Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada.
Hum Reprod. 2019 Mar 1;34(3):530-538. doi: 10.1093/humrep/dey382.
Do the stage and grade of malignancy affect the fertility preservation outcome in females?
Patients with high-grade cancer have a decreased number of retrieved mature oocytes and cryopreserved embryos.
Cancer has local and systemic effects on the host. The effects of cancer spread and aggressiveness on the ovarian function and stimulation response remain unclear.
STUDY DESIGN, SIZE, DURATION: Retrospective cohort study evaluating data of all fertility preservation treatment cycles among women with cancer at the reproductive unit of the McGill University Health Centre in the period from 2008 to 2017.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Study inclusion criteria were age 18-38 years, first stimulation cycle, GnRH-antagonist protocol and early follicular phase stimulation start. Only one stimulation cycle per patient was included. Patients with ovarian pathology, previous ovarian surgery and previous chemo- or radiotherapy were excluded. The outcomes of women with low-stage cancer (local tumor Stage I-II, no lymph node involvement, no metastases) were compared with those with high-stage disease (local tumor Stage III-IV, lymph node involvement or metastases). Similarly we compared those with low-grade (G1-2) and high-grade (G3-4) malignancies. The primary outcome measure was the number of mature oocytes retrieved. The secondary outcomes included the total number of retrieved oocytes, the number of vitrified oocytes, and the number of frozen embryos. We used Student's t-test for normally distributed data and Wilcoxon test for skewed data. To determine factors associated with good fertility preservation outcome defined as over 10 retrieved mature oocytes, we used multivariate logistic regression.
A total of 147 patients were included in the final analysis. Age, body mass index, ovarian reserve parameters of the study groups in stage- and grade-based analyses were similar. Compared to women with low-stage cancer (n = 83), those with high-stage cancer (n = 64) required a higher dose of gonadotropin (P = 0.02). The number of retrieved mature oocytes (9 (7-13) versus 8 (5-12); P = 0.37) and vitrified oocytes (10 (7-15) versus 10 (7-13); P = 0.53) were similar between the two groups. However, in cycles where fertilization of all retrieved oocytes was performed, the fertilization rate (82.7% versus 71.5%; P = 0.03) and the number of vitrified embryos (6.2 ± 3.2 versus 4.3 ± 2.1; P = 0.01) were higher in the low-stage group. Compared to patients with low-grade cancer (n = 62), those with high-grade disease (n = 85) had significantly lower number of retrieved mature oocytes (11 (7-15) versus 8 (5-11); P = 0.002) and vitrified oocytes (12 (8-15) versus 10 (7-11); P = 0.005). The number of vitrified embryos was lower in high-grade group (6.5 ± 3.5 versus 4.6 ± 2.3; P = 0.03) in cycles where the fertilization was performed. In multivariate logistical analysis, the low-grade cancer was significantly associated with retrieval of over 10 mature oocytes (OR = 4.26; 95% CI 1.82-9.98; P = 0.0009).
LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study include its retrospective design and the relatively small sample size in the embryological outcome analysis. The results of our study should be viewed with caution as different malignancy types were included in the study groups, although their distribution between the study groups was similar.
Cancer grade seems to have a negative impact on the fertility preservation outcome and the ovarian stimulation response.
STUDY FUNDING/COMPETING INTEREST(S): Authors have not received any funding to support this study. There are no conflicts of interest to declare.
恶性肿瘤的分期和分级是否会影响女性的生育力保存结果？
高分级癌症患者的成熟卵母细胞数量和可冷冻胚胎数量减少。
癌症对宿主有局部和全身影响。癌症的扩散和侵袭性对卵巢功能和刺激反应的影响尚不清楚。
研究设计、规模、持续时间：这是一项回顾性队列研究，评估了 2008 年至 2017 年期间在麦吉尔大学健康中心生殖单位接受癌症生育力保存治疗的所有女性的生育力保存治疗周期的数据。
参与者/材料、设置、方法：研究纳入标准为年龄 18-38 岁、首次刺激周期、使用 GnRH 拮抗剂方案和早卵泡期开始刺激。每位患者仅纳入一个刺激周期。排除卵巢疾病、卵巢手术、化疗或放疗史的患者。低分期癌症（局部肿瘤 I-II 期，无淋巴结受累，无转移）患者的结果与高分期疾病（局部肿瘤 III-IV 期，淋巴结受累或转移）患者进行了比较。同样，我们比较了低分级（G1-2）和高分级（G3-4）恶性肿瘤患者的结果。主要结局指标是获得的成熟卵母细胞数量。次要结局包括总获卵数、可冷冻卵母细胞数和可冷冻胚胎数。我们使用学生 t 检验进行正态分布数据检验，使用 Wilcoxon 检验进行偏态数据检验。为了确定与获得超过 10 个成熟卵母细胞的良好生育力保存结果相关的因素，我们使用了多变量逻辑回归。
共有 147 名患者纳入最终分析。基于分期和分级的分析，两组患者的年龄、体重指数、研究组卵巢储备参数相似。与低分期癌症（n=83）患者相比，高分期癌症（n=64）患者需要更高剂量的促性腺激素（P=0.02）。两组患者获得的成熟卵母细胞数量（9（7-13）与 8（5-12）；P=0.37）和可冷冻卵母细胞数量（10（7-15）与 10（7-13）；P=0.53）相似。然而，在所有回收卵母细胞均进行受精的周期中，低分期组的受精率（82.7%比 71.5%；P=0.03）和可冷冻胚胎数（6.2±3.2 比 4.3±2.1；P=0.01）较高。与低分级癌症（n=62）患者相比，高分级疾病（n=85）患者获得的成熟卵母细胞数量明显减少（11（7-15）与 8（5-11）；P=0.002）和可冷冻卵母细胞数量（12（8-15）与 10（7-11）；P=0.005）。在进行受精的周期中，高分级组的可冷冻胚胎数（6.5±3.5 比 4.6±2.3；P=0.03）较低。在多变量逻辑回归分析中，低分级癌症与获得超过 10 个成熟卵母细胞显著相关（OR=4.26；95%CI 1.82-9.98；P=0.0009）。
局限性、谨慎的原因：研究的主要局限性包括其回顾性设计和胚胎学结局分析中相对较小的样本量。由于研究组中包括不同类型的癌症，因此应谨慎看待我们的研究结果，尽管它们在研究组中的分布相似。
癌症分级似乎对生育力保存结果和卵巢刺激反应有负面影响。
研究资金/利益冲突：作者没有得到任何资金支持来支持这项研究。没有利益冲突需要申报。
