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Abstract：
OBJECTIVE: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes.
METHODS: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls.
RESULTS: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [ 95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score.
CONCLUSIONS: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.
METHODS: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls.
RESULTS: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [ 95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score.
CONCLUSIONS: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.
摘要：
目的：评估霍奇金淋巴瘤（HL）治疗对临床生殖标志物和妊娠结局的影响。
方法：这项研究嵌入了DCOGLATER-VEVO研究；荷兰，多中心，2004年至2014年的回顾性队列研究。血清抗苗勒管激素（AMH），卵泡刺激素（FSH），抑制素B,窦卵泡计数（AFC），在女性儿童HL幸存者和对照组中评估自我报告(首次)妊娠结局.
结果：包括84名HL幸存者和798名对照，评估时年龄分别为29.6岁和32.7岁。HL诊断的中位年龄为13.4岁。环磷酰胺等效剂量（CED评分）超过6000mg/m2的56名女性和14名幸存者接受了盆腔照射。幸存者的所有临床标志物均显着恶化（低AMH的比值比（10IU/l）15.3[95％CI5.7;41.1]，低抑制素B（<20ng/l）3.6[95%CI1.7;7.7]，p<0.001)。幸存者和对照组之间的妊娠结局具有可比性（±80％活产，±20%流产)。然而,幸存者在第一次怀孕时明显年轻(27.0岁vs29.0岁，P=0.04)。在幸存者中，至妊娠时间>12个月的调整后比值比为2.5[95％CI1.1;5.6]，p=0.031。在使用丙卡巴嗪和更高的CED评分治疗后，不良结果明确存在。
结论：HL存活者卵巢储备功能受损。然而,怀孕的机会在年轻时似乎令人放心。需要进一步的随访研究来评估HL幸存者的生育能力和生殖潜力。特别是对于目前推测性腺毒性较低的HL治疗。
方法：这项研究嵌入了DCOGLATER-VEVO研究；荷兰，多中心，2004年至2014年的回顾性队列研究。血清抗苗勒管激素（AMH），卵泡刺激素（FSH），抑制素B,窦卵泡计数（AFC），在女性儿童HL幸存者和对照组中评估自我报告(首次)妊娠结局.
结果：包括84名HL幸存者和798名对照，评估时年龄分别为29.6岁和32.7岁。HL诊断的中位年龄为13.4岁。环磷酰胺等效剂量（CED评分）超过6000mg/m2的56名女性和14名幸存者接受了盆腔照射。幸存者的所有临床标志物均显着恶化（低AMH的比值比（
结论：HL存活者卵巢储备功能受损。然而,怀孕的机会在年轻时似乎令人放心。需要进一步的随访研究来评估HL幸存者的生育能力和生殖潜力。特别是对于目前推测性腺毒性较低的HL治疗。
