BACKGROUND Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage. OBJECTIVE AND RATIONALE This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed. SEARCH METHODS Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents. OUTCOMES Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed. WIDER IMPLICATIONS Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically.

中文翻译：

---

化学疗法对卵巢的损害及其目前的保护方法。

背景技术抗癌疗法通常是卵巢早衰和不育的原因，因为卵巢的卵泡储备对化学疗法和放射疗法的效果极为敏感。卵母细胞，胚胎和卵巢皮质的冷冻保存可以帮助一些患有癌症的不孕症妇女实现妊娠，而开发在化疗过程中保护卵巢功能的有效方法将是一个重要的优势。目的和理由本论文批判性地讨论了最常见的化学治疗化合物对卵巢的不同破坏作用，尤其是卵巢滤泡和导致该破坏的分子途径。然后回顾了生育保护剂可能阻止化疗药物诱导的卵泡丧失的机制。搜索方法截至2019年3月，在PubMed上使用以下术语搜索英语发表的文章：卵巢，生育力保留，化学疗法，卵泡死亡，辅助治疗，环磷酰胺，顺铂，阿霉素。纳入和排除标准应用于保护剂的分析。结果最近的研究揭示了化疗药物如何影响卵巢的不同细胞成分，从而导致卵巢滤泡储备的快速耗竭。三种最常用的药物，环磷酰胺，顺铂和阿霉素，通过诱导原始卵泡死亡和/或加速活化以及增加卵泡闭锁而引起卵巢早衰。它们还导致对血管和基质腔室的损害增加，并加剧炎症。在过去的20年中，已经研究了许多化合物作为潜在的保护剂，以抵消这些不利影响。讨论了最近描述的生育保护剂与这些破坏途径的相互作用。对儿童的影响了解化疗化合物作用于卵巢各个组成部分的基本机制对于开发可以保护和延长女性生育力的有效，针对性的药理疗法至关重要。尽管有越来越多的关于潜在生育力佐剂的临床前研究，但仍缺乏临床上正在开发和测试的方法。讨论了最近描述的生育保护剂与这些破坏途径的相互作用。对儿童的影响了解化疗化合物作用于卵巢各个组成部分的基本机制对于开发可以保护和延长女性生育力的有效，针对性的药理疗法至关重要。尽管有越来越多的关于潜在生育力佐剂的临床前研究，但仍缺乏临床上正在开发和测试的方法。讨论了最近描述的生育保护剂与这些破坏途径的相互作用。对儿童的影响了解化疗化合物作用于卵巢各个组成部分的基本机制对于开发可以保护和延长女性生育力的有效，针对性的药理疗法至关重要。尽管有越来越多的关于潜在生育力佐剂的临床前研究，但仍缺乏临床上正在开发和测试的方法。对儿童的影响了解化疗化合物作用于卵巢各个组成部分的基本机制对于开发可以保护和延长女性生育力的有效，针对性的药理疗法至关重要。尽管有越来越多的关于潜在生育力佐剂的临床前研究，但仍缺乏临床上正在开发和测试的方法。对儿童的影响了解化疗化合物作用于卵巢各个组成部分的基本机制对于开发可以保护和延长女性生育力的有效，针对性的药理疗法至关重要。尽管有越来越多的关于潜在生育力佐剂的临床前研究，但仍缺乏临床上正在开发和测试的方法。