目的:探讨卵巢组织冷冻保存(OTC)在女性血液病患者中保存生育功能的效果和安全性。
方法:我们设计了一项回顾性研究。对2017年4月至2023年1月北京大学人民医院收治的OTC血液病患者的临床资料进行分析总结。
结果:本研究共纳入24例患者,其中恶性血液病患者19例,非恶性血液病患者5例。前者包括14例急性白血病患者,1例慢性白血病患者,和4名骨髓增生异常综合征患者,后5例患者为再生障碍性贫血(AA)。16例患者在OTC前接受化疗。24例患者的平均年龄为22.80±6.81岁。平均抗苗勒管激素(AMH)为1.97±2.12ng/mL,OTC前检查卵泡刺激素(FSH)平均为7.01±4.24IU/L。4例FSH大于10.0IU/L。OTC前实验室检测显示,白细胞(WBC)计数平均值为(3.33±1.35)×109/L,平均血红蛋白为91.42±22.84g/L,平均血小板(147.38±114.46)×109/L注射重组人粒细胞集落刺激因子(rhG-CSF)后,输血,在OTC前治疗中补充铁,白细胞计数平均值为(4.91±3.07)×109/L,平均血红蛋白为98.67±15.43g/L,平均血小板(156.38±103.22)×109/L在24名患者中,22例行腹腔镜双侧部分卵巢切除术和卵巢成形术,2例接受腹腔镜单侧卵巢切除术。OTC的平均持续时间为59.54±17.58分钟,平均失血量为32.1±41.6mL。最大失血量为200mL。与OTC前相比,OTC后的WBC计数和血红蛋白浓度没有显着差异。仅OTC手术后的血小板计数与手术前存在显着差异([134.54±80.84vs.156.38±103.22]×109/L,p<0.05)。24例患者无一发生OTC术后严重并发症。2例患者有轻度感染症状,但两者都恢复得很好。23例患者在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数范围为33(57)天,从OTC到HSCT的中位数和四分位数范围为41(57)天。其中7人在20天内开始HSCT预处理,并在OTC后30天内开始HSCT。所有患者均获得随访。在手术后接受HSCT的23例患者中,22例表现为闭经,1例表现为月经很少。7例患者在HSCT后接受了激素替代疗法(HRT)。一名AA患者在HSCT后3年接受了卵巢组织移植(OTT),并在OTT后6个月恢复了正常月经。
结论:卵巢组织冷冻保存在血液病患者的生育保护方面具有广阔的前景。然而,恶性血液病患者通常在OTC前接受过性腺毒性治疗,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。所以围手术期应重视患者的全血细胞计数。血液病患者OTC手术前后WBC计数和血红蛋白浓度无显著差异,血小板计数在正常范围内略有下降。感染是OTC后最常见的并发症,早在OTC后第10天就可以接受HSCT预处理。OTC对血液病患者无不良影响,不延迟HSCT治疗。对于年轻的血液病患者,OTC是一种有效的生育力保存方法。
OBJECTIVE: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases.
METHODS: 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.
RESULTS: 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) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/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) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/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] × 109/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.
CONCLUSIONS: 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.