Department of Obstetrics and Gynecology, Peking University People's Hospital, Peking University, Beijing, 100044, China.
Arch Gynecol Obstet. 2024 Jun;309(6):2863-2880. doi: 10.1007/s00404-024-07484-4. Epub 2024 Apr 4.
To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases.
We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized.
A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 10/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 10/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 10/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 10/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 10/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT.
Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.
探讨卵巢组织冻存（OTC）在血液系统疾病女性患者生育力保护中的作用和安全性。
我们设计了一项回顾性研究。分析总结了 2017 年 4 月至 2023 年 1 月期间在北京大学人民医院接受 OTC 的血液系统疾病患者的临床资料。
本研究共纳入 24 例患者，其中恶性血液病 19 例，非恶性血液病 5 例。前者包括急性白血病 14 例，慢性白血病 1 例，骨髓增生异常综合征 4 例，后者为再生障碍性贫血（AA）5 例。16 例患者在 OTC 前接受过化疗。24 例患者的平均年龄为 22.80±6.81 岁。OTC 前检查的平均抗苗勒管激素（AMH）为 1.97±2.12ng/ml，卵泡刺激素（FSH）平均为 7.01±4.24IU/L，4 例 FSH 大于 10.0IU/L。OTC 前的实验室检查显示，平均白细胞（WBC）计数为（3.33±1.35）×10/L，平均血红蛋白为 91.42±22.84g/L，平均血小板为（147.38±114.46）×10/L。在 OTC 前预处理中注射重组人粒细胞集落刺激因子（rhG-CSF）、输血和补铁后，WBC 计数平均为（4.91±3.07）×10/L，平均血红蛋白为 98.67±15.43g/L，平均血小板为（156.38±103.22）×10/L。24 例患者中，22 例行腹腔镜双侧卵巢部分切除术和卵巢成形术，2 例行腹腔镜单侧卵巢切除术。OTC 的平均持续时间为 59.54±17.58min，平均出血量为 32.1±41.6ml，最大出血量为 200ml。与 OTC 前相比，术后 WBC 计数和血红蛋白浓度无显著差异。仅术后血小板计数与术前有显著差异[（134.54±80.84）与（156.38±103.22）×10/L，p<0.05]。24 例患者 OTC 后均无严重并发症。2 例患者有轻度感染症状，但均恢复良好。23 例患者 OTC 后行造血干细胞移植（HSCT）。从 OTC 到 HSCT 预处理的中位数和四分位距为 33（57）天，从 OTC 到 HSCT 的中位数和四分位距为 41（57）天。其中 7 例患者在 20 天内开始 HSCT 预处理，在 OTC 后 30 天内开始 HSCT。所有患者均获得随访。23 例接受 HSCT 的患者中，22 例出现闭经，1 例月经稀少。7 例患者在 HSCT 后接受激素替代治疗（HRT）。1 例 AA 患者在 HSCT 后 3 年接受卵巢组织移植（OTT），OTT 后 6 个月恢复正常月经。
卵巢组织冻存技术在血液系统疾病患者生育力保护中具有广阔的前景。然而，血液系统恶性肿瘤患者在 OTC 前常接受性腺毒性治疗，可能伴有骨髓抑制，而非恶性血液病患者常伴有严重的血细胞减少。因此，应注意患者围手术期的全血细胞计数。血液系统疾病患者 OTC 前后白细胞计数和血红蛋白浓度无显著差异，血小板计数略有下降且在正常范围内。感染是最常见的 OTC 后并发症，预处理 HSCT 可在 OTC 后第 10 天接受。OTC 对血液系统疾病患者无不良影响，也不影响 HSCT 治疗。对于患有血液系统疾病的年轻患者，OTC 是一种有效的生育力保存方法。
