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异基因造血干细胞移植后卵巢组织冻存失败:首例报告及文献复习。

Ovarian tissue cryopreservation after graft failure of allogeneic hematopoietic stem cell transplantation: first report and literature review.

机构信息

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China.

Reproductive Medical Center, Peking University People's Hospital, Beijing, China.

出版信息

Front Endocrinol (Lausanne). 2024 Aug 26;15:1367241. doi: 10.3389/fendo.2024.1367241. eCollection 2024.

Abstract

BACKGROUND

Hematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT.

CASE PRESENTATION

A 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12-15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm biopsy with good viability. Four MII oocytes were obtained via maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted.

CONCLUSION

OTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

摘要

背景

造血干细胞移植(HSCT)显著改善了血液病患者的预后和生存率。然而,HSCT 后卵巢功能障碍和不孕已引起越来越多的关注。在 HSCT 前进行卵巢组织冷冻保存,并随后进行这些组织的再移植,已有活产报道。尽管 HSCT 移植物失败(GF)后卵巢组织冷冻保存(OTC)的可行性尚不清楚,但我们报告首例异基因 HSCT(allo-HSCT)GF 后 OTC,并经知情同意进行了 4 个 MII 卵母细胞的成熟冷冻保存。尽管冷冻保存的卵巢组织再移植后缺乏临床结局,但我们记录了一例 allo-HSCT GF 后女性的有趣病例,表现出功能性卵巢,并强调了一个临床难题:HSCT GF 后是否应向女性提供 OTC。

病例介绍

一名 22 岁女性,患有严重再生障碍性贫血,曾接受其兄弟 HLA 等位基因匹配(7/10)的同种异体 HSCT,预处理方案为低剂量氟达拉滨、环磷酰胺和抗胸腺细胞球蛋白。由于即将接受第二次 allo-HSCT,该患者来到我们的生殖中心进行生育力保存。我们评估了该患者的卵巢储备功能。激素评估显示抗苗勒管激素水平为 3.921ng/ml,卵泡刺激素水平为 5.88IU/L,黄体生成素水平为 10.79IU/L,雌二醇水平为 33.34pg/ml。经阴道超声检查显示窦卵泡计数为 12-15 个。所有评估均表明卵巢储备功能良好。由于第二次 allo-HSCT 迫在眉睫,患者决定进行卵巢冷冻保存。腹腔镜手术进行。使用玻璃化技术成功冷冻保存卵巢组织,组织学评估显示每个 2×2mm 活检的卵泡密度为 20 个,具有良好的活力。通过 成熟技术获得了 4 个 MII 卵母细胞并冷冻保存。第二次 HSCT 后,患者从再生障碍性贫血中缓解,但正如预期的那样,发生了医源性卵巢早衰。

结论

OTC 适用于良性血液疾病患者的 HSCT GF 期间进行生育力保存,尤其是那些即将接受第二次 HSCT 的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26e3/11382424/beb50736b976/fendo-15-1367241-g001.jpg

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