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Tsohoiyen 发表于 2019-1-4 21:41:37 | 显示全部楼层 |阅读模式
In recent years, the demand for fertility preservation for oncologic and nononcologic reasons, as well as personal reasons, has increased dramatically, and meeting this demand will prove a major challenge in the coming years. Currently, embryo cryopreservation and mature-oocyte cryopreservation after ovarian stimulation are the only methods of fertility preservation endorsed by the American Society for Reproductive Medicine. However, many experts believe that there is now enough evidence to support the use of ovarian-tissue cryopreservation as a valid and effective technique rather than as an experimental approach.
Of all the available means of fertility preservation,1 oocyte cryopreservation by means of vitrification (very rapid freezing) provides the highest yield, not only for women with benign diseases or those seeking fertility preservation for personal reasons but also for women with cancer (if treatment can be postponed). Ovarian-tissue cryopreservation is specifically indicated for adolescents and women in whom cancer treatment cannot be postponed. This review focuses on the indications for and results of these two techniques of fertility preservation.
近年来,由于肿瘤和非肿瘤原因以及个人原因对生育力保存的需求急剧增加,满足这一需求将在未来几年成为重大挑战。目前,只有胚胎冷冻保存和促排卵后的成熟卵母细胞冷冻保存是美国生殖医学学会(American Society for Reproductive Medicine)认可的生育力保存方法。然而,许多专家认为,现在有足够的证据支持将卵巢组织冷冻保存作为正规有效的生育力保存技术,而不仅仅是作为一种实验性方法。
Ovarian Reserve
The term ovarian reserveis typically used to refer to the population of primordial follicles. Initiation of the resting primordial-follicle reserve begins in the fetus, when 100 to 2000 primordial germ cells colonize the genital ridges and enter a massive proliferation process that results in 7 million potential oocytes at midgestation. In the human ovary, approximately 85% of these potential oocytes are lost before birth. The decline in the number of follicles continues throughout reproductive life, during which time approximately 450 ovulatory cycles occur, with the majority of follicles undergoing atresia during their growth phase. The serum level of antimüllerian hormone, which is correlated with the number of primordial follicles but is not a direct product of these follicles, can be used to estimate the reproductive life span.
Indications for Fertility Preservation.
Fertility preservation remains a challenge, particularly in the case of hematologic cancers (Hodgkins lymphoma, non-Hodgkins lymphoma, and leukemia) and breast cancer. These cancers constitute the most frequent indications for fertility preservation, since chemotherapy (especially with alkylating agents), radiotherapy, surgery, or a combination of these treatments can induce premature ovarian insufficiency in some circumstances1,6-10 (Table 1). The ovaries are very sensitive to cytotoxic drugs, especially alkylating agents, which are likely to cause gonadal dysfunction.6,7,11,12 Cyclophosphamide is the alkylating agent that causes the most damage to oocytes and granulosa cells, and it does so in a dose-dependent manner. In a recent review,13 it was reported that the North American Childrens Oncology Group considers the risk of premature ovarian insufficiency to be highest with busulfan administered at a dose of at least 600 mg per square meter of body-surface area, cyclophosphamide at a dose of at least 7.5 g per square meter, or ifosfamide at a dose of at least 60 g per square meter, but an international multidisciplinary panel reached no consensus on this matter.
Pelvic radiotherapy is also known to cause premature ovarian insufficiency, since exposure to 5 to 10 Gy is toxic to oocytes. Indeed, the human oocyte is very sensitive to radiation a dose of less than 2 Gy is estimated to be sufficient to destroy 50% of primordial follicles.
Ultimately, the probability that premature ovarian insufficiency will develop after chemotherapy or radiotherapy is related to the ovarian reserve. This reserve (the population of primordial follicles) can vary enormously from one woman to the next.
生育力保存仍然是一个挑战,特别是对于血液系统癌症(霍奇金淋巴瘤、非霍奇金淋巴瘤和白血病)和乳腺癌患者。由于化疗(特别是烷化剂)、放疗、手术或联合治疗在某些情况下可能导致早发性卵巢功能不全,因此上述癌症是生育力保存的最常见适应证(表11,6-10。卵巢对细胞毒性药物,特别是对可能引起性腺功能障碍的烷化剂非常敏感6,7,11,12。环磷酰胺是对卵母细胞和颗粒细胞造成最大损伤的烷化剂,且损伤程度与用药剂量相关。据近期的一次综述报道,北美儿童肿瘤研究组(North American Childrens Oncology Group)认为以下剂量的药物治疗时发生早发性卵巢功能不全的风险最高:600 mg/m2或更大剂量的白消安,7.5 g/m2或更大剂量的环磷酰胺,以及60 g/m2或更大剂量的异环磷酰胺13。但国际上多学科专家小组在此问题上未达成共识。
盆腔放疗亦同样被认为可引起早发性卵巢功能不全,因为510 Gy剂量的射线对卵母细胞有毒性作用。事实上,人类卵母细胞对射线非常敏感,估计小于2 Gy的剂量足以破坏50%的原始卵泡。
Fertility preservation should also be offered to women with certain benign conditions that carry the risk of premature ovarian insufficiency. Many autoimmune and hematologic conditions sometimes require chemotherapy, radiotherapy, or both and sometimes even bone marrow transplantation (Table 1). Other conditions can also impair future fertility, such as the presence of bilateral ovarian tumors, severe or recurrent ovarian endometriosis, and recurrent ovarian torsion.
Ovarian endometriomas lead to reduced ovarian reserve. Local intraovarian inflammation induced by the presence of endometriomas has been shown to trigger follicle burnout,characterized by activated follicular recruitment with subsequent atresia. Moreover, increasing evidence shows that performing cystectomy on endometriomas may cause considerable damage to the ovarian reserve, so fertility preservation should certainly be contemplated in case of recurrence after surgery.
Turners syndrome and a family history of premature ovarian insufficiency are additional indications for fertility preservation1 (Table 1). There is compelling evidence that certain forms of premature ovarian insufficiency have a genetic cause.
The largest group of women seeking fertility preservation consists of those who wish to postpone childbearing for various personal reasons; the biggest threat to their fertility is age. Women are increasingly seeking time outuntil they reach the right stage in their life to have a baby, often postponing childbearing because of the lack of a partner, the lack of a stable partner, or career or financial issues. The age at which women attempt their first pregnancy has been steadily rising during the past 40 years

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