Ovarian insufficiency following allogeneic hematopoietic stem cell transplantation

Abstract

Ovarian insufficiency is a serious complication for young women who undergo hematopoietic stem cell transplantation (HSCT). Reduced-intensity conditioning (RIC) has been utilized more widely due to its reduced toxicity; however, there is a lack of data concerning ovarian function after HSCT with RIC. We investigated the ovarian function in patients who received HSCT with RIC, compared to those who received myeloablative conditioning (MAC). The records of 69 female patients who received allogeneic HSCT at the institution under 40 years of age at transplantation from 1991 to 2012 were retrospectively analyzed. Prevalence of ovarian insufficiency was significantly lower in patients conditioned with RIC than in those conditioned with MAC (4/27 = 14.8% for RIC and 36/42 = 85.7% for MAC, p < 0.0001). A younger age at HSCT was associated with a lower risk of ovarian insufficiency. Among the 40 patients with ovarian insufficiency, four patients recovered ovarian function, and two conceived following hormone-replacement therapy (HRT). A higher serum E2 level prior to HRT was a significant predictor for the restoration of ovarian function (p = 0.0028). In conclusion, RIC was significantly less toxic to ovarian function compared with MAC. HSCT-associated ovarian insufficiency is not irreversible, and a higher E2 level may predict the restoration of ovarian function.

Chinese abstract

卵巢功能不全是接受造血干细胞移植 (HSCT) 年轻女性的严重并发症。减低剂量预处理 (RIC) 已被广泛应用由于它的低卵巢毒性;然而目前尚缺乏经减低剂量预处理造血干细胞移植治疗后卵巢功能的相关数据信息。我们对比了接受RIC的HSCT患者和接受清髓性预处理 (MAC) 治疗患者的卵巢情况。回顾性分析了69例于1991年至2012年间接受异基因HSCT治疗的40岁以下女性患者的卵巢情况。结果显示RIC治疗患者发生卵巢功能不全并发症数量显著低于MAC治疗患者 (RIC为4/27 ± 14.8％, MAC为36/42 = 85.7％, p < 0.0001) 。 HSCT治疗年龄越小, 发生卵巢功能不全的风险越低。在40例卵巢功能不全的患者中, 4例患者恢复卵巢功能, 2例经激素替代治疗 (HRT) 后成功怀孕。HRT治疗前的高血清E2浓度是卵巢功能是否能恢复的重要预测因子 (p = 0.0028) 。总之, 与MAC相比, RIC对卵巢功能的影响明显下降。HSCT相关的卵巢功能不全也并非是不可逆的, 高浓度的E2是卵巢功能的有效预测因子。

Keywords:

• Hematopoietic stem cell transplantation
• ovarian function
• ovarian insufficiency
• pregnancy
• reduced-intensity conditioning

Acknowledgements

The authors thank Ayumi Shintani for her statistical advice.

Declaration of interest

The authors have no conflicts of interest to disclose.

Supplementary material available online