Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function
Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function
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DOI：
10.1002/cncr.23071
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发表时间：
2007-11-15
期刊：
影响因子：
6.2
通讯作者：
Oktay, Kutluk
中科院分区：
文献类型：
--
作者：
Oktem, Ozgur;Oktay, Kutluk
背景各种化疗药物，特别是烷基化类药物，与卵巢早衰有关，但没有定量证据表明化疗诱导的人类卵巢损伤。目的是通过前瞻性对照定量组织学和体外研究，量化化疗对人类卵巢原始卵泡储备和间质功能的影响。对26名接受卵巢组织冷冻保存以保留生育能力的患者的样本进行了组织学评估和体外雌二醇产生评估。在26例患者中，10例既往接受过化疗，而16例未接受过化疗（对照组）。有17名年龄匹配的患者。我们比较了年龄匹配的对照组和化疗组患者以及接受和未接受烷化剂治疗的患者的原始卵泡计数和体外雌激素分泌。接受化疗的患者的原始卵泡计数显著低于对照组患者（5.4 +/- 1.32 vs 9.6 +/- 2.2，P = 0.05）。此外，与接受非烷化剂治疗的患者（2.9 +/- 1.1 vs 7.9 +/- 1.6，P <0.05）和未接受任何化疗的患者（2.9 +/- 1.1 vs 9.6 +/- 2.2，P <0.05）相比，接受烷化剂治疗的患者的原始卵泡计数显著降低。在体外，卵巢皮质片从个人谁是以前暴露于化疗（化疗组）产生显着减少雌二醇与那些谁没有（对照组）。在化疗组中，接受烷化剂和未接受烷化剂的患者体外雌二醇分泌量无差异。这是化疗对卵巢基础结构影响的第一个定量证据，并表明，而烷化剂可以显着降低卵巢储备，烷化剂和非烷化剂方案可能会影响卵巢基质功能。
BACKGROUND. Various chemotherapy agents, especially of the alkylating category, have been associated with premature ovarian failure but there is no quantitative evidence of chemotherapy-induced ovarian damage in humans. The aim was to quantify the impact of chemotherapy on primordial follicle reserve and stromal function in human ovary with a prospective controlled quantitative histologic and in vitro study.METHODS. Samples from 26 patients who were undergoing ovarian tissue cryopreservation for fertility preservation were assessed histologically and for in vitro estradiol production. Of the 26 patients, 10 had previously received chemotherapy whereas 16 had not (control). There were 17 age-matched patients. Primordial follicle counts and in vitro estrogen production were compared between age-matched control and chemotherapy patients as well as between those who did and did not receive alkylating agents.RESULTS. Patients who received chemotherapy had significantly lower primordial follicle counts than control patients (5.4 +/- 1.32 vs 9.6 +/- 2.2, P = .05). Furthermore patients treated with alkylating regimens had significantly lower primordial follicle counts compared with those who received nonalkylating agents (2.9 +/- 1.1 vs 7.9 +/- 1.6, P < .05) and with those who did not receive any chemotherapy (2.9 +/- 1.1 vs 9.6 +/- 2.2, P < .05). In vitro, ovarian cortical pieces from individuals who were previously exposed to chemotherapy (chemotherapy group) produced significantly less estradiol compared with those who were not (control group). In the chemotherapy group, there was no difference in in vitro estradiol production between those who received alkylating agents and those who did not.CONCLUSIONS. This is the first quantitative evidence of the impact of chemotherapy on ovarian infrastructure, and shows that, whereas alkylating agents can significantly reduce ovarian reserve, both alkylating and nonalkylating regimens may affect ovarian stromal function.