Elective and Onco-fertility preservation: factors related to IVF outcomes
Elective and Onco-fertility preservation: factors related to IVF outcomes
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DOI：
10.1093/humrep/dey321
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发表时间：
2018-12-01
影响因子：
6.1
通讯作者：
Remohi, J.
中科院分区：
文献类型：
--
作者：
Cobo, A.;Garcia-Velasco, J.;Remohi, J.
研究问题：生育力保留（FP）的适应症是否与年龄相关生育力下降的选择性FP（EFP）和癌症治疗前FP（Onco-FP）后IVF周期的成功相关？总结回答：虽然癌症患者的成功率较低，但在校正年龄和控制性卵巢刺激（COS）方案后，恶性疾病和生殖结果之间没有统计学显著相关性。已知：FP越来越多地应用于辅助生殖，但对FP患者玻璃化冷冻卵母细胞的IVF周期的结果知之甚少。对2007年1月至2018年5月期间再次尝试妊娠的女性进行的FP玻璃化冷冻周期和加温周期的回顾性、观察性多中心研究。对象/材料，地点，方法：（EFP = 5289例患者; 7044个周期+ Onco-FP = 1073例患者; 1172个周期）将其卵母细胞玻璃化冷冻用于FP。进行逻辑回归分析，以检查根据玻璃化冷冻时年龄校正的FP适应症的影响。COS使用的方案也作为可能的混杂因素纳入。主要的结局指标是卵母细胞存活率和活产。提供了基线和临床数据的详细描述，以及EFP和Onco-FP之间的比较。根据玻璃化冷冻时的年龄，分析了那些返回使用卵母细胞的患者的累积活产率（CLBR）。主要结果和机会的作用：EFP患者玻璃化冷冻时的年龄明显更大（37.2 +/- 4.9比32.3 +/- 3.5岁; P < 0.0001）。EFP中每个周期回收和玻璃化冷冻的卵母细胞较少（分别为9.6 +/- 8.4 vs. 11.4 +/- 3.5和7.3 +/- 11.3 vs. 8.7 +/- 2.1; P < 0.05），但当按患者分析时，数量变得相当（12.8 +/- 7.4 vs. 12.5 +/- 3.2和9.8 +/- 6.4 vs. 9.5 +/- 2.6）。EFP的储存时间较短（2.1 +/- 1.6 vs. 4.1 +/- 0.9年; P < 0.0001）。EFP组641例（12.1%）和Onco-FP组80例（7.4%）再次尝试妊娠（P < 0.05）。总体卵母细胞存活率相当（83.9%与81.8%; NS），但年轻（= 35岁）受试者中的肿瘤FP患者较低（81.2%与91.4%; P > 0.05）。胚胎移植完成的EFP周期数较少（50.2%比72.5%）（P < 0.05）。种植率EFP组为42.6%，Onco-FP组为32.5%（P < 0.05）。年龄= 35岁的EFP患者的持续妊娠率（57.7% vs. 35.7%）和活产率（68.8% vs. 41.1%）高于Onco-FP匹配年龄患者（P < 0.05）。FP本身的原因对卵母细胞存活率（OR = 1.484 [95%CI = 0.876-2.252]; P = 0.202）或CLBR（OR = 1.275 [95%CI = 0.711-2.284]; P = 0.414）没有影响。相反，年龄（< 36岁vs = 36岁）影响卵母细胞存活率（调整OR = 1.922 [95% CI = 1.274-2.900]; P = 0.025）和CLBR（调整OR=3.106 [95% CI = 2.039-4.733]; P < 0.0001）。Kaplan-Meier分析显示，EFP组患者活产的累积概率显著较高< 36 versus >（P < 0.0001），当有更多的卵母细胞可用于IVF时，结局会有所改善。限制，预防原因：比较IVF结局的统计学功效受到Onco-FP组中使用卵母细胞的少数女性的限制。EFP组和ONCO-PP组患者的年龄和使用的COS方案显著不同。发现的更广泛的含义：尽管在Onco-FP患者中植入率显著较低，但癌症疾病本身的影响没有得到证实。EFP患者应根据他们的年龄和可用卵母细胞的数量进行咨询。研究资金/竞争利益：本研究没有使用外部资金。作者没有利益冲突。
STUDY QUESTION: Is the indication for fertility preservation (FP) related to success in IVF cycles after elective-FP (EFP) for age-related fertility decline and FP before cancer treatment (Onco-FP)?SUMMARY ANSWER: Although success rates were lower in cancer patients, there was no statistically significant association between malignant disease and reproductive outcome after correction for age and controlled-ovarian stimulation (COS) regime.WHAT IS KNOWN ALREADY: FP is increasingly applied in assisted reproduction, but little is known about the outcome of IVF cycles with vitrified oocytes in FP patients.STUDY DESIGN, SIZE, DURATION: Retrospective, observational multicenter study of vitrification cycles for FP and of the warming cycles of women who returned to attempt pregnancy from January 2007 to May 2018.PARTICIPANTS/MATERIALS, SETTING, METHODS: In all, 6362 women (EFP = 5289 patients; 7044 cycles + Onco-FP = 1073 patients; 1172 cycles) had their oocytes vitrified for FP. A logistic regression analysis was performed to examine the impact of indication for FP corrected for age at vitrification. The protocol used for COS was also included as a possible confounder. The main outcome measures were oocyte survival and live birth. A detailed description of the baseline and clinical data is provided, with comparisons between EFP and Onco-FP. The cumulative live birth rate (CLBR) per utilized oocyte according to age at vitrification was analyzed in those patients returning to use their oocytes.MAIN RESULTS AND ROLE OF CHANCE: Age at vitrification was significantly older in EFP patients (37.2 +/- 4.9 vs. 32.3 +/- 3.5 year; P < 0.0001). Fewer oocytes were retrieved and vitrified per cycle in EFP (9.6 +/- 8.4 vs. 11.4 +/- 3.5 and 7.3 +/- 11.3 vs. 8.7 +/- 2.1, respectively; P < 0.05), but numbers became comparable when analyzed per patient (12.8 +/- 7.4 vs. 12.5 +/- 3.2 and 9.8 +/- 6.4 vs. 9.5 +/- 2.6). Storage time was shorter in EFP (2.1 +/- 1.6 vs. 4.1 +/- 0.9 years; P < 0.0001). In all, 641 (12.1%) EFP and 80 (7.4%) Onco-FP patients returned to attempt pregnancy (P < 0.05). Overall oocyte survival was comparable (83.9% vs. 81.8%; NS), but lower for onco-FP patients among younger (= 35 year) subjects (81.2% vs. 91.4%; P > 0.05). Fewer EFP cycles finished in embryo transfer (50.2% vs. 72.5%) (P < 0.05). The implantation rate was 42.6% and 32.5% in EFP versus Onco-FP (P < 0.05). Ongoing pregnancy (57.7% vs. 35.7%) and live birth rates (68.8% vs. 41.1%) were higher in EFP patients aged = 35 than the Onco-FP matching age patients (P < 0.05). The reason for FP per se had no effect on oocyte survival (OR = 1.484 [95% CI = 0.876-2.252]; P = 0.202) or the CLBR (OR = 1.275 [95% CI = 0.711-2.284]; P = 0.414). Conversely, age (< 36 vs. = 36 y) impacted oocyte survival (adj. OR = 1.922 [95% CI = 1.274-2.900]; P = 0.025) and the CLBR (adj. OR=3.106 [95% CI = 2.039-4.733]; P < 0.0001). The Kaplan-Meier analysis showed a significantly higher cumulative probability of live birth in patients < 36 versus > 36 in EFP (P < 0.0001), with improved outcomes when more oocytes were available for IVF.LIMITATIONS, REASONS FOR CAUTION: Statistical power to compare IVF outcomes is limited by the few women who came to use their oocytes in the Onco-FP group. The patients' ages and the COS protocols used were significantly different between the EFP and ONCO-PP groups.WIDER IMPLICATIONS OF THE FINDINGS: Although the implantation rate was significantly lower in the Onco-FP patients the impact of cancer disease per se was not proven'. EFP patients should be counseled according to their age and number of available oocytes.STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest.