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异基因造血干细胞移植后女性的性生活和生育相关问题。

Sexuality- and Fertility-Related Issues in Women after Allogeneic Hematopoietic Stem Cell Transplantation.

机构信息

Service d'Hématologie Adolescents Jeunes Adultes, Hôpital Saint-Louis, AP-HP, Paris, France.

Service de Dermatologie, Hôpital Saint-Louis, AP-HP, Paris, France; Centre universitaire du diabète et de ses complications, Hôpital Lariboisière, AP-HP, Paris, France.

出版信息

Transplant Cell Ther. 2021 May;27(5):432.e1-432.e6. doi: 10.1016/j.jtct.2021.02.003. Epub 2021 Feb 6.

DOI:10.1016/j.jtct.2021.02.003
PMID:33789835
Abstract

Sexual dysfunction and fertility related issues appear as major post-allogeneic hematopoietic stem cell transplantation (HSCT) late effects in young women, with a heavy impact on quality of life. The objective of the present study was to evaluate the impact of disease and treatments on sexual quality of life, ovarian function, and family planning initiatives in the context of allogeneic HSCT. Between January 2014 and January 2016, adult female patients who underwent HSCT before age 35 and had been followed for more than 2 years in our center were offered participation in the study through a self-reported survey and/or ovarian function assessment if age <40 at inclusion. A total of 63 patients were included, with a median age of 23.4 years at transplantation and 30.9 years at inclusion. Twenty-nine patients (46%) underwent HSCT for acute leukemia and 16 (25%) underwent HSCT for aplastic anemia (AA). The conditioning regimen was myeloablative conditioning (MAC) in 37 patients (59%) and reduced-intensity conditioning (RIC) in 26 (41%). Fifty-eight patients completed the survey, and 34 were evaluated for ovarian function. Symptoms of hypoestrogenism were reported by 86% of the patients and changes in sexual life were reported by 76%, due mainly to low sex drive, negative impact of infertility problems, physical sequelae, and loss of self-confidence. Premature ovarian failure (POF) occurred in 74% of patients and was significantly associated with conditioning regimen (MAC versus RIC; P = .001) and baseline disease (bone marrow failure versus acute leukemia versus others; P < .001). However, one-half of the patients developed a POF despite the use of a RIC regimen. For 27 patients (47%), disease and treatments modified their desire for pregnancy, due mainly to fear of relapse and of disease transmission to offspring. Thirteen pregnancies were reported (21%), of which 8 were spontaneous and 5 were obtained through assisted reproductive technologies, mainly oocyte donation. With a median post-transplantation follow-up of 12.2 years, the 10-year cumulative incidence of first pregnancy was 16.6% (95% CI, 8.8-30.0). Among 20 patients (32%) who engaged in a family planning initiative, 13 (65%) succeeded in having children: 11 got pregnant and 2 adopted. Sixteen patients benefited from fertility preservation techniques consisting of ovarian tissue cryopreservation, and a single autologous ovarian tissue transplantation had been performed at the time of this report. This study shows a strong impact of disease and treatments on sexual quality of life, ovarian function, and family planning initiatives in the context of HSCT. It demonstrates the need to improve clinicians' awareness of sexual health- and fertility-related issues after HSCT. The difficulty of predicting ovarian function and fertility issues after RIC supports wide indications of pretransplantation fertility preservation. Evaluation of the use of cryopreserved ovarian tissues is warranted.

摘要

在接受异基因造血干细胞移植(HSCT)后的年轻女性中,性功能障碍和与生育相关的问题是主要的晚期并发症,对生活质量有重大影响。本研究旨在评估疾病和治疗对接受 HSCT 的年轻女性的性生活质量、卵巢功能和生育计划的影响。

2014 年 1 月至 2016 年 1 月,我们中心在 35 岁之前接受过 HSCT 并随访超过 2 年的成年女性患者,通过自我报告的调查和/或如果在纳入时年龄<40 岁,则进行卵巢功能评估,邀请她们参加研究。共纳入 63 例患者,移植时的中位年龄为 23.4 岁,纳入时的中位年龄为 30.9 岁。29 例(46%)患者因急性白血病而接受 HSCT,16 例(25%)因再生障碍性贫血(AA)而接受 HSCT。37 例(59%)患者接受了清髓性预处理方案,26 例(41%)患者接受了强度降低的预处理方案。58 例患者完成了调查,34 例患者接受了卵巢功能评估。86%的患者报告出现雌激素缺乏症状,76%的患者报告性生活发生变化,主要是由于性欲下降、不孕问题的负面影响、身体后遗症和自信心丧失。74%的患者发生卵巢早衰(POF),与预处理方案(MAC 与 RIC;P=0.001)和基线疾病(骨髓衰竭与急性白血病与其他疾病;P<0.001)显著相关。然而,尽管使用了 RIC 方案,仍有一半的患者发生了 POF。由于担心复发和疾病向后代传播,27 例(47%)患者改变了生育愿望。报告了 13 例妊娠(21%),其中 8 例为自然妊娠,5 例通过辅助生殖技术获得,主要是卵母细胞捐赠。移植后中位随访 12.2 年后,10 年累积首次妊娠发生率为 16.6%(95%CI,8.8-30.0)。在 20 名(32%)参与生育计划的患者中,有 13 名(65%)成功生育:11 名怀孕,2 名收养。16 名患者受益于生育力保存技术,包括卵巢组织冷冻保存,目前已有 1 例进行了自体卵巢组织移植。

这项研究表明,疾病和治疗对 HSCT 背景下的性生活质量、卵巢功能和生育计划有很大影响。它表明需要提高临床医生对 HSCT 后与性健康和生育相关的问题的认识。RIC 后卵巢功能和生育问题预测困难支持广泛开展移植前生育力保存的适应证。评估冷冻卵巢组织的应用是合理的。

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