Asadi Azarbaijani Babak, Sheikhi Mona, Oskam Irma C, Nurmio Mirja, Laine Tiina, Tinkanen Helena, Mäkinen Sirpa, Tanbo Tom G, Hovatta Outi, Jahnukainen Kirsi
Women and Children's Division, Oslo University Hospital, Rikshospitalet, Oslo, Norway; University of Oslo, Oslo, Norway.
Division of Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Stockholm IVF, Stockholm, Sweden.
PLoS One. 2015 Jul 30;10(7):e0133985. doi: 10.1371/journal.pone.0133985. eCollection 2015.
Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance.
In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35), cryopreserved for fertility preservation before (n = 14) or after (n = 20) initiation of chemotherapy, were thawed and cultured for 7 days. The morphology and developmental stages of ovarian follicles were studied by light microscopy before and after culture. Possible associations between follicular densities, age and exposure to alkylating agents, expressed as cyclophosphamide equivalent dose (CED) were tested.
Exposure to chemotherapy significantly impaired the survival and development of ovarian follicles in culture. After seven days, significantly higher densities of intermediary, primary and secondary follicles and lower densities of atretic follicles was detected in the samples collected before chemotherapy. Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles.
This study provides quantitative in vitro evidence of the impact of chemotherapy on developmental capacity of cryopreserved human ovarian tissue. The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles. In addition, ovarian samples from younger girls show lower viability and fewer developing follicles in culture.
卵巢组织冷冻保存已被广泛认可为癌症患者生育力保存的一种选择。一些患者在卵巢组织冷冻保存之前就已接受化疗。因此，评估化疗后人卵巢组织的发育能力至关重要。
为研究既往化疗对卵巢卵泡体外发育和活力的影响，将34例中位年龄为15岁（范围1 - 35岁）的女性癌症患者的质量控制样本解冻并培养7天，这些样本在化疗开始前（n = 14）或之后（n = 20）进行了生育力保存冷冻。在培养前后通过光学显微镜研究卵巢卵泡的形态和发育阶段。测试了卵泡密度、年龄与烷化剂暴露之间可能的关联，烷化剂暴露以环磷酰胺等效剂量（CED）表示。
化疗暴露显著损害了培养中卵巢卵泡的存活和发育。7天后，在化疗前采集的样本中检测到中间卵泡、初级卵泡和次级卵泡的密度显著更高，而闭锁卵泡的密度更低。多变量线性回归分析确定烷化剂剂量增加是闭锁卵泡密度更高的独立预测因素，而患者年龄增加预示着更好的结果，卵泡闭锁更少且成熟卵泡密度更高。
本研究提供了化疗对冷冻保存的人卵巢组织发育能力影响的定量体外证据。结果表明，如果可能的话，生育力保存应在开始使用烷化剂之前进行，以保证卵巢卵泡在体外有更好的存活率。此外，来自年轻女孩的卵巢样本在培养中显示出较低的活力和较少的发育卵泡。
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