Ovarian Biology Laboratory, Department of Anatomy and Developmental Biology, Development and Stem Cells Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
Hum Reprod Update. 2020 Feb 28;26(2):161-173. doi: 10.1093/humupd/dmz041.
As cancer survival rates improve, understanding and preventing the adverse off-target and long-term impacts of cancer treatments, including impacts on fertility, have become increasingly important. Cancer therapy-mediated damage to the ovary and depletion of the primordial follicle reserve are well characterised. However, our knowledge of the full extent of damage to the rest of the female reproductive tract, in particular the uterus, is limited.
Improving our understanding of the off-target effects of cancer therapies on the entire female reproductive tract is a critical step towards developing truly effective strategies to protect the fertility of cancer survivors. The objective of this narrative review was to critically evaluate the available literature regarding the capacity for the uterus to sustain a healthy pregnancy following exposure to radiotherapy or chemotherapy.
The authors performed PubMed (Medline) searches using the following key words: uterus, cancer survivors, radiotherapy, chemotherapy, pregnancy outcome, fertility preservation, infertility. There were no limits placed on time of publication.
Overall, there were major limitations to the current available literature, meaning that interpretations should be taken with caution. Despite these drawbacks, data suggest that the uterus may sustain off-target damage, with the extent of damage dependent on the type of cancer treatment and patient age. Specifically, uterine growth is stunted and resistant to hormone replacement therapy in prepubertal girls receiving abdominal, pelvic or whole-body radiotherapy. In contrast, females treated with radiotherapy post-puberty can benefit from hormone replacement therapy, as demonstrated by increased uterine volume and function. No live births have been reported in women previously exposed to radiotherapy after transplantation of cryopreserved ovarian tissue, even when menstruation returns. However, this technique has proven to be a successful fertility preservation method for women previously treated with chemotherapy. Obstetricians commonly report that women who maintain sufficient ovarian function can achieve pregnancy naturally following radiotherapy, but they have thin and/or fibrotic myometrium at delivery, compromising safe delivery and subsequent pregnancy. Furthermore, women exposed to either radiotherapy or chemotherapy have a higher prevalence of preterm birth and low birth weight infants, even in those with normal ovarian function or when oocyte donation is utilised. The mechanisms of potential uterine damage are poorly understood. While the myometrium, vasculature and endometrial progenitor cells are possibly targets, further studies are clearly required and well-controlled animal models could provide the best avenue for these types of future investigations.
Female cancer survivors experience greater rates of early pregnancy loss and complications, suggesting that cancer therapy-induced damage to the uterus contributes to infertility. Despite clinical reports dating back to 1989, we highlight a surprising lack of detail in the literature regarding the precise nature and extent of off-target damage inflicted to the uterus in response to cancer therapies. Young women requiring cancer treatment, and the clinicians treating them, must be equipped with accurate information to aid informed decision-making regarding cancer treatment regimens as well as the development and use of effective fertility preservation measures. As the current literature on the impacts of cancer treatments is limited, we hope that our narrative review on this subject will stimulate more research in this important field.
随着癌症存活率的提高，了解和预防癌症治疗的不良靶向和长期影响，包括对生育能力的影响，变得越来越重要。卵巢和原始卵泡储备耗竭的癌症治疗介导的损伤已经得到很好的描述。然而，我们对整个女性生殖道（尤其是子宫）的其他部位的损伤程度的了解是有限的。
提高我们对癌症疗法对整个女性生殖道的靶向外效应的理解，是朝着开发真正有效策略以保护癌症幸存者生育能力迈出的关键一步。本叙述性综述的目的是批判性地评估有关子宫在暴露于放射疗法或化学疗法后维持健康妊娠的能力的现有文献。
作者使用以下关键词在 PubMed（Medline）上进行了搜索：子宫、癌症幸存者、放疗、化疗、妊娠结局、生育力保存、不孕。没有对出版时间进行限制。
总体而言，当前可用文献存在重大局限性，因此应谨慎解释。尽管存在这些缺点，但数据表明子宫可能会受到靶向外的损伤，损伤的程度取决于癌症治疗的类型和患者的年龄。具体而言，在接受腹部、盆腔或全身放疗的青春期前女孩中，子宫生长受到抑制且对激素替代疗法无反应。相比之下，接受放射治疗的青春期后女性可以受益于激素替代疗法，这表现为子宫体积和功能增加。在先前接受冷冻卵巢组织移植的妇女中，尽管月经恢复，但尚未报告在放射治疗后怀孕的情况。然而，对于先前接受过化疗的女性，这种技术已被证明是一种成功的生育力保存方法。妇产科医生通常报告说，在放射治疗后保持足够卵巢功能的妇女可以自然怀孕，但她们在分娩时的子宫壁较薄且/或纤维化，这会危及安全分娩和随后的妊娠。此外，暴露于放射疗法或化学疗法的妇女早产和低出生体重婴儿的比例较高，即使卵巢功能正常或使用卵母细胞捐赠也是如此。潜在的子宫损伤的机制尚不清楚。虽然子宫肌层、血管和子宫内膜祖细胞可能是靶标，但显然需要进一步的研究，并且良好的对照动物模型可以为这些未来的研究提供最佳途径。
女性癌症幸存者的早期妊娠丢失和并发症发生率更高，这表明癌症治疗引起的子宫损伤导致不孕。尽管早在 1989 年就有临床报告，但我们强调文献中关于癌症治疗对子宫造成的靶向外损伤的确切性质和程度的细节惊人地缺乏。需要接受癌症治疗的年轻女性以及为其治疗的临床医生，必须获得准确的信息，以帮助他们就癌症治疗方案以及有效生育力保存措施的开发和使用做出明智的决策。由于目前关于癌症治疗影响的文献有限，我们希望本主题的叙述性综述将激发该重要领域的更多研究。
