Department of Reproductive Medicine & Fertility Preservation, Hôpital Jean Verdier, Bondy, France.
Unité Inserm U1185, Université Paris-Sud, Le Kremlin Bicêtre, France.
Hum Reprod. 2022 Jun 30;37(7):1480-1488. doi: 10.1093/humrep/deac109.
Do breast cancer (BC) characteristics influence IVM of oocytes outcomes in patients undergoing fertility preservation (FP)?
Scarff-Bloom-Richardson (SBR) III grade, triple-negative BC and HER2 overexpression are independent predictors of fewer oocytes or poor IVM outcomes in young women seeking FP.
SBR grade, triple-negative status and overexpression of HER2, as well as a high Ki67 proliferation index are all established prognostic factors for BC, influencing patients' therapeutic management. Yet there are also concerns about the potential impact of cancer status on ovarian reserve and function. Previous studies analysing the results of ovarian stimulation in BC patients have shown conflicting findings. Nevertheless, there is no data on the potential impact of BC status and prognostic factors on IVM outcome in women undergoing urgent FP.
STUDY DESIGN, SIZE, DURATION: We studied 321 BC patients, 18 to 41 years of age, who were also candidates for oocyte cryopreservation following IVM. The number of oocytes recovered, maturation rate and total number of cryopreserved oocytes were assessed.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian reserve markers (antral follicle count [AFC] and serum anti-Müllerian hormone [AMH] levels) and IVM outcomes were compared according to BC characteristics (Ki67 proliferation index >20%, progesterone and/or oestrogen receptors expression, HER2 status and SBR grade). Logistic regression analysis was then performed to determine the variables that could be independently associated with poor IVM outcomes, such as oocyte retrieval rate <50%, oocyte maturation rate <60% and total number of frozen oocytes <5.
Overall, the mean age of the population was 32.3 ± 4.1 years. Mean AFC and serum AMH levels were 22.8 ± 13.9 follicles and 3.8 ± 3.1 ng/ml, respectively. AMH levels were significantly lower in case of triple-negative BC when compared with ER/PR/HER2 status positive cancer (3.1 ± 2.6 ng/ml vs 4.0 ± 3.3 ng/ml, P = 0.02). The mean number of recovered oocytes was 10.2 ± 9.1. After a mean maturation rate of 58.0 ± 26.1%, 5.8 ± 5.3 mature oocytes were cryopreserved per cycle. The number of retrieved and cryopreserved oocytes after IVM were significantly lower in patients presenting with an SBR III tumour when compared with an SBR I or II tumour (9.6 ± 8.7 vs 11.7 ± 9.8, P = 0.02 and 5.4 ± 5.4 vs 6.6 ± 5.8, P = 0.02, respectively). Multivariate statistical analysis showed that HER2 positive status was associated with a mean maturation rate <60% (odds ratio: 0.54; 95% CI (0.30-0.97)). Ki67 and hormonal status were not correlated with poor IVM outcomes.
LIMITATIONS, REASONS FOR CAUTION: A weakness is the retrospective nature of the study. Moreover, as with many studies focusing on FP in oncology patients, the lack of data after reutilization of IVM oocytes prevents drawing reliable conclusions on the fate of these frozen gametes.
BC prognostic factors might influence IVM outcomes. Moreover, HER2 is likely to be involved in the ovarian function and oocyte maturation process. Further investigations are needed to better understand the mechanisms at play and their possible impact on the competence of IVM oocytes.
STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used and there are no conflicts of interest.
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乳腺癌（BC）特征是否会影响接受生育保存（FP）的年轻女性的卵母细胞体外成熟（IVM）结果？
Scarff-Bloom-Richardson（SBR）III 级、三阴性乳腺癌和 HER2 过表达是年轻女性寻求 FP 时卵母细胞数量少或 IVM 结局不佳的独立预测因素。
SBR 分级、三阴性状态和 HER2 过表达以及高 Ki67 增殖指数都是乳腺癌的既定预后因素，影响患者的治疗管理。然而，人们也担心癌症状态对卵巢储备和功能的潜在影响。之前分析 BC 患者卵巢刺激结果的研究得出了相互矛盾的发现。然而，目前尚无关于 BC 状态和预后因素对接受紧急 FP 的女性 IVM 结局潜在影响的数据。
研究设计、大小和持续时间：我们研究了 321 名年龄在 18 至 41 岁之间的 BC 患者，这些患者也是在 IVM 后进行卵母细胞冷冻保存的候选者。评估了获得的卵母细胞数量、成熟率和可冷冻保存的卵母细胞总数。
参与者/材料、设置、方法：根据 BC 特征（Ki67 增殖指数>20%、孕激素和/或雌激素受体表达、HER2 状态和 SBR 分级）比较卵巢储备标志物（窦卵泡计数 [AFC] 和血清抗苗勒管激素 [AMH] 水平）和 IVM 结果。然后进行逻辑回归分析，以确定与 IVM 结局不佳（如取卵率<50%、卵母细胞成熟率<60%和总冷冻卵母细胞数<5）相关的变量。
总体而言，人群的平均年龄为 32.3±4.1 岁。平均 AFC 和血清 AMH 水平分别为 22.8±13.9 个卵泡和 3.8±3.1ng/ml。与 ER/PR/HER2 状态阳性癌症相比，三阴性 BC 的 AMH 水平显着降低（3.1±2.6ng/ml 与 4.0±3.3ng/ml，P=0.02）。获得的卵母细胞数量平均为 10.2±9.1。平均成熟率为 58.0±26.1%后，每个周期可冷冻保存 5.8±5.3 个成熟卵母细胞。与 SBR I 或 II 肿瘤相比，SBR III 肿瘤患者的 IVM 后获得和冷冻保存的卵母细胞数量显着减少（9.6±8.7 与 11.7±9.8，P=0.02 和 5.4±5.4 与 6.6±5.8，P=0.02）。多变量统计分析显示，HER2 阳性状态与平均成熟率<60%相关（优势比：0.54；95%CI（0.30-0.97））。Ki67 和激素状态与 IVM 结局不佳无关。
局限性、谨慎的原因：该研究的一个弱点是回顾性。此外，由于许多关注肿瘤患者 FP 的研究，缺乏 IVM 卵母细胞再利用后的数据，因此无法得出关于这些冷冻配子命运的可靠结论。
BC 预后因素可能会影响 IVM 结果。此外，HER2 可能参与卵巢功能和卵母细胞成熟过程。需要进一步研究以更好地了解潜在的作用机制及其对 IVM 卵母细胞的潜在影响。
研究资金/利益冲突：没有使用特定的资金，也没有利益冲突。
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