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乳腺癌:治疗相关不孕的最新进展。

Breast cancer: an update on treatment-related infertility.

机构信息

Gynecologic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.

Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Aldo Moro, Bari, Italy.

出版信息

J Cancer Res Clin Oncol. 2020 Mar;146(3):647-657. doi: 10.1007/s00432-020-03136-7. Epub 2020 Jan 31.

Abstract

Breast cancer (BC) is the most common malignancy in women with a significant increasing incidence during the reproductive life. However, based on the newest anti-cancer molecular targeting drugs, successful treatments lead to the disease healing particularly in young patients, thus refreshing their motherhood programs. However, as effect of the BC treatment, a premature depletion of the ovarian follicle reserve occurs in more than one-third of patients resulting in permanent infertility. To prevent the cancer treatment-related infertility (CTRI), several options are today utilized. Besides the ovary suppression by gonadotropin-releasing hormone agonist (GnRHa), other procedures include either oocytes or embryos cryopreservation as well as ovarian cortex cryopreservation that are currently adopted before anti-cancer therapies. These modern techniques appear variably successful in terms of pregnancy rate though their safety concerning the hormonal stimulation to promote the folliculogenesis is still debated in relation to the potential oncogenic risk in patients bearing hormone-sensitive tumors as BC, while the ovarian cortex re-implantation often results in a low number of regenerated follicles including oocytes of unknown quality. Recent studies on ovarian stem cells (OSCs) suggest their use for future application in CTRI. In fact, OSCs from ovarian cortex have been shown to differentiate in vitro into oocyte-like cells (OLCs) and express molecular markers of mature oocytes. Once the OSC technology will be optimized and translated to clinical use, oocytes derived from these cells will be molecularly assessed before fertilization to assure their best embryo quality resulting in a safe procedure to treat CTRI in patients as young women with BC.

摘要

乳腺癌(BC)是女性最常见的恶性肿瘤,在生育期发病率显著增加。然而,基于最新的抗癌分子靶向药物,成功的治疗方法使疾病得到治愈,尤其是在年轻患者中,从而使他们的生育计划得以恢复。然而,由于 BC 治疗的影响,超过三分之一的患者卵巢卵泡储备会过早耗尽,导致永久性不孕。为了预防癌症治疗相关的不孕(CTRI),目前有几种选择。除了用促性腺激素释放激素激动剂(GnRHa)抑制卵巢外,其他方法还包括冷冻卵子或胚胎,以及卵巢皮质冷冻保存,这些方法目前在抗癌治疗前采用。尽管这些现代技术在妊娠率方面表现出不同程度的成功,但它们在促进卵泡发生方面的激素刺激的安全性仍存在争议,因为它们可能对患有激素敏感肿瘤(如 BC)的患者存在潜在的致癌风险,而卵巢皮质再植入通常会导致再生卵泡数量较少,包括卵子质量未知的卵泡。最近关于卵巢干细胞(OSC)的研究表明,它们可用于未来的 CTRI 应用。事实上,已经证明卵巢皮质中的 OSC 可以在体外分化为卵母细胞样细胞(OLC),并表达成熟卵母细胞的分子标记。一旦 OSC 技术得到优化并转化为临床应用,这些细胞产生的卵子将在受精前进行分子评估,以确保其最佳胚胎质量,从而为年轻的 BC 患者提供安全的 CTRI 治疗方法。

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