Sebire Elinor, Spears Norah, Mitchell Rod T, Stefansdottir Agnes
Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
Biomedical Sciences, University of Edinburgh, Edinburgh, UK.
Hum Reprod Open. 2025 Jul 23;2025(3):hoaf046. doi: 10.1093/hropen/hoaf046. eCollection 2025.
Does cancer treatment during pregnancy affect gonadal development in the exposed foetus?
Our systematic review revealed that exposure to many cancer therapies does negatively impact gonadal development.
It is well known that many cancer therapies can have a detrimental impact on the fertility of children and young people who have been treated for cancer. However, it is not yet known how much these agents impact the gonadal development and subsequent fertility of an exposed foetus.
We conducted a systematic review, following PRISMA guidelines, to investigate the evidence for associations between cancer therapy exposure and gonadal development in human tissues and animal models. A systematic search was conducted across PubMed, Web of Science, and Google Scholar for titles or abstracts containing terms relating to chemotherapy or hormonal therapy agents, exposure, and reproductive outcomes. We searched all available published articles up to July 2024.
PARTICIPANTS/MATERIALS SETTING METHODS: Two independent reviewers performed title and abstract, then full-text screening, using inclusion/exclusion criteria decided . We included clinical and laboratory studies on human foetal gonads and animal studies, and , where gonadal exposure occurred during the window that corresponded with human prenatal gonadal development. Data from the included studies were independently extracted and analysed by chemotherapy and hormonal drug class, focusing on reproductive outcome measures and results. Bias and quality assessments were performed with SciRAP or tool version 2.3.
3360 titles and abstracts were screened for inclusion, following the removal of duplicates, with 57 undergoing full text review and 26 eligible studies identified for inclusion (human = 4, animal-model = 22). The collated results show clear evidence of significant germ cell loss and disruption to other gonadal cell types in male and female animal-model gonadal tissues exposed both and to various chemotherapy and hormone therapies, and human male foetal tissue exposed to chemotherapy .
The evidence provided was limited by the small number of studies available reporting on reproductive outcomes following exposure to cancer therapies, a lack of comparable outcome measures, and the use of single-drug exposures compared to the more clinically relevant multi-drug combinations.
This review provides evidence for the vulnerability of foetal gonads to cancer therapy agents and the potentially damaging effects of exposure on gonadal development and reproductive health. We hope these findings help raise awareness for the need of long-term follow-up studies to explore whether fertility is impacted in people who were exposed to cancer agents and to identify whether they may require fertility preservation strategies.
STUDY FUNDING/COMPETING INTERESTS: No specific funding was received for this study. R.T.M. is supported by a UK Research and Innovation (UKRI) Future Leaders Fellowship (Grant Reference: MR/Y011783/1). The authors declare that they have no conflicts of interest.
Study protocol-PROSPERO (RD42021272882 and CRD42021271892).
孕期进行癌症治疗会影响受暴露胎儿的性腺发育吗？
我们的系统评价显示，接触多种癌症治疗方法确实会对性腺发育产生负面影响。
众所周知，许多癌症治疗方法会对接受过癌症治疗的儿童和年轻人的生育能力产生不利影响。然而，目前尚不清楚这些药物对受暴露胎儿的性腺发育及后续生育能力有多大影响。
研究设计、规模、持续时间：我们按照PRISMA指南进行了一项系统评价，以调查癌症治疗暴露与人体组织和动物模型中性腺发育之间关联的证据。通过PubMed、科学网和谷歌学术对标题或摘要进行了系统检索，搜索词包括与化疗或激素治疗药物、暴露及生殖结局相关的词汇。我们检索了截至2024年7月的所有已发表文章。
参与者/材料、环境、方法：两名独立评审员先进行标题和摘要筛选，然后进行全文筛选，采用预先确定的纳入/排除标准。我们纳入了关于人类胎儿性腺的临床和实验室研究以及动物研究，且性腺暴露发生在与人类产前性腺发育相对应的窗口期内。纳入研究的数据由化疗和激素药物类别独立提取和分析，重点关注生殖结局指标和结果。使用SciRAP或工具版本2.3进行偏倚和质量评估。
在去除重复项后，筛选了3360篇标题和摘要以确定是否纳入，其中57篇进行了全文审查，确定26项符合条件的研究纳入（人类研究=4项，动物模型研究=22项）。整理后的结果清楚地表明，在雄性和雌性动物模型性腺组织中，暴露于各种化疗和激素治疗后，以及人类男性胎儿组织暴露于化疗后，有明显的生殖细胞丢失和其他性腺细胞类型的破坏。
局限性、谨慎的理由：现有关于癌症治疗暴露后生殖结局的研究数量有限、缺乏可比的结局指标，且与更具临床相关性的多药联合使用相比，使用的是单一药物暴露，这些因素限制了所提供的证据。
本综述为胎儿性腺对癌症治疗药物的易感性以及暴露对性腺发育和生殖健康的潜在损害作用提供了证据。我们希望这些发现有助于提高人们对长期随访研究必要性的认识，以探索接触癌症药物的人群的生育能力是否受到影响，并确定他们是否可能需要生育力保存策略。
研究资金/利益冲突：本研究未获得特定资金。R.T.M.得到了英国研究与创新署（UKRI）未来领袖奖学金的支持（资助编号：MR/Y011783/1）。作者声明他们没有利益冲突。
研究方案 - PROSPERO（RD42021272882和CRD42021271892）
