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Abstract：
Owing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment.
The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors.
PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged <25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually.
After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6-34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55-59%; median 57%; two studies. elevated FSH 17-100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33-100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0-100%; median 51.5%; 26 studies. low inhibin B 19-50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0-57%, median 17%; 21 studies and low testosterone 0-43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMHThis review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.
The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors.
PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged <25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually.
After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6-34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55-59%; median 57%; two studies. elevated FSH 17-100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33-100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0-100%; median 51.5%; 26 studies. low inhibin B 19-50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0-57%, median 17%; 21 studies and low testosterone 0-43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH
摘要：
背景：由于越来越多的年轻和青少年霍奇金淋巴瘤（HL）幸存者，对抗癌治疗的（长期）不良反应的认识增加。鉴于生殖能力受损对生活质量的影响，生殖能力受损的风险非常令人担忧。目前尚无关于儿童HL治疗后生育能力的审查。
目的：这篇叙述性综述的目的是总结现有的关于男性和女性童年生殖功能不同方面的文献，青春期,和年轻的成人HL幸存者。
方法：在PubMed和EMBASE中搜索了评估诊断时年龄<25岁的男性和女性HL幸存者生育能力的文章。在女性中，抗苗勒管激素（AMH），窦卵泡计数,卵巢早衰(POI),急性卵巢功能衰竭,月经周期,FSH,和妊娠/活产进行了评估。在男性中，精液分析,血清FSH,抑制素B,LH,睾丸激素，并纳入了妊娠/活产的报告。研究之间存在深刻的异质性，缺乏对照组；因此，无法进行荟萃分析.结果以描述性方式呈现，研究质量没有单独评估。
结果：筛选后，纳入了75篇报道儿童或青少年HL幸存者生殖标记的文章。41篇论文报道了5057名女性HL幸存者。POI的发生率为6-34％（中位数为9％；7项研究）。经常看到卵巢储备减少或卵巢功能受损的迹象（低AMH55-59％；中位数57％；两项研究。FSH升高17-100%；中位数53%；7项研究)。大多数幸存者有规律的月经周期。51项研究评估了1903年男性HL幸存者的生育能力。治疗后无精子症非常普遍（33-100％；中位数75％；29项研究）。长期随访数据有限，但是有关于治疗后12年精液恢复的报道。低抑制素B通常会升高FSH水平（FSH升高0-100％；中位数为51.5％；26项研究。低抑制素B19-50%；中位数45%；三项研究)。LH和睾酮水平受影响较小(升高的LH0-57%，中位数17%；21项研究和低睾酮0-43%；中位数6%；15项研究)。在两性中，生殖能力受损与较高剂量的累积化疗药物和盆腔放疗相关.治疗前异常标志物的存在表明疾病本身也可能对生殖功能产生负面影响（女性：AMH关于存活期间怀孕机会的报道令人放心，尽管研究有其局限性，结果难以评估。最后,卵巢储备减少并不排除活产的机会，标记异常的男性可能仍然能够怀孕。
结论：这篇综述证实了HL治疗对性腺功能的负面影响，因此年轻的HL幸存者应该被告知他们未来的生殖生活，应该考虑保护生育能力。目前的证据水平不足，需要对HL和（当前）治疗方案对生殖功能的影响进行其他试验。在这次审查中,我们对可以评估的生殖标记和(重复)测量的时间提出了建议.
目的：这篇叙述性综述的目的是总结现有的关于男性和女性童年生殖功能不同方面的文献，
方法：在PubMed和EMBASE中搜索了评估诊断时年龄<25岁的男性和女性HL幸存者生育能力的文章。
结果：筛选后，
结论：这篇综述证实了HL治疗对性腺功能的负面影响，因此年轻的HL幸存者应该被告知他们未来的生殖生活，
