How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to Cryopreservation of embrya, oocytes, or ovaries
How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to Cryopreservation of embrya, oocytes, or ovaries
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DOI：
10.1634/theoncologist.12-9-1044
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发表时间：
2007-09-01
期刊：
影响因子：
5.8
通讯作者：
Blumenfeld, Zeev
中科院分区：
文献类型：
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作者：
Blumenfeld, Zeev
暴露于化疗的妇女保持生育能力的可能性有：体外受精加胚胎冷冻保存、卵巢冷冻保存、未受精卵冷冻保存和促性腺激素释放激素（GnRH）激动剂的给药。由于这些方法都不理想，因此应考虑将几种方法结合使用。因为在联合治疗后保留性腺功能的机会对女孩来说明显好于男孩，所以模拟青春期前环境仅适用于育龄妇女。其他人和我们对霍奇金病、乳腺癌和其他恶性肿瘤患者或狼疮性肾病患者给予GnRH激动剂，同时进行化疗，已证明存活者卵巢早衰的发生率显著低于非随机对照组。几项前瞻性随机研究正在进行中。最近的一项荟萃分析发现，乳腺癌患者在化疗的基础上给予GnRH激动剂与复发率降低和上级生存率相关。促性腺激素释放激素激动剂对减少化疗相关性性腺毒性的有益作用有以下几种可能性：（a）促性腺激素低下的环境减少了进入分化阶段的原始卵泡的数量，这更容易受到化疗的影响;（B）低雌激素状态减少了卵巢灌注和化疗药物对卵巢的输送;（c）GnRH激动剂对卵巢的直接作用与促性腺激素水平无关;（d）GnRH激动剂可上调性腺内的。抗凋亡分子，如鞘氨醇-1-磷酸;（e）GnRH激动剂可以保护卵巢生殖系干细胞。
The possibilities to preserve fertility in women exposed to chemotherapy are: in vitro fertilization plus embryo cryopreservation, ovarian cryopreservation, unfertilized ova cryopreservation, and the administration of a gonadotropin-releasing hormone (GnRH) agonist. Because none of these methods is ideal, combination of several methods should be considered. Because the chances of preserving gonadal function following combined-modality treatment are significantly better for girls than for boys, simulation of a prepubertal milieu was applied only to women of reproductive age. The administration of GnRH agonists to women with Hodgkin's disease, breast cancer, and other malignancies, or to patients with lupus nephropathy, in parallel with chemotherapy, by others and by us, has demonstrated a significantly lower rate of premature ovarian failure in survivors than in nonrandomized controls. Several prospective, randomized studies are ongoing. A recent meta-analysis found that the administration of a GnRH agonist, in addition to chemotherapy, to patients with breast cancer was associated with less recurrence and superior survival. Several possibilities to explain the beneficial effect of GnRH agonists to minimize chemotherapy-associated gonadotoxicity are suggested: (a) The hypogonadotropic milieu decreases the number of primordial follicles entering the differentiation stage, which is more vulnerable to chemotherapy; (b) The hypoestrogenic state decreases ovarian perfusion and delivery of chemotherapy to the ovaries; (c) A direct effect of the GnRH agonist on the ovary occurs independently of the gonadotropin level; (d) GnRH agonists may upregulate an intragonadal. antiapoptotic molecule such as sphingosine-1-phosphate; (e) The GnRH agonist may protect ovarian germline stem cells.