Drechsel K C E, Broer S L, Stoutjesdijk F S, Twisk J W R, van den Berg M H, Lambalk C B, van Leeuwen F E, Overbeek A, van den Heuvel-Eibrink M M, van Dorp W, de Vries A C H, Loonen J J, van der Pal H J, Kremer L C, Tissing W J, Versluys B, Kaspers G J L, van Dulmen-den Broeder E, Veening M A
Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, Amsterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
J Cancer Res Clin Oncol. 2023 Nov;149(15):13677-13695. doi: 10.1007/s00432-023-05035-z. Epub 2023 Jul 31.
To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes.
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.
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/m 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.
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.
评估霍奇金淋巴瘤（HL）治疗对临床生殖指标及妊娠结局的影响。
本研究纳入了DCOG LATER - VEVO研究；这是一项2004年至2014年间在荷兰开展的多中心回顾性队列研究。对女性儿童HL幸存者及对照组评估血清抗苗勒管激素（AMH）、促卵泡生成素（FSH）、抑制素B、窦卵泡计数（AFC）以及自我报告的（首次）妊娠结局。
纳入84例HL幸存者及798例对照，评估时年龄分别为29.6岁和32.7岁。HL诊断时的中位年龄为13.4岁。56名女性的环磷酰胺等效剂量（CED评分）超过6000mg/m²，14名幸存者接受了盆腔放疗。幸存者的所有临床指标均显著恶化（低AMH（<p10）的优势比为10.1 [95%CI 4.9；20.6]；低AFC（<p10）为4.6 [95%CI 2.1；9.9]；FSH升高（>10IU/l）为15.3 [95%CI 5.7；41.1]，低抑制素B（<20ng/l）为3.6 [95%CI 1.7；7.7]，p<0.001）。幸存者与对照组的妊娠结局相当（活产率±80%，流产率±20%）。然而，幸存者首次妊娠时年龄显著更小（27.0岁对29.0岁，P = 0.04）。幸存者妊娠时间>12个月的调整优势比为2.5 [95%CI 1.1；5.6]，p = 0.031。使用丙卡巴肼治疗及较高的CED评分后尤其会出现不良结局。
HL幸存者似乎存在卵巢储备受损。然而，年轻时怀孕的机会似乎尚可。需要进一步的随访研究来评估HL幸存者的生育寿命及生殖潜力，特别是对于目前假设性腺毒性较小的HL治疗方案。
