案


随着越来越多的女性遇到生育问题，出生率持续下降。寻求生育治疗的患者可以使用辅助生殖技术，包括冷冻保存技术。冷冻保存可以对配子、胚胎或性腺组织进行，可用于希望延迟体外受精治疗的患者。本综述重点关注卵巢组织冷冻保存，即冷冻含有未成熟卵泡的卵巢皮质。卵巢组织冷冻保存是接受性腺毒性治疗的患者恢复卵巢功能的唯一可用治疗方法，其广泛采用导致其最近被美国生殖医学会指定为“不再是实验性的”。卵巢组织冷冻保存和随后的移植可以恢复天然内分泌功能，并支持患者怀孕和活产的可能性。重要的是，该过程中有多个步骤使卵巢储备功能面临受损的风险。移植物极易受到缺血再灌注损伤和大量原始卵泡生长激活，导致“倦怠”现象。在这篇综述中，我们总结了目前通过改进冷冻和解冻方案、移植技术和药物辅助治疗来对抗移植物中原始卵泡损失的努力。我们对文献进行了回顾，重点关注过去 5 年的新兴研究。关于冷冻和解冻方案，我们讨论了广泛接受的缓慢冷冻方法和较新的玻璃化方案。 对改进移植技术的讨论包括考虑卵巢组织的移植位置以及移植部位在促进新血管形成中的重要性。最后，我们讨论了正在研究的用于改善移植后组织性能的药物治疗。值得注意的是，对于用于减少缺血性损伤、改善新血管形成和抑制原始卵泡生长激活过度激活的佐剂的功效进行了重要研究。尽管“实验”标签已从卵巢组织冷冻保存和随后的移植中去除，但仍迫切需要进一步研究，以更好地了解卵巢储备损伤的来源，以改善结果。当我们考虑如何为全球女性取得最有希望的结果时，我们提供了未来的研究方向。